Case Presentation: We present a 37-year-old man with refractory hypokalemia hospitalized for resection of his sarcoma sacral lesions. History was also significant for biopsy proven mucormycosis thyroid infection three months prior with the additional finding of a right lower lobe cavitating consolidation. He underwent subsequent thyroidectomy and was initially treated with amphotericin B and posaconazole and was transitioned to only posaconazole prior to the planned sacral resection. Early in the hospitalization his potassium was noted to range between 3.0-3.4mmol/L despite regular intravenous and oral supplementation. He later experienced mild diarrhea in the setting of scheduled laxatives. His potassium quickly downtrended with the lowest level of 2.5mmol/L despite aggressive repletion. He had mild hypertension and did not have any recent vomiting or symptoms of hypokalemia. Bicarbonate levels were normal. With aggressive supplementation his potassium improved to >3.5mmol/L. He was diagnosed with posaconazole induced hypokalemia. The decision was made to stay on posaconazole until the patient could be evaluated by infectious disease and to discharge with high-dose potassium supplementation.
Discussion: Posaconazole is a triazole antifungal that covers a broad range of invasive fungal infections including mucormycosis. It generally has a favorable side effect and tolerability profile, especially compared to other systemic triazole antifungals. However, there are noted side effects of hypokalemia and hypertension with two different mechanisms theorized. One proposed mechanism is the inhibition of 11 β- Hydroxysteroid dehydrogenase 2 (11β-HSD2), which converts cortisol to inactive cortisone. Once impaired, there is increased mineralocorticoid activity despite normal production of cortisol. Another proposed mechanism is the inhibition of the 11β-hydroxylase enzyme resulting in accumulation of 11-deoxycorticosterone, which has some mineralocorticoid activity. Many authors of studies believe both mechanisms contribute to the clinical findings. Patients who have severe hypertension or refractory hypokalemia have seen success on dose reduction or cessation of posaconazole and also treatment with mineralocorticoid antagonists. An estimated 22% of patients on posaconazole have been reported to experience hypokalemia, but some portion has been attributed to the gastrointestinal side effects. This patient did have diarrhea later in the hospitalization which likely contributed to worsening hypokalemia, however, hypokalemia refractory to supplementation was present before the onset of diarrhea. In addition, majority of case reports describe hypertension, but there are case reports of patients with hypokalemia and normotension. This patient only experienced mild hypertension during this period but at baseline was normotensive.
Conclusions: Hospitalists are very familiar with electrolyte disturbances with hypokalemia present in an estimated 6.7-21% of hospitalized patients. A thorough medication history and close attention to atypical causes of electrolyte derangements is essential to accurate diagnosis.