Central Hypothyroidism Related to Pituitary Adenomas: Resistance to Central Hypothyroidism in Patients with GH Secreting Pituitary Adenomas

Abstract

Background: most frequent cause of central hypothyroidism (CeH) is pituitary adenomas, but the mechanisms remain unclear. We investigated thyroid status and GH/IGF-1 in CeH in untreated patients with pituitary non-functioning and GH-secreting adenomas. Methods: This was a retrospective cross-sectional study of cases collected from two Hospitals between 2007 and 2016. One hundred-thirty-nine cases of non-functioning (NFPA) and 150 cases of GH-secreting pituitary adenoma (GHPA) were analyzed. correlations between the thyroid status, several clinicopathological parameters, and GH/IGF-1 were examined. Findings: Twenty-four percent of NFPA patients had CeH. severity did not correlate with tumor size and age, and all cases had normal TSH levels. In contrast, only 8.7% of GHPA patients had CeH; about half had normal TSH levels and about half had low TSH levels. Serum TSH levels in GHPA patients were significantly lower and free T4 (FT4) and free T3 levels were higher than those in NFPA patients. One-fourth of GHPA patients had normal FT4 levels and low TSH levels. In addition, serum FT4 levels and serum TSH levels were positively and negatively correlated, respectively, with serum IGF-1 levels. Furthermore, IGF-1 levels in patients with GHPA decreased with age. Interpretation: 1) NFPA patients with CeH had TSH levels within a normal range. 2) GHPA patients were resistant to CeH, which may be a result of stimulated thyroid function by GH/IGF-1. 3) We found an age-dependent decrease in serum IGF-1 levels in a large cohort of GHPAs. Funding Statement: This work was supported by JSPS KAKENHI Grants 16K15493, 23591345, and 20591087 (to M.Y.) and 16K19551 (to K.H.). This work was partially supported by the Advancing Care of Hypothalamic-Pituitary Dysfunction in Japan Study (to M.Y.) from the Japan Agency for Medical Research and Development, and the Research on Rare and Intractable Disease, Health and Labour Sciences Research Grants (to M.Y.). Declaration of Interests: authors state: The authors have nothing to disclose. Ethics Approval Statement: studies were conducted in accordance with the principles of the Declaration of Helsinki and were approved by the Ethics Committee on human research of Gunma University (Approval number 535: Gunma University Human Genome Ethics Committee).