Context: Thyroid cancer cells express TSHR-mRNA and its measurement in the circulation may be useful in the diagnosis/management of differentiated thyroid cancer (DTC).

Objective: To assess the diagnostic-value of circulating TSHR-mRNA for preoperative detection of DTC in patients with thyroid-nodules.

Patients: We measured TSH-mRNA levels by RT-PCR in 258 subjects; 51 healthy-subjects and 207 patients [thyroid-nodules (n = 180); recurrent thyroid -cancer (n = 27)] with fine-needle aspirations (FNAs) and/or thyroid/neck surgery. Eighty-nine patients also had day-1 postoperative-levels.

Outcome Measures: TSHR-mRNA levels were compared with FNA cytology for cancer detection preoperatively and serum thyroglobulin and/or WBS post-operatively.

Results Based on cytology/pathology 88 patients had DTC and 119 had benign thyroid-disease. The TSHR-mRNA levels in cancer patients were significantly higher than in benign-disease (P < 0.0001). At cut-off value of 1.02ng/µg total-RNA, the TSHR-mRNA correctly classified 78.7% of patients preoperatively (sensitivity =72.0%; specificity=82.5%). Of 131 patients with FNA and surgery; 51 were FNA positive (all cancer) 17 were FNA negative (15 benign, 2 cancer) and 63 were indeterminate. TSHR-mRNA correctly diagnosed DTC in 16/24 (67%) and benign-disease in 29/39 (74%) patients with indeterminate FNA (combined sensitivity=90%; specificity=80%). Combining TSHR-mRNA and ultrasound-features for follicular-lesions correctly classified all follicular cancers and could have spared surgery in 31% of these patients with benign disease. TSHR mRNA has a short-life in circulation and normalized-levels on postoperative day-1 correlated with disease-free status whereas elevated levels predicted residual/metastatic disease.

Conclusions TSHR-mRNA with FNA, enhances the preoperative detection of cancer in patients with thyroid-nodules, reducing unnecessary surgeries and immediate postoperative levels can predict residual/metastatic disease.