Higher TSH values, even within normal ranges, have been associated with a greater risk of thyroid malignancy. The relationship between TSH and papillary thyroid cancer (PTC) has been analyzed in 10 178 patients submitted to fine needle aspiration of thyroid nodules with a cytology of PTC (nZ497) or benign thyroid nodular disease (BTND, nZ9681). In 942 patients, submitted to surgery (521 from BTND and 421 from PTC), the histological diagnosis confirmed an elevated specificity (99.6%) and sensitivity (98.1%) of cytology. TSH levels were significantly higher in PTC than in BTND both in the cytological and histological series and also in patients with a clinical diagnosis of multinodular goiter (MNG) and single/isolate nodule (S/I). A significant agedependent development of thyroid autonomy (TSH !0.4 mU/ml) was observed in patients with benign thyroid disease, but not in those with PTC, diagnosed both on cytology and histology. In patients with MNG, the frequency of thyroid autonomy was higher and the risk of PTC was lower compared to those with S/I. In all patients, the presence of thyroid auto-antibodies (TAb) was associated with a significant increase of TSH. However, both in TAb positive and TAb negative patients TSH levels were significantly higher in PTC than in BTND. Our data confirm a direct relationship between TSH levels and risk of PTC in patients with nodular thyroid diseases. Thyroid autonomy conceivably protects against the risk of PTC, while thyroid autoimmunity does not play a significant role.

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-T 4 ). 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-T 4 -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-T 4 reduces TSH levels and decreases the occurrence of clinically detectable PTC.

The risk of papillary thyroid cancer (PTC) is related to serum TSH, and the development of thyroid autonomy by reducing TSH levels decreases the frequency of PTC in patients with nodular goiter. Our aim was to investigate the effect of L-thyroxine (L-T 4 ) on the frequency of PTC diagnosed by cytology in a large series of patients with nodular goiter untreated (nZ20 055) or treated with L-T 4 (nZ7859). L-T 4 -treated patients with respect to untreated patients presented significantly lower serum TSH (median, interquartile range: 0.30 mU/ml, 0.08-0.62 mU/ml versus 0.70 mU/ml, 0.38-1.14 mU/ml; P!0.0001) and prevalence of PTC (3.2 vs 5.1%; P!0.0001). The frequency of PTC was closely related to serum TSH, with it being lowest in patients with TSH below the normal range (!0.4 mU/ml; 189/10 059, 1.9%) and highest in patients with TSH above the normal range (O3.4 mU/ml; 21/127, 16.5%), also showing a progressive increase from the lower to the upper quartile of normal range. A significantly higher proportion of L-T 4 -treated patients (6650/7859, 84.6%) had serum TSH below the median (0.90 mU/ml) with respect to untreated patients (12 599/20 055, 62.8%; c 2 P value !0.0001), with it being included in the range of TSH associated with a lower frequency of PTC. The relationship between serum TSH and frequency of PTC was unrelated to the type of nodularity (solitary versus multinodular) and was not age dependent.In conclusion, patients with nodular goiter, treatment with L-T 4 is responsible for the reduction of serum TSH and is associated with a decreased frequency of PTC.

Iodine-induced thyroid autoimmunity is related to TgAb and the unmasking of a cryptic epitope on Tg contributes to this relationship in humans.

Objective Papillary thyroid microcarcinomas (microPTC) may be ’incidental’ (Inc-microPTC), occasionally found at histology after surgery for benign disease or ‘non-incidental’ (Non-Inc-microPTC), diagnosed on clinical grounds. It is unclear whether these different microPTC reflect the same disease. The aim of the study was to compare Inc-microPTC and Non-Inc-microPTC for clinical and histological features as well as for serum TSH, a known factor involved in PTC development. Design We evaluated histology and serum TSH levels of consecutive patients submitted to thyroidectomy for goiter with compressive symptoms or for cytological diagnosis suspicious/indicative of PTC. Methods In total, 665 consecutive patients (259 with a single thyroid nodule, SN and 406 with a multinodular gland, MN) were included in the study. According to histology, patients were classified as: benign nodular goiter (Benign, n=291); Inc-microPTC (n=92); Non-Inc-microPTC (n=67) and PTC≥1cm (macroPTC, n=215). Results Inc-microPTC were significantly more frequent in MN than in SN (66/406, 16.2% vs 26/259, 10.0%, P=0.02). Patients with Inc-microPTC compared with Non-Inc-microPTC were older (mean age±s.d. 53.3±13.2 years vs 44.9±14.8 years, P=0.0002), had a smaller tumor size (median 4mm vs 9mm, P<0.0001), a higher frequency of multifocality (70/92, 76.1% vs 35/67, 52.2% P=0.001) and lower levels of TSH (median 0.6mIU/L, IR: 0.4–1.0mIU/L vs value 1. mIU/L, IR: 0.6–1.4mIU/L vs P=0.0001). Conclusion Incidental and non-incidental papillary thyroid microcarcinomas appear to be two different entities.