Ichiro Yamauchi1, Yoriko Sakane2,3, Takafumi Yamashita2, Keisho Hirota2, Yohei Ueda2, Yugo Kanai2, Yui Yamashita4, Eri Kondo2, Toshihito Fujii2, Daisuke Taura2, Masakatsu Sone2, Akihiro Yasoda2, Nobuya Inagaki2. 1. Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. ichiroy@kuhp.kyoto-u.ac.jp. 2. Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. 3. Preemptive Medicine and Lifestyle Disease Research Center, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. 4. Department of Internal Medicine, Otsu Red Cross Hospital, 1-1-35 Nagara, Otsu, Shiga, 520-8511, Japan.
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.
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 humanGH (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.
Authors: Amar Agha; Dorothy Walker; Les Perry; William M Drake; Shern L Chew; Paul J Jenkins; Ashley B Grossman; John P Monson Journal: Clin Endocrinol (Oxf) Date: 2007-01 Impact factor: 3.478
Authors: Ulla Feldt-Rasmussen; Georg Brabant; Dominique Maiter; Björn Jonsson; Andy Toogood; Maria Koltowska-Haggstrom; Aase Krogh Rasmussen; Michael Buchfelder; Bernhard Saller; Beverly M K Biller Journal: Eur J Endocrinol Date: 2013-04-15 Impact factor: 6.664
Authors: V M Darras; P Rudas; T J Visser; T R Hall; L M Huybrechts; A Vanderpooten; L R Berghman; E Decuypere; E R Kühn Journal: Domest Anim Endocrinol Date: 1993-01 Impact factor: 2.290
Authors: E Cacciari; P Tassoni; A Cicognani; P Pirazzoli; S Salardi; A Balsamo; A Cassio; S Zucchini; C Colli; D Tassinari Journal: J Clin Endocrinol Metab Date: 1994-12 Impact factor: 5.958
Authors: Paula Juiz-Valiña; María Cordido; Elena Outeiriño-Blanco; Sonia Pértega; Bárbara María Varela-Rodríguez; María Jesús García-Brao; Enrique Mena; Lara Pena-Bello; Susana Sangiao-Alvarellos; Fernando Cordido Journal: J Clin Med Date: 2020-01-28 Impact factor: 4.241
Authors: María Cordido; Paula Juiz-Valiña; Paula Urones; Susana Sangiao-Alvarellos; Fernando Cordido Journal: J Clin Med Date: 2022-02-28 Impact factor: 4.241