A 42-year-old woman on olanzapine 15 mg/day for bipolar disorder presents with amenorrhea for 3 months, galactorrhea, and gynecomastia. Her serum prolactin is 85 ng/mL (normal <25 ng/mL). Which investigation is most appropriate to confirm the mechanism of prolactin elevation?

Explanation

## Differential Diagnosis of Hyperprolactinemia The patient has clinical signs of **hyperprolactinemia** (amenorrhea, galactorrhea, gynecomastia) with markedly elevated prolactin (85 ng/mL). The mechanism must be determined: ### Causes of Drug-Induced Hyperprolactinemia | Mechanism | Examples | Prolactin Level | |-----------|----------|------------------| | **D~2~ antagonism (antipsychotics)** | Olanzapine, risperidone, haloperidol | Usually <100 ng/mL | | **Pituitary adenoma (prolactinoma)** | Autonomous secretion | Often >200 ng/mL; mass effect | | **Hypothyroidism** | ↓ TRH suppression | Mild elevation | | **Chest wall irritation** | Herpes zoster, trauma | Mild elevation | | **Renal failure** | ↓ Prolactin clearance | Mild to moderate | ## Investigation of Choice: Pituitary MRI **Key Point:** Pituitary MRI with gadolinium contrast is the investigation of choice because: - **Confirms the diagnosis** of prolactinoma if a mass is present (rules out autonomous adenoma) - **Excludes structural pathology** (pituitary apoplexy, other sellar masses) - **Determines if hyperprolactinemia is drug-induced** (normal pituitary on MRI) vs. pathological (adenoma) - **Assesses mass effect** and need for neurosurgical intervention **High-Yield:** If MRI is normal + high prolactin on antipsychotic = **drug-induced hyperprolactinemia**. If MRI shows adenoma = **prolactinoma** (may require antipsychotic switch or dopamine agonist). **Clinical Pearl:** Prolactin >200 ng/mL or symptoms of mass effect (headache, visual field defect) strongly suggest prolactinoma and mandate MRI. Prolactin 50–100 ng/mL on antipsychotics is usually drug-induced, but MRI is still warranted to exclude adenoma. **Mnemonic:** **PITUITARY MRI for HyperProlactinemia** = Prolactin >50 ng/mL + antipsychotic use → MRI to rule out adenoma [cite:Stahl's Essential Psychopharmacology 6e]