Purpose of review: In this article, we will consider the failure of thyroid hormone replacement therapy to normalize serum thyroid stimulating hormone concentrations. We will review circumstances and causes for failures, discuss pertinent unpublished personal cases of didactical value, and provide practical suggestions for providers encountering patients with similar presentations.
Recent findings: Recent data are available on the benefit of novel formulations of levothyroxine therapy on malabsorption.
Summary: Most frequently, reasons for ineffectiveness are noncompliance, inappropriate administration of levothyroxine, gastrointestinal disorders, and drug interactions. The diagnostic work-up should include careful history to elucidate the potential reasons for the ineffective therapy.