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

30 Pages Posted: 28 Jan 2019

See all articles by Tetsuya Takamizawa

Tetsuya Takamizawa

Gunma University

Kazuhiko Horiguchi

Gunma University - Division of Endocrinology and Metabolism

Yasuyo Nakajima

Gunma University

Takashi Okamura

Gunma University

Emi Ishida

Gunma University

Shunichi Matsumoto

Gunma University

Satoshi Yoshino

Gunma University

Eijiro Yamada

Gunma University

Tsugumichi Saitoh

Gunma University

Atsushi Ozawa

Gunma University

Masahiko Tosaka

Gunma University

Shozo Yamada

Toranomon Hospital

Masanobu Yamada

Gunma University

More...

Abstract

Background: The 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. The correlations between the thyroid status, several clinicopathological parameters, and GH/IGF-1 were examined.    

Findings: Twenty-four percent of NFPA patients had CeH. The 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: The authors state: "The authors have nothing to disclose."

Ethics Approval Statement: The 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).

Keywords: central hypothyroidism, non-functioning pituitary adenomas, GH secreting pituitary 19 adenomas, GH/IGF-1

Suggested Citation

Takamizawa, Tetsuya and Horiguchi, Kazuhiko and Nakajima, Yasuyo and Okamura, Takashi and Ishida, Emi and Matsumoto, Shunichi and Yoshino, Satoshi and Yamada, Eijiro and Saitoh, Tsugumichi and Ozawa, Atsushi and Tosaka, Masahiko and Yamada, Shozo and Yamada, Masanobu, Central Hypothyroidism Related to Pituitary Adenomas: Resistance to Central Hypothyroidism in Patients with GH Secreting Pituitary Adenomas (January 23, 2019). Available at SSRN: https://ssrn.com/abstract=3321494

Tetsuya Takamizawa

Gunma University

3-39-22 Showamachi, Maebashi
Gunma Prefecture, 371-8511
Japan

Kazuhiko Horiguchi (Contact Author)

Gunma University - Division of Endocrinology and Metabolism ( email )

3-39-15 Showa-machi
Gunma, 371-8511
Japan

Yasuyo Nakajima

Gunma University

3-39-22 Showamachi, Maebashi
Gunma Prefecture, 371-8511
Japan

Takashi Okamura

Gunma University

3-39-22 Showamachi, Maebashi
Gunma Prefecture, 371-8511
Japan

Emi Ishida

Gunma University

3-39-22 Showamachi, Maebashi
Gunma Prefecture, 371-8511
Japan

Shunichi Matsumoto

Gunma University

3-39-22 Showamachi, Maebashi
Gunma Prefecture, 371-8511
Japan

Satoshi Yoshino

Gunma University

3-39-22 Showamachi, Maebashi
Gunma Prefecture, 371-8511
Japan

Eijiro Yamada

Gunma University

3-39-22 Showamachi, Maebashi
Gunma Prefecture, 371-8511
Japan

Tsugumichi Saitoh

Gunma University

3-39-22 Showamachi, Maebashi
Gunma Prefecture, 371-8511
Japan

Atsushi Ozawa

Gunma University

3-39-22 Showamachi, Maebashi
Gunma Prefecture, 371-8511
Japan

Masahiko Tosaka

Gunma University

3-39-22 Showamachi, Maebashi
Gunma Prefecture, 371-8511
Japan

Shozo Yamada

Toranomon Hospital

Tokyo, 105-8470
Japan

Masanobu Yamada

Gunma University

3-39-22 Showamachi, Maebashi
Gunma Prefecture, 371-8511
Japan

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