Kuker Adriana P, Shen Wei, Jin Zhezhen, Singh Simran, Chen Jun, Bruce Jeffrey N, Freda Pamela U
Department of Medicine, Columbia University, New York, NY, USA.
Department of Pediatrics, Columbia University, New York, NY, USA.
J Endocr Soc. 2021 Feb 1;5(3):bvab004. doi: 10.1210/jendso/bvab004. eCollection 2021 Mar 1.
In active acromegaly, the lipolytic and insulin antagonistic effects of growth hormone (GH) excess alter adipose tissue (AT) deposition, reduce body fat, and increase insulin resistance. This pattern reverses with surgical therapy. Pegvisomant treats acromegaly by blocking GH receptor (GHR) signal transduction and lowering insulin-like growth factor 1 (IGF-1) levels. The long-term effects of GHR antagonist treatment of acromegaly on body composition have not been studied.
We prospectively studied 21 patients with active acromegaly who were starting pegvisomant. Body composition was examined by whole body magnetic resonance imaging, proton magnetic resonance spectroscopy of liver and muscle and dual-energy x-ray absorptiometry, and endocrine and metabolic markers were measured before and serially during 1.0 to 13.4 years of pegvisomant therapy. The data of patients with acromegaly were compared with predicted and to matched controls.
Mass of visceral AT (VAT) increased to a peak of 187% (1.56-229%) ( < .001) and subcutaneous AT (SAT) to 109% (-17% to 57%) ( = .04) of baseline. These remained persistently and stably increased, but did not differ from predicted during long-term pegvisomant therapy. Intrahepatic lipid rose from 1.75% to 3.04 % ( = .04). Although lean tissue mass decreased significantly, skeletal muscle (SM) did not change. IGF-1 levels normalized, and homeostasis model assessment insulin resistance and HbA1C were lowered.
Long-term pegvisomant therapy is accompanied by increases in VAT and SAT mass that do not differ from predicted, stable SM mass and improvements in glucose metabolism. Long-term pegvisomant therapy does not produce a GH deficiency-like pattern of body composition change.
在活动性肢端肥大症中，生长激素（GH）过量的脂解和胰岛素拮抗作用会改变脂肪组织（AT）沉积，减少体脂，并增加胰岛素抵抗。这种模式在手术治疗后会逆转。培维索孟通过阻断GH受体（GHR）信号转导和降低胰岛素样生长因子1（IGF-1）水平来治疗肢端肥大症。GHR拮抗剂治疗肢端肥大症对身体成分的长期影响尚未得到研究。
我们对21例开始使用培维索孟的活动性肢端肥大症患者进行了前瞻性研究。通过全身磁共振成像、肝脏和肌肉的质子磁共振波谱以及双能X线吸收法检查身体成分，并在培维索孟治疗1.0至13.4年之前和期间连续测量内分泌和代谢指标。将肢端肥大症患者的数据与预测数据以及匹配的对照组进行比较。
内脏AT（VAT）质量增加至基线的187%（1.56 - 229%）（P <.001），皮下AT（SAT）增加至基线的109%（-17%至57%）（P =.04）。这些指标持续稳定增加，但在长期培维索孟治疗期间与预测值无差异。肝内脂质从1.75%升至3.04%（P =.04）。尽管瘦组织质量显著下降，但骨骼肌（SM）未发生变化。IGF-1水平恢复正常，稳态模型评估的胰岛素抵抗和糖化血红蛋白（HbA1C）降低。
长期培维索孟治疗伴随着VAT和SAT质量的增加，与预测值无差异，SM质量稳定，葡萄糖代谢改善。长期培维索孟治疗不会产生类似GH缺乏的身体成分变化模式。
