Mineralocorticoids

Mineralocorticoids act on the mineralocorticoid receptor to retain sodium and excrete potassium and hydrogen ions. Fludrocortisone is the only agent in clinical use; it replaces aldosterone in primary adrenal insufficiency and salt-wasting congenital adrenal hyperplasia.

Mechanism. In the principal cells of the distal nephron, the receptor raises epithelial sodium channel and Na-K ATPase activity, so sodium and water are retained and potassium and hydrogen ions are lost. Fludrocortisone also has glucocorticoid activity about 10 times that of hydrocortisone.

Pharmacokinetics. Good oral absorption, half-life about 3.5 hours, biological effect 18 to 36 hours, so once daily dosing. Hydrocortisone at over 50 mg daily provides enough mineralocorticoid effect to omit fludrocortisone.

Fludrocortisone. 0.1 mg tablets.

Hydrocortisone. Has intrinsic mineralocorticoid activity at higher doses.

Antagonists. Spironolactone and eplerenone block the receptor and are used for heart failure, hyperaldosteronism and hypertension. They oppose the effect of fludrocortisone and are not used together for replacement.

• Primary adrenal insufficiency (adult): 0.05 to 0.2 mg once daily, adjusted by blood pressure, postural drop, sodium, potassium and plasma renin (aim for the upper normal range).
• Salt-wasting congenital adrenal hyperplasia: infants 0.05 to 0.2 mg daily plus sodium chloride 1 to 2 g (17 to 34 mmol) daily; children 0.05 to 0.1 mg daily.
• Secondary adrenal insufficiency: not needed, because the renin-angiotensin axis is intact.
• Orthostatic hypotension: 0.05 to 0.3 mg daily (off-label), with strict supine blood pressure checks.
• Illness: fludrocortisone is not increased; the hydrocortisone dose is raised instead, and given parenterally with vomiting or diarrhoea.

Special groups. Pregnancy: requirement may rise because of progesterone antagonism; titrate by blood pressure and renin. Breastfeeding: compatible. Children: dose by body surface area. Older adults: low doses, watch for supine hypertension and heart failure. Kidney impairment: caution with potassium and sodium handling. Liver impairment: caution with ascites. Regional: high sweat losses in hot climates and manual labour raise salt needs; add dietary salt during heat and exertion.

Adverse effects. Hypertension, oedema, weight gain, hypokalaemia, hypomagnesaemia, headache, heart failure, and with excess dose, proximal myopathy.

Contraindications. Systemic fungal infection, uncontrolled heart failure or hypertension in secondary adrenal insufficiency.

Interactions. Diuretics and liquorice increase hypokalaemia. NSAIDs add sodium retention. Rifampicin and phenytoin lower effect. Digoxin toxicity with hypokalaemia.

Monitoring. Lying and standing blood pressure, sodium and potassium at each review (3 to 4 weeks after any change), and plasma renin activity annually in adults.

Referral and escalation. Persistent hyperkalaemia, resistant hypotension, or adrenal crisis.