Laboratory Evaluation for Obesity to Rule Out Metabolic or Endocrine Etiologies
All adults with obesity should undergo a comprehensive metabolic panel, fasting lipid profile, TSH measurement, and hemoglobin A1c (or fasting glucose) as the essential baseline laboratory evaluation. 1
Core Laboratory Panel (Obtain in All Patients)
The following tests are universally recommended for every obese patient, regardless of clinical presentation:
Comprehensive metabolic panel to assess kidney function (creatinine, eGFR, BUN), liver enzymes (AST, ALT, alkaline phosphatase), and electrolytes—screening for non-alcoholic fatty liver disease and chronic kidney disease, both highly prevalent in obesity 1
Fasting lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol to identify dyslipidemia and estimate cardiovascular risk 1
Thyroid-stimulating hormone (TSH) measurement universally, because hypothyroidism is highly prevalent among individuals with obesity and represents a treatable secondary cause of weight gain 1, 2
Hemoglobin A1c (≥6.5% defines diabetes; 5.7–6.4% defines pre-diabetes) or fasting glucose (≥126 mg/dL defines diabetes; 100–125 mg/dL defines pre-diabetes) 1
Rationale for Universal Testing
The comprehensive metabolic panel serves dual purposes: identifying obesity-related complications (NAFLD, chronic kidney disease) and screening for metabolic derangements 1. TSH is the only endocrine test recommended universally—most other endocrine testing is not recommended in the absence of specific clinical features 2.
Conditional Endocrine Testing (Only When Specific Clinical Features Are Present)
Do not order these tests routinely. They are indicated only when specific alarm symptoms or physical examination findings are present:
Cushing's Syndrome Testing
Order overnight dexamethasone suppression test or 24-hour urinary free cortisol only if the patient exhibits:
- Thin, atrophic skin with easy bruising 1
- Proximal muscle weakness 1
- Wide (>1 cm) purple striae 1
- Rapid central weight gain with peripheral leanness 1
Polycystic Ovary Syndrome (PCOS) Evaluation
Assess reproductive-axis hormones (FSH, LH, testosterone) only when:
- Hirsutism (excess body hair in male pattern distribution) is present 1
- Acanthosis nigricans is observed 1
- Menstrual irregularities occur 3
Male Hypogonadism Assessment
Measure testosterone levels only if the patient reports:
Growth Hormone Deficiency
Consider IGF-1 testing only in patients with:
- History of pituitary disease or cranial irradiation 1
- Severe fatigue accompanied by loss of muscle mass 1
Medication Review (Critical Component)
Review all current medications that may contribute to weight gain and optimize when possible 1:
- Psychiatric agents
- Systemic corticosteroids
- Insulin
- Certain β-adrenergic blockers
Physical Examination Findings That Trigger Additional Testing
| Physical Finding | Associated Condition | Action Required |
|---|---|---|
| Acanthosis nigricans (hyperpigmented, velvety skin) | Insulin resistance | Proceed with glucose/metabolic assessment [1] |
| Hirsutism | PCOS | Evaluate reproductive hormones [1] |
| Enlarged neck circumference | Obstructive sleep apnea | Screen with STOP-BANG or Epworth Sleepiness Scale [1] |
| Thin, fragile skin with easy bruising | Cushing's syndrome | Perform endocrine work-up [1] |
Additional Risk Stratification
- Calculate Fibrosis-4 (FIB-4) index when liver enzymes are abnormal to estimate hepatic fibrosis risk 1
- Screen for obstructive sleep apnea using STOP-BANG questionnaire or Epworth Sleepiness Scale, reserving polysomnography for positive screens 1
- Measure waist circumference: metabolic syndrome requires ≥88 cm (women) or ≥102 cm (men) as one of five criteria 1
Ethnic-Specific Considerations
For South/Southeast Asian populations, apply lower thresholds 1:
- BMI ≥23 kg/m² defines overweight (vs. standard 25 kg/m²)
- Waist circumference ≥80 cm (women) or ≥90 cm (men) indicates increased risk
Critical Pitfalls to Avoid
- Do not rely on BMI alone—incorporate waist-circumference measurements and ethnicity-specific risk thresholds 1
- Do not omit thyroid testing, as hypothyroidism is a common and treatable contributor 1
- Do not order extensive endocrine panels routinely—the European Society of Endocrinology guidance confirms that most endocrine testing is not recommended in the absence of clinical features of specific endocrine syndromes 2
- Do not attribute all obesity to endocrine causes—the most common causes are overconsumption of high-fat foods, decreased activity, aging, and medication effects 4