Table 1. Causes of adrenal cortical insufficiency.
| Causes | Notes |
| Primary adrenal cortical insufficiency (AI) | |
| Isolated autoimmune adrenalitis | Autoimmune adrenalitis = most common cause of primary AI in Western countries (>80%), of which 30-40% as isolated disease, 21-Hydroxylase antibody often positive |
| Polyglandular autoimmune syndrome Type 1 |
Hypoparathyroidism, chronic mucocutaneous candidiasis, other autoimmune diseases, lymphomas (rare), mutation in the AIRE gene, autosomal recessive |
| Polyglandular autoimmune syndrome Type 2 |
Hypo/hyperthyroid, premature ovarian failure,vitiligo, type 1 diabetes mellitus, pernicious anemia, association with HLA-DR3 (approximately 60% of patients with autoimmune adrenalitis) |
| Infections | Tuberculosis (most common cause in developing countries), CMV, HIV, Mycosis (e.g. histoplasmosis) |
| Bilateral adrenal hemorrhage | Meningococcal sepsis, primary antiphospholipid syndrome, septic shock |
| Extensive adrenal metastases | e.g. renal, lung, breast, gastric, or colon carcinomas, lymphoma |
| Bilateral adrenalectomy | – |
| Drugs | e.g. mitotane, etomidate, ketoconazole, fluconazole can cause AI. Rifampicin, phenytoin, barbiturate, carbamazepine accelerate cortisol metabolism |
| Adrenogenital syndrome (AGS) | congenital enzyme defect of steroid biosynthesis (21a-hydroxylase [95%], 11 b-hydroxylase, and others), autosomal recessive, salt deficiency (75%), virilization in girls |
| Adrenoleukodystrophy | neurological disturbances (frequent), hypogonadism, X-linked recessive trait, mutation in the X-ALD gene, accumula tion of long chain fatty acids (>C24) |
| Familial glucocorticoid resistance | – |
| Familial glucocorticoid deficiency | genetic ACTH insensitivity, type 1-3 FGD |
| Congenital adrenal hypoplasia | Hypogonadotropic hypogonadism, X-linked mutation in the DAX-1 gene |
| Triple A syndrome | Achalasia, alacrima, neurological disturbances, autosomal recessive mutation in the triple-A gene |
| Secondary adrenal cortical insufficiency | |
| Tumors of the pituitary and hypothalamus regions |
e.g., pituitary adenoma, Rathke‘s cyst, craniopharyngioma, meningioma, metastases |
| Pituitary / hypothalamic surgery | – |
| Radiation to the pituitary and hypothalamus regions |
– |
| Pituitary infarction / Sheehan syndrome | – |
| Autoimmune hypophysitis | lymphocytic, IgG4 associated, drug associated (e.g. ipilimumab, tremelimumab), xanthomatous |
| Granulomatous disease | Sarcoidosis, histiocytosis X, Wegeners granulomatosis |
| Infections | Abcess, tuberculous meningitis |
| Traumatic brain injury | – |
| Genetic causes | e.g. mutations in PROP-1, LHX-4, HESX1, TPIT, POMC genes |
| Isolated ACTH deficiency | Autoimmune, mutations in PC-1, POMC, or TPIT genes |
| Tertiary adrenal cortical Insufficiency | |
| Chronic glucocorticoid therapy | – |
| Endogenous Cushings disease | – |
| Isolated CRH deficiency | – |
CRH, corticotropin releasing hormone; CMV, cytomegalovirus; HIV, human immunodeficiency virus; ACTH, adrenocorticotropic hormone