What is the initial workup for a patient presenting with amenorrhea, fatigue, and weight gain?

Initial Workup for Amenorrhea, Fatigue, and Weight Gain

The initial workup for a patient presenting with amenorrhea, fatigue, and weight gain should include a pregnancy test, baseline hormonal panel (FSH, LH, estradiol, prolactin, TSH), and pelvic/transvaginal ultrasound to evaluate structural integrity and ovarian morphology.

Step 1: Rule Out Pregnancy

• Pregnancy test (most common cause of amenorrhea in reproductive-age women)

Step 2: Hormonal Evaluation

• Baseline hormonal panel:
  • FSH/LH (to differentiate between hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, or normogonadotropic disorders)
  • Estradiol (to assess estrogen status)
  • Prolactin (elevated levels may indicate prolactinoma or other pituitary disorders)
  • TSH (hypothyroidism can cause amenorrhea, fatigue, and weight gain)
  • Free T4 (to confirm thyroid dysfunction if TSH is abnormal)

Step 3: Imaging Studies

• Pelvic/transvaginal ultrasound to:
  • Assess endometrial thickness
  • Evaluate for structural abnormalities
  • Examine ovarian morphology (≥20 follicles per ovary and/or ovarian volume ≥10ml suggests PCOS) 1
• Brain MRI with pituitary cuts if:
  • Hyperprolactinemia is present
  • Multiple hormone deficiencies are found
  • Severe headaches or visual changes are reported 2, 1

Step 4: Additional Testing Based on Initial Results

If TSH is elevated:

• Free T3 and anti-thyroid antibodies to evaluate for autoimmune thyroiditis

If prolactin is elevated:

• Repeat prolactin measurement (stress can cause transient elevation)
• Review medications that may cause hyperprolactinemia
• Brain MRI with pituitary cuts to rule out prolactinoma 1

If FSH/LH levels suggest PCOS:

• Testosterone, DHEAS, androstenedione to assess hyperandrogenism
• Fasting glucose, insulin, and lipid profile to evaluate metabolic status 1

If FSH is high (>35 IU/L):

• Consider primary ovarian insufficiency
• Anti-Müllerian hormone (AMH) to assess ovarian reserve 1

If FSH/LH are low:

• Consider hypothalamic amenorrhea
• Assess for energy deficit, excessive exercise, stress, or eating disorders
• Consider bone density testing if chronic hypoestrogenism is suspected 2

Common Diagnostic Patterns

Pattern 1: Low/normal FSH/LH + elevated TSH + weight gain + fatigue

• Suggests hypothyroidism as the cause

Pattern 2: Low FSH/LH + normal prolactin + history of stress/weight loss/exercise

• Suggests functional hypothalamic amenorrhea (FHA)
• LH:FSH ratio typically <1 in 82% of FHA patients 2, 1

Pattern 3: Normal/high LH + normal/low FSH (LH:FSH ratio >2) + polycystic ovaries on ultrasound

• Suggests polycystic ovary syndrome (PCOS)

Pattern 4: Elevated prolactin + low/normal gonadotropins

• Suggests hyperprolactinemia (medication-induced, pituitary adenoma, etc.)

Pattern 5: High FSH/LH

• Suggests primary ovarian insufficiency

Important Considerations

• The combination of amenorrhea, fatigue, and weight gain strongly suggests thyroid dysfunction, particularly hypothyroidism
• Multiple pituitary hormone deficiencies may indicate hypophysitis or other pituitary disorders 2
• Always consider adrenal insufficiency in patients with fatigue and weight loss (rather than gain), which would require morning cortisol or ACTH stimulation testing 2
• Hyperprolactinemia with thyroid dysfunction is a common contributory hormonal factor in patients with amenorrhea 3

This systematic approach will help identify the underlying cause of amenorrhea, fatigue, and weight gain, allowing for appropriate management based on the specific diagnosis.