Endocrine Abstracts

We present a case of fludrocortisone-induced hypomagnesaemia in a 27-year old female with Autoimmune Polyglandular Syndrome Type1, manifesting as adrenal insufficiency, hypothyroidism and hypoparathyroidism. Her medications were; Alfalcidol 4 mcg; Levothyroxine 100 mcg; Hydrocortisone 20 mg bid; Fludrocortisone 200 mcg mane and 100 mcg nocte. The nocturnal dose of fludrocortisone was started 4 months prior to her presentation. She presented with a history of abdominal pain and carpopedal spasm. Her admission blood tests revealed hypomagnesaemia, hypokalaemia and hypocalcaemia.

She was treated with intravenous electrolyte replacement. There was a clear temporal relation between the change in the dose of fludrocortisone and onset of symptoms and there was no other dietary or pharmacological cause for her hypomagnesaemia. An Ovid Medline search revealed no cases of fludrocortisone-induced hypomagnesaemia though there are reported cases to FDA.

Magnesium, mainly an intracellular cation with serum concentration of 0.7–1 mmol/l; 1% of total body magnesium(1) SPC does not mention hypomagnesaemia as an adverse effect (2).

The likely mechanism of action is interference of renal handling of magnesium. Approximately 80% of plasma magnesium is filtered through the glomerulus, the majority reabsorbed via the paracellular route at the thick ascending limb of the loop of Henley, dependent on electrical gradient across the membrane and 5–10% is absorbed at the distal convoluted tubule via the transcellular route, dependant on potassium secretion into the distal tubule to create a voltage gradient. The distal reabsorption is physiologically important process in fine-tuning magnesium balance and has been shown to be reduced in hypokalaemia (3). Fludrocortisone is known to produce hypokalaemia through its effects in the distal convoluted tubule.

Recommendation: We propose that fludrocortisone causes hypomagnesaemia via reduction of magnesium reabsorption at the distal convoluted tubule. We recommend that serum magnesium and calcium be checked regularly in patients taking fludrocortisone, especially after a change in dosage.