Endocrine Abstracts

A 34-year-old lady presented with a 3 year history of central weight gain, hypertension and secondary amenorrhoea. Initial 24-hour urinary free cortisol (UFC) was raised (536 nmol/24 hr) and subsequent overnight dexamethasone suppression test (DST) was elevated at 593 nmol/L. Low and high dose DST confirmed the diagnosis of Cushing’s syndrome with a slightly unusual trend of increasing cortisol levels compared with baseline. ACTH levels were undetectable while adrenal imaging revealed 4 right adrenal nodules (7–11 mm in size) and a normal left adrenal. Metyrapone was used to normalise UFC pre-operatively and she underwent right adrenalectomy. Post-operatively, cortisol levels remained elevated at 280 nmol/L with an undetectable ACTH. Pathological examination of the excised adrenal revealed characteristics of primary pigmented nodular adrenocortical disease (PPNAD), a rare familial cause of Cushing’s syndrome. No other features of Carney complex were observed in this individual. Subsequent investigation of her mother (who complained of a 10-year history of weight gain and uncontrolled hypertension despite 3 agents) also confirmed ACTH-independent Cushing’s syndrome with an increase in UFC following high dose DST. Adrenal imaging identified a 27mm left adrenal adenoma with appearances of the right adrenal reported as normal.

PPNAD is a form of micronodular adrenal hyperplasia causing ACTH-independent Cushing’s syndrome. Isolated PPNAD is an autosomal dominant inherited condition often associated with germline mutations in PRKAR1A and PDE. Bilateral adrenalectomy is the treatment of choice, although imaging may not always identify the bilateral micronodular changes. An important biochemical feature of PPNAD is a paradoxical rise in cortisol post high dose DST.

Genetic testing of these patients has failed to reveal the causative mutation thus far, although further testing of alternative candidates (e.g. PRKACA) is in progress.

This case represents an extremely unusual cause of Cushing’s syndrome (<1% of all cases) and highlights the importance of considering rare diagnoses before referring for surgery.