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Effects of growth hormone on thyroid function are mediated by type 2 iodothyronine deiodinase in humans

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Abstract

Purpose

Growth hormone (GH) therapy in adults alters thyroid function, and acromegaly often involves thyroid disease. The present study aimed to elucidate roles and mechanisms of GH in regulating thyroid function.

Methods

We performed two retrospective observational studies, which focused on consecutive patients with severe adult GH deficiency who received recombinant human GH (rhGH) therapy (n = 20) and consecutive patients with acromegaly who underwent transsphenoidal surgery (TSS) (n = 25). In both studies, serum free triiodothyronine (fT3), free thyroxine (fT4), and fT3/fT4 ratio were examined before and after the interventions. We subsequently administered GH to four human cell lines (HepG2, TSA201, MCF7, and HTC/C3) in vitro, and examined changes in mRNA levels of iodothyronine deiodinases (D1, D2, and D3).

Results

Median serum fT3 level significantly increased after rhGH therapy from 2.38 to 2.78 pg/mL (p < 0.001), and fT4 decreased from 1.115 to 1.065 ng/dL (p = 0.081). TSS significantly decreased median serum fT3 from 3.03 to 2.53 pg/mL (p < 0.001), and increased fT4 from 1.230 to 1.370 ng/dL (p < 0.001). In vitro, GH significantly increased D2 expression at the mRNA level in HTC/C3 cells (p < 0.01), as well as D2 protein and its activity.

Conclusions

GH increased serum fT3 level and decreased serum fT4 level in humans. Our results suggest that its mechanism involves D2 upregulation. Considering this GH effect on thyroid hormone metabolism, data on thyroid function could be useful in the management of GH deficiency and acromegaly.

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Acknowledgements

This work was supported by JSPS KAKENHI Grant Number 16H06902. We thank Dr. Hideo Sugawa for donating the HTC/C3 cells and providing technical advice.

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Authors and Affiliations

  1. Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Ichiro Yamauchi, Yoriko Sakane, Takafumi Yamashita, Keisho Hirota, Yohei Ueda, Yugo Kanai, Eri Kondo, Toshihito Fujii, Daisuke Taura, Masakatsu Sone, Akihiro Yasoda & Nobuya Inagaki

  2. Preemptive Medicine and Lifestyle Disease Research Center, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Yoriko Sakane

  3. Department of Internal Medicine, Otsu Red Cross Hospital, 1-1-35 Nagara, Otsu, Shiga, 520-8511, Japan

    Yui Yamashita

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  1. Ichiro Yamauchi
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  2. Yoriko Sakane
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Correspondence to Ichiro Yamauchi.

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The studies were approved by the Institutional Review Board and Ethics Committee of the Kyoto University Graduate School of Medicine, and were conducted in accordance with the principles of the Declaration of Helsinki.

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Yamauchi, I., Sakane, Y., Yamashita, T. et al. Effects of growth hormone on thyroid function are mediated by type 2 iodothyronine deiodinase in humans. Endocrine 59, 353–363 (2018). https://doi.org/10.1007/s12020-017-1495-y

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