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A TRAb-First Diagnostic Strategy for Overt Hyperthyroidism: Diagnostic Performance and Implications for Reflex

Petra Petranović Ovčariček1,2, Alfredo Campennì3, Federica D'Aurizio4

  • 1Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, 10000 Zagreb, Croatia.

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|January 28, 2026
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Summary
This summary is machine-generated.

A TSH-receptor antibody (TRAb)-first strategy is the most accurate and efficient diagnostic approach for overt hyperthyroidism. This method improves etiologic classification, reduces unnecessary imaging, and lowers costs compared to conventional pathways.

Keywords:
Graves’ diseaseTSH receptor antibodiescost-effectivenessdiagnostic strategyhyperthyroidism diagnosisreflex testingthyroid scintigraphy

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Area of Science:

  • Endocrinology
  • Diagnostic Medicine
  • Medical Imaging

Background:

  • Overt hyperthyroidism requires accurate etiologic classification for appropriate management.
  • Conventional diagnostic pathways may involve multiple imaging modalities with varying efficiency and cost.
  • TSH-receptor antibody (TRAb) testing is a key diagnostic marker for Graves' disease.

Purpose of the Study:

  • To evaluate a TSH-receptor antibody (TRAb)-first diagnostic strategy for overt hyperthyroidism.
  • To compare its diagnostic accuracy, imaging use, and cost-efficiency against conventional methods.
  • To assess the implications for etiologic classification and resource utilization.

Main Methods:

  • Multicentre retrospective study of 274 adults with newly diagnosed overt hyperthyroidism.
  • Comparison of diagnostic performance of TRAb, thyroid ultrasound, and scintigraphy.
  • Modeling of TRAb-first diagnostic algorithms and estimation of impact on workflow and resource use.

Main Results:

  • TRAb demonstrated excellent accuracy for Graves' disease (GD) (92.0% sensitivity, 96.0% specificity).
  • A TRAb-first pathway achieved 100% sensitivity and 95.8% specificity for GD, minimizing misclassification.
  • This strategy could avoid two-thirds of scintigraphies and reduce unnecessary imaging.

Conclusions:

  • A TRAb-first approach is the most accurate, efficient, and appropriate method for diagnosing overt hyperthyroidism.
  • Scintigraphy should be reserved for TRAb-negative cases; ultrasound use should be selective.
  • Reflex TRAb testing can streamline care, enabling rapid diagnosis and reducing resource use.