Endocrine Abstracts

Case history: 81 year-old female was admitted to hospital with pneumonia. Past medical history included laryngeal cancer (1996), laryngectomy, iatrogenic hypoparathyroidism, hypothyroidism, and pulmonary tuberculosis (2007). She was treated with different antibiotics without improvement. She had positive aspergillus serology, but cultures were negative. She was started on voriconazole which was later changed to itraconazole 100 mg twice daily and discharged home. She was seen in the respiratory clinic one month later and a plan was made to continue itraconazole for another 6 weeks. Subsequently she was admitted again with iatrogenic hypercalcaemia and pneumonia which responded well to antibiotics, but it was noted that her potassium was low and blood pressure was high (215/109 mmHg). There was no confirmed history of hypertension in the past. She also had mild hypomagnesaemia. Patient was not taking any diuretic. Serum potassium level remained low despite oral and intravenous replacement, high potassium diet and correction of hypomagnesaemia.

Investigations: Potassium 2.4–2.5 mmol/l [ref 3.5–5.3 mmol/l] with poor response to oral and IV replacement. Urine potassium excretion was high (32.4 mmol/l) confirming renal loss of potassium. Serum bicarbonate 48.3 mmol/L. Renin and aldosterone levels were checked after optimization of potassium level and found to be low (Renin 0.2 nmol/L/hr [Ref 0.3–2.2], Aldosterone >50 pmol/l [Ref up to 630 pmol/l]).

Results and treatment: She was treated with potassium replacement and the itraconazole treatment was stopped after discussion with the respiratory team. Her potassium levels normalized and she was discharged home with normal potassium.

Conclusions and points for discussion: Apparent mineralocorticoid excess (AME) syndrome is characterized by hypertension, hypokalaemia, metabolic alkalosis and low renin and aldosterone. It is caused by congenital deficiency or acquired suppression of 11-beta hydroxysteroid dehydrogenase type-2 (11-β-HSD-2). Substances that inhibit 11-β-HSD-2 include liquorice, carbenoxolone and flavonoinds (grapefruit). There is growing evidence that triazoles like itraconazole can cause apparent mineralocorticoid syndrome by inhibiting 11-β-HSD-2. Hypokalaemia was reported in context of treatment with itraconazole and data suggest excessive urinary loss of potassium as a mechanism. Association with worsening hypertension, oedema, metabolic alkalosis and low renin aldosterone was also reported. In vitro, suppression of 11-β-HSD-2 was described with itraconazole. Patients taking itraconazole should there for be monitored for hypokalaemia and hypertension. This case highlights this unusual and less recognized cause of hypokalaemia.