Mineralocorticoid Replacement Therapy

Mineralocorticoid replacement gives fludrocortisone to replace aldosterone, which keeps sodium in the body and potassium out. It is needed in primary adrenal insufficiency, where the adrenal cortex is destroyed, and in congenital adrenal hyperplasia with salt wasting. It is not needed in secondary adrenal insufficiency from pituitary disease, because the renin and aldosterone system is intact.

Why it matters. Without it, patients lose sodium and water, become hypotensive, hyperkalaemic and hyponatraemic, and are at risk of crisis even on adequate hydrocortisone.

Cortisol effect. Hydrocortisone also activates the mineralocorticoid receptor. At hydrocortisone 50 mg daily or more, the mineralocorticoid effect equals about 100 micrograms of fludrocortisone, so fludrocortisone is not needed at that dose.

Drug. Fludrocortisone acetate tablets 100 micrograms, taken orally once daily in the morning.

Salt. Advise normal or liberal salt intake, with extra salt in hot weather, heavy sweating and diarrhoea.

Not used. Fludrocortisone is not used for adrenal insufficiency caused by exogenous steroids, because the renin and aldosterone system is intact.

Adults. Start 50 to 100 micrograms orally once daily. The usual maintenance dose is 100 micrograms daily, within a range of 50 to 300 micrograms daily. The maximum is 300 micrograms daily, and a higher dose should be given only by an endocrinologist.

Titration. Change the dose in steps of 50 micrograms every 2 to 4 weeks. Increase for postural hypotension (a fall in systolic pressure of 20 mmHg or more on standing), salt craving, raised plasma renin or potassium over 5.0 mmol/L. Decrease for hypertension, oedema, headache, or potassium under 3.5 mmol/L.

Target. Plasma renin in the upper half of the normal range, with normal sodium and potassium and no postural drop.

Children. Infants 100 to 150 micrograms daily with sodium chloride 1 to 2 g daily (17 to 34 mmol) in divided feeds. Children aged 1 to 12 years usually need 50 to 100 micrograms daily, and the dose falls with age. Dose by weight and body surface area with paediatric endocrinology.

Interactions. Rifampicin, phenytoin and carbamazepine speed breakdown, so the dose may need to rise. Diuretics, laxatives, amphotericin B and liquorice worsen potassium loss. Non-steroidal anti-inflammatory drugs cause fluid retention and raise blood pressure.

Hot climates. Sweating increases salt loss in coastal and lowland East Africa, so patients may need more salt and, in some, an extra 50 micrograms of fludrocortisone in prolonged heat.

Pregnancy. Progesterone opposes aldosterone, so doses may need to rise, particularly in the second and third trimesters. Use blood pressure, potassium and oedema as guides and keep the lowest dose that controls postural symptoms.

Illness. Continue the usual dose. When hydrocortisone is given at 50 mg daily or more, fludrocortisone can be paused, and restarted when the hydrocortisone returns to under 50 mg daily.

Special groups. - Kidney impairment: raise potassium monitoring, since hyperkalaemia and fluid retention both occur. - Liver disease: avoid in ascites and oedema where possible, and monitor weight. - Heart failure: start at 50 micrograms and watch for fluid retention. - Older adults: start at 50 micrograms, because supine hypertension is common. - Breastfeeding: compatible.

Monitoring. Lying and standing blood pressure, sodium and potassium at 2 to 4 weeks after each change, then every 6 to 12 months. Plasma renin yearly if available. Weight and oedema at each visit.

Excess. Hypertension, oedema, hypokalaemia, headache and heart failure. Reduce the dose by 50 micrograms and review other causes.

Deficiency. Salt craving, postural hypotension, hyponatraemia and hyperkalaemia. Increase the dose by 50 micrograms.

Stopping. Treatment is lifelong in primary adrenal insufficiency and salt-wasting congenital adrenal hyperplasia.

Referral and escalation. Refer for recurrent hyperkalaemia, resistant hypertension on treatment, a dose over 300 micrograms daily, or a child with salt wasting. Admit for vomiting, hypotension, or sodium under 125 mmol/L.