PRKAR1A-negative familial Cushing's syndrome: two case reports

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Cushing's syndrome diagnosis is complex, particularly differentiating subtypes of adrenocorticotropic hormone-dependent disease.
• This study highlights challenges in diagnosing a rare form of adrenocorticotropic hormone-independent Cushing's syndrome.

Observation:

• A sibling pair presented with familial isolated primary pigmented nodular adrenocortical disease.
• The female patient had osteoporosis and hypertension, while her brother presented with cushingoid features.
• Both siblings were diagnosed with adrenocorticotropic hormone-independent Cushing's syndrome and treated with bilateral adrenalectomy.

Findings:

• Primary pigmented nodular adrenocortical disease diagnosis can be difficult, often requiring bilateral adrenalectomy.
• Computed tomography scans may show adrenal nodules or appear normal in affected patients.
• Genetic screening for Carney's complex and PRKAR1A mutations was negative in this familial case.

Implications:

• A high index of suspicion is crucial for diagnosing primary pigmented nodular adrenocortical disease in adolescents with relevant family history and clinical signs.
• Lifelong glucocorticoid and mineralocorticoid replacement is necessary post-adrenalectomy.
• Long-term surveillance is essential for patients with Carney's complex or incomplete genetic testing.