Endocrine Abstracts

Background: Patients receiving triazole antifungals can present with hypertension and hypokalaemia. These drugs are reported to cause variable inhibition of the steroidogenic enzymes 11β hydroxylase and 11β hydroxysteroid dehydrogenase type 2 (11βHSD2). The ensuing clinical picture is similar to congenital adrenal hyperplasia (CAH) due to 11β-hydroxylase deficiency or apparent mineralocorticoid excess (11βHSD2 deficiency), with posaconazole and itraconazole being most implicated. Another triazole antifungal, fluconazole, has only been associated with hypocortisolaemia to date.

Case: A 4 year-old boy presented with acute liver failure of indeterminant aetiology. Clinical deterioration was managed with intubation, Continuous Veno-Venous Hemofiltration, and 3 weeks of intravenous fluconazole for presumed fungal infection. Three days after commencing fluconazole, he developed hypoglycaemia (glucose 2.3 mmol/l) with low serum cortisol (95 nmol/l). He had suboptimal cortisol response to short synacthen tests (SST) (Table 1). He also developed hypokalaemia (nadir serum K 2.4 mmol/l), and labile blood pressure, whilst on fluconazole. The hypokalaemia was managed with multiple intravenous potassium corrections and spironolactone. A urine steroid profile (USP) following the failed SST was suggestive of 11β-hydroxylase deficiency CAH, with relative increases of 11-deoxycortisol and 11-deoxycorticosterone metabolites. CAH gene panel was normal. He underwent successful liver transplant with stress hydrocortisone cover and immunosuppressive methylprednisolone, followed by oral prednisolone 1 mg mane and hydrocortisone 2.5 mg nocte. Repeat SST and USP, performed 3 and 5 months respectively after ceasing fluconazole showed normalisation (table 1).Table 1. Short Synacthen TestsNormal peak cortisol >420nmol/L.

Conclusion: Normalisation of USP, hypokalaemia and cortisol response following cessation of fluconazole treatment suggests that the drug caused these abnormalities. Although the triazole antifungals posaconazole and itraconazole have been described to cause dose-dependent mineralocorticoid hypertension, this is the first documented case associated with fluconazole. As fluconazole is a widely used treatment for fungal infections, it is important to consider its possible impact on steroid synthesis and consider monitoring for off-target hypokalaemia, hypertension and hypocortisolaemia.