TSH lowering effects of metformin: a possible mechanism of action
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OPINION
TSH lowering effects of metformin: a possible mechanism of action R. Cannarella1 · R. A. Condorelli1 · F. Barbagallo1 · A. Aversa2 · A. E. Calogero1 · S. La Vignera1 Received: 8 August 2020 / Accepted: 7 October 2020 © The Author(s) 2020
Abstract Preliminary clinical evidence suggests that metformin has TSH lowering effects in patients with T2DM and hypothyroidism or in those with TSH serum levels in the upper normal value. Also, metformin may exert a protective role against thyroid nodules growth in patients without insulin-resistance. The cross-talk between tyrosine kinase receptors and the G proteincoupled receptors (which the TSHR belongs to) has been already shown and IRS1 may represent the hub link between TSHR and IR pathways. By influencing IRS1 phosphorylation pattern, metformin may sensitize TSHR to TSH, thus explaining the findings of clinical studies. However, the existence of this molecular pathway must be confirmed through proper studies and further prospective randomized placebo-controlled studies are needed to confirm this hypothesis. Keywords TSH · Metformin · Hypothyroidism · Insulin-resistance · Thyroid · Insulin Thyroid disease, obesity and type II diabetes mellitus (T2DM) represent the more common endocrine disorders. They are often concomitantly present in the same patient. Particularly, the prevalence of hypothyroidism in patients with T2DM is about 10–15% [1, 2]. Thus, the prescription of insulin-sensitizing drugs and, first of all, of metformin, is not infrequent among patients with hypothyroidism, goiter and thyroid nodules. This has led to consider the effects of metformin on thyroid disorders, including serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels and thyroid nodules, resulting in the publication of a relevant number of studies in the last two decades. We used the keywords “metformin” and “TSH lowering effects”, to retrieve articles providing us with data useful to clarify the relationship between metformin and thyroid function. In a prospective study-design, 101 patients with T2DM were treated with metformin. Among these, 29 hypothyroid patients were treated with levo-thyroxine (LT4), 18 hypothyroid patients did not receive LT4 and 54 were euthyroid patients. After 1 year of metformin administration, a significant decrease in TSH serum levels was reported in patients * R. Cannarella [email protected] 1
Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95123 Catania, Italy
Department of Experimental and Clinical Medicine, “Magna Graecia” University, Catanzaro, Italy
2
with T2DM and hypothyroidism (n = 47). No change was found in euthyroid patients. Furthermore, serum FT4 levels were not affected. Interestingly, the body mass index (BMI) did not differ following metformin administration, thus excluding a role for body weight decrease in the TSH lowering effect of metformin, especially in LT4 treated patients [3]. In the same study, a short-term administration of metformin (up to 24 wee
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