A 38-year-old man with schizophrenia has been on risperidone 6 mg/day for 2 years. He presents with complaints of galactorrhea, amenorrhea in his wife (who is also on psychiatric treatment), and erectile dysfunction. You suspect antipsychotic-induced hyperprolactinemia. Which investigation is most appropriate to confirm the diagnosis?

## Diagnostic Approach to Antipsychotic-Induced Hyperprolactinemia **Key Point:** Serum prolactin level (fasting, morning sample) is the investigation of choice for confirming antipsychotic-induced hyperprolactinemia. ### Why Serum Prolactin? 1. **Direct measurement** of the hormone responsible for clinical symptoms 2. **Single baseline value** is diagnostic; no stimulation needed 3. **Timing matters**: Fasting, morning sample (prolactin shows diurnal variation and is suppressed by dopamine; food and stress elevate it) 4. **Cost-effective and readily available** ### Mechanism of Antipsychotic-Induced Hyperprolactinemia ```mermaid flowchart TD A[Antipsychotic blocks D2 receptors]:::action --> B[Loss of dopamine inhibition on lactotroph cells]:::action B --> C[Increased TRH-stimulated prolactin release]:::outcome C --> D[Hyperprolactinemia]:::outcome D --> E[Galactorrhea, amenorrhea, sexual dysfunction]:::outcome ``` **High-Yield:** Risperidone and paliperidone have the highest risk of hyperprolactinemia among atypicals (due to poor blood-brain barrier penetration and systemic D2 blockade). Aripiprazole and quetiapine have the lowest risk. ### Diagnostic Criteria | Finding | Normal | Mild | Moderate | Severe | | --- | --- | --- | --- | --- | | **Serum Prolactin (ng/mL)** | < 25 | 25–50 | 50–100 | > 100 | | **Clinical Manifestation** | None | Subtle | Galactorrhea, ED | Galactorrhea + amenorrhea + ED | **Clinical Pearl:** A prolactin level > 200 ng/mL should raise suspicion for a prolactinoma or other pituitary pathology, not just antipsychotic effect. In such cases, MRI pituitary is warranted. ### Why Other Options Are Incorrect - **24-hour urinary prolactin**: Not standard; prolactin is not reliably measured in urine - **TRH stimulation test**: Used to differentiate hypothalamic from pituitary causes; not needed when antipsychotic exposure is clear - **MRI pituitary**: Reserved for prolactin > 200 ng/mL or when clinical suspicion of adenoma exists; not first-line **Tip:** Always ask about sexual dysfunction and galactorrhea in male patients on antipsychotics; these are often underreported but reversible with dose reduction or agent switch.