2
Key Points
Î Primary adrenal insufficiency (PAI) was first described in 1855 by
Thomas Addison and is therefore commonly termed Addison's disease.
Î PAI is defined by the inability of the adrenal cortex to produce
sufficient amounts of glucocorticoids and/or mineralocorticoids.
Î PAI is a severe and potentially life-threatening condition due to the
central role of these hormones in energy, salt, and fluid homeostasis.
Î Cortisol deficiency results in a decrease in feedback to the
hypothalamic-pituitary axis and subsequent enhanced stimulation of
the adrenal cortex by elevated levels of plasma ACTH. Consequent
to disruption of adrenal mineralocorticoid synthesis, renin release
by the juxtaglomerular cells of the kidneys increases. This is of
clinical, diagnostic, and therapeutic relevance because PAI needs
to be distinguished from secondary adrenocortical insufficiency due
to insufficient production of ACTH and without impact on the renin-
angiotensin-aldosterone system.
Who Should Be Tested and How
Î The Endocrine Society (ES) recommends diagnostic testing to exclude
PAI in acutely ill patients with otherwise unexplained symptoms or
signs suggestive of PAI (volume depletion, hypotension, hyponatremia,
hyperkalemia, fever, abdominal pain, hyperpigmentation or, especially
in children, hypoglycemia). (1|⊕⊕⊕
)
Î ES recommends confirmatory testing with the corticotropin
stimulation test in patients with clinical symptoms or signs suggesting
PAI when the patient's condition and circumstance allow. (1|⊕⊕⊕⊕)
Optimal Diagnostic Tests
Î ES suggests the standard dose (250 μg for adults and children ≥2
y of age, 15 μg/kg for infants, and 125 μg for children <2 y of age)
IV corticotropin stimulation (30 or 60 min) test over other existing
diagnostics tests to establish the diagnosis of adrenal insufficiency.
Peak cortisol levels below 500 nmol/L (18 μg/dL) (assay dependent)
at 30 or 60 minutes indicate adrenal insufficiency. (2|⊕⊕
)
Î ES suggests the low-dose (1 μg) corticotropin test for diagnosis of PAI
only when the substance itself is in short supply. (2|⊕⊕
)
Î If a corticotropin stimulation test is not feasible, ES suggests using
a morning cortisol <140 nmol/L (5 μg/dL) in combination with
ACTH as a preliminary test suggestive of adrenal insufficiency (until
confirmatory testing with corticotropin stimulation is available).
(2|⊕
)
Diagnosis
