Interpreting Thyroid Function Tests in Difficult Clinical Contexts: A Practical Approach to Avoiding Diagnostic Pitfalls and Accurately Diagnosing Thyroid Dysfunction

Background: Thyroid function tests (TFTs) are essential for diagnosing thyroid disease, but their interpretation is problematic during pregnancy, critical illness, and biotin interference due to physiological changes and analytic interference. Aim: To provide a practical manual for clinicians to circumvent diagnostic pitfalls and correctly interpret TFTs in these scenarios. Methods: A narrative review (PubMed, Scopus, Web of Science; 2000–2025) of English peer-reviewed studies on TFT interpretation in pregnancy, non-thyroidal illness syndrome (NTIS), and biotin interference. Data were summarized to highlight physiological processes, diagnostic challenges, and management strategies. Results: Pregnancy requires trimester-specific TFT ranges because of hormonal change, NTIS needs distinction between adaptive responses and true hypothyroidism, and biotin interference needs assay awareness and supplement withdrawal. Trimester-specific ranges, conservative NTIS management, and non-biotin-based assays improve diagnostic accuracy. Conclusion: Understanding of physiological and analytical aspects, use of good-quality assays, and adherence to guidelines are crucial for the accurate interpretation of TFT, which results in improved patient outcomes in difficult clinical circumstances.