Hashimoto's thyroiditis is associated with papillary thyroid carcinoma: role of TSH and of treatment with l-thyroxine

The possible association between Hashimoto’s thyroiditis (HT) and papillary thyroid carcinoma (PTC) is a still debated issue. We analyzed the frequency of PTC, TSH levels and thyroid autoantibodies (TAb) in 13 738 patients (9824 untreated and 3914 under L-thyroxine, L-T4). Patients with nodular-HT (nZ1593) had high titer of TAb and/or hypothyroidism. Patients with nodular goiter (NG) were subdivided in TAbKNG (nZ8812) with undetectable TAb and TAbCNG (nZ3395) with positive TAb. Among untreated patients, those with nodular-HT showed higher frequency of PTC (9.4%) compared with both TAbKNG (6.4%; PZ0.002) and TAbCNG (6.5%; PZ0.009) and presented also higher serum TSH (median 1.30 vs 0.71 mU/ml, P!0.001 and 0.70 mU/ml, P!0.001 respectively). Independently of clinical diagnosis, patients with high titer of TAb showed a higher frequency of PTC (9.3%) compared to patients with low titer (6.8%, P!0.001) or negative TAb (6.3%, P!0.001) and presented also higher serum TSH (median 1.16 vs 0.75 mU/ml, P!0.001 and 0.72 mU/ml, P!0.001 respectively). PTC frequency was strongly related with serum TSH (odds ratio (OR)Z1.111), slightly related with anti-thyroglobulin antibodies (ORZ1.001), and unrelated with anti-thyroperoxidase antibodies. In the L-T4-treated group, when only patients with serum TSH levels below the median value (0.90 mU/ml) were considered, no significant difference in PTC frequency was found between nodular-HT, TAbKNG and TAbCNG. In conclusion, the frequency of PTC is significantly higher in nodular-HT than in NG and is associated with increased levels of serum TSH. Treatment with L-T4reduces TSH levels and decreases the occurrence of clinically detectable PTC. Endocrine-Related Cancer (2011) 18 429‐437