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Context: Growth hormone (GH) deficiency in a child with short stature is diagnosed by GH secretion provocative tests. When the test response is considered adequate, the short stature is considered idiopathic (ISS). Objective: To determine the effect of GH provocative tests on the growth rate in children with idiopathic short stature. Design: Children with short stature with a normal response to at least one GH provocative test were enrolled. Height and growth velocity were measured prior to and after stimulus tests during the follow-up. Methods: Height, mid-parental height, body weight, and body mass index were measured. The height and growth rate were converted to percentiles and Standard Deviation Scores (SDS) using reference ranges standardized by age and sex. GH provocative tests employed arginine or clonidine as secretagogues. Results: Fourty-six children of both genders were enrolled. In thirty-six children, height was measured at the time of testing and on an average time prior to and after the tests of 210 days and 180 days respectively. After testing the children displayed a 3.4-fold increase in their estimated 90-day growth rate. The median (inter-quartile range, IQR) 90 days growth of children pre-and post-tests were 0.7 (0.2–1.0) cm and 2.4 (1.7–3.1) cm respectively with a mean 3,4-fold increase (p < 0.0001). The median (IQR) 90 days growth of children pre- and post-tests calculated as standard deviation scores (SDS) were −4.0 (−5.4–−2.1) SDS and 0.1 (−1.9–1.4) SDS respectively (p < 0.0001). Ten children with ISS were observed for about 5 months before the GH provocative tests. A small increase in the growth rate was seen only in 2 out of 10 children before testing while it increased in all of them after the tests. The difference in the median growth rate at the first and the second observation was not significant (p = 0.219). Conclusions: Two sequential somatotropic axis provocative tests increase the growth rate in children with idiopathic short stature. The duration of this effect is yet to be determined. [ABSTRACT FROM AUTHOR]

Purpose: Great veins invasion is considered as a rare and prognostically unfavourable event in thyroid cancer. However, current knowledge about this issue is mainly based on single case reports. Follicular thyroid cancer (FTC) represents the histotype with the most pronounced angioinvasive feature. This study is aimed at assessing the actual prevalence of great veins invasion in FTC and providing information about prognosis and the proper clinical management of these patients.Methods: Clinico-pathological and radiological data of patients with thyroid cancer undergoing thyroidectomy in our institution were retrospectively retrieved. Inclusion criteria were as follows: (a) histological diagnosis of FTC; (b) instrumental and histological evidence of great veins invasion and (c) documented follow-up entirely performed at our institution. Pre-surgical assessment of great veins status was performed in all patients by means of Doppler ultrasonography.Results: Out of 637 patients operated from 2003 to 2013, four subjects, all affected with FTC, showed great veins involvement (0.62% of the overall cohort and 7.85% of the FTC group). One of them was lost at follow-up. All three patients with available follow-up were subjected to aggressive surgery obtaining a complete eradication of neck disease. All of them achieved the 5-year survival target (60, 63 and 96 months of survival for patients 1, 2 and 3, respectively).Conclusions: Great veins invasion may not be uncommon in FTC and preoperative detection and characterisation of such condition may optimise surgical approach and improve survival. [ABSTRACT FROM AUTHOR]

Detection of BRAF mutation in cytology specimens has been proposed as a diagnostic adjunctive tool in evaluation of thyroid nodules with indeterminate cytology findings. Concurrent papillary thyroid carcinoma and Hashimoto's thyroiditis (HT), a disease characterized by thyroid lymphocytic infiltration, is a frequent occurrence. A large lymphocytic infiltrate might reduce the sensitivity of methods employed to detect BRAF mutation in thyroid cytology specimens. To determine whether testing for BRAF mutational status in fine needle aspirates (FNA) is reliable also in the presence of HT lymphocytic infiltration, we assessed the BRAF status by direct sequencing and pyrosequencing in a series of FNAs with and without concomitant HT lymphocytic infiltration. We also performed the same assessment by pyrosequencing in the corresponding tissue samples. Pyrosequencing demonstrated to be more sensitive than direct sequencing. The percentage of mutant BRAF alleles was higher in FNAs than in the corresponding tissues, probably because of the lower stromal contamination in FNA than in the sections. In the presence of lymphocytic infiltration, the percentage of mutant BRAF alleles determined by pyrosequencing was higher in FNAs than in the corresponding tissue samples ( P < 0.0001), indicating a minor lymphocytic contamination in FNA. The diagnostic value of BRAF in inconclusive FNAs was not hampered by thyroid lymphocytic infiltration. These results indicate that BRAF assessment by pyrosequencing is a reliable assay useful to refine inconclusive cytology of thyroid nodules also in the presence of concurrent HT. [ABSTRACT FROM AUTHOR]

Radioiodide ( 131I) is routinely used for the treatment of toxic adenoma, Graves’ disease, and for ablation of thyroid remnant after thyroidectomy in patients with thyroid cancer. The toxic effects of ionizing radiations on living cells can be mediated by a necrotic and/or apoptotic process. The involvement of apoptosis in radiation-induced cell death in the thyrocytes has been questioned. The knowledge of the mechanisms that underlie the thyrocyte death in response to radiations can help to achieve a successful treatment with the lowest 131I dose. We developed a method to study the effects of 131I in human thyroid tissue in culture, by which we demonstrated that 131I induces thyroid cell apoptosis. Human thyroid tissues of about 1 mm 3 were cultured in vitro and cell viability was determined up to 3 weeks by the MTT assay. Radioiodide added to the culture medium was actively taken up by the tissues. The occurrence of apoptosis in the thyrocytes was assessed by measuring the production of a caspase-cleavage fragment of cytokeratin 18 (M30) by an enzyme-linked immunoassay. Neither variation of cell number nor spontaneous apoptosis was revealed after 1 week of culture. 131I added to the culture medium induced a dose-dependent and a time-dependent generation of M30 fragment. The apoptotic process was confirmed by the generation of caspase-3 and PARP cleavage products. These results demonstrate that 131I induces apoptosis in human thyrocytes. Human thyroid tissue cultures may be useful to investigate the cell death pathways induced by 131I. [ABSTRACT FROM AUTHOR]

The genetic alterations are responsible for the altered protein expression in tumors. The knowledge of the link between the altered protein expression and genetic alterations may provide potentially important biological and clinical information. In this study, the expression of some protein markers (Gal-3, p21Kip1, CK19) known to be associated to the papillary thyroid carcinoma (PTC) was assessed in a series of surgical samples by immunohistochemistry, and the association between expression of these markers and the BRAF mutation was investigated. Gal-3 positive staining was evident in 26 % of benign nodules. The BRAF mutation and Gal-3 expression, were found in 55.5 and 87 % of PTC respectively, and were unlinked. The expression of CK19 in benign nodules was weak and limited to scattered follicular cells. Diffuse cytoplasmatic expression of CK19 was present in malignant tumors in a variable percentage of cells. A higher percentage of CK19 expressing cells was associated with BRAF ( P ≤ 0.001). All benign nodules displayed nuclear p27kip1 in more than 15 % of the cells. Twenty-nine PTC showed a cytoplasmatic staining with negative nuclei. PTC with cytoplasmatic or 0-5 % of cells with nuclear staining, 6-15 % or >15 % of cells with nuclear staining were 72 (66.7 %), 24 (22.2 %), and 12 (11.1 %) respectively. In BRAF positive tumors, the cytoplasmatic localization of p27kip1 was significantly more frequent ( P = 0.024). In conclusion, we provide evidences that BRAF is non-associated with Gal-3 expression, whereas it is associated with cytoplasmatic localization of p27kip1 and higher CK19 expression in PTC. [ABSTRACT FROM AUTHOR]