Abstract
Introduction: Cushing disease refers to the endogenous overproduction of glucocorticoid due to an ACTH-producing pituitary adenoma. It is important to recognize and treat due to the adverse health outcomes associated with it. We describe an unusual case of Cushing disease which presented very rapidly and progressively with extremely high cortisol levels mimicking those seen in ectopic production of ACTH.Case Presentation: A 43 year old Caucasian man, with no past medical history, presented with hypertensive crisis. He was discharged home with anti-hypertensive medications. Over the next 4 months, he gained 20 pounds, mainly around his abdomen, developed fatigue, and blood pressure continued to be high despite six anti-hypertensive medications, developed diabetes and hypokalemia, requiring 120 meq/day of potassium chloride. On exam, he had plethora, central obesity and wide, purple striae over his abdomen. Work-up for secondary causes of hypertension showed normal renal Doppler US, normal aldosterone and renin activity, normal plasma metanephrines, however, his 24 hour urinary free cortisol was dramatically elevated at 4022ug/day with a urine volume of 4 L, 1 mg dexamethasone suppression test showed unsuppressed serum cortisol of 55ug/dl. Morning ACTH of 125 pg/ml with concurrent serum cortisol level of 53.8 mcg/dl, indicated ACTH-dependent hypercortisolism. Inferior petrosal sinus sampling indicated a pituitary source of ACTH. Sellar MRI initially did not show a pituitary adenoma, however, repeat MRI with a 3-Tesla magnet showed a 4 mm pituitary adenoma. He was treated with ketoconazole and was started on atovaquone for PCP prophylaxis while awaiting trans-sphenoidal resection, which he had a month later. Pathology showed a 4 mm adenoma which stained strongly for ACTH. On postoperative day 1, serum cortisol dropped to 2.1 from 52.3 mcg/dl, and patient was discharged on hydrocortisone replacement. Three weeks later, he had lost 12 pounds, hyperglycemia improved with discontinuation of insulin, hypokalemia resolved and hypertension was well controlled on two anti-hypertensives. Discussion: ACTH-dependent Cushing syndrome is either caused by Cushing disease, or from ectopic ACTH production from a tumor. Cushing disease is characterized by a gradual onset and subtle manifestations of hypercortisolism. Acute, severe presentation favors an ectopic ACTH producing tumor, and is associated with much higher cortisol levels. In our patient, clinical data suggested ectopic ACTH production, yet he was found to have Cushing disease, and was treated successfully with trans-sphenoidal resection of the pituitary adenoma. It is imperative to consider all possibilities, and do the full work up so as not to miss an atypical presentation of Cushing disease, and direct treatment accordingly.