Salazar Luís, Araújo Sara Alves, Correia Mário Rui, da Silva Jorge Diogo, Matos de Figueiredo Catarina, Prior Catarina, Amaral Claúdia, Oliveira Maria João, Castro Ribeiro, Borges Teresa
Serviço de Pediatria, Centro Materno Infantil do Norte, 674892 Unidade Local de Saúde de Santo António , Porto, Portugal.
Serviço de Pediatria, Unidade Local de Saúde Entre o Douro e Vouga, Santa Maria da Feira, Portugal.
J Pediatr Endocrinol Metab. 2025 Apr 25;38(7):772-778. doi: 10.1515/jpem-2025-0056. Print 2025 Jul 28.
To describe the clinical course, diagnosis, and management of a rare pediatric case of ACTH-independent Cushing syndrome (CS), associated with developmental delay.
A three-year-old boy with global developmental delay, was referred for evaluation of rapid weight gain over the preceding three months, accompanied by increased body hair, a moon-shaped face, and sleep disturbances. Biochemical testing revealed undetectable ACTH levels and elevated cortisol levels, leading to the diagnosis of ACTH-independent CS. Abdominal magnetic resonance imaging demonstrated adrenal asymmetry, with a larger left adrenal gland, and further investigation using PET scan excluded the presence of adrenal adenomas/carcinomas. The patient was initially treated with metyrapone, which effectively reduced cortisol levels. However, after two months, a left adrenalectomy was performed. Pathological examination confirmed micronodular non-pigmented adrenal hyperplasia. One year later, cortisol levels increased again with undetectable ACTH, prompting the re-initiation of metyrapone. Due to intolerance to this medication, osilodrostat, an off-label treatment, was introduced. At the time of follow-up, 15 months after initiation of osilodrostat, both serum and urinary cortisol levels remained within normal ranges, ACTH levels remained undetectable, and the clinical symptoms of CS were well controlled.
This case underscores the diagnostic and therapeutic challenges associated with rare pediatric cases of ACTH-independent CS. The treatment course, which included metyrapone, adrenalectomy, and off-label use of osilodrostat, resulted in significant improvement in cortisol control and clinical symptoms. Ongoing genetic analysis is being conducted to explore potential underlying genetic factors contributing to the patient's non-pigmented micronodular adrenal hyperplasia and developmental delay.
描述一例罕见的与发育迟缓相关的儿童促肾上腺皮质激素（ACTH）非依赖性库欣综合征（CS）的临床病程、诊断及治疗。
一名3岁全球发育迟缓男孩因前三个月体重快速增加、伴有多毛、满月脸及睡眠障碍前来评估。生化检测显示促肾上腺皮质激素水平无法测出而皮质醇水平升高，从而诊断为ACTH非依赖性CS。腹部磁共振成像显示肾上腺不对称，左肾上腺较大，进一步的正电子发射断层扫描（PET）检查排除了肾上腺腺瘤/癌的存在。患者最初接受甲吡酮治疗，有效降低了皮质醇水平。然而，两个月后进行了左肾上腺切除术。病理检查证实为微结节性无色素性肾上腺增生。一年后，促肾上腺皮质激素仍测不出但皮质醇水平再次升高，促使重新开始使用甲吡酮。由于对该药物不耐受，引入了一种未获批准的治疗药物奥西卓司他。在随访时，即开始使用奥西卓司他15个月后，血清和尿皮质醇水平均保持在正常范围内，促肾上腺皮质激素水平仍测不出，CS的临床症状得到良好控制。
该病例凸显了罕见的儿童ACTH非依赖性CS的诊断和治疗挑战。包括甲吡酮、肾上腺切除术及奥西卓司他未获批准使用的治疗过程使皮质醇控制及临床症状有显著改善。正在进行基因分析以探索导致患者无色素性微结节性肾上腺增生和发育迟缓的潜在遗传因素。
