Diagnosis and Management of Primary Adrenal Insufficiency

Diagnostic Criteria

The Endocrine Society recommends that basal cortisol <250 nmol/L with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 1, 2
The American College of Endocrinology suggests that basal cortisol <400 nmol/L with elevated ACTH raises strong suspicion and requires confirmatory testing 1, 2
Morning paired measurement of serum cortisol and plasma ACTH is the first-line diagnostic approach, as recommended by the European Society of Endocrinology 1, 2, 3

The cosyntropin stimulation test is mandatory to confirm the diagnosis when initial results are equivocal, according to the American Association of Clinical Endocrinologists 1, 2
Peak cortisol <500 nmol/L is diagnostic of adrenal insufficiency, as stated by the Endocrine Society 1, 2
The test protocol involves administering 0.25 mg cosyntropin intramuscularly or intravenously, with serum cortisol measurements at baseline, 30 minutes, and 60 minutes post-administration 1, 2

Hyponatremia is present in 90% of newly diagnosed cases, and hyperkalemia occurs in only ~50% of cases, as reported by the European Society of Endocrinology 1, 2
Hyperpigmentation develops in primary adrenal insufficiency due to elevated ACTH, according to the American College of Endocrinology 1

Measuring 21-hydroxylase autoantibodies is the first step in establishing the etiology, as recommended by the Endocrine Society 1, 2
CT imaging of the adrenals is necessary to evaluate for structural abnormalities, according to the American Association of Clinical Endocrinologists 1, 2

Confirmed primary adrenal insufficiency requires lifelong glucocorticoid and mineralocorticoid replacement therapy, as stated by the European Society of Endocrinology 1, 2
Hydrocortisone 15-25 mg daily in divided doses is a common maintenance therapy, as recommended by the American College of Endocrinology 2
Fludrocortisone 0.05-0.1 mg daily is used for mineralocorticoid replacement, according to the Endocrine Society 2

All patients must wear a medical alert bracelet and carry a steroid emergency card, as recommended by the American Association of Clinical Endocrinologists 1, 2, 3
Patients should be instructed on stress dosing and provided with an emergency injectable hydrocortisone kit, according to the European Society of Endocrinology 2