Thyroxine Malabsorption Assessment
Initial Step: Levothyroxine Absorption Test
For patients with persistently elevated TSH despite receiving levothyroxine doses exceeding 2 mcg/kg body weight, the initial step is to perform a supervised levothyroxine absorption test to distinguish true malabsorption from pseudomalabsorption (medication nonadherence). 1, 2, 3
Standardized Testing Protocol
Patient Preparation
- Instruct the patient to fast overnight and avoid all food, beverages (except water), and medications on the morning of the test 2
- Ensure direct supervision throughout the entire testing period 2
Test Administration
- Administer a single oral dose of 1000 mcg levothyroxine (or 10 mcg/kg body weight, maximum 600 mcg as an alternative protocol) 1, 2, 3
- Use the patient's usual levothyroxine formulation 2
- Draw baseline thyroid function tests (TSH, free T4, and optionally free T3) before administration 1, 4
Monitoring Schedule
- Collect blood samples at hourly intervals for 4 hours after levothyroxine administration 2
- The 2-hour protocol (measuring at 0,60, and 120 minutes) represents a more rapid alternative that may be sufficient, as free T4 levels peak at or near 2-3 hours 4, 3
- The 3-hour timepoint appears optimal for distinguishing normal absorption from malabsorption 3
Interpretation Criteria
Normal Absorption (Excludes True Malabsorption)
- Free T4 increment >0.40 ng/dL (5.14 pmol/L) from baseline to peak (typically at 3 hours) has 97% sensitivity and 80% specificity for excluding true malabsorption 2, 3
- Total T4 increment >6 μg/dL (77.23 nmol/L) for test doses ≥300 mcg 2
- Percentage T4 absorption >60% 2
Pseudomalabsorption (Nonadherence)
- Patients demonstrating normal absorption parameters during supervised testing but with persistently elevated TSH on prescribed therapy have pseudomalabsorption 1, 4
- These patients often show high baseline thyroid hormone levels at the time of testing (indicating they took medication just before the test), yet still demonstrate further increases during the absorption test 4
- After confirming nonadherence, reduce levothyroxine to appropriate weight-based dosing (approximately 1.6 mcg/kg/day) and monitor TSH in 6-8 weeks 5, 1
True Malabsorption
- Free T4 increment ≤0.40 ng/dL (5.14 pmol/L) at 3 hours indicates true malabsorption requiring gastroenterology referral 2, 3
- Consider alternative levothyroxine formulations (liquid, soft gel capsules), increased dosing, or parenteral administration 2
Clinical Context for Testing
When to Perform Absorption Testing
- Patients requiring levothyroxine doses >2 mcg/kg body weight with persistently elevated TSH 1, 2
- Failure to achieve target TSH (0.5-4.5 mIU/L) despite apparent adequate dosing for >6 months 5, 3
- Before extensive malabsorption workup, as the test itself may induce medication adherence 4
Critical Pitfalls to Avoid
- Never assume malabsorption without formal testing—nonadherence accounts for the majority of cases with apparent levothyroxine resistance 1, 4
- Do not perform absorption testing based on a single elevated TSH value; confirm with repeat testing after 3-6 weeks, as 30-60% of elevated TSH levels normalize spontaneously 5
- Rule out other causes of elevated TSH first: medication interactions, recent iodine exposure, recovery phase thyroiditis, or concurrent adrenal insufficiency 5, 6
- Approximately 25% of patients on levothyroxine are unintentionally maintained on excessive doses—ensure the prescribed dose is appropriate before suspecting malabsorption 5
Alternative Monitoring Approach
For patients where absorption testing is not immediately available, monitor both TSH and free T4 levels 7, 8:
- TSH alone is insufficient for assessing therapy adequacy in suspected malabsorption 8
- Free T4 helps interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 5, 6
- In primary hypothyroidism, TSH remains the primary screening test with sensitivity >98% and specificity >92% 5, 8