What lab tests are recommended for evaluating weight gain?

Laboratory Evaluation for Weight Gain

For patients presenting with weight gain, order a comprehensive metabolic panel, fasting lipid profile (total cholesterol, LDL, HDL, triglycerides), thyroid function tests (TSH, free T4), and fasting blood glucose or hemoglobin A1c as the essential initial workup. 1

Core Initial Laboratory Tests

The following tests form the foundation of weight gain evaluation and should be obtained in all patients:

• Complete metabolic panel to assess liver function, kidney function, and electrolytes 1
• Fasting lipid profile including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides to evaluate cardiovascular risk and metabolic abnormalities 1
• Thyroid function tests (TSH, free T4, and free T3) to rule out hypothyroidism, which commonly causes weight gain 1
• Fasting blood glucose or hemoglobin A1c to screen for diabetes or prediabetes 1
• Complete blood count (CBC) to evaluate for underlying conditions that may contribute to weight gain 1

Important Caveat About Thyroid Testing

While thyroid dysfunction should be ruled out, recognize that elevated TSH with normal T3 and T4 may be a consequence rather than a cause of obesity 2, 3. Studies show that TSH levels are positively correlated with BMI, and borderline elevated TSH often decreases with weight reduction without hormone medication 4. The elevated TSH in obesity may be secondary to increased leptin levels from adipose tissue rather than true hypothyroidism 3, 4.

Additional Tests Based on Clinical Presentation

For Suspected Endocrine Disorders

When clinical features suggest specific endocrine pathology, proceed with targeted testing:

• Overnight dexamethasone suppression test and 24-hour urinary free cortisol if Cushing's syndrome is suspected (look for central obesity, "moon face," violaceous striae, proximal muscle weakness) 1
• Plasma aldosterone/renin ratio if hypertension accompanies unexplained weight gain 1
• 24-hour urinary fractionated metanephrines if pheochromocytoma is suspected (paroxysmal hypertension, headaches, palpitations, diaphoresis) 1
• Serum calcium and parathyroid hormone if hyperparathyroidism is suspected 1

For Metabolic Complications

• Liver function tests to evaluate for nonalcoholic fatty liver disease (NAFLD), which commonly accompanies obesity 1
• Insulin levels with calculation of HOMA-IR can help quantify insulin resistance in patients with metabolic syndrome 2, 5

For Sleep-Related Weight Gain

• Sleep studies (polysomnography) should be considered for patients with snoring, daytime sleepiness, or witnessed apneas, as obstructive sleep apnea is common in obesity 1
• Use the Berlin Questionnaire or Epworth Sleepiness Scale as screening tools before proceeding to formal sleep studies 1

Special Population Considerations

Patients on Medications

Review all current medications as many drugs cause weight gain, including antipsychotics, mood stabilizers, antidepressants, corticosteroids, and certain antihypertensives 1, 6. For patients with bipolar disorder on weight-promoting medications, regular monitoring of weight and metabolic parameters is essential 1.

Patients with Eating Disorders

• Electrocardiogram should be performed, especially for patients with restrictive eating patterns or severe purging behaviors 1
• Screen for psychological factors such as depression or binge eating disorder that contribute to weight gain 1

Diabetic Patients

• Urinary albumin-to-creatinine ratio to screen for diabetic nephropathy 1
• Vitamin B12 levels if the patient is taking metformin 1

Monitoring Strategy

For Patients Starting Integrase Inhibitors or Tenofovir Alafenamide

Document weight and BMI at baseline and every 6 months to identify excessive weight gain in patients on these antiretroviral regimens 7. Monitor blood pressure at each clinical visit to diagnose incident hypertension 7.

Longitudinal Assessment

For patients attempting weight loss or undergoing body composition changes:

• Serial body composition measurements may be justified in older individuals (who lose 1% skeletal muscle mass per year), those in long-term exercise programs, competitive athletes doing resistance training, or patients undergoing rapid weight loss or bariatric surgery 7
• Recognize that weight change reflects both fat mass and lean mass changes—approximately 25-50% of weight change may be due to lean mass rather than fat 7

Interpretation Pitfalls

Context Matters

• Lipid abnormalities and metabolic parameters should be interpreted together, not in isolation 1
• Some laboratory abnormalities may be consequences rather than causes of obesity 6
• In postmenopausal women with subclinical hypothyroidism, thyroid autoimmunity (positive TPO or TG antibodies) is associated with higher TSH, IL-6 levels, and increased prevalence of metabolic syndrome 5

Thyroid Autoimmunity

Check thyroid antibodies (TPO-Ab, TG-Ab) in obese patients with borderline elevated TSH to help distinguish primary thyroid disease from obesity-related TSH elevation 5. Obese subclinical hypothyroid women with Hashimoto's thyroiditis have higher prevalence of metabolic syndrome compared to those without thyroid autoimmunity 5.

Staging and Risk Stratification

After obtaining laboratory results, use the Edmonton Obesity Staging System (EOSS) to classify disease severity based on obesity-associated risk factors, complications, mental health, and functional limitations 7. This staging correlates with all-cause mortality and incident cardiovascular disease and cancer 7.

• Stage 0-1: Avoid further weight gain; weight loss may not be required
• Stage 2-3: Weight loss is a clinical priority; consider lifestyle, pharmacological, and surgical interventions 7

For pediatric patients aged 2-17 years, use the Edmonton Obesity Staging System for Pediatrics (EOSS-P), which evaluates metabolic, biomechanical, mental health, and social milieu domains 7.