A 48‑year‑old woman with celiac disease and hypothyroidism has a TSH of 22 µIU/mL, free T4 of 1.22 ng/dL, alkaline phosphatase of 139 U/L, trace eosinophils on differential, and LDL cholesterol of 121 mg/dL; what is the most appropriate next step in management?

Increase Levothyroxine Dose Immediately and Screen for Celiac Disease

This 48-year-old woman with known celiac disease and severe primary hypothyroidism (TSH 22 µIU/mL) requires immediate levothyroxine dose adjustment, as her current regimen is clearly inadequate and her celiac disease is likely causing levothyroxine malabsorption. 1

Immediate Management: Levothyroxine Dose Adjustment

Increase levothyroxine by 25-50 mcg immediately, as TSH >10 mIU/L mandates treatment regardless of symptoms due to ~5% annual risk of progression and associated cardiovascular dysfunction. 1 For a patient <70 years without cardiac disease, more aggressive titration using 25 mcg increments is appropriate. 1

• Recheck TSH and free T4 in 6-8 weeks after dose adjustment, targeting TSH within the reference range (0.5-4.5 mIU/L) with normal free T4. 1
• Continue dose adjustments by 12.5-25 mcg increments every 6-8 weeks until TSH normalizes. 1
• Once stable, monitor TSH every 6-12 months or with symptom changes. 1

Critical Issue: Celiac Disease and Levothyroxine Malabsorption

Her celiac disease is almost certainly causing levothyroxine malabsorption, requiring higher doses than typical. 2, 3, 4

Evidence for Malabsorption in Celiac Disease

• Hypothyroid patients with untreated celiac disease require significantly higher levothyroxine doses (mean 2.6 µg/kg vs 1.3 µg/kg in controls, p<0.001) to maintain euthyroid state. 2
• All patients with both conditions required at least 125 µg levothyroxine initially to achieve target TSH. 2
• After celiac disease treatment with gluten-free diet, levothyroxine requirements decreased significantly (154 µg to 111 µg, p=0.03), demonstrating reversible malabsorption. 2, 4
• Patients requiring ≥125 mcg/day levothyroxine have 5.6% prevalence of celiac disease, rising to 12.5% in those requiring ≥200 mcg/day. 3

Assess Celiac Disease Control

Verify strict adherence to gluten-free diet and check tissue transglutaminase (tTG) antibodies to confirm celiac disease control. 3 Poor celiac disease control directly impairs levothyroxine absorption and increases replacement requirements by up to 49%. 4

• If tTG antibodies remain elevated, reinforce strict gluten-free diet adherence, as this alone may improve levothyroxine absorption without dose increases. 4
• If already on strict gluten-free diet with negative serology, expect to need higher levothyroxine doses (potentially 1.5-2× typical replacement) due to residual intestinal damage. 2, 4

Address Additional Laboratory Abnormalities

Elevated Alkaline Phosphatase (139 U/L)

Mildly elevated ALP may reflect bone turnover from prolonged hypothyroidism or celiac-related malabsorption. 1 This should normalize with adequate thyroid hormone replacement and celiac disease control. Monitor bone density if ALP remains elevated after TSH normalization.

LDL Cholesterol (121 mg/dL)

Hypothyroidism causes elevated LDL cholesterol, which should improve with adequate levothyroxine replacement. 1 Reassess lipids after achieving euthyroid state (typically 3-4 months) before considering statin therapy.

Trace WBC Esterase

This finding is nonspecific and likely unrelated to thyroid or celiac disease. If asymptomatic, no immediate action required.

Monitoring Strategy

Follow this specific timeline:

1. Week 0: Increase levothyroxine by 25-50 mcg; verify gluten-free diet adherence; check tTG antibodies
2. Week 6-8: Recheck TSH and free T4; adjust dose by 12.5-25 mcg increments as needed 1
3. Continue 6-8 week intervals until TSH 0.5-4.5 mIU/L achieved 1
4. After stabilization: Monitor TSH every 6-12 months 1

Critical Pitfalls to Avoid

• Never assume standard levothyroxine dosing (1.6 mcg/kg/day) will suffice in celiac disease patients—expect to need 50-100% higher doses if celiac disease is active. 2, 4
• Do not increase levothyroxine dose without assessing celiac disease control first—improving gluten-free diet adherence may eliminate need for dose escalation. 4
• Avoid undertreating this severe hypothyroidism (TSH 22)—persistent elevation risks cardiovascular dysfunction, adverse lipid profiles, and quality of life deterioration. 1
• Do not overlook the need for calcium (1200 mg/day) and vitamin D (1000 units/day) supplementation in celiac disease patients with hypothyroidism to prevent bone demineralization. 1

Expected Outcomes

With adequate levothyroxine replacement and celiac disease control, expect:

• TSH normalization within 3-4 months 1
• LDL cholesterol reduction 1
• ALP normalization as bone turnover stabilizes
• Potential reduction in levothyroxine requirements if celiac disease control improves 2, 4