Endocrine Society Issues New Guidelines for Primary Adrenal Insufficiency

The Endocrine Society released a new clinical practice guideline covering diagnosis and treatment of primary adrenal insufficiency in January 2016. The European Society of Endocrinology and the American Association for Clinical Chemistry co-sponsored this document.

The Task Force— a team of 9 endocrinologists, a methodologist, and a medical writer — used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to categorize recommendations and the quality of evidence. The format, a concise summary followed by more detailed discussion, is easy to use.

This guideline emphasizes that clinicians need to suspect primary adrenal insufficiency earlier in acutely ill patients, patients with predisposing factors, and pregnant women with unexplained persistent nausea, fatigue, and hypotension.

This guideline confirms that the short corticotropin test (250 mcg) remains the gold standard for establishing a diagnosis. If a short corticotropin test is not possible, clinicians should screen initially by measuring morning plasma ACTH and cortisol levels. A plasma ACTH greater than twice the upper limit of the reference range is consistent with primary adrenal insufficiency.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency causes 80% of adrenal insufficiency in infants. Diagnosis of the underlying cause (e.g. associated autoimmune disorders, neurological features of adrenoleukodystrophy, or disorders that may lead to adrenal infiltration) should include a validated assay of autoantibodies against 21-hydroxylase.

CYP21A2 autoantibodies can develop several years before patients exhibit biochemical and clinical evidence of primary adrenal insufficiency, and 30% of patients who test positive progress to primary adrenal insufficiency within 2 years. If patients are CYP21A2 autoantibody-negative, the guideline recommends a computed tomography (CT) scan of the adrenals. This test may reveal infectious diseases like tuberculosis, or tumors.

For adults, the guideline recommends specific treatment. Once-daily fludrocortisone (with median dose of 0.1 mg) and hydrocortisone (15-25 mg/day) or cortisone acetate replacement (20-35 mg/day) given in 2 to 3 daily doses are the preferred regimens.

In pediatric patients, it recommends hydrocortisone (8 mg/m²/day).

The guideline elucidates several patient education factors. Patients need to know about stress dosing and when to use it. It also recommends giving patients a steroid emergency card, medic alert identification, and a glucocorticoid preparation for parenteral emergency administration.

Follow-up should aim at monitoring appropriate corticosteroid dosing and associated autoimmune diseases, particularly autoimmune thyroid disease.

The guideline appears in the January 2016 issue of The Journal of Clinical Endocrinology and Metabolism.