Abstract
Background: ACTH-producing pheochromocytomas (APP) are a rare cause of ectopic Cushing’s syndrome (CS), representing <6% of these cases. No guidelines exist on the management of these tumors.
Clinical case: A 41-year-old woman presented to the ED with a 6-month history of newly-diagnosed T2DM and difficult-to-control hypertension. Three weeks prior to admission she developed fatigue, dyspnea on exertion, and generalized weakness particularly severe in the lower extremities (LE) limiting her ability to ambulate. She denied headaches, palpitations and diaphoresis. Initial vital signs included HR 111 beats/min and BP 217/112 mmHg. On physical exam she had classic findings of CS with severe LE weakness. Laboratory testing was consistent with ACTH-dependent CS (ACTH 463 pg/mL [0-45], cortisol 70.8 mcg/dL [3-23], potassium 2.7 mMol/L [3.1-5.1]). She failed both the low dose (1 mg) and high dose (8 mg) dexamethasone suppression tests. MRI of the pituitary gland ruled out a pituitary lesion. IPSS was not deemed necessary by Neurosurgery. CT abdomen showed a 4.2 cm right adrenal lesion and bilateral adrenal hyperplasia. This prompted workup for pheochromocytoma that revealed elevated plasma metanephrines (4.1 nMol/L, [<0.5]) and 24hr urine metanephrines (5329 mcg/day, [182-739]). A diagnosis of APP was entertained. Doxazosin 1 mg BID was added to her other antihypertensives with improvement in blood pressure. Ketoconazole 200 mg TID was started as a bridge for surgery. Patient underwent right unilateral adrenalectomy one month after initial presentation. ACTH and cortisol levels before surgery were 534 pg/mL and 87 mcg/dL, respectively, suggesting that ketoconazole was not effective. Both ACTH and cortisol levels decreased to 26 pg/mL and 14.4 mcg/dL, respectively, immediately after surgery. There was prompt subjective symptomatic improvement, including mild recovery of LE strength. Her blood pressure normalized and only spironolactone was continued. She was started on a prednisone taper. Pathology revealed a 4.2 pheochromocytoma and diffuse adrenocortical hyperplasia. Tumor cells stained positive for ACTH on immunohistochemistry. On follow up visit 2 months after surgery patient was feeling well and ambulating without difficulty. Labs were remarkable for normal plasma fractionated metanephrines, and A1c 5.1% on metformin alone (down from 4 medications on initial presentation).
Conclusion: Diagnosis and management of APP can be challenging. Alpha-blockers should be started promptly. Definitive treatment with unilateral adrenalectomy is curative and has been recommended as the preferred approach.1 Ketoconazole may be used as bridge therapy for surgery, though some studies suggest its efficacy might be lower in ectopic CS.2 Response to other pharmacologic agents is largely unknown.
References:
1. Surgery (1995) 118: 988-94
2. Clinical Endocrinology (1991) 34: 63-70
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