Changes of Nicotinamide Phosphoribosyltransferase Expressions in Thyroid Glands of Patients with Different Thyroid Pathologies.

PURPOSE: Our aim was to analyze NAMPT expression in thyroid tissue derived from patients with Graves' disease with (GD) and without (GO) orbitopathy, patients with toxic nodular goiters (TNG) and thyroid cancers (TC), and healthy controls. METHODS: 153 thyroid tissue samples of consecutive patients who underwent thyroidectomy were collected. Previous therapy with steroids was an exclusion criterion. We collected clinicopathological data of all subjects and we assessed NAMPT expression using qPCR. RESULTS: We found the highest NAMPT expression in the thyroids of patients with GO (n = 20) and cancers (n = 40). Also, there was statistically significant NAMPT overexpression in patients with TNG (n = 30). Relatively low NAMPT expression was found in GD patients (n = 21) and in the control group (n = 39). In one-way ANCOVA, we confirmed that NAMPT expression differs between subgroups and that it is not influenced by age, BMI, or sex of patients. CONCLUSIONS: Reported alteration of NAMPT expression might suggest its involvement in thyroid pathologies. Observed NAMPT overexpression in patients with GO and its relatively low levels in thyroids of patients with GD without eye changes do not confirm causal relationship between NAMPT level and orbitopathy, but this needs further investigation.

The association between irisin and muscle metabolism in different thyroid disorders.

BACKGROUND: Irisin is a new adipo-myokine, encoded by the FNDC5 gene. Currently, there is a discussion regarding the relation between thyroid function and irisin concentration. This prospective study assesses the influence of thyrometabolic changes on serum irisin concentration in association with altered muscle metabolism. This is performed on a large cohort of patients affected by severe hypo- or hyperthyroidism, as well as by the expression of the FNDC5 gene in thyroid tissue affected by different pathologies. METHODS: The study group comprised 119 patients with newly diagnosed severe hyperthyroidism or hypothyroidism, and a control group of 45 healthy subjects. Body composition, serum irisin concentrations, and thyroid-related hormones, creatine kinase, dystrophin and titin concentrations were evaluated. FNDC5 expression was also analysed in tissue samples from 80 patients with nontoxic multinodular goitre, toxic goitre, Graves' disease and papillary thyroid cancer. RESULTS: Irisin concentration was lower in patients with prolonged hypothyroidism. There was a tendency towards lower dystrophin and titin concentrations in patients with hypothyroidism and hyperthyroidism. Restoration of euthyroidism in patients with hypothyroidism resulted in a decreased muscle mass with an increase in irisin concentrations, while the hyperthyroid group showed an increase in fat mass. Statistically significant overexpression of FNDC5 gene was found in patients with toxic goitre as compared to Graves' disease, papillary thyroid cancer and controls. CONCLUSIONS: The presented data support the theory that irisin concentration changes are associated with prolonged hypothyroidism and might primarily constitute the result of prolonged myopathy. These changes are most likely not related to the expression of the FNDC5 gene in the thyroid gland.

Nicotinamide phosphorybosiltransferase overexpression in thyroid malignancies and its correlation with tumor stage and with survivin/survivin DEx3 expression.

Nicotinamide phosphorybosiltransferase (NAMPT) plays an important role in the regulation of cellular growth, angiogenesis, and apoptosis in mammalian cells. NAMPT overexpression has been recently found in colorectal, breast, prostatic, gastric, esophageal, pancreatic cancers, and specific NAMPT inhibitors might be adjuvant therapeutic modalities. In this study, we analyzed NAMPT expression in 40 malignant and in 67 benign thyroid tissue samples using qPCR. We also investigated relationships between NAMPT expression and survivin/survivin splicing variants DEx3 and 2B expressions. NAMPT expression was significantly higher in thyroid cancers (P < 0.0001), and it was positively correlated with tumor stage (P = 0.0012; r = 0.493). NAMPT expression was significantly higher in tumors staged pT3 or pT4 (16 cases) than in tumors staged pT1 or pT2 (24 cases) (P = 0.0106). Metastases to the lymph nodes were found in 12 out of 40 cases, and NAMPT expression was higher in the metastatic group (P = 0.0258). Multifocality was not associated with higher NAMPT expression (P = 0.3451). NAMPT expression in thyroid cancers significantly correlated with survivin and with survivin splice variant DEx3 expressions (P < 0.0001; r = 0.624 and P = 0.0239; r = 0.357, respectively). There was no correlation between NAMPT and survivin 2B expressions (P = 0.3508). This is the first study demonstrating NAMPT overexpression in thyroid malignancies using quantitative RT-PCR. Moreover, it shows that NAMPT is upregulated in patients with more advanced tumor stage and metastatic disease which may prove to be clinically relevant. Further studies are needed to explain the role of NAMPT in thyroid cancer biology and the possible use of NAMPT inhibitors in thyroid cancer.

Alternative 3' acceptor site in the exon 2 of human PAX8 gene resulting in the expression of unknown mRNA variant found in thyroid hemiagenesis and some types of cancers.

PAX8 gene encodes one of the transcription factors engaged in the regulation of proper development of thyroid gland as well as Müllerian and renal/upper urinary tracts. So far, six alternatively spliced transcripts were reported, however, sequences of only four were deposited in the NCBI database. Here, we evaluate a fragment of a novel variant of PAX8 mRNA formed by an alternative 3' acceptor site located in the second exon. The molecular outcome encompasses extension of the 5' untranslated region of exon two by 97 nucleotides as is evident from mRNA. This new insert may impair binding of mRNA to the ribosome and in consequence significantly decrease expression of the PAX8 protein. Here, we show for the first time that the novel insert in exon two might be associated with congenital thyroid hemiagenesis and influence development of different types of cancer.

[Treatment of Fournier's gangrene]. / Leczenie zgorzeli Fournier'a.

Fournier's gangrene is a necrotizing fasciitis and soft-tissue infection of the perineal region. The clinical course of the disease, in many cases, is fulminant. This case presents a patient with symptoms of Fournier's gangrene that developed during hospitalization following a vehicular accident. The disease was diagnosed six days into hospitalization. The patient underwent numerous surgical procedures. Escherichia coli and Enterococcus faecalis were found in a culture of the surgical wound. Because of the progressing septic shock, the patient was admitted to the Intensive Care Unit. Treatment was based on extensive soft tissue debridement, antibiotic and hyperbaric-oxygen therapy. The patient was discharged 7 weeks after hospitalization.