Diagnosis and Management of Primary Adrenal Insufficiency

Clinical Presentation and Diagnosis

The clinical presentation of a patient with hypotension, hyponatremia, hyperkalemia, low cortisol (7 μg/dL), and markedly elevated ACTH (708 pg/mL) is diagnostic of primary adrenal insufficiency or Addison's disease 1, 2
A serum cortisol level <9 μg/dL (250 nmol/L) with elevated ACTH in acute disease is diagnostic of primary adrenal insufficiency 1, 2
Hyponatremia is present in 90% of new cases of primary adrenal insufficiency 1, 3
Hyperkalemia occurs in approximately 50% of patients at diagnosis, caused by aldosterone deficiency 1, 3
Orthostatic hypotension and tendency to orthostasis are cardinal manifestations 1

The ACTH stimulation test (cosyntropin/Synacthen test) is the gold standard for confirming the diagnosis of primary adrenal insufficiency when initial values are indeterminate or to formally document adrenal response inability 1, 2
Administer 0.25 mg of cosyntropin (tetracosactida) intramuscularly or intravenously 1, 2
Obtain baseline serum cortisol and ACTH before administration 1, 2
Measure serum cortisol at 30 and/or 60 minutes post-administration 1, 2

A peak cortisol value <500 nmol/L (<18 μg/dL) is diagnostic of primary adrenal insufficiency 1, 2
A peak cortisol value >550 nmol/L (>18-20 μg/dL) is considered a normal response 2
In the context of a patient with a basal cortisol level of 7 μg/dL, an increase of less than double (i.e., <14 μg/dL) at 60 minutes confirms adrenal response inability 2

The autoimmune cause represents approximately 85% of primary adrenal insufficiency cases in Western populations 2
Measure anti-21-hydroxylase antibodies (anti-adrenal antibodies) as the first step 1, 2
If antibodies are negative, obtain a CT scan of the adrenals to evaluate for hemorrhage, tumors, tuberculosis, or other structural causes 1, 2

Administer hydrocortisone 100 mg IV immediately in patients with significant hypotension and symptoms of adrenal crisis 2, 4, 3
Infuse 0.9% saline solution at 1 L in the first hour 2, 4, 3
Obtain blood samples for cortisol and ACTH before treatment if possible, but do not delay treatment waiting for results 1, 2, 3