A Contemporary Approach to the Diagnosis and Management of Adrenal Insufficiency

Abstract

Adrenal insufficiency (AI) can be classified into three distinct categories based on its underlying causes: primary adrenal disorders, secondary deficiencies in adrenocorticotropin, or hypothalamic suppression from external factors, most commonly glucocorticoid medications used for anti-inflammatory therapy. The hallmark clinical features of AI include fatigue, appetite loss, unintentional weight loss, low blood pressure, and hyponatremia. Individuals with primary AI additionally manifest skin hyperpigmentation, hyperkalemia, and salt craving. The diagnosis of AI is frequently delayed due to the non-specific symptoms and signs early in the disease course, which poses a significant challenge to its early detection prior to an adrenal crisis. Despite the widespread availability of lifesaving glucocorticoid medications for decades, notable challenges persist, particularly in the domains of timely diagnosis while simultaneously avoiding misdiagnosis, patient education for averting adrenal crises, and the determination of optimal replacement therapies. This article reviews recent advancements in the contemporary diagnostic strategy and approaches to optimal treatment for AI.

Keywords: Adrenal cortex; Adrenal insufficiency; Glucocorticoids; Mineralocorticoids.

Fig. 1.

Diagnostic algorithm for evaluating adrenal function. After excluding exogenous glucocorticoid use, the 8:00 AM serum cortisol is the first step. If the cortisol is conclusively low (<4 µg/dL), then plasma adrenocorticotropic hormone (ACTH) determines if it is primary or central adrenal insufficiency (AI). If the cortisol is 4 to 14 µg/dL, the patient might have AI, but it is likely partial, and the lower the 8:00 AM cortisol the more likely that some degree of AI is present. In these cases, a dehydroepiandrosterone-sulfate (DHEAS) >65 µg/dL excludes AI; if not, ACTH determines if dynamic testing with cosyntropin stimulation test (CST) or insulin tolerance test (ITT) is recommended to determine if primary or central AI is present. Clinical judgment should always take precedence over laboratory test results when making a diagnosis of AI and subjecting patients to chronic glucocorticoid therapy. GC, glucocorticoids; HPA, hypothalamic-pituitary-adrenal.