Drugs that can cause primary adrenal insufficiency
| Druga | Use | Mechanism of primary adrenal insufficiency |
|---|---|---|
| Mitotane | Adrenolytic adrenocortical carcinoma therapy | Damages adrenal cortex through free radical generation, blocks cortisol production, and alters peripheral conversion of steroids27 |
| Etomidate | Anesthetic | Etomidate and metyrapone inhibit 11-beta-hydroxylase and decrease endogenous cortisol synthesis28,29 Mifepristone in high doses blocks the glucocorticoid receptor28 |
| Metyrapone, mifepristone | Cushing syndrome therapy | |
| Ketoconazole | Antifungal | Inhibits several adrenal enzymes responsible for androgen and cortisol synthesis such as cholesterol side chain cleavage enzyme, 17-alpha-hydroxylase, 11-beta-hydroxylase, and aldosterone synthase28 |
| Levoketoconazole | Cushing syndrome therapy | |
| Rifampicin | Antitubercular | Induce CYP3A4, promote rapid cortisol clearance from the blood17 |
| Phenytoin | Antiseizure | |
| Immune checkpoint inhibitors: ipilimumab (CTLA-4), nivolumab (PD-1), pembrolizumab (PD-1) | Malignancy therapy, most often melanoma | Can cause adrenal antibodies, resulting in destruction of cortex30,31 Can also be associated with secondary adrenal insufficiency through hypophysitis |
| Abiraterone | Prostate cancer therapy | Selectively and irreversibly inhibits 17-alpha-hydroxylase/C17,20-lyase to cause androgen and glucocorticoid deficiency32 |
↵aNot all listed medications causing primary adrenal insufficiency necessarily present with both glucocorticoid and mineralocorticoid deficiency.
PD-1 = programmed cell death protein 1; CTLA-4 = cytotoxic T-lymphocyte–associated protein 4.
Based on information from references 1,17,23,27–32.