THYROID HORMONE REPLACEMENT-ONLY T4 OR A COMBINATION OF T3 AND T4?

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Hypothyroidism is a condition where your thyroid gland produces insufficient amounts of thyroid hormone. The most common cause of hypothyroidism is an autoimmune condition called Hashimoto’s Thyroiditis, where your body’s own immune system attempts to destroy your thyroid tissue.

WHAT IS THE BEST TREATMENT FOR HYPOTHYROIDISM?

  • Is it Levothyroxine T4 (Synthetic T4, Synthroid, Thyronorm, Eltroxin)?
  • Is it a combination of T4 and T3 (Levothyroxine and Cytomel)?
  • Is it compounded bioidentical combined T4 and T3?
  • Or is it thyroid glandular extracts?

The truth is there is no one right answer! It depends on what works for you!

LEVOTHYROXINE (T4) MONOTHERAPY

Using Levothyroxine to replace thyroid hormone in hypothyroidism is the standard of care all over the world. This is the view endorsed by major thyroid and endocrine associations worldwide. However, many people on synthetic T4 alone have not felt their best despite progressively increasing their T4 dosage. This can happen because of several reasons, some of them being low iron storage, poor gut health causing improper absorption of T4 or wrong time of taking T4 in relation to meals. For optimal T4 absorption, you should not take any food or supplements one hour before and one hour after taking T4. In such people who still experience fatigue, weight gain and “brain fog” and their test reports are in the” normal” range, while on T4 only, what should the doctor do? Should you consider a combination of T4 and T3? I get a lot of my patients at this point, when their regular doctor has decided that they need an anti-depressant in addition to T4 or even worse, they are told it is “all in their head” (ironically this may not be far from the truth when we consider the Type 2 Deiodinase(DIO2) enzyme in the brain! More on this later).

COMBINATION THERAPY WITH T4 AND T3 (T4/T3)

Triiodothyronine (T3) is the more active form of thyroid hormone. Your thyroid gland produces T4 and a small quality of T3. Most of the T3 in the blood comes from conversion of T4 in tissues like liver, kidneys and brain. This conversion happens through the action of certain enzymes called Deiodinases. Several studies in the past few years have suggested that in some patients, treatment with combined T4/T3 instead of monotherapy with T4 may show better results, particularly in terms of psychological well-being. Why is this so? One of the possible explanations could be a genetic variation in the DIO2 (Type 2 Deiodinase) gene, which affects the conversion of T4 to T3 in the brain. This DIO2 gene variation does not affect blood levels of thyroid hormones. So your blood levels of thyroid hormones may remain in the normal range, but you don’t feel well. However, this genetic test is not routinely available yet, other than in research settings. So what should you do? A trial of combined T4/T3 is definitely a worthwhile option.

What combinations of T4/T3 are available?

1) Synthetic T4 and Cytomel (T3)

2) Compounded combined T4/T3

Which should you choose? Depends on many variables. But as always, adequate knowledge in their use is extremely important.

WHAT ABOUT THYROID GLANDULAR EXTRACTS?

Thyroid glandular extracts are prepared from thyroid glands of pigs. Armour Thyroid and Naturethyroid are the common ones. It is a combination of T4 and T3 and on US Pharmacopeia, which means that it has standardized dosage of T4 and T3. Use of thyroid glandular extracts sometimes becomes an emotional issue, with one camp being all in favor of it and another completely against it.

One crossover study of 70 patients by Hoang et al in The Journal of Clinical Endocrinology & Metabolism (2013) found that people on Armour Thyroid felt better and about 48% of them preferred Armour over T4 mono therapy. There were no adverse effects on thyroid glandular extracts. However, one major question that this study did not answer was whether there was any change in thyroid antibody levels when on porcine glandular extracts. The study did not measure thyroid antibodies in the patients. Many of us in Functional Medicine do not recommend porcine glandular extracts in patients with positive thyroid antibodies because of the risk of increased autoimmunity from an animal protein.

Sometimes we forget how far we have come in Medicine. George R Murray’s account “The life-history of the first case of myxedema treated by thyroid extract” in BMJ 1920 reads like a beautiful story.Dr. Murray mentions that Dr. Michell Clarke in 1892 had failed to find success in using thyroid glandular extracts because his butcher had been providing him with thymus instead of thyroid glands to make glandular extracts! At least we don’t have to depend on our butcher!

 

For Readers in India: 

As far as I know Cytomel (T3) is not available in India. Compounded combined T4/T3 is not easily available either. More importantly, thyroid hormone is not easy to compound so quality control in the compounding pharmacy is very important. Moreover, compounded hormones are more expensive than the synthetic T4 (Thyronorm, Eltroxin). Thyroid glandular extracts are made from pig thyroid glands and not available in India.

You may be interested in Autoimmunity

REFERENCES:

Murray, George R. “The life-history of the first case of myxedema treated by thyroid extract.” British medical journal 1.3089 (1920): 359.

Panicker, Vijay, et al. “Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients.” The Journal of Clinical Endocrinology & Metabolism 94.5 (2009): 1623-1629.

Hoang, Thanh D., et al. “Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study.” The Journal of Clinical Endocrinology & Metabolism 98.5 (2013): 1982-1990.

Pepper, Gary M., and Paul Y. Casanova-Romero. “Conversion to Armour thyroid from levothyroxine improved patient satisfaction in the treatment of hypothyroidism.” Journal of Endocrinology, Diabetes & Obesity 2 (2014): 1055-1060.

Wiersinga, Wilmar M. “Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism.” Nature Reviews Endocrinology 10.3 (2014): 164-174.

Schmidt, Ulla, et al. “Peripheral markers of thyroid function: the effect of T4 monotherapy vs T4/T3 combination therapy in hypothyroid subjects in a randomized crossover study.” Endocrine Connections 2.1 (2013): 55-60.