What initial laboratory tests are recommended for evaluating unintended weight gain?

Laboratory Evaluation for Unintended Weight Gain

For patients presenting with unintended weight gain, the essential initial laboratory workup should include: complete metabolic panel, fasting lipid profile, thyroid function tests (TSH with reflex to free T4), fasting glucose or hemoglobin A1c, and complete blood count. 1

Core Initial Laboratory Tests

The foundational laboratory evaluation must include:

• Complete metabolic panel to assess liver function, kidney function, and electrolytes 1
• Fasting lipid profile including total cholesterol, LDL, HDL, and triglycerides to evaluate metabolic syndrome and cardiovascular risk 1
• Thyroid function tests starting with TSH, as hypothyroidism is a common reversible cause of weight gain 1, 2
  • If TSH is elevated, obtain free T4 to confirm primary hypothyroidism 3
  • Note that TSH should ideally be drawn fasting, as postprandial TSH can be suppressed by up to 26%, potentially missing subclinical hypothyroidism 4
• Fasting blood glucose or hemoglobin A1c to screen for diabetes or prediabetes, which commonly coexist with weight gain 5, 1
• Complete blood count to evaluate for underlying conditions contributing to weight gain 1

Thyroid Testing Considerations

Thyroid dysfunction is particularly important to identify, as it is both common and reversible. 1, 6

• In morbidly obese patients, the prevalence of overt and subclinical hypothyroidism reaches 19.5% 6
• Be aware that obesity itself can elevate TSH levels through leptin-mediated effects on the hypothalamic-pituitary-thyroid axis 7
• Borderline elevated TSH in obese patients may normalize with weight reduction alone, without thyroid hormone replacement 7
• Critical pitfall: Do not immediately treat borderline TSH elevations in obese patients without confirming persistent elevation and considering weight loss first 7

Additional Testing Based on Clinical Presentation

Proceed to specialized testing when specific clinical features suggest endocrine disorders:

For Cushing's Syndrome (central obesity, moon facies, violaceous striae, proximal muscle weakness):

• Overnight 1-mg dexamethasone suppression test as initial screening 1
• 24-hour urinary free cortisol for confirmation 1

For Hyperaldosteronism (hypertension with unexplained weight gain):

• Plasma aldosterone/renin ratio 1

For Pheochromocytoma (paroxysmal hypertension, headaches, palpitations, diaphoresis):

• 24-hour urinary fractionated metanephrines 1

For Hyperparathyroidism:

• Serum calcium and parathyroid hormone levels 1

For Polycystic Ovary Syndrome (women with hirsutism, irregular menses, acanthosis nigricans):

• Sex hormone levels including testosterone, DHEA-S, and LH/FSH ratio 8

Screening for Associated Conditions

Sleep Apnea Evaluation:

• Sleep studies (polysomnography) should be considered for patients with snoring, daytime sleepiness, or witnessed apneas 1
• Use Berlin Questionnaire or Epworth Sleepiness Scale as initial screening tools before formal sleep studies 1

Metabolic Liver Disease:

• Liver function tests to evaluate for nonalcoholic fatty liver disease (NAFLD), which is highly prevalent in obesity 1

Nutritional Deficiencies:

• Vitamin D levels, as deficiency is common in obesity and may affect metabolism 8
• Iron studies (serum ferritin, transferrin saturation), particularly in women of reproductive age 8

Interpretation Pitfalls

Critical considerations when interpreting results:

• Laboratory abnormalities may be consequences rather than causes of obesity—interpret in clinical context 8
• Review all current medications, as many drugs cause weight gain (antipsychotics, antidepressants, corticosteroids, insulin, sulfonylureas, beta-blockers) 1
• In patients with rapid or unexplained weight gain, prioritize screening for endocrine disorders 1
• Consider psychological factors including depression and binge eating disorder, which contribute to weight gain 1

Follow-Up Testing Strategy

• If initial tests are normal but weight gain persists: repeat testing at minimum 3-year intervals 8
• If prediabetes is identified: yearly testing is recommended 8
• If risk factors change or new symptoms develop: more frequent testing is warranted 8