Adrenal Cushing's Syndrome Treated With Preoperative Osilodrostat and Adrenalectomy

Reducing severity of Cushing's syndrome caused by an adrenal adenoma (adrenal Cushing's syndrome [ACS]) might decrease morbidity and mortality risk in adrenalectomy. We used off-label osilodrostat, approved in the United States for pituitary Cushing's disease, to reduce cortisol levels and disease severity before adrenalectomy 3 weeks later.

A 48-year-old woman with a 6-year history of obesity, depression, and anxiety and 3-year history of diabetes and hypertension was admitted with vomiting and lumbar back pain. Facial plethora and hirsutism, posterior cervicothoracic fat pad, and truncal obesity coupled with morning serum cortisol >13 μg/dL after 1 mg oral dexamethasone suppression, urinary free cortisol 1324 μg/24hr (4.0-50.0 μg/24 h), and adrenocorticotropin <5 pg/mL (6-50 pg/mL) confirmed ACS. Computed tomography with contrast revealed a 3.4-cm right adrenal mass. Osilodrostat 2 mg twice daily initiated at discharge was increased to 4 mg twice daily on day 6. Three days later, she reported nausea, vomiting, and fatigue. Despite 7.2 μg/dL morning cortisol, adrenal insufficiency was suspected; osilodrostat was reduced to 2 mg twice daily and maintenance oral hydrocortisone 20 mg daily was added with symptom resolution. Prior to adrenalectomy, morning cortisol was 5.1 μg/dL, fasting glucose was 122 mg/dL, and she self-discontinued diabetes medications. Hypertension remained unchanged (149/100 vs 151/94 mmHg). Adrenalectomy revealed a 3.4-cm focally pigmented adrenocortical adenoma.

Three-week treatment of overt ACS with off-label osilodrostat reduced cortisol and glucose levels before curative adrenalectomy. Abrupt cortisol reduction led to suspected adrenal insufficiency managed with maintenance hydrocortisone.

Osilodrostat might help reduce ACS severity before adrenalectomy. Adrenal insufficiency is a risk but can be safely managed with hydrocortisone.