Related Research
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ThyroidChange is dedicated to improving the diagnosis and treatment of thyroid disease. Below is a list of research studies that support the mission for improved thyroid health care. Please feel free to print this list for your reference. The following topics with corresponding research studies can be viewed below:
➤ Limitations of the TSH Lab Test and the Importance of Other Testing |
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Limitations of the TSH Lab Test and the Importance of Other Testing
Alevizaki, M., Mantzou, E., Cimponeriu, A. T., Alevizaki, C. C., & Koutras, D. A. (2005). TSH may not be a good marker for adequate thyroid hormone replacement therapy. Wiener Klinische Wochenschrift, 117(18), 636-640. Abstract: We conclude that patients with T4-treated hypothyroidism have lower T3 levels, lower T3/T4 ratio and lower SHBG than normal individuals with the same TSH, perhaps indicating relative tissue hypothyroidism in the liver. TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues.
Andersen S, Petersen KM, Brunn NH, Laurberg P (2002). Narrow individual variations in serum T4 and T3 in normal subjects: a clue to the understanding of subclinical thyroid disease. Journal of Clinical Endocrinology and Metabolism. 2002;87:1068–72. Abstract: High individuality causes laboratory reference ranges to be insensitive to changes in test results that are significant for the individual. Our data indicate that each individual had a unique thyroid function. The individual reference ranges for test results were narrow, compared with group reference ranges used to develop laboratory reference ranges. Accordingly, a test result within laboratory reference limits is not necessarily normal for an individual. Our data indicate that the distinction between subclinical and overt thyroid disease (abnormal serum TSH and abnormal T4 and/or T3) is somewhat arbitrary.
Becker DV, Bigos ST, Gaitan E, Morris JC, Rallison ML, Spencer CA, Sugarawa M, Van Middlesworth L, Wartofsky L. (1993). Optimal use of blood tests for assessment of thyroid function. Journal of the American Medical Association. 1993 Jun 2; 269: 273 Introduction: The decision to initiate (thyroid) therapy should be based on both clinical and laboratory findings and not solely on the results of a single laboratory test.
De Los Santos ET, Mazzaferri EL (1988). Sensitive thyroid-stimulating hormone assays: Clinical applications and limitations. Comprehensive Therapy. 1988; 14(9): 26-33. Abstract: Interpretation of the TSH value should be made with a clear understanding of its limitations. At present, it is uncertain whether clinically euthyroid patients with autonomously functioning thyroid nodules, or with multinodular goiters, or patients taking thyroid hormone who have suppressed TSH values, are actually euthyroid at a cellular level. Other factors that affect TSH levels are the biologic variation in its secretion, the presence of heterophilic antibodies in a patient's serum, and various drugs. The new ultrasensitive TSH assay does not yet replace other thyroid function tests, but it is clearly emerging as an important means of screening patients for thyroid dysfunction. It can usually separate patients with thyroid dysfunction from euthyroid individuals. Good clinical assessment is always necessary, and other thyroid function tests are often needed.
Després N, Grant A. (1998). Antibody interference in thyroid assays: a potential for clinical misinformation. Clinical Chemistry March 1998 vol. 44 no. 3 440-454. Abstract: Measurements of thyrotropin and of total and free thyroxine and triiodothyronine are widely used diagnostic methods for thyroid function evaluation. However, some serum samples will demonstrate a nonspecific binding with assay reagents that can interfere with the measurement of these hormones. Several recent case reports have described the presence of such interferences resulting in reported abnormal concentrations of thyroid hormones inconsistent with the patient’s thyroid state. Circulating thyroid hormone autoantibodies, described in thyroid and nonthyroid disorders, are an important class of interference factor and can bind to hormone tracers used in various immunoassays.
Dickey RA, Wartofsky L, Feld S. (2005). Optimal thyrotropin level: normal ranges and reference intervals are not equivalent. Thyroid. 2005 Sep;15(9):1035-9 Abstract: This paper marshals arguments in support of a narrower, optimal or true normal range for thyrotropin (TSH) of 0.4 to 2.5 mIU/L, based on clinical results and recent information on the relatively stable and narrow range of values in patients without thyroid disease. The terminology used for TSH results is clarified in an attempt to help physicians interpret, explain, and respond to TSH test results for their patients.
Goldberg A, Tirona R, Schwarz U, Kim RB, Van Uum SHM. (2001). Hypothyroidism with Very Low Free T3/Free T4 Ratio May Represent Decreased Peripheral Conversion of T4 to T3: Case Report and Differential Diagnosis. Endocrine Reviews. Vol. 32: P3-616. Abstract: A post-thyroidectomy patient exhibits a very low free T3/free T4 ratio and high TSH, suggesting hypothyroidism most likely caused by decreased conversion of T4 to T3. In this report, we discuss a diagnostic approach to the potential mechanisms of abnormal free T3/free T4 ratio.
Hoermann, R., Midgley, J. E., Giacobino, A., Eckl, W. A., Wahl, H. G., Dietrich, J. W., & Larisch, R. (2014). Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment. Clinical endocrinology. Conclusions: TSH, FT4 and FT3 each have their individual, but also interlocking roles to play in defining the overall patterns of thyroidal expression, regulation and metabolic activity. Equilibria typical of the healthy state are not invariant, but profoundly altered, for example, by L-T4 treatment. Consequently, this suggests the revisitation of strategies for treatment optimization.
Holtorf, K. (2014). Thyroid Hormone Transport into Cellular Tissue. Journal of Restorative Medicine, 3(1), 53-68. Chicago. Abstract: New research is demonstrating that thyroid hormone transport across cellular membranes plays an important role in intracellular triiodothyronine (T3) levels of peripheral and pituitary tissues and is proving to have considerable clinical significance. Reduced T4 and T3 transport into the cells in peripheral tissues is seen with a wide range of common conditions, including insulin resistance, diabetes, depression, bipolar disorder, hyperlipidemia, chronic fatigue syndrome, fibromyalgia, neurodegenerative diseases, migraines, stress, anxiety, chronic dieting and aging, while the intracellular T3 level in the pituitary often remains unaffected.
Holtorf, K. (2014). Peripheral Thyroid Hormone Conversion and Its Impact on TSH and Metabolic Activity. Journal of Restorative Medicine, 3(1), 30-52. Summary: Consequently, it is inappropriate to rely on a normal or low TSH as an adequate or sensitive indicator of normal or low tissue levels of T3 in the presence of any such conditions, making the TSH a poor marker for the body's overall thyroid level.
Holtorf, K. (2012). Hormone Replacement Therapy in the Geriatric Patient: Current State of the Evidence and Questions for the Future. Estrogen, Progesterone, Testosterone, and Thyroid Hormone Augmentation in Geriatric Clinical Practice. This article, independently written and published, is a broad study of hormone replacement in geriatric patients. In the thyroid section, written by Kent Holtorf M.D ., it details the difference between serum thyroid hormone levels and tissue thyroid hormone levels, particularly in cases of chronic and acute stress.
Pacchiarotti A, Martino E, Bartalena L, Aghini Lombardi F, Grasso L, Buratti L, Falcone M, Pinchera A (1986). Serum free thyroid hormones in subclinical hypothyroidism. Journal of Endocrinological Investigation. 1986 Aug;9(4):315-9. Abstract: These results indicate that FT4 should be measured in addition to TSH for the diagnosis of impending thyroid failure, thus showing that in many cases patients with so-called subclinical hypothyroidism are actually already mild hypothyroid.
Pritchard, E.K. (2013). Reducing the Scope of Guidelines and Policy Statements in Hypothyroidism. Journal of Orthomolecular Medicine. Volume 28, Number 2, 2013. Abstract: Although practice guidelines and policy statements on hypothyroidism are generally effective, many patients do not respond to the prescribed treatment. Significantly, clinicians routinely face the conundrum of either following the guidelines, which are ineffective, or ethically prescribing alternative (but proscribed) treatment, which might bring and has brought severe punishment by boards of medicine or medical councils.
Rowsemitt, C. and Najarian, T. (2011) TSH is Not the Answer: Rationale for a New Paradigm to Evaluate and Treat Hypothyroidism, Particularly Associated with Weight Loss. Thyroid Science; 6(4): H1-16. Conclusions: Treating to normalize thyroid hormone levels and eliminate hypothyroid symptoms results in the suppression of TSH. This is understood as a normal part of treatment once we accept that the thyroid set point has been lowered. This is not an argument to use thyroid hormones to increase metabolism above normal to achieve weight loss. Our goal is to correct the hypothyroid response in a weight loss patient and return him/her to normal metabolism so that the patient feels normal and is better able to lose weight and maintain that loss.
Ruhla, S., Arafat, A. M., Weickert, M. O., Osterhoff, M., Isken, F., Spranger, J., ... & Möhlig, M. (2011). T3/rT3-ratio is associated with insulin resistance independent of TSH. Hormone and metabolic research, 43(02), 130-134. Abstract: Here we show that the triiodothyronine/reverse triiodothyronine (T3/rT3- lab test ratio), which is supposed to reflect the tissue thyroid hormone metabolism, is significantly increased in insulin resistant subjects. This further supports a link between thyroid function and IR.
Sesmilo G, Simó O, Choque L, Casamitjana R, Puig-Domingo M (2011). Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central hypothyroidism compared with primary hypothyroidism and euthyroidism. Endocrinología y Nutrición. 2011 Jan;58(1):9-15 Conclusions: Treated patients with central hypothyroidism had a lower free T3 to free T4 ratio, similar free T3 levels and higher free T4 concentrations than euthyroid controls, whereas all these parameters were similar in central and primary hypothyroid patients treated with T4. The question of whether these findings translate into adequate tissue concentrations of free thyroid hormones in all tissues remains to be answered. Further studies should aim to determine whether clinical outcomes could be improved by a treatment achieving more physiological plasma concentrations.
Skinner GRB, Holmes D, Ahmad A, Davies JA, Benitez J (2000). Clinical Response to Thyroxine Sodium in Clinically Hypothyroid but Biochemically Euthyroid Patients. Journal of Nutritional and Environmental Medicine. Vol. 10, No. 2 , Pages 115-124. Conclusions: Clinically hypothyroid but biochemically euthyroid patients had favourable clinical response to thyroid replacement which correlated with the level of thyroid replacement. It is suggested that these findings be examined in a prospective placebo controlled clinical trial.
Skinner GR, Thomas R, Taylor M, Sellarajah M, Bolt S, Krett S, Wright A. (1997). Thyroxine should be tried in clinically hypothyroid but biochemically euthyroid patients. British Medical Journal: June 14; 314(7096).
van den Beld, A.W., Visser, T., Feelders, R., Grobbee, R., Lamberts, W.J., (2005) Effect of Exogenous Thyroid Hormone Intake on the Interpretation of Serum TSH Results. The Journal of Clinical Endocrinology & Metabolism; 90 (12): 6403-6409. Conclusions: In a population of independently living elderly men, higher FT4 and RT3 concentrations are associated with a lower physical function.
Wartofsky L, Dickey, R (2005). The Evidence for a Narrower Thyrotropin Reference Range Is Compelling. The Journal of Clinical Endocrinology & Metabolism. September 1, 2005 vol. 90 no. 9 5483-5488. Abstract: Debate and controversy currently surround the recommendations of a recent consensus conference that considered issues related to the management of early, mild, or so-called subclinical hypothyroidism and hyperthyroidism. Intimately related to the controversy is the definition of the normal reference range for TSH. Recognition and establishment of a more precise and true normal range for TSH have important implications for both screening and treatment of thyroid disease in general and subclinical thyroid disease in particular.
Woeber, K. A. (2002). Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations. Journal of endocrinological investigation, 25(2), 106-109. Abstract: These findings indicate that in hypothyroid patients L-T4-replacement, that is sufficient to maintain a normal serum TSH, is accompanied by a serum free T4 that is higher than that in untreated euthyroid patients or normal individuals and may not result in an appropriately normal serum free T3 concentration.
Alevizaki, M., Mantzou, E., Cimponeriu, A. T., Alevizaki, C. C., & Koutras, D. A. (2005). TSH may not be a good marker for adequate thyroid hormone replacement therapy. Wiener Klinische Wochenschrift, 117(18), 636-640. Abstract: We conclude that patients with T4-treated hypothyroidism have lower T3 levels, lower T3/T4 ratio and lower SHBG than normal individuals with the same TSH, perhaps indicating relative tissue hypothyroidism in the liver. TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues.
Andersen S, Petersen KM, Brunn NH, Laurberg P (2002). Narrow individual variations in serum T4 and T3 in normal subjects: a clue to the understanding of subclinical thyroid disease. Journal of Clinical Endocrinology and Metabolism. 2002;87:1068–72. Abstract: High individuality causes laboratory reference ranges to be insensitive to changes in test results that are significant for the individual. Our data indicate that each individual had a unique thyroid function. The individual reference ranges for test results were narrow, compared with group reference ranges used to develop laboratory reference ranges. Accordingly, a test result within laboratory reference limits is not necessarily normal for an individual. Our data indicate that the distinction between subclinical and overt thyroid disease (abnormal serum TSH and abnormal T4 and/or T3) is somewhat arbitrary.
Becker DV, Bigos ST, Gaitan E, Morris JC, Rallison ML, Spencer CA, Sugarawa M, Van Middlesworth L, Wartofsky L. (1993). Optimal use of blood tests for assessment of thyroid function. Journal of the American Medical Association. 1993 Jun 2; 269: 273 Introduction: The decision to initiate (thyroid) therapy should be based on both clinical and laboratory findings and not solely on the results of a single laboratory test.
De Los Santos ET, Mazzaferri EL (1988). Sensitive thyroid-stimulating hormone assays: Clinical applications and limitations. Comprehensive Therapy. 1988; 14(9): 26-33. Abstract: Interpretation of the TSH value should be made with a clear understanding of its limitations. At present, it is uncertain whether clinically euthyroid patients with autonomously functioning thyroid nodules, or with multinodular goiters, or patients taking thyroid hormone who have suppressed TSH values, are actually euthyroid at a cellular level. Other factors that affect TSH levels are the biologic variation in its secretion, the presence of heterophilic antibodies in a patient's serum, and various drugs. The new ultrasensitive TSH assay does not yet replace other thyroid function tests, but it is clearly emerging as an important means of screening patients for thyroid dysfunction. It can usually separate patients with thyroid dysfunction from euthyroid individuals. Good clinical assessment is always necessary, and other thyroid function tests are often needed.
Després N, Grant A. (1998). Antibody interference in thyroid assays: a potential for clinical misinformation. Clinical Chemistry March 1998 vol. 44 no. 3 440-454. Abstract: Measurements of thyrotropin and of total and free thyroxine and triiodothyronine are widely used diagnostic methods for thyroid function evaluation. However, some serum samples will demonstrate a nonspecific binding with assay reagents that can interfere with the measurement of these hormones. Several recent case reports have described the presence of such interferences resulting in reported abnormal concentrations of thyroid hormones inconsistent with the patient’s thyroid state. Circulating thyroid hormone autoantibodies, described in thyroid and nonthyroid disorders, are an important class of interference factor and can bind to hormone tracers used in various immunoassays.
Dickey RA, Wartofsky L, Feld S. (2005). Optimal thyrotropin level: normal ranges and reference intervals are not equivalent. Thyroid. 2005 Sep;15(9):1035-9 Abstract: This paper marshals arguments in support of a narrower, optimal or true normal range for thyrotropin (TSH) of 0.4 to 2.5 mIU/L, based on clinical results and recent information on the relatively stable and narrow range of values in patients without thyroid disease. The terminology used for TSH results is clarified in an attempt to help physicians interpret, explain, and respond to TSH test results for their patients.
Goldberg A, Tirona R, Schwarz U, Kim RB, Van Uum SHM. (2001). Hypothyroidism with Very Low Free T3/Free T4 Ratio May Represent Decreased Peripheral Conversion of T4 to T3: Case Report and Differential Diagnosis. Endocrine Reviews. Vol. 32: P3-616. Abstract: A post-thyroidectomy patient exhibits a very low free T3/free T4 ratio and high TSH, suggesting hypothyroidism most likely caused by decreased conversion of T4 to T3. In this report, we discuss a diagnostic approach to the potential mechanisms of abnormal free T3/free T4 ratio.
Hoermann, R., Midgley, J. E., Giacobino, A., Eckl, W. A., Wahl, H. G., Dietrich, J. W., & Larisch, R. (2014). Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment. Clinical endocrinology. Conclusions: TSH, FT4 and FT3 each have their individual, but also interlocking roles to play in defining the overall patterns of thyroidal expression, regulation and metabolic activity. Equilibria typical of the healthy state are not invariant, but profoundly altered, for example, by L-T4 treatment. Consequently, this suggests the revisitation of strategies for treatment optimization.
Holtorf, K. (2014). Thyroid Hormone Transport into Cellular Tissue. Journal of Restorative Medicine, 3(1), 53-68. Chicago. Abstract: New research is demonstrating that thyroid hormone transport across cellular membranes plays an important role in intracellular triiodothyronine (T3) levels of peripheral and pituitary tissues and is proving to have considerable clinical significance. Reduced T4 and T3 transport into the cells in peripheral tissues is seen with a wide range of common conditions, including insulin resistance, diabetes, depression, bipolar disorder, hyperlipidemia, chronic fatigue syndrome, fibromyalgia, neurodegenerative diseases, migraines, stress, anxiety, chronic dieting and aging, while the intracellular T3 level in the pituitary often remains unaffected.
Holtorf, K. (2014). Peripheral Thyroid Hormone Conversion and Its Impact on TSH and Metabolic Activity. Journal of Restorative Medicine, 3(1), 30-52. Summary: Consequently, it is inappropriate to rely on a normal or low TSH as an adequate or sensitive indicator of normal or low tissue levels of T3 in the presence of any such conditions, making the TSH a poor marker for the body's overall thyroid level.
Holtorf, K. (2012). Hormone Replacement Therapy in the Geriatric Patient: Current State of the Evidence and Questions for the Future. Estrogen, Progesterone, Testosterone, and Thyroid Hormone Augmentation in Geriatric Clinical Practice. This article, independently written and published, is a broad study of hormone replacement in geriatric patients. In the thyroid section, written by Kent Holtorf M.D ., it details the difference between serum thyroid hormone levels and tissue thyroid hormone levels, particularly in cases of chronic and acute stress.
Pacchiarotti A, Martino E, Bartalena L, Aghini Lombardi F, Grasso L, Buratti L, Falcone M, Pinchera A (1986). Serum free thyroid hormones in subclinical hypothyroidism. Journal of Endocrinological Investigation. 1986 Aug;9(4):315-9. Abstract: These results indicate that FT4 should be measured in addition to TSH for the diagnosis of impending thyroid failure, thus showing that in many cases patients with so-called subclinical hypothyroidism are actually already mild hypothyroid.
Pritchard, E.K. (2013). Reducing the Scope of Guidelines and Policy Statements in Hypothyroidism. Journal of Orthomolecular Medicine. Volume 28, Number 2, 2013. Abstract: Although practice guidelines and policy statements on hypothyroidism are generally effective, many patients do not respond to the prescribed treatment. Significantly, clinicians routinely face the conundrum of either following the guidelines, which are ineffective, or ethically prescribing alternative (but proscribed) treatment, which might bring and has brought severe punishment by boards of medicine or medical councils.
Rowsemitt, C. and Najarian, T. (2011) TSH is Not the Answer: Rationale for a New Paradigm to Evaluate and Treat Hypothyroidism, Particularly Associated with Weight Loss. Thyroid Science; 6(4): H1-16. Conclusions: Treating to normalize thyroid hormone levels and eliminate hypothyroid symptoms results in the suppression of TSH. This is understood as a normal part of treatment once we accept that the thyroid set point has been lowered. This is not an argument to use thyroid hormones to increase metabolism above normal to achieve weight loss. Our goal is to correct the hypothyroid response in a weight loss patient and return him/her to normal metabolism so that the patient feels normal and is better able to lose weight and maintain that loss.
Ruhla, S., Arafat, A. M., Weickert, M. O., Osterhoff, M., Isken, F., Spranger, J., ... & Möhlig, M. (2011). T3/rT3-ratio is associated with insulin resistance independent of TSH. Hormone and metabolic research, 43(02), 130-134. Abstract: Here we show that the triiodothyronine/reverse triiodothyronine (T3/rT3- lab test ratio), which is supposed to reflect the tissue thyroid hormone metabolism, is significantly increased in insulin resistant subjects. This further supports a link between thyroid function and IR.
Sesmilo G, Simó O, Choque L, Casamitjana R, Puig-Domingo M (2011). Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central hypothyroidism compared with primary hypothyroidism and euthyroidism. Endocrinología y Nutrición. 2011 Jan;58(1):9-15 Conclusions: Treated patients with central hypothyroidism had a lower free T3 to free T4 ratio, similar free T3 levels and higher free T4 concentrations than euthyroid controls, whereas all these parameters were similar in central and primary hypothyroid patients treated with T4. The question of whether these findings translate into adequate tissue concentrations of free thyroid hormones in all tissues remains to be answered. Further studies should aim to determine whether clinical outcomes could be improved by a treatment achieving more physiological plasma concentrations.
Skinner GRB, Holmes D, Ahmad A, Davies JA, Benitez J (2000). Clinical Response to Thyroxine Sodium in Clinically Hypothyroid but Biochemically Euthyroid Patients. Journal of Nutritional and Environmental Medicine. Vol. 10, No. 2 , Pages 115-124. Conclusions: Clinically hypothyroid but biochemically euthyroid patients had favourable clinical response to thyroid replacement which correlated with the level of thyroid replacement. It is suggested that these findings be examined in a prospective placebo controlled clinical trial.
Skinner GR, Thomas R, Taylor M, Sellarajah M, Bolt S, Krett S, Wright A. (1997). Thyroxine should be tried in clinically hypothyroid but biochemically euthyroid patients. British Medical Journal: June 14; 314(7096).
van den Beld, A.W., Visser, T., Feelders, R., Grobbee, R., Lamberts, W.J., (2005) Effect of Exogenous Thyroid Hormone Intake on the Interpretation of Serum TSH Results. The Journal of Clinical Endocrinology & Metabolism; 90 (12): 6403-6409. Conclusions: In a population of independently living elderly men, higher FT4 and RT3 concentrations are associated with a lower physical function.
Wartofsky L, Dickey, R (2005). The Evidence for a Narrower Thyrotropin Reference Range Is Compelling. The Journal of Clinical Endocrinology & Metabolism. September 1, 2005 vol. 90 no. 9 5483-5488. Abstract: Debate and controversy currently surround the recommendations of a recent consensus conference that considered issues related to the management of early, mild, or so-called subclinical hypothyroidism and hyperthyroidism. Intimately related to the controversy is the definition of the normal reference range for TSH. Recognition and establishment of a more precise and true normal range for TSH have important implications for both screening and treatment of thyroid disease in general and subclinical thyroid disease in particular.
Woeber, K. A. (2002). Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations. Journal of endocrinological investigation, 25(2), 106-109. Abstract: These findings indicate that in hypothyroid patients L-T4-replacement, that is sufficient to maintain a normal serum TSH, is accompanied by a serum free T4 that is higher than that in untreated euthyroid patients or normal individuals and may not result in an appropriately normal serum free T3 concentration.
The Need for Additional Treatment Options
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Acosta B, Bianco, A C (2010). New insights into thyroid hormone replacement therapy. Medicine Reports. 2010; 2: 34. Abstract: Physicians continue to report benefits from combined levothyroxine-triidothyronine therapy for some hypothyroid patients. Recently, a large prospective study reported that the benefit of the combined levothyroxine-triidothyronine therapy is associated with the Thr92Ala polymorphism in the type 2 deiodinase gene, which is present in about 15% of the general population. If confirmed, these findings indicate that personalized medicine is rapidly catching up with modern thyroidology.
Appelhof, B. C., Fliers, E., Wekking, E. M., Schene, A. H., Huyser, J., Tijssen, J. G., ... & Wiersinga, W. M. (2005). Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial. The Journal of Clinical Endocrinology & Metabolism, 90(5), 2666-2674. Abstract: Patients preferred combined LT4/LT3 therapy to usual LT4 therapy, but changes in mood, fatigue, well-being, and neurocognitive functions could not satisfactorily explain why the primary outcome was in favor of LT4/LT3 combination therapy. Decrease in body weight was associated with satisfaction with study medication.
Baisier, W.V., Hertoghe, J., and Eeckhaut, W. (2001). Thyroid Insufficiency: Is Thyroxine the Only Valuable Drug? Journal of Nutritional and Environmental Medicine, 11:159-166, 2001. Results: A number of these patients were followed up during treatment with natural desiccated thyroid (NDT): 40 T4 treated patients and 278 untreated patients. Both groups responded equally favourably to NDT. Conclusions: Combined T3 + T4 treatment seems to be more effective than treatment with T4 alone in hypothyroid patients.
Benevicius R, Kazanavicius G, Zalinkovicius R, Prange AJ (1999). Effects of thyroxine (T4) as compared with thyroxine (T4) plus triiodothyronine (T3) in patients with hypothyroidism. New England Journal of Medicine.1999; 340: 424-9. Conclusions: In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine (medication) may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland.
Biondi, B., & Wartofsy, L. (2012). Combination Treatment with T4 and T3: Toward Personalized Replacement Therapy in Hypothyroidism?. The Journal of Clinical Endocrinology & Metabolism. Conclusions: Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.
Celi, F. S., Zemskova, M., Linderman, J. D., Smith, S., Drinkard, B., Sachdev, V., ... & Pucino, F. (2011). Metabolic effects of liothyronine therapy in hypothyroidism: a randomized, double-blind, crossover trial of liothyronine versus levothyroxine. The Journal of Clinical Endocrinology & Metabolism,96(11), 3466-3474. Results: Liothyronine (l-T3) resulted in significant weight loss [l-T4, 70.6 ± 12.5, vs. l-T3, 68.5 ± 11.9 kg (P = 0.009)] and in a 10.9 ± 10.0% decrease in total cholesterol (P = 0.002), 13.3 ± 12.1% decrease in low-density lipoprotein-cholesterol (P = 0.002), and an 18.3 ± 28.6% decrease in apolipoprotein B (P = 0.018). Conclusions: The substitution of l-T3 for Levothyroxine (l-T4) at equivalent doses (relative to the pituitary) reduced body weight and resulted in greater thyroid hormone action on the lipid metabolism, without detected differences in cardiovascular function or insulin sensitivity.
Chakera, A.J., Pearce, S.H., Vaidya, B. (2012) Treatment for primary hypothyroidism: current approaches and future possibilities. Drug Des Devel Ther.; 6: 1-11. Conclusion: Treatment for primary hypothyroidism: current approaches and future possibilities. Primary hypothyroidism is the most common endocrine disease. Although the diagnosis and treatment of hypothyroidism is often considered simple, there are large numbers of people with this condition who are suboptimally treated. Even in those people with hypothyroidism who are biochemically euthyroid on levothyroxine replacement there is a significant proportion who report poorer quality of life. This review explores the historical and current treatment options for hypothyroidism, reasons for and potential solutions to suboptimal treatment, and future possibilities in the treatment of hypothyroidism.
Chernow B, Burman KD, Johnson DL, McGuire RA, O'Brian JT, Wartofsky L, Georges LP (1983). T3 may be a better agent than T4 in the critically ill hypothyroid patient: evaluation of transport across the blood-brain barrier in a primate model. Critical Care Medicine. 1983 Feb;11(2):99-104. Conclusions: These data suggest: (a) T4, T3, and reverse T3 are all capable of bidirectional transfer across the blood brain barrier, (b) T3 may be a better agent than T4 in treating patients with myxedema coma because T3 crosses more rapidly and more completely from serum to cerebrospinal fluid (CSF).
Cooper-Kazaz, R., Apter, J. T., Cohen, R., Karagichev, L., Muhammed-Moussa, S., Grupper, D., ... & Lerer, B. (2007). Combined treatment with sertraline and liothyronine in major depression: a randomized, double-blind, placebo-controlled trial. Archives of general psychiatry, 64(6), 679-688. Conclusions: These results demonstrate enhancement of the antidepressant effect of sertraline by concurrent treatment with liothyronine without a significant increase in adverse effects. The antidepressant effect of liothyronine may be directly linked to thyroid function.
Escobar-Morreale HF, del Rey FE, Obregon MJ, de Escobar GM (1996). Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat. Endocrinology. 1996 Jun;137(6):2490-502 Abstract: We have recently shown that it is not possible to restore euthyroidism completely in all tissues of thyroidectomized rats infused with T4 alone. Results: Combined replacement therapy with T4 and T3 (in proportions similar to those secreted by the normal rat thyroid) completely restored euthyroidism in thyroidectomized rats at much lower doses of T4 than those needed to normalize T3 in most tissues when T4 alone was used. If pertinent to man, these results might well justify a change in the current therapy for hypothyroidism.
Gautam Das, Shweta Anand & Parijat De (2007). Does synthetic thyroid extract work for everybody? Endocrine Abstracts (2007) 13 P316.
Introduction: Synthetic levothyroxine (L-Thyroxine) is the treatment of choice for hypothyroidism. It is safe, effective and generally well tolerated. Some patients, however, cannot tolerate L-Thyroxine. There is still some controversy about the effectiveness of combination T4 & T3 therapy. We describe 3 patients who were successfully treated with Armour thyroid (pork extract of T4 & T3) after being intolerant to L-Thyroxine. Although L-Thyroxine remains the treatment of choice in the majority, a trial of Armour could be considered in patients who have not responded to this conventional treatment and who remain symptomatic with raised serum TSH levels.
Gullo, D., Latina, A., Frasca, F., Le Moli, R., Pellegriti, G., & Vigneri, R. (2011). Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One, 6(8), e22552. Conclusions: Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients.
Hoang, T., Olsen, C., Mai, V., Clyde, P., Shakir, M. (2013). Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study. The Journal of Clinical Endocrinology & Metabolism; May 1, 2013 vol. 98 no. 5 1982-1990. Conclusion: Desiccated thyroid extract (DTE) therapy did not result in a significant improvement in quality of life (over levothyroxine); however, DTE caused modest weight loss and nearly half (48.6%) of the study patients expressed preference for DTE over l-T4. DTE therapy may be relevant for some hypothyroid patients.
Hoermann, R., Midgley, J. E., Giacobino, A., Eckl, W. A., Wahl, H. G., Dietrich, J. W., & Larisch, R. (2014). Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment. Clinical endocrinology. Conclusions: TSH, FT4 and FT3 each have their individual, but also interlocking roles to play in defining the overall patterns of thyroidal expression, regulation and metabolic activity. Equilibria typical of the healthy state are not invariant, but profoundly altered, for example, by L-T4 treatment. Consequently, this suggests the revisitation of strategies for treatment optimization.
Holtorf, K. (2014). Thyroid Hormone Transport into Cellular Tissue. Journal of Restorative Medicine, 3(1), 53-68. Chicago. Abstract: New research is demonstrating that thyroid hormone transport across cellular membranes plays an important role in intracellular triiodothyronine (T3) levels of peripheral and pituitary tissues and is proving to have considerable clinical significance....A combination of both clinical and laboratory assessment, which may include a T3/reverse T3 ratio and the level of sex hormone binding globulin (SHBG), should be used to determine the likely overall thyroid status and if a therapeutic trail of straight T3 or a T4/T3 combination is indicated and not based solely on standard thyroid function tests.
Lowe, J.C. (1995) T3-Induced Recovery from Fibromyalgia by a Hypothyroid Patient Resistant to T4 and Desiccated Thyroid. Journal Myofascial Ther., 1(4):26-31. Conclusions: Studies have shown no other therapies for fibromyalgia to be significantly effective,[16] while millions of fibromyalgia patients suffer non-remitting symptoms.[17] Because of this, clinicians and researchers should not ignore the possible benefits of T3 therapy for their fibromyalgia patients.
Nygaard B, Jensen EW, Kvetny J, Jarlov A, Faber J (2009). Effect of combination therapy with thyroxine (T4) and 3,5,3′-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study. European Journal of Endocrinology. December 161 895-902. Objective: To compare the effect of combination therapy with thyroxine (T4) and T3 versus T4 monotherapy in patients with hypothyroidism on stable T4 substitution. Conclusion: In a study design, where morning TSH levels were unaltered between groups combination therapy, (treated with T3 20 μg once daily) was superior to monotherapy by evaluating several QOL, depression and anxiety rating scales as well as patients own preference.
Pepper GM and Casanova-Romero PY (2014). Conversion to Armour Thyroid from Levothyroxine Improved Patient Satisfaction in the Treatment of Hypothyroidism. Journal of Endocrinology, Diabetes & Obesity. September, 11 2014. Conclusion: AT treatment was preferred over LT4 replacement therapy by 78% of patients with hypothyroidism in the sub-group with persistent subjective complaints while on T4-only therapy. No serious adverse events were noted while on AT treatment including 30 subjects aged 65 yrs or older. AT could be a reasonable alternative choice for treating this sub-group of patients with hypothyroidism.
Pritchard, E.K. (2013). Reducing the Scope of Guidelines and Policy Statements in Hypothyroidism. Journal of Orthomolecular Medicine. Volume 28, Number 2, 2013. Abstract: Although practice guidelines and policy statements on hypothyroidism are generally effective, many patients do not respond to the prescribed treatment. Significantly, clinicians routinely face the conundrum of either following the guidelines, which are ineffective, or ethically prescribing alternative (but proscribed) treatment, which might bring and has brought severe punishment by boards of medicine or medical councils.
Robertas Bunevičius, M.D., Ph.D., Gintautas Kažanavičius, M.D., Ph.D., Rimas Žalinkevičius, M.D., and Arthur J. Prange, Jr., M.D. (1999). Effects of Thyroxine as Compared with Thyroxine plus Triiodothyronine in Patents with Hypothyroidism. New England Journal of Medicine
; 340:424-429. Conclusions: In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland.
Snyder, S., Listecki, R.E (2012) Bioidentical thyroid replacement therapy in practice: Delivering a physiologic T4:T3 ratio for improved patient outcomes with the Listecki-Snyder protocol. International Journal of Pharmaceutical Compound; 16(5): 376-378. Conclusion: Bioidentical thyroid replacement therapy in practice: Delivering a physiologic T4:T3 ratio for improved patient outcomes with the Listecki-Snyder protocol
Effective thyroid replacement therapy may be elusive to some patients, and compounding pharmacists have an opportunity to deliver more effective therapy. Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th edition states that the body usually secretes T4:T3 in an 11:1 ratio but cautions against pursuing combined thyroid replacement due to the short halflife of T3 that necessitates multiple daily dosing; no commercial availability and lack of benefit were shown in trials.
Weltman, N. Y., Ojamaa, K., Schlenker, E. H., Chen, Y. F., Zucchi, R., Saba, A., ... & Gerdes, A. M. (2014). Low-dose T3 replacement restores depressed cardiac T3 levels, preserves coronary microvasculature, and attenuates cardiac dysfunction in experimental diabetes mellitus. Molecular medicine (Cambridge, Mass.). Abstract: We conclude that cardiac dysfunction in chronic diabetes mellitus (DM) may be associated with tissue hypothyroidism despite normal serum thyroid hormone levels. Low-dose T3 replacement appears to be a safe and effective adjunct therapy to attenuate and/or reverse cardiac remodeling and dysfunction induced by experimental DM.
Wiersinga, W. M., & DeGroot, L. J. (2010). Adult hypothyroidism. Thyroid Disease Manager. Available at: www. thyroidmanager. org/chapter/adulthypothyroidism/# toc-9-2-definition-and-epidemiology-of-hypothyroidism. Accessed: Nov, 16, 2011. See section 9.8 "Treatment of Hypothyroidism".
Woeber, K. A. (2002). Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations. Journal of endocrinological investigation, 25(2), 106-109. Abstract: These findings indicate that in hypothyroid patients L-T4-replacement, that is sufficient to maintain a normal serum TSH, is accompanied by a serum free T4 that is higher than that in untreated euthyroid patients or normal individuals and may not result in an appropriately normal serum free T3 concentration.
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Acosta B, Bianco, A C (2010). New insights into thyroid hormone replacement therapy. Medicine Reports. 2010; 2: 34. Abstract: Physicians continue to report benefits from combined levothyroxine-triidothyronine therapy for some hypothyroid patients. Recently, a large prospective study reported that the benefit of the combined levothyroxine-triidothyronine therapy is associated with the Thr92Ala polymorphism in the type 2 deiodinase gene, which is present in about 15% of the general population. If confirmed, these findings indicate that personalized medicine is rapidly catching up with modern thyroidology.
Appelhof, B. C., Fliers, E., Wekking, E. M., Schene, A. H., Huyser, J., Tijssen, J. G., ... & Wiersinga, W. M. (2005). Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial. The Journal of Clinical Endocrinology & Metabolism, 90(5), 2666-2674. Abstract: Patients preferred combined LT4/LT3 therapy to usual LT4 therapy, but changes in mood, fatigue, well-being, and neurocognitive functions could not satisfactorily explain why the primary outcome was in favor of LT4/LT3 combination therapy. Decrease in body weight was associated with satisfaction with study medication.
Baisier, W.V., Hertoghe, J., and Eeckhaut, W. (2001). Thyroid Insufficiency: Is Thyroxine the Only Valuable Drug? Journal of Nutritional and Environmental Medicine, 11:159-166, 2001. Results: A number of these patients were followed up during treatment with natural desiccated thyroid (NDT): 40 T4 treated patients and 278 untreated patients. Both groups responded equally favourably to NDT. Conclusions: Combined T3 + T4 treatment seems to be more effective than treatment with T4 alone in hypothyroid patients.
Benevicius R, Kazanavicius G, Zalinkovicius R, Prange AJ (1999). Effects of thyroxine (T4) as compared with thyroxine (T4) plus triiodothyronine (T3) in patients with hypothyroidism. New England Journal of Medicine.1999; 340: 424-9. Conclusions: In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine (medication) may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland.
Biondi, B., & Wartofsy, L. (2012). Combination Treatment with T4 and T3: Toward Personalized Replacement Therapy in Hypothyroidism?. The Journal of Clinical Endocrinology & Metabolism. Conclusions: Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.
Celi, F. S., Zemskova, M., Linderman, J. D., Smith, S., Drinkard, B., Sachdev, V., ... & Pucino, F. (2011). Metabolic effects of liothyronine therapy in hypothyroidism: a randomized, double-blind, crossover trial of liothyronine versus levothyroxine. The Journal of Clinical Endocrinology & Metabolism,96(11), 3466-3474. Results: Liothyronine (l-T3) resulted in significant weight loss [l-T4, 70.6 ± 12.5, vs. l-T3, 68.5 ± 11.9 kg (P = 0.009)] and in a 10.9 ± 10.0% decrease in total cholesterol (P = 0.002), 13.3 ± 12.1% decrease in low-density lipoprotein-cholesterol (P = 0.002), and an 18.3 ± 28.6% decrease in apolipoprotein B (P = 0.018). Conclusions: The substitution of l-T3 for Levothyroxine (l-T4) at equivalent doses (relative to the pituitary) reduced body weight and resulted in greater thyroid hormone action on the lipid metabolism, without detected differences in cardiovascular function or insulin sensitivity.
Chakera, A.J., Pearce, S.H., Vaidya, B. (2012) Treatment for primary hypothyroidism: current approaches and future possibilities. Drug Des Devel Ther.; 6: 1-11. Conclusion: Treatment for primary hypothyroidism: current approaches and future possibilities. Primary hypothyroidism is the most common endocrine disease. Although the diagnosis and treatment of hypothyroidism is often considered simple, there are large numbers of people with this condition who are suboptimally treated. Even in those people with hypothyroidism who are biochemically euthyroid on levothyroxine replacement there is a significant proportion who report poorer quality of life. This review explores the historical and current treatment options for hypothyroidism, reasons for and potential solutions to suboptimal treatment, and future possibilities in the treatment of hypothyroidism.
Chernow B, Burman KD, Johnson DL, McGuire RA, O'Brian JT, Wartofsky L, Georges LP (1983). T3 may be a better agent than T4 in the critically ill hypothyroid patient: evaluation of transport across the blood-brain barrier in a primate model. Critical Care Medicine. 1983 Feb;11(2):99-104. Conclusions: These data suggest: (a) T4, T3, and reverse T3 are all capable of bidirectional transfer across the blood brain barrier, (b) T3 may be a better agent than T4 in treating patients with myxedema coma because T3 crosses more rapidly and more completely from serum to cerebrospinal fluid (CSF).
Cooper-Kazaz, R., Apter, J. T., Cohen, R., Karagichev, L., Muhammed-Moussa, S., Grupper, D., ... & Lerer, B. (2007). Combined treatment with sertraline and liothyronine in major depression: a randomized, double-blind, placebo-controlled trial. Archives of general psychiatry, 64(6), 679-688. Conclusions: These results demonstrate enhancement of the antidepressant effect of sertraline by concurrent treatment with liothyronine without a significant increase in adverse effects. The antidepressant effect of liothyronine may be directly linked to thyroid function.
Escobar-Morreale HF, del Rey FE, Obregon MJ, de Escobar GM (1996). Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat. Endocrinology. 1996 Jun;137(6):2490-502 Abstract: We have recently shown that it is not possible to restore euthyroidism completely in all tissues of thyroidectomized rats infused with T4 alone. Results: Combined replacement therapy with T4 and T3 (in proportions similar to those secreted by the normal rat thyroid) completely restored euthyroidism in thyroidectomized rats at much lower doses of T4 than those needed to normalize T3 in most tissues when T4 alone was used. If pertinent to man, these results might well justify a change in the current therapy for hypothyroidism.
Gautam Das, Shweta Anand & Parijat De (2007). Does synthetic thyroid extract work for everybody? Endocrine Abstracts (2007) 13 P316.
Introduction: Synthetic levothyroxine (L-Thyroxine) is the treatment of choice for hypothyroidism. It is safe, effective and generally well tolerated. Some patients, however, cannot tolerate L-Thyroxine. There is still some controversy about the effectiveness of combination T4 & T3 therapy. We describe 3 patients who were successfully treated with Armour thyroid (pork extract of T4 & T3) after being intolerant to L-Thyroxine. Although L-Thyroxine remains the treatment of choice in the majority, a trial of Armour could be considered in patients who have not responded to this conventional treatment and who remain symptomatic with raised serum TSH levels.
Gullo, D., Latina, A., Frasca, F., Le Moli, R., Pellegriti, G., & Vigneri, R. (2011). Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One, 6(8), e22552. Conclusions: Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients.
Hoang, T., Olsen, C., Mai, V., Clyde, P., Shakir, M. (2013). Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study. The Journal of Clinical Endocrinology & Metabolism; May 1, 2013 vol. 98 no. 5 1982-1990. Conclusion: Desiccated thyroid extract (DTE) therapy did not result in a significant improvement in quality of life (over levothyroxine); however, DTE caused modest weight loss and nearly half (48.6%) of the study patients expressed preference for DTE over l-T4. DTE therapy may be relevant for some hypothyroid patients.
Hoermann, R., Midgley, J. E., Giacobino, A., Eckl, W. A., Wahl, H. G., Dietrich, J. W., & Larisch, R. (2014). Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment. Clinical endocrinology. Conclusions: TSH, FT4 and FT3 each have their individual, but also interlocking roles to play in defining the overall patterns of thyroidal expression, regulation and metabolic activity. Equilibria typical of the healthy state are not invariant, but profoundly altered, for example, by L-T4 treatment. Consequently, this suggests the revisitation of strategies for treatment optimization.
Holtorf, K. (2014). Thyroid Hormone Transport into Cellular Tissue. Journal of Restorative Medicine, 3(1), 53-68. Chicago. Abstract: New research is demonstrating that thyroid hormone transport across cellular membranes plays an important role in intracellular triiodothyronine (T3) levels of peripheral and pituitary tissues and is proving to have considerable clinical significance....A combination of both clinical and laboratory assessment, which may include a T3/reverse T3 ratio and the level of sex hormone binding globulin (SHBG), should be used to determine the likely overall thyroid status and if a therapeutic trail of straight T3 or a T4/T3 combination is indicated and not based solely on standard thyroid function tests.
Lowe, J.C. (1995) T3-Induced Recovery from Fibromyalgia by a Hypothyroid Patient Resistant to T4 and Desiccated Thyroid. Journal Myofascial Ther., 1(4):26-31. Conclusions: Studies have shown no other therapies for fibromyalgia to be significantly effective,[16] while millions of fibromyalgia patients suffer non-remitting symptoms.[17] Because of this, clinicians and researchers should not ignore the possible benefits of T3 therapy for their fibromyalgia patients.
Nygaard B, Jensen EW, Kvetny J, Jarlov A, Faber J (2009). Effect of combination therapy with thyroxine (T4) and 3,5,3′-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study. European Journal of Endocrinology. December 161 895-902. Objective: To compare the effect of combination therapy with thyroxine (T4) and T3 versus T4 monotherapy in patients with hypothyroidism on stable T4 substitution. Conclusion: In a study design, where morning TSH levels were unaltered between groups combination therapy, (treated with T3 20 μg once daily) was superior to monotherapy by evaluating several QOL, depression and anxiety rating scales as well as patients own preference.
Pepper GM and Casanova-Romero PY (2014). Conversion to Armour Thyroid from Levothyroxine Improved Patient Satisfaction in the Treatment of Hypothyroidism. Journal of Endocrinology, Diabetes & Obesity. September, 11 2014. Conclusion: AT treatment was preferred over LT4 replacement therapy by 78% of patients with hypothyroidism in the sub-group with persistent subjective complaints while on T4-only therapy. No serious adverse events were noted while on AT treatment including 30 subjects aged 65 yrs or older. AT could be a reasonable alternative choice for treating this sub-group of patients with hypothyroidism.
Pritchard, E.K. (2013). Reducing the Scope of Guidelines and Policy Statements in Hypothyroidism. Journal of Orthomolecular Medicine. Volume 28, Number 2, 2013. Abstract: Although practice guidelines and policy statements on hypothyroidism are generally effective, many patients do not respond to the prescribed treatment. Significantly, clinicians routinely face the conundrum of either following the guidelines, which are ineffective, or ethically prescribing alternative (but proscribed) treatment, which might bring and has brought severe punishment by boards of medicine or medical councils.
Robertas Bunevičius, M.D., Ph.D., Gintautas Kažanavičius, M.D., Ph.D., Rimas Žalinkevičius, M.D., and Arthur J. Prange, Jr., M.D. (1999). Effects of Thyroxine as Compared with Thyroxine plus Triiodothyronine in Patents with Hypothyroidism. New England Journal of Medicine
; 340:424-429. Conclusions: In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland.
Snyder, S., Listecki, R.E (2012) Bioidentical thyroid replacement therapy in practice: Delivering a physiologic T4:T3 ratio for improved patient outcomes with the Listecki-Snyder protocol. International Journal of Pharmaceutical Compound; 16(5): 376-378. Conclusion: Bioidentical thyroid replacement therapy in practice: Delivering a physiologic T4:T3 ratio for improved patient outcomes with the Listecki-Snyder protocol
Effective thyroid replacement therapy may be elusive to some patients, and compounding pharmacists have an opportunity to deliver more effective therapy. Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th edition states that the body usually secretes T4:T3 in an 11:1 ratio but cautions against pursuing combined thyroid replacement due to the short halflife of T3 that necessitates multiple daily dosing; no commercial availability and lack of benefit were shown in trials.
Weltman, N. Y., Ojamaa, K., Schlenker, E. H., Chen, Y. F., Zucchi, R., Saba, A., ... & Gerdes, A. M. (2014). Low-dose T3 replacement restores depressed cardiac T3 levels, preserves coronary microvasculature, and attenuates cardiac dysfunction in experimental diabetes mellitus. Molecular medicine (Cambridge, Mass.). Abstract: We conclude that cardiac dysfunction in chronic diabetes mellitus (DM) may be associated with tissue hypothyroidism despite normal serum thyroid hormone levels. Low-dose T3 replacement appears to be a safe and effective adjunct therapy to attenuate and/or reverse cardiac remodeling and dysfunction induced by experimental DM.
Wiersinga, W. M., & DeGroot, L. J. (2010). Adult hypothyroidism. Thyroid Disease Manager. Available at: www. thyroidmanager. org/chapter/adulthypothyroidism/# toc-9-2-definition-and-epidemiology-of-hypothyroidism. Accessed: Nov, 16, 2011. See section 9.8 "Treatment of Hypothyroidism".
Woeber, K. A. (2002). Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations. Journal of endocrinological investigation, 25(2), 106-109. Abstract: These findings indicate that in hypothyroid patients L-T4-replacement, that is sufficient to maintain a normal serum TSH, is accompanied by a serum free T4 that is higher than that in untreated euthyroid patients or normal individuals and may not result in an appropriately normal serum free T3 concentration.
Cognitive and Emotional Impairment with Thyroid Disease
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Boillet, D., Szoke, A. (1998). Psychiatric manifestations as the only clinical sign of hypothyroidism. Apropos of a case. Encephale: 24(1):65-8. Conclusion: The endocrine investigation has documented, in spite of the absence of any suggestive physical signs, a thyroid insufficiency. After the replacement treatment, all symptoms but the cognitive dysfunction disappeared. The patient's evolution is presented clinically, also rated on MMSE and MADRS scales, and biologically (TSH and T4 determination) for a 4 months period. The absence of any pathognomonical psychiatric finding, the possibility of the absence of other signs and symptoms (namely physical) in the hypothyroid state, the presence of potentially irreversible cognitive deterioration, as well as the inocuity and sensibility of thyroid hormones examination justify the systematic thyroid evaluation for all new psychiatric patients.
Carta, MG., Hardoy, MC., Carpiniello, B., Murru, A., Marci, AR., Carbone, F., Deiana, l., Cadeddu, M., Mariotti, S. (2005). A case control study on psychiatric disorders in Hashimoto disease and Euthyroid Goitre: not only depressive but also anxiety disorders are associated with thyroid autoimmunity. Clin Pract Epidemiol Ment Health; 10:1-23. Conclusion: The study seems to confirm that risk for depressive disorders in subjects with thyroiditis is independent of the thyroid function detected by routine tests and indicates that not only mood but also anxiety disorders may be associated with Hashimoto disease.
Davis, A.T. (1989). Psychotic states associated with disorders of thyroid function. Int J Psychiatry Med. 1989;19(1):47-56. Conclusions: Thyroid-related psychoses continue to pose diagnostic and treatment challenges for clinicians. Two case histories illustrate diverse clinical states associated with hyper- and hypo-thyroidism respectively and highlight the need to consider the possibility of thyroid disorder in all patients presenting with acute psychotic mental disorder. They also demonstrate treatment methods directed at control of psychotic symptoms and restoration of an euthyroid state.
Gold, M.S., Pottash, A.L., Extein, I. (1982). "Symptomless" autoimmune thyroiditis in depression. Psychiatry Res. 1982 Jun; 6(3):261-9. Conclusion: The magnitude of the thyroid-stimulating hormone (TSH) response induced by thyrotropin-releasing hormone (TRH) helps identify patients whosethyroid is failing. Many of these patients have been found to have Hashimoto's thyroiditis, symptomless autoimmune thyroiditis (SAT), and subclinical hypothyroidism. While patients with SAT are clinically euthyroid, what might be "symptomless" for the endocrinologist might be a syndrome presenting with psychiatric symptoms to the psychiatrist. As a preliminary test of this hypothesis, we tested 100 consecutive admissions to a psychiatric hospital who complained of depression or lack of energy. Fifteen (15%) of 100 patients were identified from the baseline thyroxin (T4), triiodothyronine (T3) resin uptake (RU), T3 radioimmunoassay (T3RIA), TSH, and TRH test who met criteria for either subclinical, mild, or overt hypothyroidism. Of these 15 patients, 9 (60%) had positive thyroid microsomal antibodies with titers of greater than or equal to 1:10. Our data suggest that SAT is not symptomless and may be an important diagnosis to consider in the evaluation of depressed, anergic, or atypical patients.
Hage, M.P., Azar, S.T. (2011). The Link between Thyroid Function and Depression. Journal of Thyroid Research; Vol. 2012 (Article ID 590648). Conclusion: Clinical investigators have long recognized the link between thyroid and depression. While patients with hypothyroidism commonly manifest features of depression, hyperthyroidism presents with a wider spectrum of neuropsychiatric symptoms including both depression and anxiety...Screening patients presenting with depression for thyroid dysfunction seems reasonable particularly those with refractory symptoms. However, the use of thyroid hormones as an adjunct therapy to antidepressants in the absence of subclinical or clinical hypothyroidism should be further investigated. In addition, specifying a particular patient population that might benefit from this combination as determined by individual genetic variants should be addressed.
Haggerty, J.J., Jr., Evans, D.L., Golden, R.N., Pedersen, C.A., Simon, J.S., Nemeroff, C.B. (1990). The presence of antithyroid antibodies in patients with affective and nonaffective psychiatric disorders. Biol Psychiatry; 27(1):51-60. Conclusions: Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder, even in the absence of lithium exposure. However, as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders, the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation.
Hall, R C W, Popkin M, Devaul R, Hall, A K, Gardner E, Beresford T (1982). Psychiatric Manifestations of Hashimoto’s Thyroiditis. Psychosomatics. Volume 23, Issue 4, April 1982, Pages 337-342. Abstract: The mental symptoms associated with Hashimoto's thyroiditis may precede the full-blown, classic picture of hypothyroidism. The psychiatric symptoms include various mental aberrations, depression, irritability, and confusion. Indeed, patients may be mislabeled as having psychotic depression, paranoid schizophrenia, or the manic phase of a manic depressive disorder. The workup must include a thorough evaluation of thyroid function, including tests for autoantibodies. Patients usually respond favorably to thyroid replacement hormone therapy.
Hendrick, V., Altshuler, L., Whybrow, P. (1998) Psychoneuroendocrinology of mood disorders. The hypothalamic-pituitary-thyroid axis. Psychiatr Clin North Am. 1998 Jun;21(2):277-92. Conclusions: Abnormal thyroid functioning can affect mood and influence the course of unipolar and bipolar disorder. Even mild thyroid dysfunction has been associated with changes in mood and cognitive functioning. Thyroid hormone supplementation may have role in the treatment of certain mood disorders, particularly rapid-cycling bipolar disorder. Women are more vulnerable to thyroid dysfunction than men and also respond better to thyroidaugmentation. This article reviews the relationship between thyroid function and mood, and the use of thyroid hormones in the treatment of mood disorders. The impact of gender on these issues is also discussed.
Jackson, I.M. (1998). Thyroid Axis and Depression. Thyroid: 8 (10): 951-6. Conclusion: It is known that in human depression there is a functional disconnection of the hypothalamus with impairment of the inhibitory glucocorticoid feedback pathway from the hippocampus to the hypothalamus that results in the typical elevated cortisol levels and impaired dexamethasone suppression. It is postulated that a similar situation prevails with regards to the thyroid axis and that the increased T4 in depression, as well as the blunted TSH response to exogenous TRH, reflects glucocorticoid activation of the TRH neuron leading to increased TRH secretion with resultant down regulation of the TRH receptor on the thyrotrope. Normalization of thyroid function after treatment may result in part from an inhibitory response of the TRH neuron to antidepressant medication, although other effects may also be responsible.
McGaffee, J. Barnes, MA, Lippmann, S. (1981) Psychiatric Presentations of Hypothyroidism. American Family Physician; 23 (5): 129-133. Conclusion: Hypothyroidism can often be misdiagnosed as psychiatric illness. The hypothyroid patient may present with depression, an organic mental disorder, apathy and/or frank psychosis (usually with paranoid symptoms). Psychiatric manifestations of the endocrinopathy will abate with thyroid hormone replacement therapy, unless the disease state has been sufficiently prolonged to cause some irreversible brain damage. This irreversibility mandates prompt diagnosis and specific hormonal replacement therapy. Thus, thyroid function screening is recommended for patients presenting with depression, psychosis or organic mental disorder.
Placidi, G.P.A., Boldrini M., Patronelli A., Fiore E., Chiovato L., Perugi G., Marazziti D. (1998) Prevalence of Psychiatric Disorders in Thyroid Diseased Patients. Neuropsychobiology; 38:222–225. Conclusion: The results showed higher rates of panic disorder, simple phobia, obsessive-compulsive disorder, major depressive disorder, bipolar disorder and cyclothymia in thyroid patients than in the general population. These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities.
Rack, S.K., Makela, E.H. (2000) Hypothyroidism and depression: a therapeutic challenge. Ann Pharmacother; 34(10):1142-5. Conclusions: Depressed patients should be screened for hypothyroidism. In hypothyroid patients, depression may be more responsive to a replacement regimen that includes T3 rather than T4 alone. Therefore, inclusion of T3 in the treatment regimen may be warranted after adequate trial with T4 alone.
Reed K, Bland RC (1977). Masked "myxedema madness". Acta Psychiatr Scand. 1977 Nov;56(5):421-6. Abstract: Hypothyroidism can present a wide range of psychiatric manifestations, including personality disturbance, neurotic traits and psychotic features. Psychiatric treatment techniques without recognition and correction of the endocrine root of the mental disturbance will result in a failure of treatment. However, severe hypothyroidism can exist with a poverty of classical signs and symptoms such that both internist and psychiatrist may easily overlook endocrine dysfunction as a possible etiology of the mental disorder. A case of long-standing paranoid illness whose etiology was severe myxedema with such a poverty of signs and symptoms is presented.
Wiersinga, W. M., & DeGroot, L. J. (2010). Adult hypothyroidism. Thyroid Disease Manager. Available at: www. thyroidmanager. org/chapter/adulthypothyroidism/# toc-9-2-definition-and-epidemiology-of-hypothyroidism. Accessed: Nov, 16, 2011. See section 9.5.3 "Nervous System" and Table 9-10 "Incidence of symptoms and signs in hypothyroidism".
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Boillet, D., Szoke, A. (1998). Psychiatric manifestations as the only clinical sign of hypothyroidism. Apropos of a case. Encephale: 24(1):65-8. Conclusion: The endocrine investigation has documented, in spite of the absence of any suggestive physical signs, a thyroid insufficiency. After the replacement treatment, all symptoms but the cognitive dysfunction disappeared. The patient's evolution is presented clinically, also rated on MMSE and MADRS scales, and biologically (TSH and T4 determination) for a 4 months period. The absence of any pathognomonical psychiatric finding, the possibility of the absence of other signs and symptoms (namely physical) in the hypothyroid state, the presence of potentially irreversible cognitive deterioration, as well as the inocuity and sensibility of thyroid hormones examination justify the systematic thyroid evaluation for all new psychiatric patients.
Carta, MG., Hardoy, MC., Carpiniello, B., Murru, A., Marci, AR., Carbone, F., Deiana, l., Cadeddu, M., Mariotti, S. (2005). A case control study on psychiatric disorders in Hashimoto disease and Euthyroid Goitre: not only depressive but also anxiety disorders are associated with thyroid autoimmunity. Clin Pract Epidemiol Ment Health; 10:1-23. Conclusion: The study seems to confirm that risk for depressive disorders in subjects with thyroiditis is independent of the thyroid function detected by routine tests and indicates that not only mood but also anxiety disorders may be associated with Hashimoto disease.
Davis, A.T. (1989). Psychotic states associated with disorders of thyroid function. Int J Psychiatry Med. 1989;19(1):47-56. Conclusions: Thyroid-related psychoses continue to pose diagnostic and treatment challenges for clinicians. Two case histories illustrate diverse clinical states associated with hyper- and hypo-thyroidism respectively and highlight the need to consider the possibility of thyroid disorder in all patients presenting with acute psychotic mental disorder. They also demonstrate treatment methods directed at control of psychotic symptoms and restoration of an euthyroid state.
Gold, M.S., Pottash, A.L., Extein, I. (1982). "Symptomless" autoimmune thyroiditis in depression. Psychiatry Res. 1982 Jun; 6(3):261-9. Conclusion: The magnitude of the thyroid-stimulating hormone (TSH) response induced by thyrotropin-releasing hormone (TRH) helps identify patients whosethyroid is failing. Many of these patients have been found to have Hashimoto's thyroiditis, symptomless autoimmune thyroiditis (SAT), and subclinical hypothyroidism. While patients with SAT are clinically euthyroid, what might be "symptomless" for the endocrinologist might be a syndrome presenting with psychiatric symptoms to the psychiatrist. As a preliminary test of this hypothesis, we tested 100 consecutive admissions to a psychiatric hospital who complained of depression or lack of energy. Fifteen (15%) of 100 patients were identified from the baseline thyroxin (T4), triiodothyronine (T3) resin uptake (RU), T3 radioimmunoassay (T3RIA), TSH, and TRH test who met criteria for either subclinical, mild, or overt hypothyroidism. Of these 15 patients, 9 (60%) had positive thyroid microsomal antibodies with titers of greater than or equal to 1:10. Our data suggest that SAT is not symptomless and may be an important diagnosis to consider in the evaluation of depressed, anergic, or atypical patients.
Hage, M.P., Azar, S.T. (2011). The Link between Thyroid Function and Depression. Journal of Thyroid Research; Vol. 2012 (Article ID 590648). Conclusion: Clinical investigators have long recognized the link between thyroid and depression. While patients with hypothyroidism commonly manifest features of depression, hyperthyroidism presents with a wider spectrum of neuropsychiatric symptoms including both depression and anxiety...Screening patients presenting with depression for thyroid dysfunction seems reasonable particularly those with refractory symptoms. However, the use of thyroid hormones as an adjunct therapy to antidepressants in the absence of subclinical or clinical hypothyroidism should be further investigated. In addition, specifying a particular patient population that might benefit from this combination as determined by individual genetic variants should be addressed.
Haggerty, J.J., Jr., Evans, D.L., Golden, R.N., Pedersen, C.A., Simon, J.S., Nemeroff, C.B. (1990). The presence of antithyroid antibodies in patients with affective and nonaffective psychiatric disorders. Biol Psychiatry; 27(1):51-60. Conclusions: Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder, even in the absence of lithium exposure. However, as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders, the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation.
Hall, R C W, Popkin M, Devaul R, Hall, A K, Gardner E, Beresford T (1982). Psychiatric Manifestations of Hashimoto’s Thyroiditis. Psychosomatics. Volume 23, Issue 4, April 1982, Pages 337-342. Abstract: The mental symptoms associated with Hashimoto's thyroiditis may precede the full-blown, classic picture of hypothyroidism. The psychiatric symptoms include various mental aberrations, depression, irritability, and confusion. Indeed, patients may be mislabeled as having psychotic depression, paranoid schizophrenia, or the manic phase of a manic depressive disorder. The workup must include a thorough evaluation of thyroid function, including tests for autoantibodies. Patients usually respond favorably to thyroid replacement hormone therapy.
Hendrick, V., Altshuler, L., Whybrow, P. (1998) Psychoneuroendocrinology of mood disorders. The hypothalamic-pituitary-thyroid axis. Psychiatr Clin North Am. 1998 Jun;21(2):277-92. Conclusions: Abnormal thyroid functioning can affect mood and influence the course of unipolar and bipolar disorder. Even mild thyroid dysfunction has been associated with changes in mood and cognitive functioning. Thyroid hormone supplementation may have role in the treatment of certain mood disorders, particularly rapid-cycling bipolar disorder. Women are more vulnerable to thyroid dysfunction than men and also respond better to thyroidaugmentation. This article reviews the relationship between thyroid function and mood, and the use of thyroid hormones in the treatment of mood disorders. The impact of gender on these issues is also discussed.
Jackson, I.M. (1998). Thyroid Axis and Depression. Thyroid: 8 (10): 951-6. Conclusion: It is known that in human depression there is a functional disconnection of the hypothalamus with impairment of the inhibitory glucocorticoid feedback pathway from the hippocampus to the hypothalamus that results in the typical elevated cortisol levels and impaired dexamethasone suppression. It is postulated that a similar situation prevails with regards to the thyroid axis and that the increased T4 in depression, as well as the blunted TSH response to exogenous TRH, reflects glucocorticoid activation of the TRH neuron leading to increased TRH secretion with resultant down regulation of the TRH receptor on the thyrotrope. Normalization of thyroid function after treatment may result in part from an inhibitory response of the TRH neuron to antidepressant medication, although other effects may also be responsible.
McGaffee, J. Barnes, MA, Lippmann, S. (1981) Psychiatric Presentations of Hypothyroidism. American Family Physician; 23 (5): 129-133. Conclusion: Hypothyroidism can often be misdiagnosed as psychiatric illness. The hypothyroid patient may present with depression, an organic mental disorder, apathy and/or frank psychosis (usually with paranoid symptoms). Psychiatric manifestations of the endocrinopathy will abate with thyroid hormone replacement therapy, unless the disease state has been sufficiently prolonged to cause some irreversible brain damage. This irreversibility mandates prompt diagnosis and specific hormonal replacement therapy. Thus, thyroid function screening is recommended for patients presenting with depression, psychosis or organic mental disorder.
Placidi, G.P.A., Boldrini M., Patronelli A., Fiore E., Chiovato L., Perugi G., Marazziti D. (1998) Prevalence of Psychiatric Disorders in Thyroid Diseased Patients. Neuropsychobiology; 38:222–225. Conclusion: The results showed higher rates of panic disorder, simple phobia, obsessive-compulsive disorder, major depressive disorder, bipolar disorder and cyclothymia in thyroid patients than in the general population. These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities.
Rack, S.K., Makela, E.H. (2000) Hypothyroidism and depression: a therapeutic challenge. Ann Pharmacother; 34(10):1142-5. Conclusions: Depressed patients should be screened for hypothyroidism. In hypothyroid patients, depression may be more responsive to a replacement regimen that includes T3 rather than T4 alone. Therefore, inclusion of T3 in the treatment regimen may be warranted after adequate trial with T4 alone.
Reed K, Bland RC (1977). Masked "myxedema madness". Acta Psychiatr Scand. 1977 Nov;56(5):421-6. Abstract: Hypothyroidism can present a wide range of psychiatric manifestations, including personality disturbance, neurotic traits and psychotic features. Psychiatric treatment techniques without recognition and correction of the endocrine root of the mental disturbance will result in a failure of treatment. However, severe hypothyroidism can exist with a poverty of classical signs and symptoms such that both internist and psychiatrist may easily overlook endocrine dysfunction as a possible etiology of the mental disorder. A case of long-standing paranoid illness whose etiology was severe myxedema with such a poverty of signs and symptoms is presented.
Wiersinga, W. M., & DeGroot, L. J. (2010). Adult hypothyroidism. Thyroid Disease Manager. Available at: www. thyroidmanager. org/chapter/adulthypothyroidism/# toc-9-2-definition-and-epidemiology-of-hypothyroidism. Accessed: Nov, 16, 2011. See section 9.5.3 "Nervous System" and Table 9-10 "Incidence of symptoms and signs in hypothyroidism".
The Connection Between Adrenal Function and Thyroid Health
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Backhaus, J., Junghanns, K., Hohagen, F. (2004). Sleep disturbances are correlated with decreased morning awakening salivary cortisol
Psychoneuroendocrinology; Volume 29, Issue 9, Pages 1184–1191. Results: Cortisol after awakening was significantly decreased in primary insomnia. Salivary cortisol at the time of awakening correlated negatively with the subjective estimation of sleep quality, i.e. a low salivary cortisol level directly after awakening correlated with a higher frequency of nightly awakenings, a diminished sleep quality and a decreased feeling of recovery after awakening.
Di Giorgio, A., Hudson, M., Jerjes, W., Cleare, A. (2005). 24-Hour Pituitary and Adrenal Hormone Profiles in Chronic Fatigue Syndrome.
Psychosomatic Medicine; vol. 67 no. 3 433-440 Conclusions: Patients with CFS demonstrated subtle alterations in HPA axis activity characterized by reduced ACTH over a full circadian cycle and reduced levels during the usual morning physiological peak ACTH secretion. This provides further evidence of subtle dysregulation of the HPA axis in CFS. Whether this dysregulation is a primary feature of the illness or instead represents a biologic effect secondary to having the illness itself remains unclear.
Head, K.A., Kelly, G.S. (2009) Nutrients and Botanicals for Treatment of Stress: Adrenal Fatigue, Neurotransmitter Imbalance, Anxiety, and Restless Sleep. Alternative Medicine Review; Jun;14(2):114-40. Abstract: Research shows a dramatic increase in use of the medical system during times of stress, such as job insecurity. Stress is a factor in many illnesses - from headaches to heart disease, and immune deficiencies to digestive problems. A substantial contributor to stress-induced decline in health appears to be an increased production of stress hormones and subsequent decreased immune function. Non-pharmaceutical approaches have much to offer such patients. This article focuses on the use of nutrients and botanicals to support the adrenals, balance neurotransmitters, treat acute anxiety, and support restful sleep.
Hills, S.R., Reiss, R.S., Orsham, P.H., George, W.T. (1950) The effect of adrenocorticotropin and cortisone on thyroid function: thyroidadrenocortical interrelationships. The Journal of Clinical Endocrinology & Metabolism, vol. 10 no. 11. Excerpt: A depression of thyroid function in animals and in man has been reported following stress, the administration of cortisone acetate (11-dehydro-17-hydroxycorticosterone acetate), ACTH (adrenocorticotropic hormone) and epinephrine (25–29). In patients with Addison's disease, the thyroid depression induced by cortisone was preceded by an initial stimulation. The availability of ACTH, TSH and cortisone for clinical use and the improvement in the techniques of measuring thyroid and adrenal cortical function have stimulated further work on the thyroid-adrenal relationship.
Holtorf, K. (2007). Diagnosis and treatment of hypothalamic-pituitary-adrenal (HPA) axis dysfunction in patients with chronic fatigue syndrome (CFS) and fibromyalgia (FM). Journal of Chronic Fatigue Syndrome, 14(3), 59-88. Abstract: Because treatment with low physiologic doses of cortisol (<15 mg) has been shown to be safe and effective and routine dynamic ACTH testing does not have adequate diagnostic sensitivity, it is reasonable to give a therapeutic trial of physiologic doses of cortisol to the majority of patients with CFS and FM, especially to those who have symptoms that are consistent with adrenal dysfunction, have low blood pressure or have baseline cortisol levels in the low or low-normal range.
Kamilaris, C.T., Debold, C.R., Pavlous, S.N., Island, D.P., Hoursanidis, A. Orth, D.N. (1987) Effect of Altered Thyroid Hormone Levels on Hypothalamic-Pituitary-Adrenal Function. The Journal of Clinical Endocrinology & Metabolism; vol. 65 no. 5 994-999. Conclusions: These results indicate that thyroid hormone deficiency of short duration 1) increases corticotroph sensitivity to oCRH, 2) may diminish the plasma ACTH response to metyrapone-induced hypocortisolemia, and 3) has no apparent effect on the acute adrenal response to ACTH. These data together with those of previous studies that have shown reduced responses of the hypothalamic-pituitary-adrenal axis to metyrapone and hypoglycemia in hypothyroid patients suggest that the release of hypothalamic CRH and/or other ACTH secretagogues may be decreased in hypothyroidism.
Musselman, D.L., Nemeroff, C.B. (1996). Depression and endocrine disorders: focus on the thyroid and adrenal system. The British Journal of Psychiatry. 1996(30):123-128. Abstract: Concerning the HPT axis, depressed patients have been reported to have: (a) alterations in thyroid-stimulating hormone response to thyrotropin-releasing hormone (TRH); (b) an abnormally high rate of antithyroid antibodies; and (c) elevated cerebrospinal fluid (CSF) TRH concentrations. Moreover, tri-iodothyronine has been shown conclusively to augment the efficacy of various antidepressants. Concerning the HPA axis, depressed patients have been reported to exhibit: (a) adrenocorticoid hypersecretion; (b) enlarged pituitary and adrenal gland size; and (c) elevated CSF corticotropin-releasing factor concentrations.
Peterson, R.E. (1958) The Influence of the Thyroid on Adrenal Cortical Function. The Journal of Clinical Investigation; vol 37(5). Conclusions: It is suggested from these data that there is a homeostatic mechanism mediated through the liver-pituitary-adrenals which results in a decreased synthesis of cortisol in patients with myxedema in whom the rate of removal of cortisol by the liver is impaired, and an increased synthesis of cortisol in patients of thyrotoxicosis in whom the rate of removal of cortisol by the liver is accelerated.
Rodríguez-Gutiérrez, R., González-Velázquez, C., González-Saldívar, G., Villarreal-Pérez, J. Z., & González-González, J. G. (2014). Glucocorticoid Functional Reserve in Full-Spectrum Intensity of Primary Hypothyroidism.International Journal of Endocrinology, 2014. Conclusion: Patients with different degrees of intensity of primary hypothyroidism had improved cortisol response after reaching euthyroidism. The incidence of adrenal insufficiency was 6.7–18.3% and more than 50% of the cases had a normal cortisol response after L-T4 therapy. This finding could have important clinical implications especially in the setting of acute stress situations occurring during the period while a euthyroid state is still not achieved.
Scott, L.V., Salahuddin, F., Cooney, J., Svec, F., Dinan, T. (1999). Differences in adrenal steroid profile in chronic fatigue syndrome, in depression and in health. Journal of Affective Disorders; vol 5: issues 1-2: 129-137. Results: DHEA and DHEA-S levels were significantly lower in the CFS compared to the healthy group; DHEA-S levels, but not DHEA, were lower in the depressives; cortisol and 17-alphahydroxyprogesterone did not differ between the three groups. Conclusions: A potential role for DHEA, both therapeutically and as a diagnostic tool, in CFS, is suggested.
Van Den Eede F., Moorkens G., Van Houdenhove B., Cosyns P, Claes S. (2007) Hypothalamic-Pituitary-Adrenal Axis Function in Chronic Fatigue Syndrome. Neuropsychobiology; Vol. 55, No. 2, 2007. Abstract: There is evidence for a hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis in a proportion of the patients with chronic fatigue syndrome (CFS), despite the negative studies and methodological difficulties. In this review, we focus on challenge studies and on the role of the HPA axis in the pathogenesis of CFS. Mild hypocortisolism, blunted adrenocorticotropin response to stressors and enhanced negative feedback sensitivity to glucocorticoids are the main findings. Several underlying mechanisms have been proposed. Currently, it is a matter of debate whether these disturbances have a primary role in the pathogenesis of CFS. However, even if the HPA axis dysfunctions are secondary to other factors, they are probably a relevant factor in symptom propagation in CFS.
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Backhaus, J., Junghanns, K., Hohagen, F. (2004). Sleep disturbances are correlated with decreased morning awakening salivary cortisol
Psychoneuroendocrinology; Volume 29, Issue 9, Pages 1184–1191. Results: Cortisol after awakening was significantly decreased in primary insomnia. Salivary cortisol at the time of awakening correlated negatively with the subjective estimation of sleep quality, i.e. a low salivary cortisol level directly after awakening correlated with a higher frequency of nightly awakenings, a diminished sleep quality and a decreased feeling of recovery after awakening.
Di Giorgio, A., Hudson, M., Jerjes, W., Cleare, A. (2005). 24-Hour Pituitary and Adrenal Hormone Profiles in Chronic Fatigue Syndrome.
Psychosomatic Medicine; vol. 67 no. 3 433-440 Conclusions: Patients with CFS demonstrated subtle alterations in HPA axis activity characterized by reduced ACTH over a full circadian cycle and reduced levels during the usual morning physiological peak ACTH secretion. This provides further evidence of subtle dysregulation of the HPA axis in CFS. Whether this dysregulation is a primary feature of the illness or instead represents a biologic effect secondary to having the illness itself remains unclear.
Head, K.A., Kelly, G.S. (2009) Nutrients and Botanicals for Treatment of Stress: Adrenal Fatigue, Neurotransmitter Imbalance, Anxiety, and Restless Sleep. Alternative Medicine Review; Jun;14(2):114-40. Abstract: Research shows a dramatic increase in use of the medical system during times of stress, such as job insecurity. Stress is a factor in many illnesses - from headaches to heart disease, and immune deficiencies to digestive problems. A substantial contributor to stress-induced decline in health appears to be an increased production of stress hormones and subsequent decreased immune function. Non-pharmaceutical approaches have much to offer such patients. This article focuses on the use of nutrients and botanicals to support the adrenals, balance neurotransmitters, treat acute anxiety, and support restful sleep.
Hills, S.R., Reiss, R.S., Orsham, P.H., George, W.T. (1950) The effect of adrenocorticotropin and cortisone on thyroid function: thyroidadrenocortical interrelationships. The Journal of Clinical Endocrinology & Metabolism, vol. 10 no. 11. Excerpt: A depression of thyroid function in animals and in man has been reported following stress, the administration of cortisone acetate (11-dehydro-17-hydroxycorticosterone acetate), ACTH (adrenocorticotropic hormone) and epinephrine (25–29). In patients with Addison's disease, the thyroid depression induced by cortisone was preceded by an initial stimulation. The availability of ACTH, TSH and cortisone for clinical use and the improvement in the techniques of measuring thyroid and adrenal cortical function have stimulated further work on the thyroid-adrenal relationship.
Holtorf, K. (2007). Diagnosis and treatment of hypothalamic-pituitary-adrenal (HPA) axis dysfunction in patients with chronic fatigue syndrome (CFS) and fibromyalgia (FM). Journal of Chronic Fatigue Syndrome, 14(3), 59-88. Abstract: Because treatment with low physiologic doses of cortisol (<15 mg) has been shown to be safe and effective and routine dynamic ACTH testing does not have adequate diagnostic sensitivity, it is reasonable to give a therapeutic trial of physiologic doses of cortisol to the majority of patients with CFS and FM, especially to those who have symptoms that are consistent with adrenal dysfunction, have low blood pressure or have baseline cortisol levels in the low or low-normal range.
Kamilaris, C.T., Debold, C.R., Pavlous, S.N., Island, D.P., Hoursanidis, A. Orth, D.N. (1987) Effect of Altered Thyroid Hormone Levels on Hypothalamic-Pituitary-Adrenal Function. The Journal of Clinical Endocrinology & Metabolism; vol. 65 no. 5 994-999. Conclusions: These results indicate that thyroid hormone deficiency of short duration 1) increases corticotroph sensitivity to oCRH, 2) may diminish the plasma ACTH response to metyrapone-induced hypocortisolemia, and 3) has no apparent effect on the acute adrenal response to ACTH. These data together with those of previous studies that have shown reduced responses of the hypothalamic-pituitary-adrenal axis to metyrapone and hypoglycemia in hypothyroid patients suggest that the release of hypothalamic CRH and/or other ACTH secretagogues may be decreased in hypothyroidism.
Musselman, D.L., Nemeroff, C.B. (1996). Depression and endocrine disorders: focus on the thyroid and adrenal system. The British Journal of Psychiatry. 1996(30):123-128. Abstract: Concerning the HPT axis, depressed patients have been reported to have: (a) alterations in thyroid-stimulating hormone response to thyrotropin-releasing hormone (TRH); (b) an abnormally high rate of antithyroid antibodies; and (c) elevated cerebrospinal fluid (CSF) TRH concentrations. Moreover, tri-iodothyronine has been shown conclusively to augment the efficacy of various antidepressants. Concerning the HPA axis, depressed patients have been reported to exhibit: (a) adrenocorticoid hypersecretion; (b) enlarged pituitary and adrenal gland size; and (c) elevated CSF corticotropin-releasing factor concentrations.
Peterson, R.E. (1958) The Influence of the Thyroid on Adrenal Cortical Function. The Journal of Clinical Investigation; vol 37(5). Conclusions: It is suggested from these data that there is a homeostatic mechanism mediated through the liver-pituitary-adrenals which results in a decreased synthesis of cortisol in patients with myxedema in whom the rate of removal of cortisol by the liver is impaired, and an increased synthesis of cortisol in patients of thyrotoxicosis in whom the rate of removal of cortisol by the liver is accelerated.
Rodríguez-Gutiérrez, R., González-Velázquez, C., González-Saldívar, G., Villarreal-Pérez, J. Z., & González-González, J. G. (2014). Glucocorticoid Functional Reserve in Full-Spectrum Intensity of Primary Hypothyroidism.International Journal of Endocrinology, 2014. Conclusion: Patients with different degrees of intensity of primary hypothyroidism had improved cortisol response after reaching euthyroidism. The incidence of adrenal insufficiency was 6.7–18.3% and more than 50% of the cases had a normal cortisol response after L-T4 therapy. This finding could have important clinical implications especially in the setting of acute stress situations occurring during the period while a euthyroid state is still not achieved.
Scott, L.V., Salahuddin, F., Cooney, J., Svec, F., Dinan, T. (1999). Differences in adrenal steroid profile in chronic fatigue syndrome, in depression and in health. Journal of Affective Disorders; vol 5: issues 1-2: 129-137. Results: DHEA and DHEA-S levels were significantly lower in the CFS compared to the healthy group; DHEA-S levels, but not DHEA, were lower in the depressives; cortisol and 17-alphahydroxyprogesterone did not differ between the three groups. Conclusions: A potential role for DHEA, both therapeutically and as a diagnostic tool, in CFS, is suggested.
Van Den Eede F., Moorkens G., Van Houdenhove B., Cosyns P, Claes S. (2007) Hypothalamic-Pituitary-Adrenal Axis Function in Chronic Fatigue Syndrome. Neuropsychobiology; Vol. 55, No. 2, 2007. Abstract: There is evidence for a hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis in a proportion of the patients with chronic fatigue syndrome (CFS), despite the negative studies and methodological difficulties. In this review, we focus on challenge studies and on the role of the HPA axis in the pathogenesis of CFS. Mild hypocortisolism, blunted adrenocorticotropin response to stressors and enhanced negative feedback sensitivity to glucocorticoids are the main findings. Several underlying mechanisms have been proposed. Currently, it is a matter of debate whether these disturbances have a primary role in the pathogenesis of CFS. However, even if the HPA axis dysfunctions are secondary to other factors, they are probably a relevant factor in symptom propagation in CFS.
The Connection Between Nutritional Deficiencies and Thyroid Health
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VITAMIN D
Bozkurt NC, Karbek, B., Ucan B, Sahin M, Cakal E, Ozbek M, Delibasi T (2013). The Association Between Severity of Vitamin D Deficiency and Hashimoto's Thyroiditis. Endocrine Practice; 2013 Jan 21:1-14. Conclusions: We showed that serum 25OHD (Vitamin D) levels of patients with Hashimoto's Thyroiditis (HT) were significantly lower than controls and severity of vitamin-D deficiency correlated with duration of HT, thyroid volume and antibody levels. These findings may suggest a potential role of 25OHD in development of Hashimoto's thyroiditis and/or its progression to hypothyroidism.
Camurdan OM, Döğer E, Bideci A, Celik N, Cinaz P. (2012). Vitamin D status in children with Hashimoto thyroiditis. Journal of Pediatric Endocrinology & Metabolism. 2012;25(5-6):467-70. Conclusions: The higher vitamin D deficiency rates besides lower vitamin D levels in the Hashimoto group together with the inverse correlation between vitamin D and anti-TPO suggest that vitamin D deficiency may have a role in the autoimmune process in Hashimoto thyroiditis in children.
Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Dankó K, Szekanecz Z, Langevitz P, Shoenfeld Y. (2011). Vitamin D and autoimmune thyroid diseases. Cellular & Molecular Immunology; 8(3): 243-7. Conclusions: The prevalence of vitamin D deficiency was significantly higher in patients with autoimmune thyroid diseases (AITDs) compared with healthy individuals, as well as in patients with Hashimoto's thyroiditis compared to patients with non-AITDs. Vitamin D deficiency also correlated to the presence of antithyroid antibodies and abnormal thyroid function tests. Significantly low levels of vitamin D were documented in patients with AITDs that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests, suggesting the involvement of vitamin D in the pathogenesis of AITDs and the advisability of supplementation.
McDonnell, DP, Pike, JW, O'Malley, BW (1988). The Vitamin D receptor: A primitive steroid receptor related to thyroid hormone receptor. Journal of Steroid Biochemistry, Volume 30, Issues 1–6, Pages 41–46. Abstract: The vitamin D3 receptor contains a 60 amino acid portion at its carboxyl terminus (C3) which exhibits homology with the receptor for thyroid hormone. Conservation in this region of the molecule is found only between homologous or closely related receptors. This indicates a relationship between the vitamin D3 receptor and the receptor for thyroid hormone and may suggest that they evolved from a single primordial gene.
Tetsuyuki Yasuda, Yasuyuki Okamoto, Noboru Hamada, Kazuyuki Miyashita, Mitsuyoshi Takahara, Fumie Sakamoto, Takeshi Miyatsuka, Tetsuhiro Kitamura, Naoto Katakami, Dan Kawamori, Michio Otsuki, Taka-aki Matsuoka, Hideaki Kaneto, and Iichiro Shimomura (2012). Serum vitamin D levels are decreased and associated with thyroid volume in female patients with newly onset Graves’ disease. Endocrine. 2012 December; 42(3): 739–741. Introduction: It has been shown that vitamin D deficiency is associated with autoimmune diseases..and that vitamin D supplementation prevents the onset and/or development of these autoimmune diseases. Furthermore, it was reported more recently that patients with Hashimoto’s thyroiditis had lower vitamin D levels. In the present study, we evaluated the vitamin D status in female patients with newly onset GD and the association of serum vitamin D levels with the clinical factors related to GD. Although further study would be necessary to conclude, these results suggest that the vitamin D status may be involved in the pathogenesis of GD.
VITAMIN B12
Carmel, R, Spencer, CA (1982). Clinical and Subclinical Thyroid Disorders Associated With Pernicious Anemia. Archives of Internal Medicine 1982;142(8):1465-1469. Abstract: Of 162 patients with pernicious anemia whom we studied, 24.1% had clinical thyroid disease; 11.7% were hypothyroid and 8.6% were hyperthyroid...We conclude that TSH screening in patients with pernicious anemia uncovers frequent abnormalities, which are superimposed on a higher coincidence of overt thyroid disease than previously described.
Jabbar A, Yawar A, Waseem S, Islam N, UI Haque N, Zuberi L, Khan A, Akhter J. (2008). Vitamin B12 deficiency common in primary hypothyroidism. Journal of Pakistan Medical Association. May;58(5):258-61. Conclusions: There is a high (approx 40%) prevalence of B12 deficiency in hypothyroid patients. Traditional symptoms are not a good guide to determining presence of B12 deficiency. Screening for vitamin B12 levels should be undertaken in all hypothyroid patients, irrespective of their thyroid antibody status. Replacement of B12 leads to improvement in symptoms, although a placebo effect cannot be excluded, as a number of patients without B12 deficiency also appeared to respond to B12, administration.
Okuda, K., Chow, B. (1961). The Thyroid and Absorption of Vitamin B12 in Rats. Endocrinology April 1, 1961 vol. 68 no. 4 607-615 .
Abstract: The thyroidal influence on the absorption of vitamin B-2 is not mediated through the production of IF. A possible hormonal regulation acting directly on the intestinal wall for the absorption of vitamin B12 has been discussed.
Perros, P., Singh, RK, Ludlam, CA, Frier, BM (2000). Prevalence of pernicious anaemia in patients with Type 1 diabetes mellitus and autoimmune thyroid disease. Diabetic Medicine. Volume 17, Issue 10, pages 749-751. Conclusions: Patients who have both Type 1 diabetes mellitus and autoimmune thyroid disease are at risk of developing pernicious anaemia.
IRON AND FERRITIN
Beard, JL, Borel, MJ, Derr, J. (1996). Impaired thermoregulation and thyroid function in iron-deficiency anemia. The Journal of Biological Chemistry; May 1996, 271, 12017-12023. Conclusions: We conclude that T3 can functionally regulate the iron-responsive elements binding activity of the iron regulatory protein. These observations provide evidence of a novel mechanism for T3 to up-regulate hepatic ferritin expression, which may in part contribute to the elevated serum ferritin levels seen in hyperthyroidism.
Beard J, Tobin B, Green W. (1989). Evidence for thyroid hormone deficiency in iron-deficient anemic rats. The Journal of Nutrition. [1989, 119(5):772-778] . Abstract: Iron-deficient anemic rats have previously been shown to have low plasma levels of thyroid hormone and a poor plasma thyroid hormone response to acute cold exposure. Decreased rates of T3 production in iron-deficient anemic rats, as documented by turnover studies, may be related to decreased deiodinase activity and reduced peripheral formation of T3. The dampened TSH responses to TRH further facilitate or perpetuate this T3 deficiency. We propose that this abnormal thyroid state is partially responsible for impaired thermogenesis in iron-deficiency anemia.
Fein, HG, Rivlin, RS (1975). Anemia in thyroid diseases. Medical Clinics of North America. Sep;59(5):1133-45. Abstract: Pernicious anemia has been strongly associated with hypothyroidism, hyperthyroidism, and thyroiditis. Complete correction of anemia often requires restoration of thyroid function as well as specific hematinic therapy. Continued attention to hematologic status is essential in the management of patients with thyroid diseases.
Hess S, Zimmermann MB, Arnold M, Langhans, W, Hurrell, R (2002). Iron Deficiency Anemia Reduces Thyroid Peroxidase Activity in Rats. The Journal of Nutrition. vol. 132 no. 7 1951-1955. Abstract: Studies in animals and humans have shown that iron deficiency anemia (IDA) impairs thyroid metabolism. However, the mechanism is not yet clear. The objective of this study was to investigate whether iron (Fe) deficiency lowers thyroid peroxidase (TPO) activity. These data indicate that Fe deficiency sharply reduces TPO activity and suggest that decreased TPO activity contributes to the adverse effects of IDA on thyroid metabolism.
Zimmermann, MB, Köhrle, J (2002). The Impact of Iron and Selenium Deficiencies on Iodine and Thyroid Metabolism: Biochemistry and Relevance to Public Health. Thyroid. October 2002, 12(10): 867-878. Abstract: Several minerals and trace elements are essential for normal thyroid hormone metabolism, e.g., iodine, iron, selenium, and zinc. Coexisting deficiencies of these elements can impair thyroid function. Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase. Iron-deficiency anemia blunts and iron supplementation improves the efficacy of iodine supplementation. Combined selenium and iodine deficiency leads to myxedematous cretinism.
Watts, D. L. (1989). The nutritional relationships of the thyroid. Journal of Orthomolecular Medicine, 4(3). A number of nutritional deficiencies are known
to develop in subclinical hypothyroidism. The most recognized is iron deficiency...Other related deficiencies are protein deficiency, perhaps due to accompanying
hypochlorhydria; deficiency in vitamins A, C, B6,B5, B1; and mineral deficiency: phosphorus (P), manganese (Mn), magnesium (Mg), potassium (K), sodium (Na), and chromium (Cr). Keyvani, et al, found that low vitamin A levels are associated with an increase in the prevalence of goiter in subjects under 18.
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DISCLAIMER: The information contained on the website and social media pages of ThyroidChange is for general information only and is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. ThyroidChange, Denise Roguz, guest writers, and partners are not responsible or liable for any advice or course of treatment that visitors choose to embark on. Please consult with your own health care practitioner regarding information or consults obtained through ThyroidChange or Denise Roguz. All material presented on this website is intended to be used for educational purposes only.
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VITAMIN D
Bozkurt NC, Karbek, B., Ucan B, Sahin M, Cakal E, Ozbek M, Delibasi T (2013). The Association Between Severity of Vitamin D Deficiency and Hashimoto's Thyroiditis. Endocrine Practice; 2013 Jan 21:1-14. Conclusions: We showed that serum 25OHD (Vitamin D) levels of patients with Hashimoto's Thyroiditis (HT) were significantly lower than controls and severity of vitamin-D deficiency correlated with duration of HT, thyroid volume and antibody levels. These findings may suggest a potential role of 25OHD in development of Hashimoto's thyroiditis and/or its progression to hypothyroidism.
Camurdan OM, Döğer E, Bideci A, Celik N, Cinaz P. (2012). Vitamin D status in children with Hashimoto thyroiditis. Journal of Pediatric Endocrinology & Metabolism. 2012;25(5-6):467-70. Conclusions: The higher vitamin D deficiency rates besides lower vitamin D levels in the Hashimoto group together with the inverse correlation between vitamin D and anti-TPO suggest that vitamin D deficiency may have a role in the autoimmune process in Hashimoto thyroiditis in children.
Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Dankó K, Szekanecz Z, Langevitz P, Shoenfeld Y. (2011). Vitamin D and autoimmune thyroid diseases. Cellular & Molecular Immunology; 8(3): 243-7. Conclusions: The prevalence of vitamin D deficiency was significantly higher in patients with autoimmune thyroid diseases (AITDs) compared with healthy individuals, as well as in patients with Hashimoto's thyroiditis compared to patients with non-AITDs. Vitamin D deficiency also correlated to the presence of antithyroid antibodies and abnormal thyroid function tests. Significantly low levels of vitamin D were documented in patients with AITDs that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests, suggesting the involvement of vitamin D in the pathogenesis of AITDs and the advisability of supplementation.
McDonnell, DP, Pike, JW, O'Malley, BW (1988). The Vitamin D receptor: A primitive steroid receptor related to thyroid hormone receptor. Journal of Steroid Biochemistry, Volume 30, Issues 1–6, Pages 41–46. Abstract: The vitamin D3 receptor contains a 60 amino acid portion at its carboxyl terminus (C3) which exhibits homology with the receptor for thyroid hormone. Conservation in this region of the molecule is found only between homologous or closely related receptors. This indicates a relationship between the vitamin D3 receptor and the receptor for thyroid hormone and may suggest that they evolved from a single primordial gene.
Tetsuyuki Yasuda, Yasuyuki Okamoto, Noboru Hamada, Kazuyuki Miyashita, Mitsuyoshi Takahara, Fumie Sakamoto, Takeshi Miyatsuka, Tetsuhiro Kitamura, Naoto Katakami, Dan Kawamori, Michio Otsuki, Taka-aki Matsuoka, Hideaki Kaneto, and Iichiro Shimomura (2012). Serum vitamin D levels are decreased and associated with thyroid volume in female patients with newly onset Graves’ disease. Endocrine. 2012 December; 42(3): 739–741. Introduction: It has been shown that vitamin D deficiency is associated with autoimmune diseases..and that vitamin D supplementation prevents the onset and/or development of these autoimmune diseases. Furthermore, it was reported more recently that patients with Hashimoto’s thyroiditis had lower vitamin D levels. In the present study, we evaluated the vitamin D status in female patients with newly onset GD and the association of serum vitamin D levels with the clinical factors related to GD. Although further study would be necessary to conclude, these results suggest that the vitamin D status may be involved in the pathogenesis of GD.
VITAMIN B12
Carmel, R, Spencer, CA (1982). Clinical and Subclinical Thyroid Disorders Associated With Pernicious Anemia. Archives of Internal Medicine 1982;142(8):1465-1469. Abstract: Of 162 patients with pernicious anemia whom we studied, 24.1% had clinical thyroid disease; 11.7% were hypothyroid and 8.6% were hyperthyroid...We conclude that TSH screening in patients with pernicious anemia uncovers frequent abnormalities, which are superimposed on a higher coincidence of overt thyroid disease than previously described.
Jabbar A, Yawar A, Waseem S, Islam N, UI Haque N, Zuberi L, Khan A, Akhter J. (2008). Vitamin B12 deficiency common in primary hypothyroidism. Journal of Pakistan Medical Association. May;58(5):258-61. Conclusions: There is a high (approx 40%) prevalence of B12 deficiency in hypothyroid patients. Traditional symptoms are not a good guide to determining presence of B12 deficiency. Screening for vitamin B12 levels should be undertaken in all hypothyroid patients, irrespective of their thyroid antibody status. Replacement of B12 leads to improvement in symptoms, although a placebo effect cannot be excluded, as a number of patients without B12 deficiency also appeared to respond to B12, administration.
Okuda, K., Chow, B. (1961). The Thyroid and Absorption of Vitamin B12 in Rats. Endocrinology April 1, 1961 vol. 68 no. 4 607-615 .
Abstract: The thyroidal influence on the absorption of vitamin B-2 is not mediated through the production of IF. A possible hormonal regulation acting directly on the intestinal wall for the absorption of vitamin B12 has been discussed.
Perros, P., Singh, RK, Ludlam, CA, Frier, BM (2000). Prevalence of pernicious anaemia in patients with Type 1 diabetes mellitus and autoimmune thyroid disease. Diabetic Medicine. Volume 17, Issue 10, pages 749-751. Conclusions: Patients who have both Type 1 diabetes mellitus and autoimmune thyroid disease are at risk of developing pernicious anaemia.
IRON AND FERRITIN
Beard, JL, Borel, MJ, Derr, J. (1996). Impaired thermoregulation and thyroid function in iron-deficiency anemia. The Journal of Biological Chemistry; May 1996, 271, 12017-12023. Conclusions: We conclude that T3 can functionally regulate the iron-responsive elements binding activity of the iron regulatory protein. These observations provide evidence of a novel mechanism for T3 to up-regulate hepatic ferritin expression, which may in part contribute to the elevated serum ferritin levels seen in hyperthyroidism.
Beard J, Tobin B, Green W. (1989). Evidence for thyroid hormone deficiency in iron-deficient anemic rats. The Journal of Nutrition. [1989, 119(5):772-778] . Abstract: Iron-deficient anemic rats have previously been shown to have low plasma levels of thyroid hormone and a poor plasma thyroid hormone response to acute cold exposure. Decreased rates of T3 production in iron-deficient anemic rats, as documented by turnover studies, may be related to decreased deiodinase activity and reduced peripheral formation of T3. The dampened TSH responses to TRH further facilitate or perpetuate this T3 deficiency. We propose that this abnormal thyroid state is partially responsible for impaired thermogenesis in iron-deficiency anemia.
Fein, HG, Rivlin, RS (1975). Anemia in thyroid diseases. Medical Clinics of North America. Sep;59(5):1133-45. Abstract: Pernicious anemia has been strongly associated with hypothyroidism, hyperthyroidism, and thyroiditis. Complete correction of anemia often requires restoration of thyroid function as well as specific hematinic therapy. Continued attention to hematologic status is essential in the management of patients with thyroid diseases.
Hess S, Zimmermann MB, Arnold M, Langhans, W, Hurrell, R (2002). Iron Deficiency Anemia Reduces Thyroid Peroxidase Activity in Rats. The Journal of Nutrition. vol. 132 no. 7 1951-1955. Abstract: Studies in animals and humans have shown that iron deficiency anemia (IDA) impairs thyroid metabolism. However, the mechanism is not yet clear. The objective of this study was to investigate whether iron (Fe) deficiency lowers thyroid peroxidase (TPO) activity. These data indicate that Fe deficiency sharply reduces TPO activity and suggest that decreased TPO activity contributes to the adverse effects of IDA on thyroid metabolism.
Zimmermann, MB, Köhrle, J (2002). The Impact of Iron and Selenium Deficiencies on Iodine and Thyroid Metabolism: Biochemistry and Relevance to Public Health. Thyroid. October 2002, 12(10): 867-878. Abstract: Several minerals and trace elements are essential for normal thyroid hormone metabolism, e.g., iodine, iron, selenium, and zinc. Coexisting deficiencies of these elements can impair thyroid function. Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase. Iron-deficiency anemia blunts and iron supplementation improves the efficacy of iodine supplementation. Combined selenium and iodine deficiency leads to myxedematous cretinism.
Watts, D. L. (1989). The nutritional relationships of the thyroid. Journal of Orthomolecular Medicine, 4(3). A number of nutritional deficiencies are known
to develop in subclinical hypothyroidism. The most recognized is iron deficiency...Other related deficiencies are protein deficiency, perhaps due to accompanying
hypochlorhydria; deficiency in vitamins A, C, B6,B5, B1; and mineral deficiency: phosphorus (P), manganese (Mn), magnesium (Mg), potassium (K), sodium (Na), and chromium (Cr). Keyvani, et al, found that low vitamin A levels are associated with an increase in the prevalence of goiter in subjects under 18.
(Back to Top)
DISCLAIMER: The information contained on the website and social media pages of ThyroidChange is for general information only and is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. ThyroidChange, Denise Roguz, guest writers, and partners are not responsible or liable for any advice or course of treatment that visitors choose to embark on. Please consult with your own health care practitioner regarding information or consults obtained through ThyroidChange or Denise Roguz. All material presented on this website is intended to be used for educational purposes only.
