Side Effects of Glucocorticoid Over-Replacement in Primary Adrenal Insufficiency

Immediate Clinical Signs of Over-Replacement

Excessive glucocorticoid dosing, even 5-10 mg above physiological levels, causes weight gain, insomnia, and peripheral edema as primary clinical manifestations of over-replacement in patients with primary adrenal insufficiency 1, 2, 3, 4
Weight gain is the most consistent early indicator of over-replacement and should prompt immediate dose reduction 1, 2, 3, 4
Insomnia, particularly when doses are taken too late in the day or total daily dose exceeds physiological needs, is a sign of over-replacement 1, 2, 5
Peripheral edema results from the mineralocorticoid effects of excess glucocorticoids 1, 2, 3, 4

Normal adrenal function produces 5-10 mg of cortisol per m² of body surface area per day, translating to an oral replacement dose of 15-25 mg hydrocortisone daily 2, 3, 4
The equivalent prednisolone dose is 4-5 mg daily 5, 6

Clinical assessment is the primary monitoring method, as plasma ACTH and serum cortisol are not useful parameters for glucocorticoid dose adjustment 1, 2, 3, 4
Patient weight trends, sleep quality, presence of peripheral edema, general feelings of energy, mental concentration, and daytime somnolence should be monitored 1, 2, 3, 4

Do not compensate for under-replacement of mineralocorticoids by over-replacing glucocorticoids, as this leads to long-term adverse outcomes from glucocorticoid excess and continued predisposition to adrenal crises 6
All patients with primary adrenal insufficiency require fludrocortisone 0.05-0.2 mg daily in addition to appropriate glucocorticoid dosing 6