Effectiveness of Peripheral Thyrotropin Receptor mRNA in Follow-Up of Differentiated Thyroid Cancer

Thyroid cells in peripheral circulation have been linked to thyroid cancer (TC). These cells express thyrotropin receptor (TSHR) messenger RNA (mRNA), which has been studied as a marker of initial TC diagnosis. We examined the utility of TSHR mRNA in long-term follow-up of TC patients. From 2002 to 2007, TSHR mRNA was prospectively measured by quantitative reverse-transcription polymerase chain reaction (RT-PCR) from peripheral blood samples in 259 patients, and those followed ≥3 months since initial thyroidectomy were studied. TSHR mRNA levels were correlated to thyroglobulin (Tg), imaging studies, and disease status during follow-up. Thirty-four patients underwent 20 ± 14 months median follow-up for papillary (n = 31, 91%), follicular (n = 2) or Hurthle cell (n = 1) TC. Advanced-stage disease occurred in 24% at presentation, and 11 (32%) developed cervical node metastases or recurrence requiring reoperation during follow-up. Of 52 simultaneous TSHR mRNA and serum Tg measurements, 52% were concordant. TSHR mRNA missed disease in 21% patients, but was better than Tg in 27%, including all those with Tg antibodies. TSHR mRNA concurred with whole-body scan detectable disease for 11/14 patients (79%) and accurately predicted overall TC disease status in 77% patients. In discordant cases, TC recurrence was apparent from other imaging modalities [positron emission tomography (PET) scan or ultrasound]. TSHR mRNA in conjunction with Tg diagnosed TC recurrence with 90% sensitivity and 94% specificity. We conclude that TSHR mRNA demonstrates high concordance rates with present methods of detecting TC recurrence, and appears to be more accurate in patients with Tg antibodies. As a novel adjunct, TSHR mRNA may enhance long-term management of TC patients.