A paraneoplastic potassium and acid-base disturbance

TREATMENT OF CUSHING SYNDROME DUE TO ECTOPIC ACTH SECRETION

6. Which of the following is most appropriate medical therapy for suppression of cortisol secretion in Cushing syndrome due to ectopic ACTH secretion?

• Spironolactone
• Dexamethasone
• Somatostatin
• Estrogen
• Ketoconazole

Hyperglycemia, hypokalemia, hypertension, psychiatric disturbances, venous thromboembolism, and systemic infections appear to be common in ectopic ACTH syndrome and often correlate with the degree of hypercortisolemia. Severe Cushing syndrome due to ectopic ACTH secretion is an emergency requiring prompt control of cortisol secretion.

First-line treatments include steroidogenesis inhibitors (ketoconazole, metyrapone, etomidate, mitotane) and glucocorticoid receptor antagonists (mifepristone). High-dose spironolactone and eplerenone can also be used to treat the hypertension and hypokalemia associated with mineralocorticoid receptor stimulation. Definitive treatment involves surgical resection, chemotherapy, or radiotherapy when applicable.^24,25

After confirmation of the diagnosis, the patient is prescribed ketoconazole and spironolactone, with substantial improvement. He subsequently is started on combination chemotherapy and radiation therapy for his small-cell lung carcinoma.

DISCUSSION

The differential diagnosis for hypokalemia is broad and relies on information obtained during the history and physical examination, followed by interpretation of selected laboratory results. Myriad pathologies in diverse organ systems, eg, diarrhea, renal tubular acidosis, and adrenal disease, may be responsible for a low serum potassium. Further categorizing potassium depletion on the basis of an associated acid-base disturbance, such as metabolic alkalosis, allows one to use an algorithmic approach that can identify specific etiologies responsible for both the potassium and the acid-base disturbances.

Using the spot urine chloride in the setting of hypokalemic metabolic alkalosis with or without hypertension can narrow the differential diagnosis and allow additional clinical findings to guide clinical problem-solving and decision-making, even for conditions not commonly encountered in routine medical practice.

Obtaining renin and aldosterone measurements in patients with potassium depletion, metabolic alkalosis, high urine chloride excretion, and hypertension permits further categorization into 3 clinical groups: elevated aldosterone and renin (secondary hyperaldosteronism), elevated aldosterone and low renin (primary hyperaldosteronism), or apparent mineralocorticoid excess wherein neither renin nor aldosterone are responsible for the syndrome.

The patient in our case had apparent mineralocorticoid excess as a consequence of an ACTH-producing small-cell carcinoma.