Abstract. Objective: the aim of present study is to determine possible contributions of INF-γ inducible chemochine CXCL-10 in the thyroid color doppler ultrasound (CDU) parameters typical of autoimmune disorders. Methods: we studied a consecutive series of 25 patients with autoimmune thyroid disease and 10 healthy control subjects. All subjects underwent a thyroid CDU examination by the same investigator, who was unaware of the laboratory values at the time of the examination. Moreover, all subjects underwent a clinical evaluation, CXCL-10 and thyroid hormonal assessment. Results: CXCL-10 levels were significantly higher in patients with autoimmune diseases and as well as in subjects with an increased thyroid vascularization at CDU. Moreover, CXCL-10 levels were significantly (p<0.05) correlated with inferior thyroid arteria peak systolic velocity (ITA-PSV; r = 0.376) and with thyroid volume even after adjustment for confounding factors. No difference was observed between vascular thyroid pattern at CDU and thyroid circulating hormones while, ITA-PSV was significantly associated with TSH (Adj. r = -0.373; p<0.05). Conclusions: our data seem to suggest that CXCL-10 could play an important role in the intra-thyroid angiogenesis modulation, explaining, at least partiality, CDU findings typical of thyroid autoimmune diseases. Moreover we confirmed previous reports considering ITA-PSV as the best CDU parameters in the differential diagnosis of thyroid autoimmune disorders.

The molecular mechanisms leading to adrenocortical tumorigenesis have been only partially elucidated so far. Because the pituitary hormone ACTH, via activation of the cAMP pathway, regulates both cell proliferation/differentiation and steroid synthesis in the adrenal cortex, in this study we focused on the cAMP-dependent transcription factors cAMP responsive element modulator (CREM) and cAMP responsive element binding protein (CREB). We studied CREM and CREB expression by RT-PCR in human normal adrenal cortex (n = 3), adrenocortical adenomas (n = 8), and carcinomas (n = 8). We found transcripts corresponding to the isoforms alpha, beta, gamma, and tau2 of the CREM gene in all of the normal adrenal tissues, in the adenomas, and in seven of eight carcinomas. On the other hand, mRNA for the inducible cAMP early repressor isoforms, which derive from an internal promoter of CREM gene, was detected in the normal adrenal and in seven of eight adenomas, but in only three of eight carcinomas. Similarly, CREB transcripts were readily detectable in all normal adrenals and adenomas, whereas they were not found in four of eight adrenal carcinomas. To further characterize the carcinomas, telomerase activity and the expression of the ACTH receptor gene were determined. Telomerase activity in the carcinomas resulted in levels significantly higher than in the adenomas, whereas the levels of ACTH receptor mRNA were lower in the carcinomas. No correlation was found in the carcinomas between the levels of the ACTH receptor transcript and the loss of expression of CREB/inducible cAMP early repressor, suggesting that this alteration is not secondary to an upstream disregulation at the receptor level. In conclusion, our results suggest that an alteration in cAMP signaling may be associated with malignancies of the adrenal cortex.

Objective: Reduced expression or defective targeting of the sodium/iodide symporter (NIS) to the cell membrane in thyroid tumours has been reported. The expression of the NIS gene is up-regulated by TSH through the cAMP pathway and the characterization of the promoter region of the rat NIS gene revealed the existence of a degenerate cAMP response element (CRE) sequence. The cAMPdependent transcription factor cAMP response element-binding protein (CREB) binds to CRE acting, upon phosphorylation, as a transcriptional activator. In this study we evaluated the expression of CREB and NIS gene in thyroid non-functioning adenomas ðn ¼ 18Þ and carcinomas ðn ¼ 20Þ; as well as in the corresponding normal tissue. Methods: The levels of CREB and NIS mRNA were determined by quantitative real-time RT-PCR, whereas CREB protein (total and phosphorylated) was analyzed by Western blot. Results: The levels of CREB mRNA in thyroid carcinomas, but not in adenomas, were significantly lower than in the corresponding normal tissue ð4:63^0:89 vs 9:51^2:01 pg/mg total RNA, meansŜ .E., P ¼ 0:025Þ: CREB protein levels, which were determined in a subset of samples, were in quite good agreement with mRNA data. NIS mRNA levels did not differ in adenomas or carcinomas, compared with the corresponding normal tissue and no significant relationship with the levels of CREB mRNA was observed. Conclusions: Our results have indicated for the first time that reduced levels of CREB expression are a feature of thyroid carcinomas, and confirm that different factors are likely to modulate NIS expression.

Background. The aim of this observational study was to investigate for which nodules a better response to radiofrequency thermoablation (RFA) for nonfunctioning benign thyroid nodules is likely. Methods. Aesthetic score, compressive score, and volume of 32 benign nodules from 32 patients were registered during follow-up at baseline, 1, 3, 6, and 12 months. Results. A volume reduction rate (VRR) of 72.56% at 12 months after the procedure ( P = .009) was registered. A significant ( P < .001) improvement in the compressive and aesthetic scores was observed. Nodules with a baseline volume <20 mL had VRRs at 3 and 6 months that were significantly greater than those with volume >20 mL ( P = .037). Conclusions. RFA was shown to be a safe and effective procedure for the management of benign thyroid nodules and that there is a correlation between the initial size of the nodule and the response to treatment.

Objective: The pathogenesis of thyroid hyperfunctioning adenomas is still only partially understood and controversy exists about the frequency of gain-of-function mutations of the TSH receptor or G s a gene, which activate the cAMP pathway. The nuclear transcription factors cAMP-responsive element binding protein (CREB) and inducible cAMP early repressor (ICER) are among the final targets of this signalling cascade. Design: In our study we focused on the expression of CREB and ICER genes in the nodular as well as in the extranodular tissue of hyperfunctioning tumours of the thyroid. Methods: RT-PCR and Western blot analysis were performed in a series of 14 patients. The presence of an activating mutation of the TSH receptor or of the G s a gene was ascertained by direct sequencing. Results: The levels of CREB transcripts did not significantly differ in the adenomas and in the normal tissues (CREB/GAPDH, mean optical density^S.E.: 0:98^0:18 vs 0:88^0:27 respectively, P = not significant (N.S.)), although case-to-case variability was observed. The absence of a significant difference between the adenoma and the surrounding normal tissue was maintained after dividing the patients into two groups, according to TSH receptor status. Accordingly, no significant difference in the levels of CREB protein (total and Ser 133 -phosphorylated) was observed between the nodular and the extranodular tissue. In addition, no difference was found in the levels of ICER transcripts (ICER/GAPDH, mean optical density^S.E.: 0:52^0:11; nodule vs 0:36^0:11; normal thyroid, P ¼ N:S:), independently of the TSH receptor gene status (i.e. wild-type or mutated). Conclusions: Our results support the recent hypothesis that the activation of the cAMP pathway in hyperfunctioning adenomas of the thyroid might be counteracted by opposite events and suggest that complex molecular mechanisms might take part in the pathogenesis of hyperfunctioning tumours.