• Increased TSH levels in patients on levothyroxine may indicate absorption problems due to medications, supplements, or underlying malabsorption disorders.
• Iron and calcium supplements, proton pump inhibitors, and other medications can interfere with levothyroxine absorption, leading to elevated TSH levels.
• Recommendations include reviewing medication lists, performing levothyroxine absorption tests, and considering workup for malabsorption syndromes like celiac disease.

The article addresses the clinical problem of rising TSH levels in patients with hypothyroidism who are being treated with levothyroxine. It presents a scenario involving a 24-year-old woman whose TSH levels increased despite consistent levothyroxine use. The article investigates potential causes, including medication interactions, changes in thyroid hormone demand (due to weight changes or pregnancy), and malabsorption disorders, providing guidance on diagnosis and management.

• What: The article explains why TSH levels might increase in patients with hypothyroidism who are taking levothyroxine, focusing on absorption issues and medication interactions.
• Who: The key individuals involved are patients with hypothyroidism, particularly premenopausal women with Hashimoto thyroiditis and potential iron deficiency. Experts include Douglas S. Paauw and Veda Gadiraju, who provide insights and recommendations.
• When: The information is presented in the context of a follow-up visit where a patient's TSH levels have recently increased (over 6 weeks). Recommendations are for current and future levothyroxine use.
• Where: The scenario takes place in a clinical setting (University of Washington Medical Center), but the information is applicable to any location where levothyroxine is prescribed and monitored.

The article provides a practical and clinically relevant analysis of a common problem in managing hypothyroidism. It emphasizes the importance of considering factors beyond medication adherence when TSH levels rise. The detailed list of medications and conditions that can interfere with levothyroxine absorption is particularly valuable. The recommendation for a levothyroxine absorption test offers a concrete step for diagnosis. The inclusion of study findings (TEARS study) strengthens the evidence-based approach.

The most common cause of these absorption problems is other medications that block levothyroxine absorption.

The article concludes that increased TSH levels despite levothyroxine use require a thorough investigation of potential causes, particularly medication interactions and absorption issues. It recommends a detailed medication history, levothyroxine absorption test, and consideration of malabsorption syndromes. Proper timing of levothyroxine administration is crucial for optimal absorption and thyroid hormone management. Continued monitoring and adjustments are necessary for effective treatment.