Board Review

A 28-year-old woman is being discharged from the hospital with a diagnosis of autoimmune adrenalitis. Medical history is otherwise unremarkable, and she was on no medications prior to admission.

On physical examination, temperature is 37.0 °C (98.6 °F), blood pressure is 120/80 mm Hg, pulse rate is 80/min, and respiration rate is 12/min. BMI is 22. Increased skin pigmentation is noted over the extensor surfaces of the extremities bilaterally. The remainder of her examination is normal.

Which of the following is the most appropriate long-term medication regimen for this patient?

A) Dexamethasone, 1 mg once daily

B) Fludrocortisone, 0.05 mg once daily

C) Hydrocortisone, 10 mg three times daily

D) Prednisone, 5 mg once daily, and fludrocortisone, 0.05 mg once daily

Answer: D - Prednisone, 5 mg once daily, and fludrocortisone, 0.05 mg once daily

Objective: Manage primary adrenal failure.

Key Point

Patients with primary adrenal failure require both glucocorticoid and mineralocorticoid replacement in physiologic doses.

The most appropriate regimen for the long-term treatment of this patient's primary adrenal failure would be prednisone, 5 mg once daily, and fludrocortisone, 0.05 mg once daily. In primary adrenal failure, there is a failure in the production of all the hormones of the adrenal cortex. Patients therefore require both glucocorticoid and mineralocorticoid replacement. Because she is no longer ill, physiologic replacement doses are appropriate. Prednisone primarily has glucocorticoid activity, with 5 mg being considered a physiologic replacement dose. It is also long-acting so may be administered once daily in combination with fludrocortisone, which has almost pure mineralocorticoid properties. Physiologic replacement doses of fludrocortisone are 0.05 to 2 mg per day.

Dexamethasone is primarily a glucocorticoid and could be used as the glucocorticoid portion of combination replacement therapy with a mineralocorticoid such as fludrocortisone. However, dexamethasone alone would not be appropriate therapy for primary adrenal failure due to its intrinsic lack of mineralocorticoid activity.

Fludrocortisone alone is also inappropriate because it would not provide glucocorticoid replacement.

Hydrocortisone has both glucocorticoid and mineralocorticoid properties, with primarily glucocorticoid activity at physiologic replacement doses of 12.5 to 25 mg in two to three divided doses daily. At total daily doses above 50 mg, hydrocortisone has adequate mineralocorticoid activity to allow for its use as monotherapy. However, treatment with hydrocortisone, 10 mg three times daily, does not provide adequate mineralocorticoid replacement, while it supplies a supraphysiologic amount of glucocorticoid that could lead to iatrogenic Cushing syndrome if administered on a long-term basis.

Patients with primary adrenal failure require additional glucocorticoid at times of physiologic stress. Treatment for minor stress (upper respiratory infection, fever, minor surgery under local anesthesia) is typically two to three times the basal dose of hydrocortisone (or equivalent), for moderate stress (minor or moderate surgery with general anesthesia) usually 45 to 75 mg/day, and major stress (major surgery, trauma, critical illness, or childbirth) up to 150 to 200 mg/day with a gradual taper following resolution of the stress.

Neary N, Nieman L. Adrenal insufficiency: etiology, diagnosis and treatment. Curr Opin Endocrinol Diabetes Obes. 2010 Jun;17(3):217-23. Link Out