Dr. Ladenson on Diagnosis of Thyroid Nodules

Paul W. Ladenson, MD
Published: Tuesday, May 29, 2012

Paul W. Ladenson, MD, John Eager Howard Professor of Endocrinology and Metabolism, Professor of Medicine, Pathology, Oncology, and Radiology & Radiological Sciences, Director, Division of Endocrinology and Metabolism, Johns Hopkins Medicine, discusses differential diagnosis for cytologically indeterminate thyroid nodules.

Currently, about 1 in 5 biopsies lead to diagnoses of indeterminacy, and about one-third of those patients prove to have thyroid cancer. Without further diagnostic certainty, many such patients are being advised to have surgery.

Two molecular diagnostic strategies are currently being explored. The first is a thyroid cancer candidate gene approach, in which clinicians can look for a set of genes known to be associated with thyroid cancer, such as BRAF, RET, PTC rearrangements, and RAS mutations. In the absence of such mutations, the physician can feel more confident that the nodule is benign. This approach has a theoretical limit of achieving a negative predictive value in the 85% range.

The second molecular approach being explored is gene expression analysis. The approach began with the profiling of almost 250,000 mRNA transcripts in nodules that were benign and malignant. This transcription helped to identify genes that were over- and under-expressed in benign nodules. With this technique, the 142 genes that were ultimately selected as informative and their profiles are employed in indeterminate nodule biopsy material in order to determine if it is benign. The negative predictive value of this testing appears to be 95% to 96%, akin to getting a benign cytologic diagnosis.

Ladenson says that, as these molecular tests now enter clinical practice, fewer patients with indeterminate nodules will have unnecessary surgeries.

Paul W. Ladenson, MD, John Eager Howard Professor of Endocrinology and Metabolism, Professor of Medicine, Pathology, Oncology, and Radiology & Radiological Sciences, Director, Division of Endocrinology and Metabolism, Johns Hopkins Medicine, discusses differential diagnosis for cytologically indeterminate thyroid nodules.

Currently, about 1 in 5 biopsies lead to diagnoses of indeterminacy, and about one-third of those patients prove to have thyroid cancer. Without further diagnostic certainty, many such patients are being advised to have surgery.

Two molecular diagnostic strategies are currently being explored. The first is a thyroid cancer candidate gene approach, in which clinicians can look for a set of genes known to be associated with thyroid cancer, such as BRAF, RET, PTC rearrangements, and RAS mutations. In the absence of such mutations, the physician can feel more confident that the nodule is benign. This approach has a theoretical limit of achieving a negative predictive value in the 85% range.

The second molecular approach being explored is gene expression analysis. The approach began with the profiling of almost 250,000 mRNA transcripts in nodules that were benign and malignant. This transcription helped to identify genes that were over- and under-expressed in benign nodules. With this technique, the 142 genes that were ultimately selected as informative and their profiles are employed in indeterminate nodule biopsy material in order to determine if it is benign. The negative predictive value of this testing appears to be 95% to 96%, akin to getting a benign cytologic diagnosis.

Ladenson says that, as these molecular tests now enter clinical practice, fewer patients with indeterminate nodules will have unnecessary surgeries.


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