Comte-Perret Sophie, Zanchi Anne, Gomez Fulgencio
Service of Endocrinology Diabetology and Metabolism, Department of Medicine , CHUV-University Hospital , Lausanne, CH-1011 , Switzerland.
Endocrinol Diabetes Metab Case Rep. 2014;2014:140083. doi: 10.1530/EDM-14-0083. Epub 2014 Dec 1.
Medical therapy for Cushing's syndrome due to bilateral macronodular adrenal hyperplasia (BMAH) is generally administered for a limited time before surgery. Aberrant receptors antagonists show inconsistent efficacy in the long run to prevent adrenalectomy. We present a patient with BMAH, treated for 10 years with low doses of ketoconazole to control cortisol secretion. A 48-year-old woman presented with headaches and hypertension. Investigations showed the following: no clinical signs of Cushing's syndrome; enlarged lobulated adrenals; normal creatinine, potassium, and aldosterone; normal urinary aldosterone and metanephrines; elevated urinary free cortisol and steroid metabolites; and suppressed plasma renin activity and ACTH. A screening protocol for aberrant adrenal receptors failed to show any illegitimate hormone dependence. Ketoconazole caused rapid normalisation of cortisol and ACTH that persists over 10 years on treatment, while adrenals show no change in shape or size. Ketoconazole decreases cortisol in patients with Cushing's syndrome, and may prevent adrenal overgrowth. Steroid secretion in BMAH is inefficient as compared with normal adrenals or secreting tumours and can be controlled with low, well-tolerated doses of ketoconazole, as an alternative to surgery.
Enlarged, macronodular adrenals are often incidentally found during the investigation of hypertension in patients harboring BMAH. Although laboratory findings include low ACTH and elevated cortisol, the majority of patients do not display cushingoid features.Bilateral adrenalectomy, followed by life-long steroid replacement, is the usual treatment of this benign condition, and alternative medical therapy is sought. Therapy based on aberrant adrenal receptors gives disappointing results, and inhibitors of steroidogenesis are not always well tolerated.However, ketoconazole at low, well-tolerated doses appeared appropriate to control adrenal steroid secretion indefinitely, while preventing adrenal overgrowth. This treatment probably constitutes the most convenient long-term alternative to surgery.
对于双侧大结节性肾上腺增生（BMAH）所致库欣综合征的药物治疗，通常在手术前进行有限时间的给药。从长远来看，异常受体拮抗剂在预防肾上腺切除术方面疗效并不一致。我们报告一名BMAH患者，用低剂量酮康唑治疗10年以控制皮质醇分泌。一名48岁女性出现头痛和高血压。检查结果如下：无库欣综合征的临床体征；肾上腺增大呈分叶状；肌酐、钾和醛固酮正常；尿醛固酮和间甲肾上腺素正常；尿游离皮质醇和类固醇代谢产物升高；血浆肾素活性和促肾上腺皮质激素（ACTH）受抑制。一项针对异常肾上腺受体的筛查方案未显示任何非法激素依赖性。酮康唑使皮质醇和ACTH迅速恢复正常，在治疗10年期间一直保持，而肾上腺的形状和大小没有变化。酮康唑可降低库欣综合征患者的皮质醇水平，并可能预防肾上腺过度生长。与正常肾上腺或分泌肿瘤相比，BMAH中的类固醇分泌效率低下，低剂量、耐受性良好的酮康唑可作为手术的替代方法来控制类固醇分泌。
在对患有BMAH的患者进行高血压调查时，常偶然发现肾上腺增大呈大结节状。尽管实验室检查结果包括ACTH降低和皮质醇升高，但大多数患者没有库欣样特征。双侧肾上腺切除术，随后进行终身类固醇替代治疗，是这种良性疾病的常用治疗方法，人们正在寻求替代药物治疗。基于异常肾上腺受体的治疗效果令人失望，类固醇生成抑制剂的耐受性也不总是很好。然而，低剂量、耐受性良好的酮康唑似乎适合无限期控制肾上腺类固醇分泌，同时预防肾上腺过度生长。这种治疗可能是手术最方便的长期替代方法。
