SAT-346 - A Systematic Review of Biochemical Thresholds Utilized in the Identification and Classification of Hypothyroidism and Its Subtypes

Objectives: This systematic literature review (SLR) assesses how biochemical thresholds classify hypothyroid patients in real-world and clinical settings, examining inconsistencies in reference ranges and cut-off values across regions, populations, and clinical contexts that may impact classification, treatment, and management.

Methods: This SLR followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and included English‑language, peer‑reviewed studies in PubMed and Embase (Jan 2010 to Oct 2025). An AI-enhanced platform screened titles and abstracts alongside human reviewers, with an independent adjudicator addressing any disagreements. Two independent reviewers conducted full-text screening.

Results: Of the 2,911 unique publications identified, there was broad consensus that overt hypothyroidism is defined by elevated thyroid-stimulating hormone (TSH) and low free thyroxine (FT4), with subclinical hypothyroidism characterized by elevated TSH with FT4 in the reference range. However, substantial inconsistency in biochemical thresholds was observed. TSH upper limits for the adult population ranged from 4.0 to 10 mIU/L, with Korean studies using 4.05 μIU/mL, Brazilian studies 4.94 mIU/L, German studies 4.0 mIU/L, and large European elderly cohorts using 4.50 mIU/L. In contrast, some Iranian studies defined overt hypothyroidism at TSH >10 mIU/L. FT4 lower limits also varied, with thresholds ranging from 0.7 to 0.93ng/dL, depending on country and assay. The varied thresholds highlight unclear treatment goals, leading to ambiguity in defining treatment targets, and may complicate the identification of patients with suboptimal or unstable control. Country-specific differences suggest that treatment algorithms derived in one setting may not be directly transferable across populations.
In pregnancy, stricter TSH cut-offs were utilized (e.g., < 2.5 mIU/L in the first trimester), though population- and ethnicity-specific percentiles were also reported. Overall, the use of population specific thresholds indicates that a universal LT4 control paradigm may not be suitable for all patients. Use of thyroid peroxidase antibody status was inconsistent, indicating etiology is frequently underutilized in treatment stratification. Collectively, these variations led to differences in diagnosis and reported regional prevalence.

Conclusion: Despite broad agreement on biochemical definitions of hypothyroidism, there is no universal standard for TSH and FT4 thresholds. Lack of standardization contributes to inconsistent care, unstable long-term control, and delays in recognizing patients who may benefit from alternative management approaches. These findings highlight the need for harmonized population- and context-specific reference intervals to improve consistency in hypothyroidism care.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*