Case Presentation: A 61 year old woman presented to the hospital with dyspnea and chest pain. She had been gaining weight, and experiencing night sweats and lower extremity swelling for several months. She had a 30 pack year smoking history. Physical examination revealed fingernail clubbing, 1+ pitting edema, and a blood pressure of 220/97—despite taking Hydralazine and Spironolactone for months. Labs revealed a potassium level of 2.6 mmol/L, a bicarbonate level of 31.0 mmol/L, a hemoglobin of 15.2 gm/dL, and a WBC count of 15.66 x103 cells per µl. A PET/CT scan showed a suspicious mass that was hypermetabolic, and a bronchoscopy with biopsy revealed small cell carcinoma of the lung, that was already metastatic.
Despite treatment, her hypertension and hypokalemia persisted. A urine potassium level of 30.7 mmol/L indicated renal potassium wasting. An abdominal MRA showed patent renal arteries, ruling out renal artery stenosis. Normal renin and aldosterone levels ruled out primary aldosteronism. However, cortisol levels were elevated at 67 mcg/dL, prompting a 24-hour urinary-free cortisol excretion, which showed a urinary cortisol level of 3336 mcg/24 hr. An overnight dexamethasone suppression test showed persistent high morning cortisol levels. These tests, coupled with the patient’s persistent hypertension and known cancer prompted a diagnosis of paraneoplastic Cushing’s syndrome.
Discussion: Ectopic adrenocorticotropic hormone production is a rare cause of Cushing’s syndrome, and has been found in approximately 1%-5% of small cell lung cancers. Although not a classic symptom of Cushing’s syndrome, hypokalemia can affect up to 57% of patients with Cushing’s syndrome, as excessive cortisol can act as a weak mineralocorticoid. The initial work-up of hypokalemia includes obtaining a urine potassium level, which can distinguish urinary potassium losses from others. If urinary potassium is inappropriately increased, then hypertension may suggest a primary or secondary hyperaldostone state. Obtaining renin and aldosterone levels can help in further classification. If renin and aldosterone levels are normal, one should investigate serum cortisol levels. Elevated cortisol levels warrant further work-up, including a 24-hour urinary cortisol collection and a dexamethasone suppression test to confirm the diagnosis of paraneoplastic Cushing’s syndrome.
Conclusions: In a patient with hypertension and malignancy with evidence of metastasis, the differential diagnosis is broad, including renovascular disease, a renin secreting tumor, primary aldosteronism, and Cushing’s syndrome. Diagnosing paraneoplastic Cushing’s syndrome early is important as it alters the patient’s prognosis and requires additional treatment.