A 22-year-old woman with a 2-year history of secondary amenorrhea undergoes evaluation. Laboratory investigations reveal elevated prolactin (68 mIU/L), normal TSH, normal LH/FSH ratio, and normal androgen levels. MRI pituitary is normal. Which of the following is NOT a recognized cause of hyperprolactinemia in this patient?

Explanation

## Hyperprolactinemia and Secondary Amenorrhea The patient presents with **secondary amenorrhea + elevated prolactin + normal TSH + normal LH/FSH ratio + normal MRI pituitary**. This suggests a **functional/physiological cause of hyperprolactinemia**, not a pituitary adenoma. ### Causes of Hyperprolactinemia | Category | Mechanism | Examples | LH/FSH Ratio | Androgen Level | |----------|-----------|----------|--------------|----------------| | **Dopamine Antagonists** | Block D~2~ receptors | Metoclopramide, antipsychotics, domperidone | Normal | Normal | | **Hypothyroidism** | ↑ TRH → ↑ prolactin | Primary hypothyroidism | Normal | Normal | | **Pituitary Stalk Compression** | Loss of dopamine inhibition | Adenomas, craniopharyngiomas | Normal | Normal | | **PCOS** | Hyperandrogenism + insulin resistance | Elevated LH/FSH ratio | **↑ (abnormal)** | **↑ (abnormal)** | | **Prolactinoma** | Lactotroph adenoma | Pituitary tumor | Normal | Normal | ## Key Point: **PCOS does NOT cause hyperprolactinemia.** PCOS causes secondary amenorrhea through **hyperandrogenism and insulin resistance**, not through elevated prolactin. The patient's normal prolactin level and normal LH/FSH ratio rule out PCOS. **High-Yield:** The question stem explicitly states **"normal LH/FSH ratio"** — this is the critical clue that rules out PCOS, which characteristically presents with **elevated LH/FSH ratio (typically 2:1 to 3:1)**. ## Why the Correct Options Fit: 1. **Metoclopramide**: D~2~ receptor antagonist → blocks dopamine inhibition of prolactin → hyperprolactinemia ✓ 2. **Hypothyroidism**: Elevated TRH stimulates lactotroph cells → hyperprolactinemia ✓ 3. **Pituitary stalk compression**: Loss of tonic dopamine inhibition → hyperprolactinemia ✓ ## Clinical Pearl: **PCOS is a diagnosis of hyperandrogenism, NOT hyperprolactinemia.** If a patient with amenorrhea has elevated prolactin, PCOS is unlikely unless there is concurrent hyperprolactinemia from another cause (e.g., hypothyroidism). **Mnemonic: Causes of Hyperprolactinemia — "CHIMPANZEES"** - **C**hemicals (dopamine antagonists: metoclopramide, antipsychotics) - **H**ypothyroidism (↑ TRH) - **I**diopathic (functional) - **M**acroprolactinemia (bound prolactin) - **P**rolactinoma (lactotroph adenoma) - **A**denoma (other pituitary tumors compressing stalk) - **N**ipple stimulation (reflex arc) - **Z**one compression (stalk compression) - **E**xercise, stress, sleep (physiological) - **E**strogen (oral contraceptives, HRT) - **S**eizures, renal failure (chronic kidney disease) **Warning:** Do not confuse PCOS with hyperprolactinemia. PCOS presents with elevated **androgens** and **LH/FSH ratio**, not elevated prolactin. [cite:Jeffcoate's Principles of Gynaecology 15e Ch 5; Harrison Principles of Internal Medicine 21e Ch 375]