Hypertension Management in Patients with Addison’s Disease

Assessment of Replacement Therapy Over‑Replacement

Over‑replacement with glucocorticoids or mineralocorticoids can precipitate hypertension; therefore both regimens should be evaluated in patients with Addison’s disease on hormone replacement. [@2, @1]
Clinical signs of glucocorticoid excess include weight gain, central adiposity, insomnia, and peripheral edema. [@2]
Clinical signs of mineralocorticoid excess include peripheral edema, elevated sitting and standing blood pressure, and volume overload. [@2]
Laboratory assessment should include serum electrolytes and plasma renin activity to detect mineralocorticoid excess. [@2]
The Endocrine Society notes that overtreatment with hydrocortisone or fludrocortisone is a recognized cause of hypertension in this population. [@2, @1]

When hypertension develops, the first step is to reduce the fludrocortisone dose from the usual 0.1 mg daily to 0.05 mg daily if clinical or biochemical evidence of mineralocorticoid excess (e.g., edema, suppressed renin) is present. [@1]
Blood pressure should be re‑checked 1–2 weeks after the dose reduction to assess response. [@1]

If blood pressure remains elevated after optimal hormone replacement and the patient is euvolemic, initiate an ACE inhibitor or an angiotensin II receptor blocker (ARB) as first‑line therapy while maintaining the appropriate fludrocortisone dose. [@1, @4]
ACE inhibitors/ARBs mitigate the vasoconstrictive effects of angiotensin II that may persist despite adequate mineralocorticoid replacement. [@1, @4]
Continuation of fludrocortisone at a dose guided by clinical assessment and plasma renin activity is recommended. [@1]
Dihydropyridine calcium‑channel blockers may be added as second‑line agents if additional blood pressure control is needed. [@1, @4]

Loop or thiazide diuretics should be avoided because they can precipitate adrenal crisis in patients with Addison’s disease. [@1, @4]
Aldosterone‑receptor antagonists (e.g., spironolactone, eplerenone) are contraindicated. [@1, @4]

Hypertension can coexist with Addison’s disease despite the classic association of adrenal insufficiency with hypotension. [@2, @1]
Primary (essential) hypertension may also occur independently in these patients, necessitating standard antihypertensive treatment while preserving appropriate hormone replacement. [@2, @1]

Measure both sitting and standing blood pressure at every clinical visit. [@2, @1]
Periodically check serum sodium and potassium levels. [@2, @1]
Aim for plasma renin activity in the upper normal range as an indicator of adequate mineralocorticoid replacement. [@2, @1]
Evaluate clinical symptoms such as salt craving, orthostatic dizziness, or peripheral edema. [@2, @1]

Do not use ACTH levels to titrate glucocorticoid dosing, as this can lead to over‑replacement and hypertension. [@2]
Avoid substances that enhance mineralocorticoid activity, such as licorice and grapefruit juice. [@2, @4]