A 28-year-old woman presents to the gynecology clinic with a 6-month history of amenorrhea. She reports recent weight loss of 8 kg over 3 months, increased stress at work, and denies pregnancy. Physical examination reveals BMI 18.5 kg/m², normal breast development, and normal external genitalia. Serum β-hCG is negative. FSH level is 3.2 mIU/mL (normal follicular phase: 3.5–12.5 mIU/mL), LH is 2.1 mIU/mL (normal: 2.4–12.6 mIU/mL), and prolactin is 12 ng/mL (normal: 4–29 ng/mL). TSH and free T4 are normal. Pelvic ultrasound shows normal uterus and ovaries with no follicles visible. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Hypothalamic Amenorrhea ### Key Clinical Features **Key Point:** This patient presents with the classic triad of hypothalamic amenorrhea: recent stress, weight loss (BMI still normal but recent loss is significant), and amenorrhea with low-normal or suppressed gonadotropins. ### Hormonal Pattern Analysis | Parameter | Patient Value | Normal Range | Interpretation | |-----------|---------------|--------------|----------------| | FSH | 3.2 mIU/mL | 3.5–12.5 | Low-normal to low | | LH | 2.1 mIU/mL | 2.4–12.6 | Low-normal to low | | Prolactin | 12 ng/mL | 4–29 | Normal | | TSH/Free T4 | Normal | Normal | Normal | | β-hCG | Negative | Negative | Not pregnant | **High-Yield:** In hypothalamic amenorrhea, GnRH secretion is suppressed by stress and metabolic stress (weight loss, low energy availability). This results in **secondary hypogonadotropic hypogonadism** — both FSH and LH are low or low-normal, distinguishing it from primary ovarian failure (where gonadotropins are high). ### Pathophysiology 1. **Stress and energy deficit** → decreased GnRH pulsatility 2. **Reduced GnRH** → decreased FSH and LH secretion 3. **Low gonadotropins** → lack of follicular development and estrogen production 4. **Result:** Amenorrhea with normal prolactin and thyroid function **Clinical Pearl:** The normal prolactin rules out prolactinoma or medication-induced hyperprolactinemia. Normal TSH/free T4 rules out hypothyroidism. The bilateral suppression of both FSH and LH (not just one) indicates central, not peripheral, pathology. ### Diagnostic Criteria Met - Amenorrhea ≥3 months ✓ - Negative pregnancy test ✓ - Normal thyroid and prolactin ✓ - Low-normal gonadotropins (hypogonadotropic) ✓ - Recent stressor (work stress + weight loss) ✓ - Normal ovarian ultrasound morphology ✓ **Mnemonic:** **FUN** = **F**unctional (hypothalamic) **U**ndernutrition/**U**ndue stress → **N**o GnRH → **N**o menses. ### Management Approach 1. Counsel on stress reduction and adequate nutrition 2. Target BMI 19–25 kg/m² if underweight 3. Monitor for spontaneous recovery (often occurs within 3–6 months with lifestyle modification) 4. Hormone replacement therapy (HRT) if prolonged amenorrhea to preserve bone density