Cushing's syndrome due to phaeochromocytoma secreting the precursors of adrenocorticotropin

• Published in: The journal of clinical endocrinology and metabolism Vol. 85; no. 12; pp. 4771 - 4775
• Main Authors: WHITE, A, RAY, D. W, TALBOT, A, ABRAHAM, P, THODY, A. J, BEVAN, J. S
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.12.2000
• Subjects: Adrenal Gland Neoplasms - complications; Adrenal Gland Neoplasms - metabolism; Adrenal Gland Neoplasms - surgery; Adrenalectomy; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adrenocorticotropic Hormone - metabolism; Adult; alpha-MSH - metabolism; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Cushing Syndrome - etiology; Cushing Syndrome - surgery; Dexamethasone - pharmacology; Endocrinopathies; Female; Humans; Hydrocortisone - metabolism; Medical sciences; Metyrapone - pharmacology; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pheochromocytoma - complications; Pheochromocytoma - metabolism; Pheochromocytoma - surgery; Tumor Cells, Cultured - metabolism; Endocrinopathy; Human; Corticosteroid; Dexamethasone; Pheochromocytoma; Adrenal cortex diseases; Adrenal glands; Treatment efficiency; Cushing syndrome; Metyrapone; Hyperadrenocorticism; Ectopic secretion; Prohormone; Secretory tumor; Case study; Chemotherapy; Adrenocorticotropic hormone; Adenohypophyseal hormone; Etiology; Surgery; Adrenal gland diseases; Adult; Female
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.85.12.4771

Adrenal phaeochromocytoma rarely causes ectopic ACTH syndrome. We describe a 44-yr-old hypertensive woman who was Cushingoid and markedly pigmented. Laboratory studies indicated severe hypokalaemia, abnormal liver function tests, and random serum cortisols greater than 1660 nmol/L. Urinary catecholamines were markedly increased. An abdominal computed tomography scan showed a 4-cm left adrenal mass and an hypertrophied right adrenal. ACTH levels were elevated at 200 pmol/L, but ACTH precursors, which cross-react in the ACTH assay, were more highly elevated at 1625 pmol/L. The tumor cells cultured in vitro also secreted ACTH precursors, whereas ACTH levels were undetectable. Because the patient was highly pigmented, we measured circulating concentrations of alpha-MSH, which were undetectable and certainly insufficient to stimulate melanogenesis, suggesting that tumorderived ACTH precursors or ACTH were responsible for the pigmentation. A laparoscopic adrenalectomy resulted in remission of the Cushing's syndrome and dramatic reduction in the pigmentation. Before operation, treatment of the patient with metyrapone and replacement dexamethasone decreased cortisol from more than 1660 to less than 20 nmol/L. Surprisingly, this resulted in a decrease in ACTH precursors to 100 pmol/L and ACTH to 9.0 pmol/L. In vitro treatment of the tumor cells with dexamethasone for 24 or 40 h increased ACTH precursor secretion. In summary, this phaeochromocytoma causing Cushing's syndrome secreted primarily ACTH precursors, which seemed to cause the marked pigmentation. In vivo and in vitro evidence suggests that glucocorticoids induced ACTH precursor secretion.