Impact of metformin on hypothalamic-pituitary-thyroid axis activity in women with autoimmune and non-autoimmune subclinical hypothyroidism: a pilot study

Pharmacol Rep. 2024 Feb;76(1):195-206. doi: 10.1007/s43440-023-00556-3. Epub 2023 Dec 5.

Abstract

Background: Metformin reduces plasma TSH levels if these levels are elevated. No study has investigated whether the hormonal effects of metformin are impacted by thyroid autoimmunity. The current study aimed to compare the effect of metformin on hypothalamic-pituitary-thyroid axis activity between subjects with mild hypothyroidism of different origins.

Methods: The study population consisted of two groups of women with prediabetes and mildly elevated TSH levels, matched by age, insulin sensitivity, TSH, and thyroid hormone levels. Group A included 26 women with autoimmune thyroiditis, while group B enrolled 26 individuals with hypothyroidism of non-autoimmune origin. Both groups were treated with metformin (2.55-3 g daily). Circulating levels of TSH, total and free thyroid hormones, glucose, insulin, prolactin, high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D, concentrations of thyroid antibodies, and structure parameters of thyroid homeostasis were assessed at baseline and 6 months later.

Results: All patients completed the study. At baseline, both groups differed in concentrations of thyroid peroxidase antibodies, thyroglobulin antibodies, hsCRP, and 25-hydroxyvitamin D. The drug reduced TSH and Jostel's index, with no difference between the study groups. The improvement in insulin sensitivity, observed in both groups, was more pronounced in group B than in group A. In women with autoimmune hypothyroidism, the drug increased SPINA-GT and decreased hsCRP levels. The remaining markers did not change throughout the study.

Conclusions: The obtained results suggest that, despite differences in thyroid output, the impact of metformin on TSH levels is similar in hypothyroid women with and without thyroid autoimmunity.

Keywords: 5′-Adenosine monophosphate-activated protein kinase; Hypothalamic–pituitary–thyroid axis; Metformin; Thyroid function tests; Thyroiditis.

MeSH terms

  • C-Reactive Protein / metabolism
  • Female
  • Hashimoto Disease*
  • Humans
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothyroidism* / drug therapy
  • Hypothyroidism* / metabolism
  • Insulin Resistance*
  • Metformin* / pharmacology
  • Metformin* / therapeutic use
  • Pilot Projects
  • Thyroid Hormones
  • Thyroiditis, Autoimmune*
  • Thyrotropin

Substances

  • Metformin
  • C-Reactive Protein
  • Thyrotropin
  • Thyroid Hormones

Supplementary concepts

  • Hypothyroidism, Autoimmune