What initial laboratory tests should be ordered for an adult patient with obesity to screen for metabolic, endocrine, and organ‑specific complications and secondary causes of weight gain?

Laboratory Work-Up for Obesity

All adults with obesity require a comprehensive metabolic panel, fasting lipid profile, thyroid-stimulating hormone (TSH), and hemoglobin A1c or fasting glucose as the essential baseline laboratory evaluation. 1, 2, 3

Core Laboratory Panel (Required for All Patients)

Metabolic Assessment

• Comprehensive metabolic panel assesses kidney function (creatinine, eGFR, BUN), liver enzymes (AST, ALT, alkaline phosphatase), and electrolytes to screen for non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease, both highly prevalent in obesity. 1, 2, 3
• Fasting glucose ≥ 126 mg/dL defines diabetes; 100–125 mg/dL defines pre-diabetes. 3
• Hemoglobin A1c ≥ 6.5% defines diabetes; 5.7–6.4% defines pre-diabetes. The U.S. Preventive Services Task Force specifically recommends screening for abnormal blood glucose in adults aged 40–70 years with overweight or obesity as part of cardiovascular risk assessment. 1, 2, 3

Lipid Evaluation

• Fasting lipid profile must include total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol to identify dyslipidemia and estimate cardiovascular risk. 1, 2, 3
• This panel is critical because lipid abnormalities are extremely common in obesity and contribute to metabolic syndrome diagnosis. 2

Thyroid Screening

• TSH measurement is universally recommended because hypothyroidism is highly prevalent among individuals with obesity and represents a treatable secondary cause of weight gain. 1, 2, 3
• If TSH is abnormal, reflex testing of free T4 (and free T3 when indicated) should be performed. 2

Liver Function Assessment

• Liver function tests (AST, ALT, alkaline phosphatase, bilirubin, albumin) are advised to screen for NAFLD and non-alcoholic steatohepatitis (NASH), which affect approximately 66% of individuals with class III obesity. 3, 4
• When liver enzymes are abnormal, calculation of the Fibrosis-4 (FIB-4) index is recommended to estimate hepatic fibrosis risk. 3
• A critical pitfall: do not assume normal transaminases exclude NAFLD—imaging may be warranted even with normal liver enzymes in severe obesity. 4

Additional Tests Based on Clinical Findings

Screen for Secondary Causes of Obesity (Only When Specific Features Present)

Cushing's Syndrome — Test only if the following are observed:

• Thin, atrophic skin with easy bruising 3, 4
• Proximal muscle weakness 3
• Wide (>1 cm) purple striae 3, 4
• Rapid central weight gain with peripheral leanness 3
• Testing options: Overnight dexamethasone suppression test or 24-hour urinary free cortisol 2

Polycystic Ovary Syndrome (PCOS) — Evaluate when:

• Hirsutism or acanthosis nigricans is present 3, 4
• Menstrual irregularities or signs of androgen excess are observed 2
• Testing options: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) may be indicated 2

Male Hypogonadism — Assess testosterone levels if:

• Decreased libido, erectile dysfunction, loss of muscle mass, or gynecomastia are reported 3

Growth Hormone Deficiency — Consider IGF-1 testing for:

• Patients with a history of pituitary disease or cranial irradiation 3
• Those with severe fatigue accompanied by loss of muscle mass 3

Screening for Obesity-Related Comorbidities

Metabolic Syndrome Diagnosis requires ≥3 of the following criteria:

• Waist circumference ≥ 88 cm (women) or ≥ 102 cm (men) 2, 3, 4
• Triglycerides ≥ 150 mg/dL 2, 3
• Fasting glucose ≥ 100 mg/dL 2, 3
• Blood pressure ≥ 130/85 mmHg 2, 3
• HDL-cholesterol < 40 mg/dL (men) or < 50 mg/dL (women) 2, 3

Obstructive Sleep Apnea (OSA) Screening:

• Use the STOP-BANG questionnaire or Epworth Sleepiness Scale as initial screening tools 2, 3, 4
• Polysomnography is reserved for positive screens 3
• Neck circumference measurement can help screen for OSA risk 2
• This is critical: Untreated obesity-hypoventilation syndrome carries a 1- to 2-year mortality of up to 24%. 4

Additional Cardiovascular Risk Assessment:

• Blood pressure measurement is a core component 2
• 12-lead ECG is recommended for any adult with ≥1 cardiovascular risk factor to detect left ventricular hypertrophy, ischemia, or arrhythmias 4

Special Considerations

Medication Review

• Review all current medications that may contribute to weight gain, including psychiatric drugs, corticosteroids, insulin, and specific β-adrenergic receptor blockers. 1, 2, 5
• Consider medication-induced weight gain when interpreting results. 2

Physical Examination Findings to Document

• Acanthosis nigricans (associated with insulin resistance) 1
• Hirsutism (associated with PCOS) 1
• Large neck circumference (associated with obstructive sleep apnea) 1
• Thin, atrophic skin (associated with Cushing's disease) 1

Ethnic-Specific Thresholds

• Standard BMI cut-points may underestimate cardiometabolic risk in South/Southeast Asian populations, who develop complications at lower BMI thresholds (≥23 kg/m² for overweight). 1
• Waist circumference thresholds for South/Southeast Asian populations: ≥80 cm (women) or ≥90 cm (men). 1

Common Pitfalls to Avoid

• Do not rely on BMI alone—incorporate waist-circumference measurements and ethnicity-specific risk factors. 1, 4
• Do not skip thyroid testing—hypothyroidism is a highly prevalent and treatable cause of weight gain. 1, 3
• Do not assume normal liver enzymes exclude NAFLD—imaging is indicated in severe obesity regardless of transaminase levels. 4
• Do not overlook sleep apnea screening—OSA is extremely common in obesity and carries significant mortality risk if untreated. 4
• Do not forget to screen for psychological factors such as depression or binge-eating disorder, which can contribute to weight gain. 2, 5