Context: Thyroid stimulating hormone (TSH) is a known thyroid growth factor, but the pathogenic role of TSH in thyroid oncogenesis is unclear.

Objective: The aim was to examine the relationship between preoperative TSH and differentiated thyroid cancer (DTC).

Design: Retrospective cohort

Setting, Participants: Between May 1994 and January 2007, 1198 patients underwent thyroid surgery at a single hospital. Data from the 843 patients with preoperative serum TSH concentration were recorded.

Main Outcome Measures: Serum TSH concentration was measured with a sensitive assay. Diagnoses of DTC versus benign thyroid disease were based on surgical pathology reports.

Results: Twenty-nine percent (241/843) of patients had DTC on final pathology. On both univariate and multi-variable analyses, risk of malignancy correlated with higher TSH level (p=0.007). The likelihood of malignancy was 16% (9/55) when TSH was <0.06 mIU/L versus 52% (15/29) when 5.00 mIU/L (p=0.001). When TSH was between 0.40 to 1.39 mIU/L the likelihood of malignancy was 25% (85/347) versus 35% (109/308) when TSH was between 1.40 mIU/L and 4.99 mIU/L (p=0.002). The mean TSH was 4.9 ± 1.5 mIU/L in patients with stage III/IV disease versus 2.1 ± 0.2 mIU/L in patients with stage I/II disease (p=0.002).

Conclusions: The likelihood of thyroid cancer increases with higher serum TSH concentration. Even within normal TSH ranges, a TSH level above the population mean is associated with significantly greater likelihood of thyroid cancer than a TSH below the mean. Shown for the first time, higher TSH level is associated with advanced stage DTC.