Congenital Pyriform Sinus Fistula: Management of an Extra-Delayed and Atypical Case.

Clinical presentations of pyriform sinus fistulas vary, and this sometimes leads to a delay in diagnosis and treatment. Recently, we experienced a case of recurrent cervical abscesses occurring after thyroidectomy in an adult affected by a bifidus pyriform sinus fistula. The diagnostic dilemma was related to the timing of events, with a single episode of acute suppurative thyroiditis having occurred 16 years before the onset of the more recent clinical scenario. An endoscopic approach allowed effective management of this clinical case.

Adjuvant mitotane treatment for adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma is a rare neoplasm characterized by a high risk of recurrence after radical resection. Whether the use of mitotane is beneficial as an adjuvant treatment has been controversial. Our aim was to evaluate the efficacy of adjuvant mitotane in prolonging recurrence-free survival. METHODS: We performed a retrospective analysis involving 177 patients with adrenocortical cancer who had undergone radical surgery at 8 centers in Italy and 47 centers in Germany between 1985 and 2005. Adjuvant mitotane was administered to 47 Italian patients after radical surgery (mitotane group), whereas 55 Italian patients and 75 German patients (control groups 1 and 2, respectively) did not receive adjuvant treatment after surgery. RESULTS: Baseline features in the mitotane group and the control group from Italy were similar; the German patients were significantly older (P=0.03) and had more stage I or II adrenocortical carcinomas (P=0.02) than did patients in the mitotane group. Recurrence-free survival was significantly prolonged in the mitotane group, as compared with the two control groups (median recurrence-free survival, 42 months, as compared with 10 months in control group 1 and 25 months in control group 2). Hazard ratios for recurrence were 2.91 (95% confidence interval [CI], 1.77 to 4.78; P<0.001) and 1.97 (95% CI, 1.21 to 3.20; P=0.005), respectively. Multivariate analysis indicated that mitotane treatment had a significant advantage for recurrence-free survival. Adverse events associated with mitotane were mainly of grade 1 or 2, but temporary dose reduction was needed in 13% of patients. CONCLUSIONS: Adjuvant mitotane may prolong recurrence-free survival in patients with radically resected adrenocortical carcinoma.

Cushing's syndrome in a patient with bilateral macronodular adrenal hyperplasia responding to cisapride: an in vivo and in vitro study.

Cortisol secretion in adrenal Cushing's syndrome can be regulated by aberrant hormone receptors, such as gastric inhibitory polypeptide, V1 vasopressin, catecholamines, LH/human chorionic gonadotropin, and serotonin receptors. We report the case of a patient with Cushing's syndrome due to bilateral adrenal macronodular hyperplasia. Extensive in vivo testing for the presence of aberrant receptors revealed a 5-fold increase of plasma cortisol after the administration of cisapride, an agonist of the serotonin 4 (5-HT(4)) receptor. Primary cell cultures were established from adrenocortical specimens obtained at surgery, and in vitro studies also showed that cisapride determined an increase [133.7 +/- 5.5% (mean +/- SE) of baseline, considered 100%) of cortisol secretion from cultured cells. The presence of 5-HT(4) receptor transcript, and in particular of isoforms c, g, and n, was confirmed by RT-PCR, and the determination of the mRNA levels by real-time RT-PCR revealed a higher expression than in normal adrenal glands. To our knowledge, this is one of the first reports of Cushing's syndrome in which cortisol secretion is regulated mainly by the 5-HT(4) receptor, among known aberrant receptors. In addition, it is noteworthy that hypocortisolism ensued after the removal of the most enlarged adrenal gland, but the in vivo response to cisapride persisted.

Expression of cAMP response element-binding protein and sodium iodide symporter in benign non-functioning and malignant thyroid tumours.

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 cAMP-dependent 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 (n=18) and carcinomas (n=20), 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 (4.63+/-0.89 vs 9.51+/-2.01 pg/microg total RNA, means+/-s.e., P=0.025). 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.

Expression of cAMP-responsive element binding protein and inducible cAMP early repressor in hyperfunctioning thyroid adenomas.

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)alpha 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)alpha 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=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.