Workup for Severe Fatigue, Weight Gain, and Brain Fog in a Patient with BMI 28
Begin with basic laboratory evaluation including comprehensive metabolic panel, fasting lipid profile, and thyroid function tests (TSH, free T4) to screen for secondary causes of weight gain and fatigue. 1
Initial Laboratory Assessment
The foundational workup should include:
- Comprehensive metabolic panel to evaluate glucose, electrolytes, renal function, and liver function 1
- Thyroid function tests (TSH and free T4) as hypothyroidism commonly causes fatigue, weight gain, and cognitive symptoms ("brain fog") 1, 2
- Fasting lipid profile to assess cardiovascular risk factors associated with overweight status 1
- Complete blood count with differential to evaluate for anemia or other hematologic abnormalities that contribute to fatigue 1, 2
Secondary Causes to Screen
Given the symptom constellation, evaluate for:
- Medications associated with weight gain including antipsychotics, antidepressants, corticosteroids, and anticonvulsants 1
- Sleep disorders, particularly obstructive sleep apnea (assess for large neck circumference during physical exam, as this is associated with sleep apnea) 1
- Depression and anxiety, as emotional distress is a major contributor to fatigue 1
- Insulin resistance markers (fasting glucose, hemoglobin A1c) since acanthosis nigricans on exam suggests insulin resistance 1
Physical Examination Focus
The exam should specifically assess for:
- Waist circumference or waist-to-hip ratio, as central obesity is an independent mortality risk factor 1
- Acanthosis nigricans (darkened, velvety skin in body folds) indicating insulin resistance 1
- Thin, atrophic skin suggesting Cushing's syndrome 1
- Hirsutism suggesting polycystic ovarian syndrome 1
- Large neck circumference suggesting obstructive sleep apnea 1
Brain Fog Considerations
The cognitive symptoms described as "brain fog" warrant specific attention:
- Brain fog in the context of obesity may reflect decreased prefrontal cortex metabolic activity, which correlates with impaired executive function and memory 3, 4
- Obesity-associated brain changes include frontal lobe, hippocampal, and thalamic atrophy even in cognitively normal individuals 5
- Hypothyroidism is a critical reversible cause of both cognitive impairment and weight gain that must be excluded 1, 2
Additional Testing if Initial Workup is Normal
If basic labs are unrevealing, consider:
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to evaluate for inflammatory processes 1, 2
- Iron studies (serum ferritin, transferrin saturation) as iron deficiency causes fatigue even before anemia develops 6
- Vitamin D level since deficiency is prevalent in overweight individuals and contributes to fatigue 6
- Vitamin B12 and folate as deficiencies cause fatigue and cognitive symptoms 6
- Cortisol testing (morning cortisol or 24-hour urine free cortisol) if Cushing's syndrome is suspected based on physical findings 1
Common Pitfalls to Avoid
- Do not assume fatigue is solely due to excess weight without excluding treatable medical conditions 1
- Do not overlook sleep apnea screening, as it is highly prevalent in overweight patients and causes both fatigue and cognitive impairment 1
- Do not dismiss "brain fog" as vague or psychosomatic—it may represent measurable cognitive dysfunction related to metabolic or endocrine disorders 7, 3
- Do not delay thyroid testing, as hypothyroidism is one of the most common and reversible causes of this symptom triad 1, 2
Risk Stratification
This patient with BMI 28 (overweight category) should be counseled that:
- Even modest weight loss of 3-5% produces clinically meaningful health benefits including improvements in triglycerides, blood glucose, and risk of developing type 2 diabetes 1
- Weight management is indicated if cardiovascular risk factors (hypertension, hyperlipidemia, hyperglycemia, elevated waist circumference) are identified 1
- Addressing obesity decreases risk of multiple cancers and improves gastrointestinal disorders including NAFLD and GERD 1