Prednisolone Maintenance Dose in Primary Adrenal Insufficiency

Standard Dosing Regimens

The recommended maintenance dose of prednisolone for primary adrenal insufficiency is 4-5 mg daily, typically given as a single dose upon awakening, or alternatively as a divided regimen of 3 mg on awakening and 1-2 mg at 14:00h, as suggested by the Journal of Internal Medicine 1, 2
Prednisolone 4-5 mg taken upon awakening is the preferred single daily dose for compliance 1, 2
A single-dose approach should be considered when patients have compliance problems or marked fluctuations of energy 1
A divided dose regimen of 3 mg on awakening and 1-2 mg at 14:00h is useful for patients working long shifts 1, 2
The second dose should not be taken later than 4-6 hours before bedtime to avoid insomnia 2

Prednisolone should only be considered as a second-line option when hydrocortisone or cortisone acetate is not tolerated or when there are compliance problems 1
The dose equivalence is approximately 20 mg hydrocortisone = 5 mg prednisolone 2

All patients with primary adrenal insufficiency require fludrocortisone 0.05-0.2 mg daily in addition to glucocorticoid replacement 2
Under-replacement of mineralocorticoids is common and may predispose patients to recurrent adrenal crises 1
The dose should be adjusted based on blood pressure, salt cravings, and electrolyte levels 1

Clinical symptoms are the primary method for monitoring adequacy of replacement 2
Signs of over-replacement include weight gain, insomnia, and peripheral edema 2
Signs of under-replacement include lethargy, nausea, poor appetite, weight loss, and increased pigmentation 2
Several medications increase prednisolone requirements, including anti-epileptics, barbiturates, and antituberculosis medications 1, 2
Substances that may decrease prednisolone requirements include grapefruit juice and liquorice 1, 2

Patients can wake earlier to take the first dose, then return to sleep to relieve morning nausea symptoms 2
Night shift workers should adjust their dosing schedule according to their sleep-wake pattern, taking the first dose upon awakening before work 2
Higher fludrocortisone doses may be needed in the last trimester of pregnancy when progesterone counteracts mineralocorticoids 1

Do not compensate for under-replacement of mineralocorticoids by over-replacing glucocorticoids, as this practice may lead to long-term adverse outcomes from glucocorticoid excess while still predisposing patients to adrenal crises from inadequate mineralocorticoid replacement 1