For years, an indeterminate thyroid biopsy meant diagnostic surgery but molecular testing is now changing that reality entirely. On this episode of the BackTable ENT podcast, Dr. Ashley Agan interviews endocrinologist Dr. Erik Alexander about how molecular testing and a systematic, layered approach to thyroid nodule evaluation are reducing diagnostic surgeries and enabling more individualized patient care.

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Timestamps

00:00 - Introduction02:48 - Incidence, Presentation, and Workup of Thyroid Nodules 06:26 - Hormonal Impact and Indications for FNA 10:49 - FNA workflow and Bethesda Categories 16:10 - Role of Molecular Testing for Indeterminate Nodules19:59 - Evolution of Molecular Testing and Afirma 23:51 - Basics of DNA based Testing and RNA based Testing 28:34 - Comparing DNA based and RNA Based Testing 32:10 - Utility of Molecular Testing and Sampling Techniques 35:55 - Cost Coverage and Practical Limits39:20 - Clinical Implications and Future Impact42:00 - Final Takeaways

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More about this episode

Together they walk through the full evaluation pathway, including ultrasound risk stratification using the TI-RADS criteria, the role of TSH testing, and how FNA indications have shifted from biopsying every solid nodule to a more selective, risk-adapted approach. The discussion covers the Bethesda classification system and addresses why the one-third of patients landing in indeterminate categories (Bethesda III, IV, and V) have historically been the most challenging and most overtreated group. The conversation then explores molecular diagnostics as an additional layer of risk assessment, highlighting key differences between DNA-based mutation panels and RNA-based expression classifiers. Dr. Alexander also discusses practical considerations like insurance coverage, sampling technique, turnaround time, and the future potential of molecular testing to move beyond diagnosis toward individualized prognosis.

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Resources

American College of Radiology: TI-Rads Guidelines https://edge.sitecorecloud.io/americancoldf5f-acrorgf92a-productioncb02-3650/media/ACR/Files/RADS/TI-RADS/TI-RADS-Assessment-Categories.pdf

American Thyroid Association - Nodule Guidelineshttps://pmc.ncbi.nlm.nih.gov/articles/PMC4739132/

Bethesda System for Reporting Thyroid Ctyopathology https://www.ncbi.nlm.nih.gov/books/NBK278969/table/thyroid-nod-canc-eld.T.bethesda_system_f/

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