Randomized Trial Comparing Performance of Molecular Markers for Indeterminate Thyroid Nodules

1. All patients undergoing thyroid FNA within the UCLA Health System will be randomized at
the time of FNA to a single molecular test (GSC or ThyroSeq v.3). In the previous phase
of the study, patients were randomized to the previous versions of a single molecular
test (GEC or ThyroSeq v.2).

2. During the FNA, a sample will be collected for the molecular test.

3. If the cytology results are indeterminate (Bethesda categories 3 or 4), the molecular
test will be reflexively sent off.

4. We will help patients with indeterminate thyroid nodules to establish care with an
endocrinologist, if they do not already have one. The physicians will make treatment
recommendations using best practices and incorporating the results of the molecular
test. We anticipate that most patients with a positive molecular test will undergo
surgery, while the majority with a negative test will be surveiled.

5. Patients who undergo surgery will have histopathologic evaluation of the thyroid, which
will determine whether the index thyroid nodule was benign or malignant.

6. Patients who do not undergo surgery will have a followup ultrasound at 6 and 12 months,
or sooner at the discretion of the treating physician.

7. We will assess thyroid-specific quality of life at baseline (following initial diagnosis
of an indeterminate thyroid nodule) and during followup (at 6 and 12 months) using the
short version of Thyroid-Related Patient-Reported Outcome.

Inclusion Criteria:

- Patients with a thyroid nodule who have a thyroid biopsy performed at UCLA health will
be eligible for the study and consented if they agree to participate.

- Patients who have an indeterminate FNA biopsy result (Bethesda category 3 or 4) will
be enrolled in the study if they agree to participate.

Exclusion Criteria:

- Patients who do not have an indeterminate biopsy result (either patients who have a
benign, insufficient, or malignant result).