How should I evaluate and manage a 21‑year‑old male with persistent fatigue, low vitamin D, normal thyroid function, normal complete blood count, normal comprehensive metabolic panel, and normal erythrocyte sedimentation rate, who feels better after moving from Utah to Washington?

Evaluation and Management of Persistent Fatigue in a Young Adult with Vitamin D Deficiency

Treat the vitamin D deficiency with cholecalciferol 50,000 IU weekly and systematically evaluate for geographic/environmental triggers, nutritional deficiencies, and sleep disorders before pursuing additional blood work.

Immediate Vitamin D Supplementation

• Initiate cholecalciferol 50,000 IU orally once weekly for 8 weeks, then transition to maintenance dosing of 2,000-4,000 IU daily to achieve target 25(OH)D levels >30 ng/mL 1, 2.
• Vitamin D deficiency (defined as <20 ng/mL) has been directly linked to fatigue in controlled trials, with significant improvement in fatigue scores after supplementation 3.
• In a randomized controlled trial, a single 100,000 IU dose of vitamin D3 significantly reduced fatigue scores by 3.3 points compared to 0.8 points with placebo (P=0.01), with 72% of treated patients reporting improvement versus 50% with placebo 3.
• Recheck 25(OH)D levels in 3 months to confirm adequate response 2.

Geographic Symptom Pattern: Environmental Allergen Evaluation

• The patient's report of feeling "constantly sick in Utah" but "okay in Washington" strongly suggests environmental allergen exposure or air quality differences as a contributing factor 4.
• Utah has significantly higher particulate matter and allergen burden compared to coastal Washington, which can trigger chronic inflammatory responses manifesting as fatigue 4.
• Consider referral to allergy/immunology for comprehensive allergen testing (molds, pollens, dust mites) and evaluation for allergic rhinitis or chronic sinusitis, both of which cause persistent fatigue 4.
• Air quality-related inflammation can elevate systemic inflammatory markers and contribute to the fatigue phenotype even with normal ESR 4.

Comprehensive Nutritional Assessment

• Check vitamin B12, folate, vitamin B6, magnesium, zinc, and copper levels, as these deficiencies frequently contribute to fatigue even in apparently well-nourished young adults 2, 5.
• Measure serum ferritin to evaluate iron stores, as iron deficiency is a common reversible cause of fatigue in this age group and may exist despite normal hemoglobin 2, 5.
• Nutritional deficiencies often cluster together and correcting multiple deficits simultaneously produces better outcomes than addressing vitamin D alone 2.

Sleep Quality and Disorder Screening

• Despite the patient's denial of sleep issues, formal assessment using the Pittsburgh Sleep Quality Index (PSQI) is warranted, as subjective sleep perception often differs from objective sleep quality 2.
• Screen for obstructive sleep apnea even without reported snoring, as young adults can have positional or mild OSA that manifests primarily as fatigue rather than classic symptoms 6, 2.
• Evaluate for delayed sleep phase syndrome, common in young adults, which causes chronic sleep deprivation despite adequate time in bed 2.
• Sleep disturbances are present in 30-75% of patients with chronic fatigue and often go unrecognized 6.

Psychological and Mood Assessment

• Screen for depression and anxiety using validated instruments (PHQ-9, GAD-7), as these are leading causes of persistent fatigue in young adults and commonly coexist with vitamin D deficiency 2, 5.
• The patient's caffeine cessation may have unmasked underlying mood symptoms that were previously self-medicated 2.
• Depression screening is essential even when patients do not endorse classic depressive symptoms, as fatigue may be the primary presentation 6, 5.

Medication and Lifestyle Review

• Review all current medications, supplements, and over-the-counter agents for fatigue-inducing effects or interactions 2, 5.
• Assess for deconditioning, which perpetuates fatigue: inquire about baseline activity level, exercise patterns, and ability to accomplish normal daily activities 6, 2.
• Caffeine withdrawal can cause transient fatigue lasting 2-4 weeks, but persistent symptoms beyond this timeframe suggest other etiologies 2.

Exercise Prescription

• Initiate moderate-intensity aerobic exercise (walking, swimming, cycling) 30-60 minutes per session, 2-3 times weekly, starting at low intensity if significantly deconditioned 2, 5.
• Exercise has been shown to lower fatigue levels in multiple populations, though convincing fatigued patients requires starting with low-level activities and gradually increasing 6, 2.
• Physical activity improves both vitamin D metabolism and mood, creating synergistic benefits 2.

When to Pursue Additional Blood Work

Repeat laboratory testing is NOT indicated at this time given the recent normal TSH, CBC, CMP, and ESR just 3 months ago 6.

• The USPSTF gives an "I" statement (insufficient evidence) for routine vitamin D screening in asymptomatic adults, and current evidence is inadequate to determine whether screening for and treating asymptomatic low 25(OH)D levels improves clinical outcomes 6.
• However, since vitamin D deficiency has already been identified and the patient is symptomatic, treatment is appropriate 2, 3.
• Repeat blood work should be considered only if:
  • Fatigue persists after 3 months of vitamin D supplementation and correction of identified deficiencies 2
  • New symptoms develop (unintentional weight loss >5%, fever, night sweats, focal neurologic symptoms) 4, 5
  • The patient develops signs of inflammatory arthropathy (morning stiffness >30 minutes, joint pain that improves with activity) 4

Follow-Up Strategy

• Reassess fatigue severity using a 0-10 numeric rating scale at 4-6 weeks after initiating vitamin D supplementation 2, 5.
• Provide sleep hygiene education: maintain regular sleep schedule, create dark/quiet sleep environment, avoid screens before bed 2, 5.
• Recheck 25(OH)D levels at 3 months to ensure adequate response to supplementation 2.
• If fatigue persists despite vitamin D correction and implementation of above measures, consider referral to specialists (allergy/immunology for environmental triggers, sleep medicine for formal sleep study) 2, 5.

Critical Pitfalls to Avoid

• Do not dismiss the geographic symptom pattern as psychosomatic—it provides crucial diagnostic information about environmental triggers 4.
• Do not over-test: repeating recent normal labs wastes resources and may lead to false-positive results requiring unnecessary follow-up 6.
• Do not assume normal thyroid levels exclude thyroid-related fatigue—some patients experience symptoms despite biochemically euthyroid status, though this is uncommon in young adults 2.
• Avoid attributing all symptoms to vitamin D deficiency alone: while vitamin D supplementation improves fatigue in deficient individuals, the effect size is modest and other contributing factors must be addressed 3, 7.
• One large Mendelian randomization study found little evidence for a causal effect of vitamin D on fatigue (OR 1.05,95% CI 0.87-1.27), suggesting that while supplementation helps deficient individuals, it is not a panacea 8.