What initial tests should be ordered for a 44-year-old female with a 14-pound weight gain over 6 months?

Initial Laboratory Evaluation for Weight Gain in a 44-Year-Old Female

Order a comprehensive metabolic panel, fasting lipid profile, thyroid function tests (TSH, free T4), and fasting blood glucose or hemoglobin A1c as your initial laboratory workup. 1

Essential First-Line Tests

The core laboratory evaluation should include:

• Comprehensive metabolic panel to assess liver function, kidney function, and electrolytes 2, 1
• Fasting lipid profile including total cholesterol, LDL, HDL, and triglycerides 2, 1
• Thyroid function tests (TSH at minimum; add free T4 and free T3 if TSH is abnormal) to rule out hypothyroidism, a common cause of weight gain in middle-aged women 2, 1, 3
• Fasting blood glucose or hemoglobin A1c to screen for diabetes or prediabetes, particularly important given her age and weight gain 2, 1

This recommendation is based on the 2017 AGA guidelines which specifically state that "basic laboratory evaluation should include a comprehensive metabolic panel, fasting lipid profile, and thyroid function tests" for patients presenting with weight gain 2. The U.S. Preventive Services Task Force recommends screening for abnormal blood glucose in adults aged 40-70 years with overweight or obesity 2.

Physical Examination Findings That Guide Additional Testing

Before ordering additional tests, perform a focused physical examination looking for:

• Acanthosis nigricans (darkened, velvety skin in body folds) suggesting insulin resistance 2
• Hirsutism or menstrual irregularities suggesting polycystic ovary syndrome 2
• Large neck circumference (>16 inches in women) suggesting obstructive sleep apnea 2
• Thin, atrophic skin, central obesity, "moon face," or violaceous striae suggesting Cushing's syndrome 2, 1, 4

Conditional Second-Tier Tests

Order these only if clinical suspicion exists based on history and physical examination:

If Cushing's syndrome is suspected (central obesity with facial rounding, purple striae, proximal muscle weakness):

• Overnight dexamethasone suppression test 1
• 24-hour urinary free cortisol 1

If obstructive sleep apnea is suspected (snoring, daytime sleepiness, witnessed apneas, large neck circumference):

• Use Epworth Sleepiness Scale or STOP-BANG questionnaire as screening tools 2, 1
• Refer for polysomnography if screening is positive 1

If PCOS is suspected (hirsutism, menstrual irregularities, acne):

• Total or free testosterone levels 5
• Consider prolactin if galactorrhea is present 5

Important Clinical Context

A 14-pound (6.4 kg) weight gain over 6 months in a 44-year-old woman warrants evaluation, as this represents approximately 1 kg per month. Research demonstrates that even moderate weight gain in middle-aged women (5-10 kg) significantly increases risk of type 2 diabetes, hypertension, and cardiovascular disease 6. The evaluation should focus on identifying treatable secondary causes before attributing weight gain to lifestyle factors alone 3.

Common Pitfalls to Avoid

• Don't skip thyroid testing: Hypothyroidism is a common and treatable cause of weight gain in middle-aged women, and treatment can reverse the weight gain 3, 7
• Don't order extensive endocrine testing without clinical indicators: Reserve tests like cortisol studies for patients with specific physical findings suggestive of Cushing's syndrome 2, 1
• Don't forget to review medications: Many common medications cause weight gain, including psychiatric drugs, corticosteroids, insulin, and certain beta-blockers 2, 3
• Measure waist circumference: A waist circumference ≥88 cm (35 inches) in women indicates increased metabolic risk even if BMI appears normal 2