Learning Objective
By the end of this section, students should be able to recognize common endocrine and reproductive adverse effects caused by medications, identify the responsible agents, and understand key clinical presentations, a high-yield topic for USMLE Step 1 pharmacology.
Drug-Induced Endocrine / Reproductive Reactions
| Reaction | Causal Agents | Notes / Clinical Presentation |
|---|---|---|
| Adrenocortical insufficiency | Chronic exogenous glucocorticoids | Abrupt withdrawal → adrenal crisis; due to HPA axis suppression |
| Diabetes insipidus | Lithium, Demeclocycline | Nephrogenic DI; polyuria, polydipsia |
| Gynecomastia | Ketoconazole, Cimetidine, Spironolactone, GnRH analogs/antagonists, Androgen receptor inhibitors, 5α-reductase inhibitors | Breast tissue enlargement in men; may be reversible upon drug discontinuation |
| Hot flashes | SERMs (Tamoxifen, Clomiphene, Raloxifene) | Common in patients treated for breast cancer or infertility |
| Hyperglycemia | Tacrolimus, Protease inhibitors, Niacin, HCTZ, Glucocorticoids | Risk of steroid-induced or drug-induced diabetes |
| Hyperprolactinemia | Typical antipsychotics (Haloperidol), Atypical antipsychotics (Risperidone), Metoclopramide, Methyldopa, Verapamil | Presents with hypogonadism (infertility, amenorrhea, erectile dysfunction) and galactorrhea |
| Hyperthyroidism | Amiodarone, Iodine, Lithium | Thyrotoxicosis can cause weight loss, palpitations, and heat intolerance |
| Hypothyroidism | Amiodarone, Lithium | Fatigue, weight gain, cold intolerance (“I am lethargic”) |
| SIADH | Carbamazepine, Cyclophosphamide, SSRIs | Hyponatremia, low serum osmolality; “Can’t Concentrate Serum Sodium.” |
Activity
USMLE Step 1 Pearls
- HPA suppression → adrenal crisis after abrupt steroid withdrawal.
- Lithium → nephrogenic DI; treat with amiloride.
- Ketoconazole & spironolactone → gynecomastia; spironolactone blocks androgen receptors.
- Amiodarone → hypo- or hyperthyroidism; monitor TSH/T4.
- SSRIs / carbamazepine → SIADH; monitor sodium.
- Risperidone → hyperprolactinemia may cause galactorrhea in both sexes.
