Nivolumab-induced hypophysitis causing secondary adrenal insufficiency after transient ACTH elevation
Nivolumab-induced hypophysitis causing secondary adrenal insufficiency after transient ACTH elevation
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DOI：
10.1507/endocrj.ej19-0076
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发表时间：
2019-01-01
影响因子：
2
通讯作者：
Atsumi, Tatsuya
中科院分区：
文献类型：
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作者：
Sekizaki, Tomonori;Kameda, Hiraku;Atsumi, Tatsuya
一名62岁的男性在接受纳武利尤单抗治疗肾细胞癌期间因血浆ACTH和皮质醇水平升高而被转诊至我科。虽然他的ACTH和皮质醇水平一直保持在其参考范围内，但在8个疗程的纳武利尤单抗治疗后，它们分别升高至232. 7 pg/mL和21. 9 μ g/dL，没有任何主观症状或库欣征。他住院接受内分泌检查。ACTH和皮质醇在第1天清晨恢复至正常范围（分别为29.18 μ g/mL和11.4 μ g/dL），但在第2天清晨分别急剧下降至3.7 μ g/mL和1.6 μ g/dL，无主观症状或生命体征变化。脑部磁共振成像显示他的脑垂体没有异常。ACTH对CRH的反应明显正常，但皮质醇对ACTH的增加无反应。快速促肾上腺皮质激素刺激试验显示皮质醇对外源性促肾上腺皮质激素的反应略有降低（1-24）。这些结果和他的临床病程表明继发性肾上腺功能不全由nivolumab诱导的垂体炎引起。在以前的报告中，大多数免疫检查点抑制剂（ICH诱导的垂体炎）病例是根据肾上腺功能不全症状或低钠血症伴低ACTH和皮质醇诊断的。在本病例中观察到的ACTH升高可能反映了脑垂体的破坏，这一发现对早期发现ICI诱导的垂体炎可能很重要。我们的病例强调了在ICI给药期间观察到ACTH升高时，密切监测随后肾上腺功能不全发作的必要性。
A 62-year-old man was referred to our department for elevation of plasma ACTH and cortisol levels during nivolumab administration for renal cell carcinoma. Although his ACTH and cortisol levels had been maintained within their reference ranges, they were elevated to 232.7 pg/mL and 21.9 mu g/dL respectively, after eight courses of nivolumab without any subjective symptoms or Cushing' s sign. He was hospitalized for endocrinological investigation. ACTH and cortisol returned to their normal ranges (29.18 mu g/mL and 11.4 mu g/dL, respectively) in the early morning on day 1, but fell down sharply to 3.7 mu g/mL and 1.6 mu g/dL, respectively, in the early morning on day 2 without subjective symptoms or vital sign changes. Brain magnetic resonance imaging showed no abnormality in his pituitary gland. ACTH response to CRH was apparently normal, but cortisol did not respond to increased ACTH. A rapid ACTH stimulation test showed slightly reduced response of cortisol to exogenous ACTH (1-24). These findings and his clinical course suggested secondary adrenal insufficiency arising from nivolumab-induced hypophysitis. In previous reports, most cases of immune checkpoint inhibitor (ICH-induced hypophysitis were diagnosed based on adrenal insufficiency symptoms or hyponatremia with low ACTH and cortisol. The ACTH elevation observed in the present case may reflect destruction of the pituitary gland, suggesting that this finding may be important for early detection of ICI-induced hypophysitis. Our case underlines the necessity of close monitoring for subsequent onset of adrenal insufficiency when ACTH elevation is observed during ICI administration.