GH-induced LH hyporesponsiveness as a potential mechanism for hypogonadism in male patients with acromegaly

Rie Nishio; Akira Takeshita; Toyoyoshi Uchida; Takashi Herai; Kenichi Sakamoto; Yuichiro Shimizu; Makoto Arai; Keita Tatsushima; Noriaki Fukuhara; Mitsuo Okada; Hiroshi Nishioka; Shozo Yamada; Noriyuki Koibuchi; Hirotaka Watada; Yasuhiro Takeuchi

doi:10.1507/endocrj.EJ20-0596

ORIGINAL

GH-induced LH hyporesponsiveness as a potential mechanism for hypogonadism in male patients with acromegaly

Rie Nishio, Akira Takeshita, Toyoyoshi Uchida, Takashi Herai, Kenichi Sakamoto, Yuichiro Shimizu, Makoto Arai, Keita Tatsushima, Noriaki Fukuhara, Mitsuo Okada, Hiroshi Nishioka, Shozo Yamada, Noriyuki Koibuchi, Hirotaka Watada, Yasuhiro Takeuchi

Author information

Rie Nishio
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo 105-8470, Japan
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
Akira Takeshita
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo 105-8470, Japan
Okinaka Memorial Institute for Medical Research, Tokyo 105-8470, Japan
Toyoyoshi Uchida
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
Takashi Herai
Department of Clinical Laboratory, Toranomon Hospital, Tokyo 105-8470, Japan
Kenichi Sakamoto
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo 105-8470, Japan
Department of Endocrinology, Hematology, and Gerontology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
Yuichiro Shimizu
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo 105-8470, Japan
Shimizu Clinic, Tokyo 107-0052, Japan
Makoto Arai
Division of Molecular Physiology and Metabolism, Faculty of Medicine, Tohoku University, Miyagi 980-8575, Japan
Keita Tatsushima
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo 105-8470, Japan
Okinaka Memorial Institute for Medical Research, Tokyo 105-8470, Japan
Noriaki Fukuhara
Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo 105-8470, Japan
Okinaka Memorial Institute for Medical Research, Tokyo 105-8470, Japan
Mitsuo Okada
Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo 105-8470, Japan
Hiroshi Nishioka
Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo 105-8470, Japan
Okinaka Memorial Institute for Medical Research, Tokyo 105-8470, Japan
Shozo Yamada
Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo 105-8470, Japan
Hypothalamic and Pituitary Center, Moriyama Memorial Hospital, Tokyo 134-0081, Japan
Okinaka Memorial Institute for Medical Research, Tokyo 105-8470, Japan
Noriyuki Koibuchi
Department of Integrative Physiology, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan
Hirotaka Watada
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
Yasuhiro Takeuchi
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo 105-8470, Japan
Okinaka Memorial Institute for Medical Research, Tokyo 105-8470, Japan

Keywords: Acromegaly, Hypogonadism, Growth hormone, Luteinizing hormone, Testosterone

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2021 Volume 68 Issue 8 Pages 953-968

DOI https://doi.org/10.1507/endocrj.EJ20-0596

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Abstract

Male patients with acromegaly frequently have hypogonadism. However, whether excess GH affects gonadal function remains unclear. We retrospectively compared clinical features affecting total testosterone (TT) and free testosterone (FT) levels between 112 male patients with acromegaly and 100 male patients with non-functioning pituitary adenoma (NFPA) without hyperprolactinemia. Median maximum tumor diameter (14.4 vs. 26.5 mm) and suprasellar extension rate (33 vs. 100%) were lower in acromegaly, but LH, FSH, TT, and FT were not significantly different. In acromegaly, TT was less than 300 ng/dL in 57%, and FT was below the age-specific reference range in 77%. TT and FT were negatively correlated with GH, IGF-1, and the tumor size, and positively correlated with LH. In NFPA, they were positively correlated with IGF-1, LH, FSH, ACTH, cortisol, and free T4, reflecting hypopituitarism. Multiple regression analysis showed that TT and FT had the strongest correlation with GH in acromegaly, and with LH in NFPA. Surgical remission was achieved in 87.5% of 56 follow-up patients with acromegaly. TT and FT increased in 80.4 and 87.5%, respectively, with a significant increase in LH. In acromegaly, the degree of postoperative increase in TT(FT) correlated with the fold increase of TT(FT)/LH ratio, a potential parameter of LH responsiveness, but not with fold increase of LH, whereas in NFPA it correlated with both. These results suggest that excessive GH is the most relevant factor for hypogonadism in male acromegaly, and may cause impaired LH responsiveness as well as the suppression of LH secretion.

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