What is the recommended further workup for a 45-year-old female (F) with complaints of fatigue, normal sleep patterns, recent dilation and curettage (D&C), normal complete blood count (CBC), normal thyroid-stimulating hormone (TSH) level of 1.13, and adequate ferritin level of 46?

Workup Recommendations for Fatigue in a 45-Year-Old Woman

This patient requires iron supplementation despite a ferritin of 46 ng/mL, along with a focused evaluation for other treatable contributing factors including depression, sleep disturbance, and medication effects. 1, 2

Severity Assessment and Initial Approach

• First, quantify her fatigue using a 0-10 numeric scale to determine if she has moderate-to-severe fatigue (score ≥4), which would warrant the focused evaluation outlined below 1, 3
• If her fatigue scores 4-10, proceed with a comprehensive assessment rather than stopping at basic labs 1

Iron Supplementation is Indicated

Despite her ferritin of 46 ng/mL being technically "normal," iron supplementation is specifically recommended for premenopausal women with unexplained fatigue when ferritin is <50 µg/L in the absence of anemia. 2

• High-quality evidence demonstrates that iron-deficient women (ferritin <50 µg/L) with normal hemoglobin who receive iron supplementation experience significant improvement in fatigue, with 65% showing reduced fatigue compared to 53% with placebo 4
• The same study showed 33% achieved a 50% reduction in fatigue scores versus only 16% with placebo 4
• Her recent D&C likely contributed to iron depletion, making supplementation even more appropriate 2

Focused History for Treatable Contributing Factors

Document the following specific details about her fatigue 1, 3:

• Onset and pattern: When did it start relative to her D&C? Is it constant or fluctuating?
• Temporal changes: Has it worsened, improved, or remained stable since the D&C?
• Functional impact: What specific daily activities can she no longer perform?
• Associated symptoms: Screen specifically for the red flags below

Screen for Red Flag Symptoms

Actively ask about 1:

• Fever or drenching night sweats
• Unintentional weight loss
• New or worsening pain
• Pulmonary complaints (dyspnea, cough)
• Lymphadenopathy or skin changes

If any red flags are present, consider imaging studies and more extensive workup for systemic disease 1

Assess Common Contributing Factors

Depression and anxiety screening 1, 5:

• Use a validated tool (PHQ-9 or GAD-7) as depression is present in 25-33% of fatigued patients 5
• Depression and fatigue are independent conditions that frequently co-occur 5

Sleep disturbance evaluation 1, 5:

• Assess sleep quality, quantity, and sleep hygiene practices 1
• Screen for sleep apnea, particularly if she has gained weight or has other risk factors 5
• Sleep disturbances occur in 30-75% of fatigued patients 5

Medication review 1, 5:

• Review all prescriptions, over-the-counter medications, herbals, and supplements 5
• Specifically assess for beta-blockers, sleep aids, pain medications, or antiemetics that may contribute to fatigue 5, 1

Activity and deconditioning 1, 5:

• Document her current exercise patterns and any changes since developing fatigue 5
• Assess whether she can accomplish normal daily activities 5

Additional Laboratory Testing

Beyond the CBC, TSH, and ferritin already obtained, consider 1:

• Comprehensive metabolic panel: Assess electrolytes, hepatic and renal function 1
• ESR and CRP: Screen for inflammatory conditions 1
• These tests are specifically recommended for moderate-to-severe fatigue (scores 4-10) 1

Management Approach

Initiate iron supplementation 2, 4:

• Oral iron is first-line for most patients 2
• If oral iron is not tolerated, intravenous ferric carboxymaltose is an effective alternative 4

Address identified contributing factors 1:

• Treat depression or anxiety if present 1
• Implement cognitive behavioral therapy for insomnia and improve sleep hygiene if sleep disturbance is identified 1
• Optimize pain management if applicable 1

Recommend structured physical activity 1:

• Initiate a progressive exercise program with stretching and aerobic activity 2-3 times weekly for 30-60 minutes 1
• This is recommended for all patients with fatigue regardless of cause 1

Follow-Up

• Rescreen at regular intervals to monitor symptom evolution 1
• Reassess ferritin levels after 8-12 weeks of iron supplementation to ensure repletion 2
• If fatigue persists despite addressing contributing factors and iron repletion, consider referral to appropriate specialists based on clinical findings 5

Common Pitfalls to Avoid

• Don't dismiss ferritin of 46 ng/mL as adequate in a premenopausal woman with fatigue—supplementation is indicated below 50 µg/L 2
• Don't overlook medication side effects as potential contributors 3
• Don't assume fatigue is purely physical—screen for depression and anxiety as these frequently cluster with fatigue 5, 1