The Differential Diagnosis of Discrepant Thyroid Function Tests: Insistent Pitfalls and Updated Flow-Chart Based on a...

Area of Science:

• Endocrinology
• Thyroidology
• Clinical Diagnostics

Background:

• Discrepant thyroid function tests (TFTs) are characteristic of inappropriate TSH secretion (IST), a rare condition including TSH-secreting adenomas (TSHoma) and Resistance to Thyroid Hormone (RTHβ).
• Differentiating between TSHoma and RTHβ presents significant clinical challenges.
• This study shares experience with patients exhibiting discrepant TFTs to identify diagnostic pitfalls.

Purpose of the Study:

• To analyze the diagnostic challenges and pitfalls in patients with discrepant TFTs.
• To evaluate diagnostic strategies for differentiating TSHoma from RTHβ.
• To propose an improved diagnostic flowchart for IST.

Main Methods:

• Retrospective analysis of 100 patients with discrepant TFTs.
• Utilized dynamic testing (TRH test, T3-suppression test, somatostatin analog), THRB sequencing, and pituitary imaging.
• Evaluated diagnostic accuracy of various tests and identified misdiagnosed cases.

Main Results:

• 88 patients were correctly diagnosed with RTHβ (n=59) or TSHoma (n=23).
• 14 patients had atypical presentations or were misdiagnosed, including assay interference, misclassified TSHomas, and atypical TSHoma presentations.
• The T3-suppression test demonstrated 100% specificity for differentiating TSHoma and RTHβ. Diagnostic delay averaged 26 months.

Conclusions:

• Diagnostic delays and inappropriate treatments persist for patients with discrepant TFTs suggestive of central hyperthyroidism.
• Common pitfalls include assay interference, atypical presentations, and misinterpretation of imaging.
• A revised diagnostic flowchart is proposed to minimize errors and optimize resource allocation.