Serum Leptin in Overt and Subclinical Hypothyroidism: Effect of Levothyroxine Treatment and Relationship to Menopausal Status and Body Composition

Background: The relationship between thyroid status, including subclinical hypothyroidism (SH) and serum leptin is controversial or uncertain. Therefore we evaluated serum leptin in SH and overt hypothyroidism (OH) and determined the effects of levothyroxine (LT4) replacement on serum leptin in these disorders. Methods: Serum leptin, thyrotropin (TSH), free thyroxine, insulin, glucose, and body composition parameters were compared in 55 SH, 20 OH, and 28 euthyroid (EU) pre- and postmenopausal women. In addition, the effect of LT4 treatment on serum leptin in SH and OH was assessed. Results: The mean +/- SD (median) serum leptin concentrations in the OH and SH groups were higher than in the EU group (35.1 +/- 27.2 [33.0] and 36.6 +/- 21.9 [30.6] ng/mL, respectively, vs. 23.2 +/- 19.3 [17.9] ng/mL, p = 0.011), but the difference was only significant in postmenopausal women. The body mass index (BMI), fat mass index (FMI), and the homeostasis model assessment-insulin resistance (HOMA-IR) index values were not different among these groups. In premenopausal women there was no correlation between leptin, BMI, or FMI and serum TSH levels (r(s) = 0.009, p = 0.474; r(s) = 0.043, p = 0.367; r(s) = 0.092, p = 0.232). In the postmenopausal women, the partial correlation coefficient between TSH and leptin was present, even when controlling for BMI (r(s) = 0.297, p = 0.042) and FMI (r(s) = 0.275, p = 0.050). LT4 treatment was associated with a reduction of serum leptin concentrations in the OH group (p = 0.008). In SH group there were no differences between LT4 replacement or no treatment, since a fall in serum leptin levels was detected in both SH subgroups, despite a more pronounced fall with LT4 use. Treatment of the SH and OH groups with LT4 did not influence HOMA-IR index or body composition. Conclusions: Serum leptin concentrations are elevated in postmenopausal women with SH or OH. A relationship between thyroid status and serum leptin is further supported by the fact that LT4 treatment, to restore the EU status, reduced serum leptin levels in OH in the absence of significant effects on BMI. In women, hypothyroidism influences either leptin secretion or degradation and this effect is more pronounced in postmenopausal than in premenopausal women.