What is the usual dose of hydrocortisone for adrenal insufficiency?

From the Guidelines

The usual dose of hydrocortisone for adrenal insufficiency is 15-25 mg per day, typically divided into 2-3 doses with a larger portion given in the morning to mimic the body's natural cortisol rhythm. This dosing regimen is based on the most recent and highest quality study available, which recommends that most patients with primary adrenal insufficiency should take 15–25 mg of hydrocortisone (HC) daily in split doses 1. A common regimen is 10-15 mg in the morning, 5 mg in the early afternoon, and sometimes an additional 5 mg in the early evening. Patients should take the medication with food to reduce stomach irritation.

During times of physical stress such as illness, injury, or surgery, the dose needs to be increased to 2-3 times the maintenance dose, sometimes requiring 50-100 mg per day, as recommended by a more recent study 1. Patients with adrenal insufficiency should always carry emergency hydrocortisone for injection (typically 100 mg) and wear a medical alert bracelet. The dosing aims to replace the cortisol that the adrenal glands cannot produce, which is essential for regulating metabolism, immune response, and stress management. Too little replacement can lead to adrenal crisis, while excessive doses can cause Cushingoid side effects like weight gain, hypertension, and glucose intolerance.

Some key considerations for hydrocortisone dosing include:

• Using hydrocortisone allows for recreation of the diurnal rhythm of cortisol, with 2/3 of the dose given in the morning and 1/3 in the early afternoon 1
• Long-acting steroids such as prednisone, rather than short-acting hydrocortisone, carry risk of over replacement but can be used in special circumstances 1
• All patients need education on stress dosing for sick days, use of emergency injectables, when to seek medical attention for impending adrenal crisis, and a medical alert bracelet or necklace for adrenal insufficiency to trigger stress dose corticosteroids by emergency medical personnel 1

From the FDA Drug Label

The initial dose of SOLU-CORTEF Sterile Powder is 100 mg to 500 mg, depending on the specific disease entity being treated In pediatric patients, the initial dose of hydrocortisone may vary depending on the specific disease entity being treated. The range of initial doses is 0. 56 mg/kg/day to 8 mg/kg/day in three or four divided doses The initial dosage of hydrocortisone tablets may vary from 20 mg to 240 mg of hydrocortisone per day depending on the specific disease entity being treated.

The usual dose of hydrocortisone for adrenal insufficiency is not explicitly stated in the provided drug labels. However, based on the available information, the initial dose of hydrocortisone can range from 20 mg to 240 mg per day for oral administration 2 and 100 mg to 500 mg for intravenous administration 3, depending on the specific disease entity being treated and the patient's response.

• The dose may need to be adjusted based on the patient's clinical status, individual drug responsiveness, and exposure to stressful situations.
• In pediatric patients, the initial dose can range from 0.56 mg/kg/day to 8 mg/kg/day in three or four divided doses 3.
• It is essential to individualize the dosage and monitor the patient's response to determine the lowest effective dose.

From the Research

Hydrocortisone Dosing for Adrenal Insufficiency

• The usual dose of hydrocortisone for adrenal insufficiency is not strictly defined, but studies suggest that a dose of 15-25 mg/day in divided doses is commonly used 4.
• A study found that a regimen of 10 + 5 + 5 mg at 0730,1200, and 1630 h, respectively, was the most effective in achieving physiological target concentrations 5.
• Weight-related dosing has also been recommended, with a fixed 10-mg hydrocortisone dose overexposing patients to cortisol by 6.3%, whereas weight-adjusted dosing decreased interpatient variability in maximum cortisol concentration 6.
• The timing of hydrocortisone administration is also important, with food taken before hydrocortisone delaying its absorption 6.
• Monitoring of hydrocortisone replacement therapy is crucial, with serum cortisol measured 4 h after hydrocortisone predicting cortisol AUC 6.

Factors Affecting Hydrocortisone Dosing

• Body weight is the most important predictor of hydrocortisone clearance 6.
• Food intake can affect the absorption of hydrocortisone 6.
• Individualized dose adjustment is necessary to achieve optimal cortisol exposure 5, 7.
• The natural circadian rhythm of cortisol release should be replicated as closely as possible 8, 7.

Current Treatment Outcomes

• Despite current glucocorticoid replacement therapy, morbidity remains high and life expectancy is reduced in patients with adrenal insufficiency 7.
• Over- or under-treatment with hydrocortisone can result in Cushing-like symptoms or adrenal crisis, respectively 7.
• Improved treatment strategies, such as modified-release hydrocortisone preparations, are being developed to more closely mimic the physiological circadian pattern of cortisol secretion 8.