What is the best course of action for a 45-year-old female patient with fatigue, elevated fasting cholesterol, and a body mass index (BMI) of 18.9, who has normal complete blood count (CBC), thyroid-stimulating hormone (TSH) level of 1.23, ferritin level of 68, and hemoglobin A1c (HbA1c) level of 5.2%?

Further Workup for 45-Year-Old Female with Fatigue and Elevated Cholesterol

This patient requires a comprehensive lipid panel with LDL-C measurement, liver function tests, and iron studies including transferrin saturation to guide management of her elevated cholesterol and evaluate potential causes of fatigue. 1

Essential Laboratory Testing

The initial laboratory evaluation should include the following tests that were not yet performed 1:

• Complete lipid profile including LDL-C, HDL-C, and triglycerides (can be done non-fasting unless triglycerides are suspected to be very elevated) 2
• Liver function tests (ALT, AST) to assess for hepatic causes of fatigue and establish baseline before potential statin therapy 1
• Iron studies including serum iron, transferrin, and transferrin saturation—ferritin alone is insufficient, particularly given her low-normal BMI 3, 4
• Basic metabolic panel including electrolytes, BUN, and creatinine 1

Rationale for Additional Iron Studies

While her ferritin of 68 ng/mL appears adequate, ferritin can be misleadingly normal or elevated in inflammatory states and does not reliably reflect iron stores when used in isolation 3. A complete iron profile including transferrin saturation is necessary to truly assess iron status 3. The correlation between iron deficiency and fatigue is well-established, and iron deficiency can exist even with ferritin levels in the 60s range 1.

Cardiovascular Risk Assessment

Given her elevated cholesterol at age 45, calculate her 10-year ASCVD risk using the pooled cohort equation 5. This will determine the intensity of lipid management needed:

• If 10-year ASCVD risk ≥7.5%: moderate- to high-intensity statin is recommended 5
• If 10-year ASCVD risk 5-7.5%: consider moderate-intensity statin, especially with risk-enhancing factors 5
• If 10-year ASCVD risk <5%: lifestyle modifications are primary unless risk-enhancing factors present 5

Risk-enhancing factors to assess include family history of premature ASCVD, and consider high-sensitivity CRP or coronary artery calcium scoring if risk stratification is uncertain 5.

Evaluation for Secondary Causes of Dyslipidemia

Since her TSH is normal, evaluate for other secondary causes 1:

• Liver function tests to exclude hepatic dysfunction 1
• Renal function tests (BUN, creatinine) and urinalysis 1
• Fasting glucose is already normal at 5.2%, ruling out diabetes 1

Additional Fatigue Workup Considerations

Beyond the standard laboratory tests, assess for 1:

• Sleep disturbances: screen for sleep apnea, insomnia, or disrupted sleep patterns 1
• Depression screening: fatigue correlates with depression in approximately 25-33% of cases 1
• Medication review: evaluate all current medications, over-the-counter drugs, and supplements that may contribute to fatigue 1
• Activity level assessment: determine if deconditioning is contributing 1
• Nutritional assessment: evaluate caloric intake, weight changes, and dietary patterns 1

Low BMI Considerations

Her BMI of 18.9 is at the lower end of normal (normal range 18.5-24.9), which warrants attention 1:

• Assess for adequate nutritional intake and unintentional weight loss 1
• Low BMI may be associated with lower cholesterol levels, making her elevated cholesterol more significant 4
• Rule out malabsorption or other causes of inadequate nutrition 1

Common Pitfalls to Avoid

• Do not rely on ferritin alone to exclude iron deficiency; obtain complete iron studies with transferrin saturation 3
• Do not assume elevated cholesterol is benign in a younger woman with low BMI; this may indicate familial hyperlipidemia requiring more aggressive management 5
• Do not overlook sleep disorders as a treatable cause of fatigue 1
• Do not delay lipid management while pursuing fatigue workup; these can be addressed simultaneously 1, 5

Immediate Next Steps

1. Order comprehensive lipid panel with calculated LDL-C and non-HDL-C 1, 2
2. Complete iron studies (serum iron, TIBC, transferrin saturation) 1, 3
3. Obtain liver function tests and basic metabolic panel 1
4. Calculate 10-year ASCVD risk once LDL-C is available 5
5. Screen for depression and sleep disorders 1
6. Initiate lifestyle counseling for heart-healthy diet and regular physical activity regardless of risk score 5