DECREASE IN ACROMEGALY-ASSOCIATED THYROID ENLARGEMENT AFTER NORMALIZATION OF IGF-1 LEVELS: A PROSPECTIVE OBSERVATION AND IN VITRO STUDY

Objective: Goiter occurs at high frequency in acromegaly patients. Whether normalization of insulin-like growth factor 1 (IGF-1) levels could decrease goiter and thyroid volume remains unclear. Methods: Thyroid hormone levels and ultrasound measurements were assessed in 101 acromegaly patients, compared with 108 patients with nonfunctioning pituitary adenoma (NFPA) and 55 healthy controls. Thirty-four acromegaly patients underwent repeat evaluation 1 year post-transsphenoidal surgery. The effect of IGF-1 on thyroid cell proliferation, cell cycle, and apoptosis was evaluated in vitro. Results: Acromegaly patients showed larger thyroid volume than those with NFPAs (18.32 mL vs. 9.91 mL; P<.001) and healthy controls (18.32 mL vs. 9.63 mL; P<.001). Duration of acromegaly was shown to be independently associated with thyroid volume enlargement (B = 0.259; 95% confidence interval, 0.162 to 0.357) in multivariate analysis. At follow-up, the median thyroid volume decreased from 22.74 to 17.87 mL in the cured group (n = 20; P = .003), but the number of nodular goiters showed no significant change. Serum free thyroxine levels decreased from 13.76 to 10.08 pmol/L in the cured group (P = .006) but increased from 9.28 to 12.09 pmol/L in the active group (P = .013). Change in thyroid volume was significantly correlated with IGF-1 level (r = 0.37; P = .029). In vitro, IGF-1 time- and dose-dependently promoted proliferation and secretory function of thyroid cells by enhancing cell cycle shift from the G1/S to G2/M phase and suppressing apoptosis. Conclusion: Acromegaly-associated thyroid volume increase, but not nodular goiter, could be reversed in cured acromegaly. IGF-1 time- and dose-dependently promoted the proliferation and secretory function of thyroid cells. Abbreviations: CCK-8 = Cell Counting Kit-8; fT3 = free triiodothyronine; fT4 = free thyroxine; GH = growth hormone; IGF-1 = insulin-like growth factor 1; MRI = magnetic resonance imaging; NFPA = nonfunctioning pituitary adenoma; qRT-PCR = quantitative real-time-polymerase chain reaction; TSH = thyroid-stimulating hormone