Thyroid Resistance | Introducing T4 Medication

Q&A Doctor Series: Thyroid Resistance, Introducing T4 Medication, and Free T3/Reverse T3 Ratios (Answer by David Borenstein, MD)

2/23/2015

This Week's Question
Submitted by Justine W. of Rochester, MI, USA

Hello, I'm currently on T3-only (Cytomel) for thyroid resistance (I also have adrenal issues which my doctor and I are addressing). However, I'm confused about how we will know if I'm ready to introduce NDT or T4-only medication to my T3 medication. Also, I would love more information about Reverse T3 and Free T3/Reverse T3 ratios. Thank you! My questions are below:

1. What indicators tell you that a patient is ready to introduce T4-only medication or natural desiccated thyroid medication to their T3-only medication that he/she might have been on for thyroid resistance?

2. What are optimal values for Reverse T3? How do you evaluate Reverse T3 and Free T3? Is their an optimal ratio between the two labs?

Response by: David Borenstein, MD (Manhattan Integrative Medicine).
Dr. Borenstein is one of New York's leading integrative medicine physicians specializing in thyroid disease, adrenal dysfunction, and other metabolic disorders. Read his bio below.

Hi Justine. Thank you for your questions. Let me address your questions in 3 parts:

Thyroid Resistance and T3 Drugs

Thyroid resistance refers to the situation where T3 -- the active thyroid hormone -- is not able to effectively enter cells -- delivering oxygen and energy. This leaves people hypothyroid at the cellular level. They are physiologically hypothyroid, and may experience hypothyroid symptoms, but TSH, and even Free T4 and Free T3 may appear to fall within the "normal" reference range.

There are several causes for this situation. In some cases, there is insufficient Free T3 -- unbound, available T3 -- to sufficiently meet the body's needs. Insufficient Free T3 can be due to the body's ability to convert T4 into T3 - as a result of chronic stress, adrenal dysfunction, genetic factors and/or nutritional deficiencies, among other causes.

In other cases, even if conversion is taking place, there is simply not enough Free T3 to "do the job," because there is not enough Free T4 available for conversion or the conversion is imperfect. There is also a situation known as cellular resistance, where cells essentially block the T3 from entering. This can be due to genetic issues, or can result from the presence of thyroid-like substances that mimic thyroid hormone and block the transport ability of the T3 to get into cells. Some of these thyroid-lilke substances include estrogens and phytogestrogens - such as soy.

Finally, T4 is converted into either T3, or Reverse T3. Reverse T3 production goes up during periods of chronic stress, illness, or in the presence of nutritional deficiencies. Reverse T3 is an inactive form of T3 that does not deliver oxygen and energy to cells. Instead, it merely takes up space, and can in some cases actually block the cell's ability to take on active T3.

Some physicians prescribe a straight T3 drug -- a synthetic form of T3 -- whether in form of the brand name Cytomel, the generic liothyronine, or a time-released or sustained-release preparation of liothyronine prepared by a compounding pharmacy. The idea is that by providing the actual T3 hormone, the T3 will at minimum reach the cells and resolve the cellular hypothyroidism, and in some cases, help to overcome thyroid resistance, and transport problems, which the causes of these issues are addressed.

Some of my patients have found that they feel best on T3-only thyroid hormone replacement. While they are on T3-only therapy, I also work with them on the other underlying issues, including:

* Optimizing and balancing adrenal function - ideally we want to see a healthy and sufficient cortisol levels throughout the day, following the normal daily cortisol curve that includes highest cortisol levels in the morning. This can involve dietary changes, supplements and adaptogenic herbs, lifestyle changes and stress management, treating underlying chronic infections, and in some cases, DHEA and pregnenolone supplementation, and prescription hydrocortisone treatment.

* Dealing with nutritional deficiencies and imbalances, particularly in the areas of B vitamins, tyrosine, selenium, iodine, Vitamin D, and iron.

* Dealing with other hormone imbalances, including estrogen, progesterone, and testosterone.

* Dealing with any gut and digestive issues, including food sensitivities, gluten or wheat intolerance or sensitivity, inflammation in the intestines ("Leaky Gut") and other issues that impair absorption. These issues are addressed through dietary changes and supplementation.

When patients have achieved a healthy adrenal balance without the need for supplemental hydrocortisone, and do not have any other areas of significant nutritional or hormonal imbalance, or gut/digestive dysfunction we can consider a switch to a T4/T3 medication. I don't typically go from a T3-only therapy to a T4-only therapy, as the majority of my hypothyroid patients -- even those without a history of adrenal imbalance or elevated Reverse T3 -- typically feel their best and have optimal thyroid function on a T4/T3 combination therapy of some sort.

I would typically introduce a small amount of synthetic T4, and then recheck in 8 to 12 weeks (TSH, Free T4, Free T3 and Reverse T3) to determine if that T4 is converting properly. If the Reverse T3 is elevated and the Free T3 is low, this tells me that conversion is not likely happening. If conversion is happening, and symptoms haven't worsened, I would increase the dose of synthetic T4, and drop the T3 to compensate, and again, recheck. If a patient has a strong preference, or a past history of doing better with natural desiccated thyroid (NDT), I can instead introduce NDT, and again, follow the same process of rechecking and recalibrating. All in all, it's a trial and error process that takes time, that relies on not only testing, but careful assessment of symptoms, to determine at which point to stabilize the thyroid treatment approach.

Reverse T3 and T3/Reverse T3 Ratios

Reverse T3 can be measured a blood test. Some amount of Reverse T3 is considered normal. But high or high-normal Reverse T3 can be evidence that T3 is not reaching the cells, meaning that some degree of resistance is present, and T3 therapy may be indicated in a hypothyroid patient.

Some physicians compare the ratio of T3 to Reverse T3 - and consider certain cutoff points to be evidence of dysfunction. For example, some physicians feel that the Free T3/Reverse T3 ratio should be at least 20. (That means, that if Reverse T3 is 10, Free T3 should be at least 200.)

When Total T3 is used (Free T3 measurement is preferable) the Total T3/Reverse T3 ratio should fall above 10.

Keep in mind that you need to use the same unit of measurement for the Free T3 (or Total T3), and the Reverse T3.

These measurements are:

* pmol/L - Picomoles per liter
* pg/Ml - Picograms per milliliter
* pg/Dl - Picograms per deciliter
* ng/Dl 0 Nanograms per deciliter

If you have results in two different units, then convert to the same units. there's a handy online converter at the EndMemo site, at www.endmemo.com/sconvert/pg_mlng_dl.php

Lowering Reverse T3

Lowering Reverse T3 is best done under the guidance of a knowledgeable practitioner, who can help patients best determine the most effective approaches for them, which can include:

* Changing the T4/T3 ratio in thyroid hormone replacement medications, or switching to a T3-only drug
* Addressing adrenal deficiencies and balancing adrenal function
* Managing chronic physical stress, such as infections, allergies, sensitivities
* Managing chronic life stress, including lack of sleep, emotional stress
* Testing for and managing ferritin deficiency
* Nutritional and digestive support
* Detoxification and liver function support

David Borentein, MD (www.davidborensteinmd.com): is one of New York's leading integrative medicine physicians and practices at Manhattan Integrative Medicine in New York, NY, specializing in thyroid disease, adrenal fatigue, and other metabolic disorders. Dr. Borenstein is certified with the American Academy of Anti-Aging Medicine and with the American Academy of Environmental Medicine. Dr. Borenstein has also held many prestigious clinical appointments and positions in leading medical facilities and is published in the European Journal of Ultrasound.

The Q&A Doctor Series brings some of the world's leading experts in thyroid healthcare together to answer your important questions! This ongoing series aims to highlight the best practices in thyroid healthcare to an international audience. Click here to read more Q&A responses.

Send us your thyroid-related patient questions! Email tc.doctorquestions@gmail.com. Please keep your message concise but with relevant information. Your text may be edited for clarity and length. If selected, you will be notified that your question will be answered by one of our qualified experts and featured in this continuing series. Click here to read more Q&A responses.

ThyroidChange is an online movement that is dedicated to improving the diagnosis and treatment of thyroid disease through a physician-patient cooperative approach.

DISCLAIMER: The information provided in this series is for general information only and is not intended to replace a diagnosis or treatment. ThyroidChange and participating physicians are not responsible nor liable for any advice or course of treatment that individuals choose to embark on. Please review all information regarding any medical condition with your physician.

18 Comments

Sharon Hagen

2/23/2015 09:32:14 am

My rT3 rose very high out of lab range and in low ratio to FT3. I was taking a combination of Mylan generic T4 + Cytomel ( 150 / 35 ) already so I lowered myT4 and supplemented with T3 until I was at the equivalent of my total thyroid hormone dose on T3 only, which I then took in split doses 4X a day instead of my previous 1X a day dose of the combo. It was interesting that I had an immediate return of tinnitus and I could use that as an alarm clock for when I needed to take a new dose of T3 : about every 4-5 hours my ears would start ringing loudly and it would die down about 15 minutes after I took Cytomel. I was taking 80 mg of Cytomel a day but it was obviously not enough as I had a BAD return of symptoms and gained 25 lbs. (documented in my doctor's office) in 2 months after stopping T4 completely. She was afraid to prescribe more T3. However, I had blood tests every 5 weeks during that time. The rT3 dropped very quickly down to the lowest level in the range (6, from a high of 36) after I stopped T4. After 3 months of T3 only I stayed off T3 for 32 hours and then had labs drawn. My TSH is always low and it stayed the same... .02....yep, that's right. It's never been higher than 1.89 and that was when I had the WORST hypo symptoms and wasn't medicated. My FT4 came back below the normal lab range and my FT3 came back at the very bottom number of the lab range. One would assume I need thyroid hormones in SOME combination, right ? The endocrinologist my PCP sent me to to review these results said in his report that I would probably benefit from not one but TWO medications for bi-polar disorder, which I do not have. That was his only recommendation. My PCP was appalled.

I gradually reintroduced T4 and lowered T3 to compensate. As soon as I added T4 my rT3 rose again and continued to rise in concert with lowering Cytomel. To achieve mid-range FT4, instead of taking 150 mcg T4 I only had to take 88 mcg. My previous Cytomel dose of 35 mcg to achieve previous upper quarter quadrant returned to the same from 80 mcg. I never lost the 25 lbs. I have never felt as well as I felt before the rT3 rose out of range. I am now on 2 grains Westhroid and 20 mcg Cytomel. My rT3 / FT3 ratio is finally at 25, the best it has ever been. I still feel like crap, though better than I did on synthetics only. I was recently put on 100 mg Spironolactone because of my continuing hair loss and non-pitting edema. The edema decreased immediatley and my hair stopped falling out in golf-ball-sized hunks every time I washed it. But on the same doses of thyroid meds, my FT4 went to the top of the lab range, my FT3 went high out of range, and my cortisol went high out of range at every time of day and night, though previously it had been normal in the morning, too low at noon and early evening and too high at night. I don't understand anything. Seems to me, as I've said to these idiot endos all along, that I have a hypothalamus dysfunction and I KNOW I have a pituitary non-secreting adenoma (multiple whiplash/concussion accidents) = ACTH elevated with spironolactone made the thyroid produce more hormones ? WTF ? So confused. My cholesterol and glucose are rising again, as is my BP. Not sleeping much. Exhausted.

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MALCOLM MACLEAN

2/23/2015 06:51:40 pm

That was a nice review of Thyroid Hormone Resistance. Thank you.

Thyroid Hormone Resistance was originally thought to be a rare genetic disorder. Well, it is BUT, it is now recognised that acquired Thyroid Hormone Resistance is much more common.
This may be caused by low adrenal function, low Ferritin and inadequate T4->T3 conversion.
However, a major cause of acquired Thyroid Hormone Resistance is inflammation. One of the commonest causes of inflammation is Gluten Disease (tests only identify approx. 20% of true cases, so misdiagnosis common- better assume you have this condition if you are a thyroid case.
I salute the emphasis placed on diet, specifically where gluten disease is addressed.
Inflammation shuts down glycolysis, so "mitochondrial combustibles" never reach reach the mitochondria to start generating energy.
Result?
It doesn't matter how much/what variety of thyroid hormone in whatever combination you take, metabolism (And energy) will not pick up until that gluten induced inflammation had died down. If you try the thyroid route in this situation, e.g upping dosage, you are liable to feel worse.

H Hamilton

5/11/2015 11:22:51 pm

Thyroid hormone resistance commonly runs in families and in these cases is genetic, not acquired. Any treatment which does not involve T3 will not fix the problem. This was the protocol developed by Dr John Lowe in the USA and used by him for over 40 years.

3/30/2017 05:36:47 pm

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4/26/2015 06:09:04 am

David Borentein's work on thyroid change is excellent and admirable. He used some useful measurement which is good for patients. Seriously commendable job.

Mandy Avey

4/17/2016 11:43:00 am

I had a partial thyroidectomy in December of 2010. This came after a doctor noticed my neck was swollen, after further investigation and ultrasound a thyroid nodule was found. A needle biopsy was never performed and surgery was the recommendation. Leading up to this I had a lot of the same symptoms just not near as severe as today. The few months following the surgery I felt great in fact my levels showed the remaining thyroid was doing its job I was told I did not need a supplement. I slowly notice my body falling apart but it was always defined as something else. I was diagnosed as having IBS, ADD, ADHD, PMDD, Depression, and lately told it was just related to turning 40. Throughout the last 4 years I have went from a size 5 to a size 14. I have invested lots of time and money into diets and programs and nothing has worked. I have had several thyroid test done and every time I’m told my levels are fine. I have reached a point where I have given up. When I look at myself in a mirror I don’t recognize the person looking back at me. I told myself that under no circumstances would I go out and buy for the 4th time larger clothes, and a couple months ago is when I decided to have my doctor look into it. She noticed my thyroid looked enlarged and ordered an ultrasound and full thyroid panel test.
Again TSH levels are normal however ultrasound detected 2 nodules both with Calcifications 1-8mm 2nd- 2.5mm.
Fatigue I feel fatigued, exhausted all the time, Increased sensitivity to cold, Pre mature age spots on legs and face, Unexplained rapid weight gain 60lbs over 4yrs, Puffy face and neck, I have puffiness and swelling around the eyes and face, Discoloration of the whites of the eyes (using viseine to mask)., Hoarseness, Elevated blood cholesterol level, Vitamin D deficiency, Muscle aches and pain, Muscle weakness Pain, stiffness or swelling in your joints, Heavier than normal or irregular menstrual periods (diagnosed with PMDD), My muscles feel weak, particularly the upper arms and thighs, I am having difficulty staying asleep, I frequently require more than 8 hours of sleep at night,I feel better if I am able to take an afternoon nap every day, I am unable to tolerate exercise, I have less stamina or energy than others Thin skin and hair, facial skin looks or feels thinner, Noticing premature wrinkle’s, My hair is coarse and dry, breaking, brittle hasn’t grown in 4 years, My skin is coarse, dry, scaly, Dry skin Cracked skin on heels, My eyebrows are thinning, especially the outer 1/3, I am always colder than others around me I typically wear a sweater, even in the summer ,cold hands and feet, I am having more breakouts ON THIGHS, I have pains, aches in joints, hands and feet, I experience numbness or tingling in my hands & fingers, I feel restless, or anxious
My moods change easily, I have more feelings of sadness Depressed mood most of the time, I seem to be losing interest in normal daily activities, I have difficulty concentrating or focusing. Impaired memory, I can’t seem to remember things I’m more forgetful lately, I have no sex drive, My eyes feel gritty and dry, My eyes feel sensitive to light, Weakening vision, I am having difficulty swallowing or feeling a lump in my throat, I feel some lightheartedness or dizziness, I have severe menstrual cramps, Loose skin more cellulite, week leaky urine, uncontrollable bladder

malcolm MACLEAN link

6/7/2016 07:31:54 am

It sounds as though you are in a bad way.

I think the best way forward is to do some reading on thyroid, adrenal and methylation processes.

When someone is in as bad shape as you seem to be, the answer is sometimes a mouthful of dental amalgam, leaking mercury into the body, Mercury being one of the most toxic substances known to man.

For reading: Thyroid: Dr Peatfield's book
Adrenal: Dr Wilson's book: Adrenal Fatigue
Methylation: 1. Dr Walsh: Nutrient Power
2. Google Dr Amy Lasko

For details of Mercury toxicity: "Amalgam Illness" by Andy Cutler.

I am not saying that you have chronic mercury toxicity. However, if you have dental amalgams, you likely have. In that case you may be interested in this guide (reproduced below) which I prepared for members of The Andy Culter Think Tank (worth Googling), which serves the need of those suffering from chronic mercury toxicity. Incidentally, chronic mercury toxicity tends not to be recognised by the dental profession or the medical profession. However, if you are processing Mercury industrially, a range of safety precautions for prevention of Mercury dispersal are enforced by law. OK to put in your mouth then? Go figure!
TEXT BEGINS:
Part 1.
Writing as one who has studied biochemistry and endocrinology, it pains me when I see people struggling unnecessarily with chelation, because they have not first tackled the key toxic effects of Mercury: adrenal failure, thyroid failure, methylation failure, disturbance of the transulfuration pathway and for females, Estradiol/Progesterone balance. I believe that if these are addressed first, chelation becomes so much easier. Very little is written about this. It would be great to see these remedies referred to, Paula, at the start of your video.
Part 2
(Development of the theme that regularizing critical metabolic dysfunctions, induced by Mercury, (or co-existent) are best addressed before embarking on chelation):
This text is inevitably incomplete.
Where possible, rectification of the following metabolic defects, should be progressed with the guidance of an experienced alternative medicine practitioner.
I appreciate that this is not always possible for a variety of reasons. In that situation, one may have to take responsibility oneself, with the assistance of dedicated Internet Forums, some of which are mentioned below.
The critical metabolic pathways are:
Methylation (The Methylation Cycle= The Homocysteine Cycle)
Adrenal synthesis
Thyroid Hormone Synthesis
Transulfuration Pathway
Estrogen/Progesterone balance (“Estrogen Dominance”)
1. Methylation
Very, very briefly, methylation defects can be addressed using Active B vitamins: Active B Complex (Swansons) and Methyl B 12 (Solgar). Note: these are not standard Folate or standard Vitamin B12, which paradoxically can make things worse. These are non-toxic and the dose is highly individual. These are excellent for resolving Mercury-induced sleep disorder for example, because they overcome hypoglycaemia- a cause of so much debility and unhappiness, but usually unrecognised. Generally speaking, most people who have dysfunction of methylation have an under-performing methylation cycle, which can be addressed in the manner just described. However, a minority are “over-methylaters”, in which case, methylation in the manner just described, may set them back. For this minority group, over-methylation can be down-regulated by flushing Niacin (Not by the non-flushing variety of Niacin). Those using Niacin in this situation should start at a low, e.g. 10 mg dose and escalate by 10 mg doses on a daily basis. A “Google” search for “Dr Abraham Hoffer Niacin” will lead to extensive data on this topic. Can tests distinguish these two groups? Yes but not reliably.
2. Adrenal Function
Adrenal test? Saliva test of adrenal function: the Adrenal Stress Index (24 hour profile). This is important not just for looking at your Cortisol level but to check your DHEA level, which may become elevated because of Mercury-induced metabolic block in the adrenal gland. In that situation, the use of DHEA as a supplement (Commonly advised) is liable to make a bad situation worse.
3. Thyroid Function
Thyroid Test? The gold standard: 24-hour urine excretion of T4 and T3. Armed with these results, go to one of these two websites and join the forums: STTM and TPAUK. There you will find fellow sufferers to hold your hand as you progress rectifying any adrenal/thyroid disorder.
(Note, if the cost of these tests is prohibitive, the Dr Rind website describes temperature measurement as a simple and economic approach to determine whether adrenal dysfunction is the main issue, whether thyroid dysfunction is the main issue or whether combined adrenal & thyroid dysfunction is the issue).
4. Transulfuration Pathway.
In the situation of Mercury toxicity, the important pathway leading to Gluta

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Q&A Doctor Series: Thyroid Resistance, Introducing T4 Medication, and Free T3/Reverse T3 Ratios (Answer by David Borenstein, MD)

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