G. Di Coscio

Lower levels of TSH are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role.

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 (n=497) or benign thyroid nodular disease (BTND, n=9681). 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 age-dependent development of thyroid autonomy (TSH <0.4 microU/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.

Real-Time Elastosonography: Useful Tool for Refining the Presurgical Diagnosis in Thyroid Nodules with Indeterminate or Nondiagnostic Cytology

BACKGROUND Indeterminate and nondiagnostic patterns represent the main limitation of fine-needle aspiration (FNA) cytology of thyroid nodules, clinical and echographic features being poorly predictive of malignancy. The newly developed real-time ultrasound elastography (USE) has been previously applied to differentiate malignant from benign lesions. The aim of this study was to get further insights into the role of USE in the presurgical diagnosis of nodules with indeterminate or nondiagnostic cytology. PATIENTS The study included 176 patients who had one (n=138) or multiple (n=38) nodules with indeterminate or nondiagnostic cytology on FNA, for whom histology was available after thyroidectomy. A total of 195 nodules (142 indeterminate, 53 nondiagnostic) were submitted to USE, and elasticity was scored as 1 (high), 2 (intermediate), or 3 (low). RESULTS In indeterminate lesions, the score 1, describing high elasticity, was strongly predictive of benignity, being found in 102 of 111 benign nodules and in only one of 31 carcinomas (P<0.0001). By combining the scores 2 and 3, USE had a sensitivity of 96.8% and a specificity of 91.8%. In nodules with nondiagnostic cytology, score 1 was found in 39 of 45 benign nodules and in only one of eight carcinomas (P<0.0001). By combining the scores 2 and 3, USE had a sensitivity of 87.5% and a specificity of 86.7%. CONCLUSIONS USE may represent an important tool for the diagnosis of thyroid cancer in nodules with indeterminate or nondiagnostic cytology and may prove useful in selecting patients who are candidates for surgery.

Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: results from a series of 505 consecutive patients

Objective  The cytological patterns of follicular and Hϋrthle cell nodules are included among the indeterminate results of fine‐needle aspiration cytology, because distinction between benign and malignant lesion can only be made on histological criteria. The diagnostic value of atypia at cytology, clinical parameters and echographic patterns were examined to establish the risk of malignancy in 505 patients with follicular and Hϋrthle cell thyroid nodules at cytology.

Thyroid carcinoma in thyrotoxic patients treated by surgery

We report the incidence of thyroid cancer in a series of 1832 consecutive patients seen for thyrotoxicosis of any etiology during 1970 and 1985 in our department. Surgical treatment for thyrotox-icosis was selected as the treatment of choice in 179 patients (9.8%), 86 with toxic diffuse goiter (TDG), 21 with toxic nodular goiter (TNG) and 40 with toxic adenoma (TA). The presence of thyroid cancer was found in 11 patients for a total incidence of 6.1%. Six patients had TDG (percent incidence in this group 6.9%), 4 patients had TNG (7.5%) and 1 had TA (2.5%). While the presence of thyroid cancer was totally unsuspected in TNG and TA, in TDG 4 out of 6 patients found to have a cancer, had been suspected before surgery. When a thyroid nodule was present in a toxic diffuse goiter the possibility to face with a malignant lesion reached 22.2% of the cases (4 out of 18 cases), while only 2 out of 68 patients (2.9%) with TDG and no nodule had thyroid cancer. These results confirm recent other series reporting the frequent association of hyperthyroidism and thyroid cancer and suggest that in thyrotoxic patients any nodule must be screened carefully to rule out malignancy.

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

Clinical features of thyroid autoimmunity are associated with thyroiditis on histology and are not predictive of malignancy in 570 patients with indeterminate nodules on cytology who had a thyroidectomy

Background  The relationship between thyroid autoimmunity and cancer is still uncertain.

L-thyroxine-treated patients with nodular goiter have lower serum TSH and lower frequency of papillary thyroid cancer: results of a cross-sectional study on 27 914 patients

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 (LT(4)) on the frequency of PTC diagnosed by cytology in a large series of patients with nodular goiter untreated (n=20 055) or treated with L-T(4) (n=7859). L-T(4)-treated patients with respect to untreated patients presented significantly lower serum TSH (median, interquartile range: 0.30 muU/ml, 0.08-0.62 microU/ml versus 0.70 muU/ml, 0.38-1.14 muU/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 muU/ml; 189/10 059, 1.9%) and highest in patients with TSH above the normal range (>3.4 muU/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 muU/ml) with respect to untreated patients (12,599/20,055, 62.8%; chi(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.

Papillary thyroid cancer, although strongly associated with lymphocitic infiltration on histology, is only weakly predicted by serum thyroid auto-antibodies in patients with nodular thyroid diseases

Objective: We evaluated the association between thyroid autoimmunity and thyroid cancer in a retrospective series of unselected thyroid nodules submitted to fine-needle aspiration (FNA) cytology. Design: Anti-thyroid antibodies (TAb) were measured in patients with multinodular goiter (MNG) and single/isolated thyroid nodule (S/I) submitted to FNA. Thyroid lymphocytic infiltration (LI) on histology was studied in a subgroup of patients submitted to thyroidectomy; 13,021 patients were included: on cytology 622 had papillary thyroid cancer (c-PTC) and 12,399 benign thyroid nodular diseases (c-BTN). LI was evaluated in histological samples of 688 patients: 304 with PTC (h-PTC) and 384 with BTN (h-BTN). Results: TAb prevalence was not different in c-BTN and c-PTC (38.7% vs 35.6%). TAb were more frequent in c-BTN than c-PTC in females with MNG (40.1% vs 32.5%, p=0.02), and in c-PTC than in c-BTN in males with S/I (31.2% vs 20.4%, p=0.02) and, although not significantly, in females younger than 30 yr (35.1% vs 30.7%). The frequency and severity of LI was significantly higher in h-PTC than h-BTN, both in MNG (82.5% vs 45.0%, p<0.001) and S/I (85.6% vs 71.0%, p<0.001), but a higher number of patients with h-PTC had negative circulating TAb, despite the presence of moderate/severe LI. Conclusions: TAb are weakly associated to PTC in males and young females, while they are more frequent in older females with BTN. The frequency and severity of LI is significantly higher in PTC than in BTN, but in cancer patients TAb are frequently negative, despite the evidence of histological thyroiditis. These data suggest that different kinds of immune response may be involved in PTC and BTN.

Large needle aspiration biopsy for reducing the rate of inadequate cytology on fine needle aspiration specimens from palpable thyroid nodules

From 1980 to 1996, 1,907 consecutive euthyroid subjects with palpable thyroid nodules were examined by fine needle aspiration (FNA) cytology plus large needle aspiration biopsy (LNAB) histology. There were 1,630 (85%) women and 277 (14.5%) men aged from 17 to 80 years. A single nodule was palpated in 1,419 subjects (74.4%) while 488 (25.6%) showed multiple nodules. The nodule size ranged between 1 and 7.5 cm. The number of inadequate specimens at the first examination, FNA cytology of LNAB histology, were 261 (13%) or 398 (20.8%), respectively. LNAB performed on the 261 nodules with nondiagnostic cytology showed findings which were adequate for diagnosis in 130 (49.8%) and inadequate in 131 (50.2%). Among the 261 patients with inadequate initial cytological findings 61 were subjected to repeated FNA and 36 repeated LNAB. More than 60% of the nodules on which FNA was repeated achieved a cytological diagnosis; more than 80% of the nodules reinvestigated by LNAB were finally diagnosed by histology. The mean nodule size was larger in the group with inadequate result than in that with adequate FNA or LNAB result. Among the 261 patients with inadequate cytological finding at the first FNA 28 were operated on; 20 were in the group with adequate LNAB histological findings and eight in the group with an inadequate LNAB. Two papillary cancers, one per group, were found at postoperative histology. However, one was diagnosed by LNAB and one at the second FNA. The remaining 26 nodules were all found to be benign postoperatively. This study shows that the addition of LNAB to FNA leads to a histological diagnosis in 50% of the palpable thyroid nodules with inadequate cytology at the first FNA and that LNAB can be used even for those nodules which remain uncharacterized after repeat FNA.

PERCUTANEOUS ETHANOL INJECTION THERAPY OF ADENOMATOUS HYPERPLASTIC NODULES IN CIRRHOTIC LIVER-DISEASE

Adenomatous hyperplastic nodules (AHNs) in cirrhotic liver are considered a precancerous condition which may lead to hepatocellular carcinoma (HCC). In this study, we treated a total of 23 AHNs in 15 patients with percutaneous ethanol injection (PEI). The treatment included 6 to 8 PEIs, performed on an out-patient basis under sonographic guidance. A 22 G (0.7 mm) spinal needle was used. The total amount of alcohol delivered into each lesion was 8 to 25 ml (mean 14.9 ml). At the end of treatment, complete necrosis of the nodule was proved in all cases by multiple fine-needle biopsies and confirmed by CT and MR findings. During follow-up (9–41 months, mean 24 months) no recurrences were demonstrated. However, HCC occurred elsewhere in the liver of 4 patients and additional AHNs were detected in 2 patients. Thus, PEI proved able to cause complete ablation of AHNs, presumably preventing their malignant transformation. However, patients with AHN remain at high risk for developing HCC.