Frohman Lawrence A, Bonert Vivien
Section of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, IL 60608, USA.
Pituitary. 2007;10(3):283-9. doi: 10.1007/s11102-007-0042-x.
Several classes of pharmacological agents are approved for the medical therapy of acromegaly, including dopamine agonists, somatostatin analogs and a growth hormone receptor antagonist. Pegvisomant, a growth hormone receptor antagonist, suppresses IGF-1 levels into the normal range in over ninety percent of patients. However, increased tumor volume was reported in patients receiving pegvisomant who had not received prior radiotherapy.
To describe two patients with acromegaly who developed significant tumor enlargement on pegvisomant and discuss the potential mechanisms involved.
Both patients received long-acting somatostatin analog (octreotide) therapy subsequent to incomplete transsphenoidal tumor resection. Octreotide did not normalize GH/IGF-1 levels in either patient but did control tumor mass size. Pegvisomant therapy was initiated after discontinuing octreotide.
Both patients exhibited suppression of IGF-1 into the normal range during pegvisomant therapy. However, significant tumor enlargement occurred in both. Potential mechanisms for tumor enlargement include the natural tendency of the tumor to grow with time, discontinuation of tumor suppressive effects of the somatostatin analog, or a direct effect of pegvisomant. The presumed mechanism of tumor enlargement is by loss of the inhibitory effect on tumor growth when IGF-1 levels are reduced. This could also explain the increase in circulating GH levels in patients with acromegaly receiving pegvisomant; patient 1 demonstrated an 18-fold increase in circulating GH levels while receiving the drug.
The mechanisms of tumor enlargement in patients with acromegaly on pegvisomant are likely multifactorial. Patients, especially those who have not received prior radiotherapy, should be closely monitored for tumor enlargement.
几类药物被批准用于肢端肥大症的医学治疗，包括多巴胺激动剂、生长抑素类似物和生长激素受体拮抗剂。培维索孟是一种生长激素受体拮抗剂，可使超过90%的患者的胰岛素样生长因子-1（IGF-1）水平降至正常范围。然而，在未接受过放疗的接受培维索孟治疗的患者中，有肿瘤体积增大的报道。
描述两名肢端肥大症患者在接受培维索孟治疗后出现显著肿瘤增大的情况，并探讨其中可能涉及的机制。
两名患者在经蝶窦肿瘤不完全切除术后均接受了长效生长抑素类似物（奥曲肽）治疗。奥曲肽未能使任何一名患者的生长激素（GH）/IGF-1水平恢复正常，但确实控制了肿瘤大小。在停用奥曲肽后开始使用培维索孟治疗。
两名患者在接受培维索孟治疗期间，IGF-1均被抑制至正常范围。然而，两人均出现了显著的肿瘤增大。肿瘤增大的潜在机制包括肿瘤随时间自然生长的趋势、生长抑素类似物肿瘤抑制作用的中断或培维索孟的直接作用。推测肿瘤增大的机制是IGF-1水平降低时对肿瘤生长的抑制作用丧失。这也可以解释接受培维索孟治疗的肢端肥大症患者循环GH水平的升高；患者1在接受该药物治疗时循环GH水平增加了18倍。
接受培维索孟治疗的肢端肥大症患者肿瘤增大的机制可能是多因素的。应密切监测患者，尤其是那些未接受过放疗的患者，以防肿瘤增大。
