6
Diagnosis
Table 2. Major Etiologies of PAI and Associated Features
(cont'd)
Etiology Associated Features
ACTH insensitivity
syndromes
Type 1: ACTH receptor, melanocortin 2 receptor gene
MC2R
Type 2: MRAP
Familial glucocorticoid deficiency (MCM4, NNT,
TXNRD2)
TripleA (Allgrove's) syndrome, achalasia, Addison's
disease, alacrima, AAAS gene mutation
Drug-induced Adrenal enzyme inhibitors: mitotane, ketoconazole,
metyrapone, etomidate, aminoglutethimide, drugs that
may accelerate cortisol metabolism and induce adrenal
insufficiency
T4 also accelerates cortisol metabolism (at least in part
through stimulation of 11β-HSD2)
CTLA-4 inhibitors may enhance autoimmunity and
cause PAI
Other metabolic
disorders
Mitochondrial disease (rare)
Adrenoleukodystrophy in males
Wolman's disease
Derived from E. Charmandari E, et al: Adrenal insufficiency. Lancet. 2014;383:2152–
2167, with permission. © Elsevier.
