Effects of Metformin on TSH Levels and Benign Nodular Goiter Volume in Patients Without Insulin Resistance or Iodine Insufficiency

Abstract

Objectives: To evaluate the impact of metformin (MTF) use on TSH levels, thyroid volume and volume of benign thyroid nodules (TNs). Additionally, to study if iodine status influences the outcomes. Methods: A total of 23 euthyroid patients (42 TNs) with benign thyroid nodules, diagnosed by fine needle aspiration biopsy, were randomly assigned to MTF or placebo (P) use for 6 months. Serum TSH, homeostatic model assessment for insulin resistance (HOMA-IR), and urinary iodine concentrations (UIC) were assessed. Ultrasound was used to evaluate TNs and thyroid volumes (TV) and their variations throughout the study. Diabetic patients, those undergoing levothyroxine replacement, and/or using thyroid- or insulin level-influencing drugs were excluded. Results: The sample consisted predominantly of patients without IR. Both intervention groups were similar regarding several confounding variables and showed a comparable median UIC. Serum TSH decreased significantly after MTF (−0.21 vs. 0.09 mUI/L in the P group; p = 0.015). At 6 months, no significant variations were found between groups with respect to TN volumes, TV, HOMA-IR, or body mass index (BMI). However, a tendency toward enlargement of TV with placebo (16.0%; p = 0.09) and a protective effect of MTF on growing TN (OR: 0.25; CI 0.05–1.20) was detected after excluding patients with IR (a lower UIC subgroup). The reduction on TSH levels with MTF maintained in the population without iodine insufficiency (−0.24 vs. +0.07 in the P group; p = 0.046) and was accentuated in those with excessive or more than adequate UIC (−0.69; p = 0.043). A protective effect of MTF on growing TN was suggested (OR: 0.11; IC: 0.02–0.84) in those with higher UIC. Conclusions: This study demonstrated that MTF caused a reduction in TSH levels in benign nodular goiter. This effect was more accentuated in patients with higher levels of UIC and was accompanied by a suggested protective effect on TN enlargement.

The role of thyroid hormone in metabolism and metabolic syndrome

“…199,200 Recent studies give support to this hypothesis, showing that metformin, a drug used to improve insulin sensitivity, may cause a reduction in serum TSH levels. 201,202 Different mechanisms have been proposed and the activation of the AMPactivated protein kinase (AMPK) pathway may be enrolled. 158,159,203,204 Thyroid function acting on glucose metabolism Hypothyroidism is associated with peripheral IR due to a reduction in glucose uptake, and on the other hand, hyperthyroidism increases glycemia due to an increase in liver production.…”

“…199,200 Recent studies give support to this hypothesis, showing that metformin, a drug used to improve insulin sensitivity, may cause a reduction in serum TSH levels. 201,202 Different mechanisms have been proposed and the activation of the AMP-activated protein kinase (AMPK) pathway may be enrolled. 158,159,203,204…”

A breakthrough-like effect of metformin reduces peripheral resistance to triiodothyronine in euthyroid, non-insulin-resistant, type 2 diabetic patients

“…On the other hand, there are some studies showing decreasing TSH levels as a result of metformin therapy ( 30 , 31 ). Still, there are significant differences between the above-mentioned populations and ours.…”

Exploring the Effect of Metformin to Lower Thyroid-Stimulating Hormone in Euthyroid and Hypothyroid Type-2 Diabetic Patients

“…Hence patients treated with metformin have a reduced thyroid volume and a lesser risk of incident goiter [ 10 ]. This is in contrast to hyperinsulinemia, commonly associated with type-2 DM, in which individuals have a greater thyroid volume and a higher incidence of thyroid nodules and cancers [ 11 ].…”