What is the diagnosis for a 16-year-old girl with secondary amenorrhea (absence of menstruation), normal Thyroid-Stimulating Hormone (TSH), Follicle-Stimulating Hormone (FSH), and Luteinizing Hormone (LH) levels, and recent significant weight loss with reduced appetite?

Diagnosis: Functional Hypothalamic Amenorrhea (FHA) Secondary to Weight Loss and Energy Deficit

This 16-year-old girl has functional hypothalamic amenorrhea (FHA) caused by significant weight loss (6 kg from 45 kg) and grossly reduced appetite, resulting in chronic energy deficit that has suppressed her hypothalamic-pituitary-ovarian axis. 1, 2

Why This Diagnosis is Clear

Clinical Presentation Matches FHA Perfectly

• Weight loss of 6 kg from an already low baseline of 45 kg represents approximately 13% body weight loss, which is a classic precipitant of FHA 2, 3
• Grossly reduced appetite indicates ongoing energy deficit, the primary driver of hypothalamic suppression 1, 3
• Secondary amenorrhea for 4 months following previously regular menses is the hallmark presentation of FHA 4, 5
• Normal TSH, FSH, and LH levels effectively rule out thyroid dysfunction, primary ovarian insufficiency, and PCOS 1, 2

Hormonal Profile Confirms FHA

• Normal (low-normal) FSH and LH levels are characteristic of FHA, where gonadotropin-releasing hormone (GnRH) pulsatility is functionally suppressed rather than elevated as in PCOS or primary ovarian failure 2, 6
• An LH:FSH ratio of approximately 1.0 effectively excludes PCOS, which typically shows LH:FSH ratio >2 2, 4
• The normal gonadotropin levels indicate the hypothalamus has reduced its pulsatile GnRH secretion in response to energy deficit, leading to decreased LH pulses and subsequent amenorrhea 6, 7

Energy Deficit is the Root Cause

• Energy availability below 30 kcal/kg fat-free mass/day inhibits LH pulsation and causes menstrual disorders 3
• The combination of weight loss and reduced appetite creates negative energy balance, which directly affects LH pulses through decreased glucose availability and altered metabolic hormones (decreased leptin, insulin, T3; increased cortisol, ghrelin) 8, 6
• Even without excessive exercise or overt eating disorder, simple caloric restriction from reduced appetite is sufficient to cause FHA 1, 5

Critical Differential Considerations

Why This is NOT PCOS

• PCOS would show LH:FSH ratio >2, not the ratio of ~1.0 seen with normal FSH and LH 2, 4
• PCOS patients typically have hyperandrogenism, insulin resistance, and higher BMI—none of which fit this patient's presentation of weight loss and reduced appetite 4, 9
• The temporal relationship between weight loss/reduced appetite and amenorrhea onset is diagnostic of FHA, not PCOS 2

Why This is NOT Primary Ovarian Insufficiency

• Primary ovarian insufficiency would show elevated FSH and LH levels, not normal levels 4
• The patient's age (16 years) and recent onset make premature ovarian failure extremely unlikely 4

Why This is NOT Hyperprolactinemia

• While prolactin wasn't explicitly measured, hyperprolactinemia accounts for only 20% of secondary amenorrhea cases and typically presents with galactorrhea 4
• The clear history of energy deficit with weight loss makes FHA the primary diagnosis 1, 2

Immediate Clinical Concerns

Bone Health is at Critical Risk

• FHA causes hypoestrogenism that puts patients at significant risk for decreased bone mineral density and osteoporosis 2, 7
• The hypoestrogenic state creates a post-menopausal-like physiology in this adolescent, affecting peak bone mass acquisition during a critical developmental period 8, 7
• Bone mineral density testing should be performed given the 4-month duration of amenorrhea 1, 7

Cardiovascular and Metabolic Effects

• Hypoestrogenism in FHA induces endothelial dysfunction and poor lipid profiles (elevated LDL, total cholesterol, triglycerides) 8
• The metabolic adaptations include decreased resting metabolic rate, low insulin levels, decreased T3, and elevated cortisol 6, 7

Psychological Considerations

• FHA patients present significantly higher rates of depression and anxiety compared to healthy subjects 7
• Stress and psychological factors can perpetuate the hypothalamic suppression even after nutritional rehabilitation begins 5, 6

Treatment Approach

Nutritional Rehabilitation is Primary Treatment

• Increase caloric intake to achieve energy availability >30 kcal/kg fat-free mass/day 3
• Ensure regular meals throughout the day to avoid negative energy balance, as glucose directly affects LH pulses and T3/cortisol concentrations 3
• Target body fat percentage >22% may be required to restore menstrual function; even a 1 kg increase in body fat mass increases likelihood of menstruation by 8% 3

Weight Restoration Goals

• Aim for weight restoration toward pre-amenorrhea weight of 45 kg as minimum target 1, 3
• Treatment should focus on body composition (increasing fat mass), not just body weight 3
• Recommended daily caloric intake of 1800-2000 kcal for weight restoration when BMI <18.5 kg/m² 1

Monitoring and Follow-Up

• Monitor menstrual patterns every 3-6 months to assess treatment response 1
• Bone mineral density testing every 2 years for patients with prolonged hypoestrogenic states 1
• Consider hormone replacement therapy (0.3-0.625 mg conjugated estrogens daily) to prevent bone loss if amenorrhea persists despite nutritional intervention 1, 7

Psychological Support

• Incorporate cognitive-behavioral therapy to address underlying stress and eating behaviors 3, 9
• Address any psychological stressors that may be contributing to reduced appetite 5, 6

Common Pitfalls to Avoid

• Do not misdiagnose as PCOS if ultrasound incidentally shows polycystic ovarian morphology—41.9-48% of FHA patients have PCOM, creating the FHA-PCOM subtype that still requires FHA-directed treatment 4
• Do not delay treatment waiting for spontaneous recovery—the longer the hypoestrogenic state persists, the greater the bone density loss 7, 9
• Do not prescribe oral contraceptives as primary treatment—this masks the problem without addressing the underlying energy deficit and provides false reassurance while bone loss continues 9
• Do not focus solely on weight—body composition and energy availability are more important than absolute weight 3