5
Table 2. Major Etiologies of PAI and Associated Features
Etiology Associated Features
Autoimmune
Isolated Not associated with other autoimmune disorders
APS type 1 (APECED) Chronic cutaneous candidiasis, hypoparathyroidism
APS type 2 Autoimmune thyroid disease, type 1 diabetes
Adrenal—infiltration/injury
Adrenal hemorrhage Associated with sepsis, anticoagulants, anti-cardiolipin/
lupus anti-coagulant syndrome
Adrenal metastases Malignancies: lung, breast, colon, melanoma, lymphoma
Infections: adrenalitis Tuberculosis, HIV/AIDS, CMV, candidiasis, histoplasmosis,
syphilis, African trypanosomiasis, paracoccidioidomycosis
(eg, in South America)
Infiltration Hemochromatosis, primary amyloidosis
Bilateral adrenalectomy Procedure for intractable Cushing's syndrome or bilateral
pheochromocytoma
CAH: most forms can
cause salt loss
Commonest cause of PAI in children (80%)
May be diagnosed in older individuals
21-Hydroxylase
deficiency
Commonest type of CAH is 21-hydroxylase deficiency,
with associated hyperandrogenism
11β-hydroxylase
deficiency
Hyperandrogenism, hypertension (in older children and
adults)
3β-hydroxysteroid
dehydrogenase II
deficiency
Ambiguous genitalia in boys, hyperandrogenism in girls
P450 side-chain
cleavage deficiency
(CYP11A1 mutations)
XY sex reversal
P450 oxidoreductase
deficiency
Skeletal malformations, abnormal genitalia
Congenital lipoid adrenal
hyperplasia
(StAR mutations)
XY sex reversal
Adrenal hypoplasia
congenita
X-linked NROB1, Xp21 deletion (with Duchenne's
muscular deficiency), SF-1 mutations, (XY sex reversal),
IMAGe syndrome
