RESUMO
INTRODUCTION: 10% of corticotrophin (ACTH)-dependent Cushing's syndrome arises from secretion by extrapituitary tumours, with phaeochromocytoma implicated in a few cases. Ectopic secretion by phaeochromocytoma of corticotropin-releasing hormone (CRF), with secondary corticotroph hyperplasia, is even rarer, with only five cases in the literature hitherto. However, such cases may be classified as 'ectopic ACTH' due to incomplete verification. CLINICAL CASES: We describe three patients with phaeochromocytoma and ACTH-dependent Cushing's syndrome in whom biochemical cure was achieved following unilateral adrenalectomy. Although unable to access a validated CRF assay within the timeframe for sample storage, we nevertheless inferred CRF secretion in 2 of 3 cases by tumour immunostaining (positive for CRF; negative for ACTH), supported in one case by pre-operative inferior petrosal sinus sampling (IPSS) indicative of pituitary ACTH source. Both cases were characterized by rapid postoperative wean off glucocorticoids, presumed to reflect the pituitary stimulatory-effect of CRF outweighing central negative feedback inhibition by hypercortisolaemia. By contrast, the tumour excised in a third case exhibited positive immunostaining for ACTH - negative for CRF - and postoperative recovery of hypothalamic-pituitary-adrenal axis took significantly longer. DISCUSSION: Ectopic CRF production is biochemically indistinguishable from ectopic ACTH secretion, except that IPSS mimics pituitary Cushing's disease and cortisol dynamics may normalize rapidly postadrenalectomy. CRF secretion can be inferred through tumour immunohistochemistry, even if no CRF assay is available. Unrecognized phaeochromocytoma ACTH secretion may underpin some cases of cardiovascular collapse postadrenalectomy through acute hypocortisolaemia. Despite advances in phaeochromocytoma genetics since previous reports, we were unable to identify somatic DNA defects associated with either ACTH or CRF secretion.
