Low thyroglobulin concentrations after thyroidectomy increase the prognostic value of undetectable thyroglobulin levels on levo-thyroxine suppressive treatment in low-risk differentiated thyroid cancer.

DESIGN: Recombinant human TSH-stimulated thyroglobulin (Tg) levels (rhTSH-Tg) are sufficient for early follow-up of low-risk differentiated thyroid cancer (DTC) patients after thyroidectomy and radioiodine (131I) remnant ablation (RAI). Serum Tg levels at the time of remnant ablation (ablation-Tg) is thought to be related with rhTSH-Tg and may be predictive of recurrent disease. During long-term follow-up, Tg levels on levo-T4 (L-T4) suppressive treatment (suppressive-Tg) is sufficiently sensitive to avoid further evaluations in patients with undetectable rhTSH-Tg. The aim of our study was to verify whether, in a subgroup of low-risk DTC patients, the association of low ablation-Tg levels (<10 microg/l) with undetectable suppressive-Tg concentrations has a sufficient negative predictive value (NPV) for recurrence of disease, leading to avoid rhTSH testing. METHODS: We enrolled 169 low-risk DTC patients treated by thyroidectomy + RAI and undetectable suppressive-Tg at 12-month followup. In all patients, we retrospectively evaluated ablation-Tg and rhTSH-Tg. For all patients, 2-yr follow-up was available. RESULTS: Based on rhTSH-Tg>2 microg/l, relapsing disease was histologically proven in 2 patients. rhTSH-Tg levels between 0.6-2.0 microg/l, with no evidence of disease, was observed in 10 patients (6%). One hundred and fifty-seven patients showed undetectable rhTSH-Tg. The NPV of undetectable suppressive- Tg was 92.8%. The ablation-Tg level was <10 microg/l in 140 patients. In this group, the NPV of undetectable suppressive- Tg was 100%. CONCLUSION: Our data indicate that undetectable suppressive-Tg value, combined with ablation- Tg levels <10 microg/l, may avoid a significant number of high-cost rhTSH-Tg test.

Characterization of thyroid 'follicular neoplasms' in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application.

The distinction of benign from malignant follicular thyroid neoplasms remains a difficult task in diagnostic fine-needle aspiration cytology, and some discrepant results have been reported for the individual immunocytochemical markers of malignancy proposed so far. The aim of this study was to test if the combined use of a panel of markers could improve the diagnostic accuracy in the preoperative cytological evaluation of 'follicular neoplasms' in an attempt to reduce the number of thyroidectomies performed for benign lesions. The immunocytochemical expression of galectin-3, HBME-1, thyroperoxidase, cytokeratin-19 and keratan-sulfate was retrospectively analyzed in 125 consecutive fine-needle aspiration samples (cell blocks) of indeterminate diagnoses of 'follicular thyroid neoplasm', and compared with their corresponding surgical specimens, including 33 follicular carcinomas, 42 papillary carcinomas and 50 follicular adenomas. Statistical analysis on each marker confirmed that galectin-3 and HBME-1 were the most sensitive (92% and 80% respectively) and specific (94% and 96% respectively) molecules. The use of these two markers sequentially in non-oncocytic lesions (testing HBME-1 as a second marker whenever galectin-3 proved negative) increased the sensitivity and specificity up to 97% and 95% respectively. In oncocytic lesions, HBME-1 proved to be less sensitive, and the sequential combination of galectin-3 and cytokeratin-19 reached 100% of both specificity and sensitivity. Our data showed that, as compared with the use of single markers, the sequential combination of two markers represents the most accurate immunohistochemical panel in managing patients with a fine-needle aspiration biopsy diagnosis of 'follicular neoplasms', especially in otherwise controversial categories such as oncocytic tumours. The combination of three or more markers did not substantially improve the diagnostic accuracy of the test.

Osteonecrosis of the jaw in a patient receiving cabozantinib.

Since the discovery of bisphosphonate-related osteonecrosis of the jaw, there has been increasing evidence in recent years of osteonecrosis induced by drugs other than bisphosphonates, mainly agents with antiangiogenic and antiosteoclastic activity. Mandibular osteonecrosis was observed in a 51-year-old female with medullary thyroid cancer receiving cabozantinib, a new tyrosine kinase inhibitor having antiangiogenic activity. The bone necrosis appeared after a dental extraction. The clinical, radiographic and histologic picture of a chronic non-healing extraction socket was consistent with drug-induced osteonecrosis of the jaw. Healing was achieved by segmental ostectomy. The osteonecrosis was likely associated with a vascular endothelial growth factor (VEGF) pathway inhibition, implying inhibition of angiogenesis and hampering of the local host defence mechanisms.

Goiter prevalence and urinary iodine status in urban and rural/mountain areas of Piedmont region.

Piedmont region was reported in the 70s as a mild iodine-deficient area with a goiter prevalence > 10%. This study aimed at characterizing the current status of iodine deficiency in Piedmont, with special attention to putative differences between urban and rural/mountain areas. A cross-sectional, observational study was performed according to the surveillance methods for iodine deficiency disorders recommended by the World Health Organization (WHO). Ultrasound local thyroid volume reference values and median urinary iodine concentration were obtained in 2178 schoolchildren aged 11-15 yr, resident in Piedmont region for more than 5 yr to assess both goiter prevalence and iodine intake. Anamnestic and anthropometric data, thyroid volume by both bimanual palpation and ultrasound were assessed, and spot urinary iodine samples were collected. The median urinary iodine concentration was 115.8 microg/l and the prevalence of goiter 3.1%, indicating this area as iodine-sufficient. Nevertheless, 39% of the schoolchild population had urinary iodine levels < 100 microg/l and 6.8% < 50 microg/l. No differences in goiter prevalence and median urinary iodine excretion were observed between urban and rural/ mountain populations. In conclusion, Piedmont is now an iodine-sufficient region. As no programs of salt iodization have been carried out in the last 30 yr, a silent iodine replacement has occurred. Despite a sufficient median urinary iodine excretion, a program of iodine prophylaxis is strongly recommended due to a large part of iodine-deficient population.

Thyroid volume and urinary iodine excretion in the schoolchild population of a Northwestern Italian sub-Alp metropolitan area.

Iodine deficiency is recognised as a major preventable public-health worldwide problem. The aim of this study is to assess local reference values for thyroid volume, and give a snapshot of the epidemiology of goiter and iodine nutritional status of the Turin schoolchild population. Sonographic thyroid volume and median urinary iodine excretion were obtained in 1067 schoolchildren aged 11-15 yr resident in Turin for more than 5 yr to assess both goiter prevalence and iodine intake. All the subjects were asked to fill in a questionnaire about their life habits. Anamnestic and anthropometric data, thyroid volume by both bimanual palpation and ultrasonography were assessed, and spot urinary iodine samples were collected. The results show that the median urinary iodine concentration is 113.1 microg/l and the prevalence of goiter <5%, indicating this area as iodine-sufficient. Nevertheless, 40.5% of the schoolchild population has urinary iodine levels lower than the cut-off level recommended as iodine-sufficiency. Interestingly, the high relative prevalence of ultrasound features of autoimmune thyroid disease suggests autoimmune-thyroiditis as a frequent thyroid disease in Turin schoolchildren. As no active programs of salt, milk or water iodisation have ever been carried out, a silent iodine prophylaxis has probably occurred in the city. Despite a sufficient median urinary iodine excretion, a focused program of iodine prophylaxis should be developed due to the presence of a large rate of iodine-deficient population.

Galectin-3: presurgical marker of thyroid follicular epithelial cell-derived carcinomas.

Preoperative follicular lesion characterisation represents an unsolved diagnostic problem in thyroid nodular disease. Although fine-needle aspiration biopsy is the most reliable preoperative diagnostic procedure, it shows inherent limitations in differentiating adenoma from follicular carcinoma and, sometimes, follicular variants of papillary carcinoma. Galectin-3 cytoplasmic neoexpression has been proposed as a peculiar feature of thyroid malignant cells, easily detectable in cytological and histological samples. The aim of this study was to re-evaluate the galectin-3 expression in a large sample of thyroid lesions using an immunohistocytochemical biotin-free detection system and a specific anti-human-galectin-3 monoclonal antibody in order to avoid the interference of technical factors, a cause of conflicting results recently reported by some authors. We analysed galectin-3 expression of 39 follicular carcinomas, 26 papillary carcinomas, and 105 adenomas in both cell-block samples and their histological counterparts. All cell-block and histological papillary carcinoma samples showed high levels of galectin-3 immunoreactivity. Thirty-four follicular carcinomas were positive, whereas 5 were negative in cell-blocks but positive in their histological counterparts. Twelve out of 105 adenomas expressed galectin-3 in cell-blocks and histological samples. The diagnostic accuracy of preoperative galectin-3 evaluation in adenomas vs follicular carcinomas was 90.0%. Galectin-3 expression was also investigated in 22 minimally-invasive follicular carcinomas. All of them showed galectin-3 immunoreactivity in both cytological and histological specimens with the exception of two cases, where galectin-3 positivity was observed only in the surgical material. The routine correct use of galectin-3, by increasing the diagnostic accuracy of conventional cytology, improves the management of thyroid nodules and can lead to a sensitive reduction of useless thyroid surgeries.