Misinterpretation of Relationship Between TFTs, Diabetes and Effects of Metformin

Misinterpretation of Relationship Between TFTs, Diabetes and Effects of Metformin

Misinterpretation of Relationship Between TFTs, Diabetes and Effects of Metformin

A anxious reader wrote in to specific his worry above a recent posting that raised worries more than the use of Metformin:

Dear Dr. Dean:

Your close friend Dr. Sears has arrive out in opposition to metformin, citing a new European study. Do you know about this study and do you nevertheless propose Metformin?

On your suggestions many years back, I have been having Metformin, and want to know if I must continue. I am 78.

Several thanks, Ed R.

Pricey Mr. R.,

Thanks for your attention-grabbing dilemma.  Yes, I noticed the letter you pointed out from Dr. Sears, and reviewed the research that he curiously cited that allegedly supported his flawed conclusions.

Frankly, I doubt that Dr. Sears wrote the letter that induced your question—and will bet that he never ever even saw it in advance of it was unveiled to the general public!  Dr. Sears is a ton smarter than that.  I suppose it was prepared and sent out by just one of his properly-meaning but ill-knowledgeable, above-eager marketers.

First, the short reply.  I still suggest metformin to just about every person, apart from those people unlucky unusual people who are allergic to it. Preserve having your metformin.

Whoever wrote Dr. Sears’ piece accurately claimed that metformin tends to result in a reduction in TSH (thyroid-stimulating hormone) — but misinterpreted minimal TSH as an indication of impaired thyroid purpose.  Whoever wrote the letter does not recognize endocrinology nor the mechanisms of metformin.

Please re-examine “Dr. Sears’” letter (here’s a link, Al Sears Initial Letter).  The letter cites an Iranian research that appropriately claimed that Metformin results in a reduction in TSH in individuals with a superior-normal TSH amount.1   Even so, from there the letter goes “downhill.”

1st, TSH is not a “thyroid hormone.”  TSH is made by the pituitary, in reaction to TRH (thyrotropin releasing hormone) from the hypothalamus, and stimulates the thyroid gland to release thyroxine (T4).  T4 is “deiodinated” by the system and transformed into tri-iodothyronine (T3—the lively thyroid hormone).  When levels of T4 and T3 are optimum, TSH and TRH are diminished, because of to detrimental feedback inhibition on the pituitary and hypothalamus, as revealed in Determine 1.  When concentrations of T3 and T4 are reduced (as in hypothyroidism), TRH and TSH will increase, to check out to encourage the thyroid to produce additional hormone.

Fig. 1.
 Hypothalamus-pituitary=thyroid axis, illustrating
the responses mechanism that maintains thyroid homeostasis.

The short article cited by Dr. Sears which claimed the TSH-decreasing impact of metformin was verified by an even a lot more recent report in a extra prestigious journal.2   In this comprehensive review, the scientists noted that “Patients treated with metformin have a scaled-down thyroid quantity and a decrease threat of goiter, thyroid nodules and most cancers. Metformin inhibits the advancement of thyroid cells and thyroid cancer cells by impacting the insulin/IGF1 and mTOR pathways. Metformin procedure is connected with a lower in the stages of thyroid-stimulating hormone (TSH) in diabetic sufferers …by enhancing the results of thyroid hormones in the pituitary and activating adenosine monophosphate-activated protein kinase (AMPK). Metformin seems to be a promising therapeutic resource in people with thyroid illness.”  They concluded that “Metformin lowers TSH, lowers the nodular quantity, inhibits the advancement of thyroid carcinoma and potentiates the antimitogenic influence of chemotherapeutic agents. These results counsel a broader use of this drug not only for sort 2 diabetics with or without having proliferative thyroid illness but also for these with metabolic syndrome and obesity.”

Consequently, it is apparent that Dr. Sears’ letter has it backwards.  He then goes on to say:

“Low TSH concentrations improve your possibility of diabetic issues.

A new study proves it. Researchers in the Netherlands seemed at 8,452 individuals with no diabetic issues.  They found that all those with the lowest TSH amounts had a 20% better risk of acquiring diabetic issues than people with the best amounts. But for people with prediabetes, the danger of progressing to complete diabetes was a whopping 40%.”

But that’s NOT what the analyze “proved.”  In actuality, it proved the Opposite!   Dr. Sears’ cite by Chaker, et al, from the Netherlands, was from a poster session at a conference.  However, the authors afterwards released a extra extensive report of their conclusions in the journal, BMC Drugs.4 In this post, the authors noted that “Higher TSH ranges had been involved with a higher diabetic issues hazard,” and that “Higher FT4 [free T4] degrees ended up related with a decrease diabetes hazard among all participants”

This is plainly illustrated in the determine that accompanied their report.

Fig. 2. The 7-yr absolute threat of development from prediabetes to
sort 2 diabetic issues is plotted towards thyroid-stimulating hormone
(TSH) and free thyroxine (FT4) values in just the standard range.

These findings affirm what my mentor, Professor Vladimir Dilman identified a lot of several years in the past, that metformin acts to boost hypothalamic (and peripheral) receptor sensitivity to negative feedback inhibition by most hormones.  Although Metformin is commonly viewed as a peripheral insulin receptor sensitizer, performing on insulin receptors in muscle and fat tissues, Dilman shown that it was a “multi-hormone receptor sensitizer,” acting on central (hypohthalamic and pituitary) and peripheral hormone receptors for not only insulin, but also cortisol, estrogen, testosterone, progesterone, and so forth.  Although Dilman implied that metformin also improved thyroid hormone receptor sensitivity, he did not conduct distinct scientific studies in this regard.

Nonetheless, the scientific tests cited below validate what Dilman had before hypothesized—that Metformin improves the outcome of thyroid hormone as very well, ensuing in reduced amounts of TSH!

As a result, a lessen TSH as documented in Dr. Sears’ piece and the supporting reference basically confirms that metformin boosts the result of thyroid hormone by its impact onthe hypothalamus-pituitary axis.

As I explained, keep taking your metformin.


Ward Dean, MD

May possibly 11, 2017


1.Karimifar M, Aminorroaya A, Amini M, et al. Result of metformin on thyroid stimulating hormone and thyroid quantity in clients with prediabetes: A randomized placebo-controlled scientific trial. J Res Med Sci: The Formal Journal of Isfahan University of Medical Sciences. 201419(11):1019-1026.
2. Meng X, Xu S, Chen G, Derwahl M, and Liu C. Metformin and thyroid disease. J Endocrinol April 1, 2017 233 R43-R51.
3. Chaker L, Ligthart, Korevaar TIM, et al. “OR33-2: Thyroid Perform and type 2 diabetes threat: a populace-based possible cohort examine.” Introduced at: ENDO 2016 April 1-4, 2016 Boston, MA.
4. Chaker L, Ligthart S, Korevaar TI, Hofman A, Franco OH, Peeters RP, Dehghan A. Thyroid operate and threat of variety 2 diabetic issues: a inhabitants-based prospective cohort research. BMC Med. 2016 Sep 3014(1):150.



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