Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Preemptive Medicine and Lifestyle Disease Research Center, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Endocrine. 2018 Feb;59(2):353-363. doi: 10.1007/s12020-017-1495-y. Epub 2017 Dec 22.
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.
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).
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.
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.
生长激素（GH）治疗会改变成年人的甲状腺功能，而肢端肥大症常涉及甲状腺疾病。本研究旨在阐明 GH 调节甲状腺功能的作用和机制。
我们进行了两项回顾性观察研究，分别聚焦于接受重组人生长激素（rhGH）治疗的严重成年生长激素缺乏症患者（n=20）和接受经蝶窦手术（TSS）的肢端肥大症患者（n=25）。在这两项研究中，均检测了干预前后血清游离三碘甲状腺原氨酸（fT3）、游离甲状腺素（fT4）和 fT3/fT4 比值。随后，我们在体外向 HepG2、TSA201、MCF7 和 HTC/C3 四种细胞系给予 GH，并检测碘甲状腺原氨酸脱碘酶（D1、D2 和 D3）mRNA 水平的变化。
rhGH 治疗后，血清 fT3 中位数从 2.38 增加到 2.78pg/mL（p<0.001），fT4 从 1.115 减少到 1.065ng/dL（p=0.081）。TSS 显著降低了血清 fT3 的中位数，从 3.03 降至 2.53pg/mL（p<0.001），同时增加了 fT4，从 1.230 增加到 1.370ng/dL（p<0.001）。在体外，GH 显著增加了 HTC/C3 细胞中 D2 表达的 mRNA 水平（p<0.01），以及 D2 蛋白及其活性。
GH 增加了人类血清 fT3 水平并降低了血清 fT4 水平。我们的结果表明，其机制涉及 D2 的上调。鉴于 GH 对甲状腺激素代谢的这种影响，甲状腺功能的数据可能有助于生长激素缺乏症和肢端肥大症的管理。
