Immunohistochemically ACTH positivity in an adrenal adenoma that mimicks pheochromocytoma in terms of clinical and radiological findings

INTRODUCTION: Ectopic ACTH secretion is a rare cause of endogenous hypercortisolism. Herein, a case of an immunhistochemically ACTH (+) adrenocortical adenoma with typical pheochromocytoma-like clinical and imaging findings on admission is presented. CLINICAL CASE: A 41 years-old male was admitted because of an incidentally detected adrenal mass. He complained about attacks of hypertension, headache and facial flashing that occurred unregularly for the last four years although he was on candesartan. Hypertension was common in his family with no sudden death. BMI was 36.61kg/m2, blood pressure was 130/80mmHg. The only pathologic finding was fire-red flashing at his face. Abdominal MRI exhibited a mass, 91×89×86mm in size, at left adrenal gland, compatible with pheochromocytoma. His 24 hours urinary metanephrine was 375.49mcg (44–261), normetanephrine was 786.26mcg (119–451). Routine laboratory tests, electrolytes were normal. Following two-weeks of preparation with hydration and doxazosin, an open-left adrenalectomy was performed safely. His postoperative follow-up was uneventful. Hypertension resolved completely. 24-hour urinary metanephrines returned to normal, 5-HIIA was normal, as well. Pathological examination of the operation specimen was reported as adrenocortical neoplasia, 420 gr. in weight. Only necrosis was positive considering about Weiss criteria. Chromogranin-A and synaptophysin were positive. Ki-67 index was below 1%. The unexpected pathological results alarmed us for measurement of adrenal steroids. DHEA-S was low [60.60mcg/dl (80–560)], total testosterone normal [3.08ng/ml (2.41–8.27)], early-morning cortisol was 9.56µg/dL. Short synacthen test was performed, stimulated cortisol was 12.14µg/dL, which was compatible with adrenal failure. Prednisolon 5mg/day was introduced. He was considered as adrenal Cushing syndrome and preoperative mildly high metanephrines were attributed to induction of Phenylethanolamine N Methyltransferase activity in adrenal medulla by high cortisol in neighbourhood. At follow-up visits, he seemed well with any complaints. His periodic abdominal imagings were normal. He was compliant to glucocorticoid replacement, but surprisingly his baseline cortisol levels kept being low, dropped to lower levels; even to 2.7mcg/dl. At third post-operative year, he still required prednisolon, his plasma ACTH was 320pg/ml and early-morning cortisol was 4.8mcg/dl. His baseline medical records were re-evaluated, contralateral adrenal seemed normal at diagnosis. ACTH immunohistochemical staining of operation specimen was performed and was found positive. CONCLUSION: This case has serious take home messages. First, glucocorticoid axis should be evaluated for each adrenal mass regardless of clinical and imaging findings. Second, although it is very rare, ectopic ACTH secretion should be kept in mind in cases, who exhibit long-lasting adrenal failure with even worsening cortisol levels following adrenalectomy. [Figure: see text]