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生长激素替代治疗对垂体功能减退症患者甲状腺轴的影响:体内和体外研究

The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

作者信息

Glynn Nigel, Kenny Helena, Quisenberry Leah, Halsall David J, Cook Paul, Kyaw Tun Tommy, McDermott John H, Smith Diarmuid, Thompson Christopher J, O'Gorman Donal J, Boelen Anita, Lado-Abeal Joaquin, Agha Amar

机构信息

Department of Endocrinology, Beaumont Hospital & RCSI Medical School, Dublin 9, Ireland.

School of Health and Human Performance, Dublin City University, Dublin, Ireland.

出版信息

Clin Endocrinol (Oxf). 2017 May;86(5):747-754. doi: 10.1111/cen.13272. Epub 2016 Dec 19.

DOI:10.1111/cen.13272
PMID:27809356
Abstract

OBJECTIVE

Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement.

DESIGN

A prospective, observational study of patients receiving GH replacement as part of routine clinical care.

PATIENTS

Twenty adult hypopituitary men.

MEASUREMENTS

Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue.

RESULTS

The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy.

CONCLUSIONS

In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle.

摘要

目的

已有报道称生长激素(GH)替代治疗后下丘脑-垂体-甲状腺轴会发生改变。本研究旨在探讨GH替代治疗前后血清甲状腺激素浓度变化与皮下脂肪组织中脱碘酶活性之间的关系。

设计

一项对接受GH替代治疗作为常规临床护理一部分的患者进行的前瞻性观察研究。

患者

20名成年垂体功能减退男性。

测量指标

在GH替代治疗前后测量血清促甲状腺激素(TSH)、甲状腺激素——游离和总甲状腺素(T4)、三碘甲状腺原氨酸(T3)及反三碘甲状腺原氨酸(rT3)、甲状腺球蛋白和甲状腺结合球蛋白(TBG)水平。将血清激素水平的变化与皮下脂肪组织中脱碘酶同工酶(DIO1、DIO2和DIO3)的活性进行比较。

结果

生长激素(GH)的平均每日剂量为0·34±0·11毫克(范围为0·15 - 0·5毫克)。GH替代治疗后,平均游离T4水平下降(-1·09±1·99皮摩尔/升,P = 0·02)。反T3水平也下降(-3·44±1·42纳克/分升,P = 0·03),游离T3水平显著升高(+0·34±0·15皮摩尔/升,P = 0·03)。在皮下脂肪中,DIO2酶活性下降;GH替代治疗后DIO1和DIO3活性保持不变。GH治疗未改变血清TSH、甲状腺球蛋白和TBG水平。

结论

对垂体功能减退人类受试者的皮下脂肪组织进行体外分析表明,GH替代治疗与脱碘酶同工酶活性的显著变化有关。然而,观察到的酶活性变化并不能解释GH替代治疗引起的循环甲状腺激素浓度变化。在包括肝脏和肌肉在内的其他组织中,脱碘酶同工酶可能受GH的不同调节。

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