Post-translational modifications of transthyretin affect the triiodonine-binding potential.

Transthyretin (TTR) is a visceral protein, which facilitates the transport of thyroid hormones in blood and cerebrospinal fluid. The homotetrameric structure of TTR enables the simultaneous binding of two thyroid hormones per molecule. Each TTR subunit provides a single cysteine residue (Cys10 ), which is frequently affected by oxidative post-translational modifications. As Cys10 is part of the thyroid hormone-binding channel within the TTR molecule, PTM of Cys10 may influence the binding of thyroid hormones. Therefore, we analysed the effects of Cys10 modification with sulphonic acid, cysteine, cysteinylglycine and glutathione on binding of triiodothyronine (T3) by molecular modelling. Furthermore, we determined the PTM pattern of TTR in serum of patients with thyroid disease by immunoprecipitation and mass spectrometry to evaluate this association in vivo. The in silico assays demonstrated that oxidative PTM of TTR resulted in substantial reorganization of the intramolecular interactions and also affected the binding of T3 in a chemotype- and site-specific manner with S-glutathionylation as the most potent modulator of T3 binding. These findings were supported by the in vivo results, which indicated thyroid function-specific patterns of TTR with a substantial decrease in S-sulphonated, S-cysteinylglycinated and S-glutathionylated TTR in hypothyroid patients. In conclusion, this study provides evidence that oxidative modifications of Cys10 seem to affect binding of T3 to TTR probably because of the introduction of a sterical hindrance and induction of conformational changes. As oxidative modifications can be dynamically regulated, this may represent a sensitive mechanism to adjust thyroid hormone availability.

Iodine status in Turkish populations and exposure to iodide uptake inhibitors.

Perchlorate, nitrate, and thiocyanate are competitive inhibitors of the sodium iodide symporter of the thyroid membrane. These inhibitors can decrease iodine uptake by the symporter into the thyroid gland and may disrupt thyroid function. This study assesses iodine status and exposure to iodide uptake inhibitors of non-pregnant and non-lactating adult women living in three different cities in Turkey (Istanbul, Isparta and Kayseri). We measured iodine and iodide uptake inhibitors in 24-hr urines collected from study participants (N = 255). All three study populations were mildly iodine deficient, with median urinary iodine (UI) levels of 77.5 µg/L in Istanbul, 58.8 µg/L in Isparta, and 69.8 µg/L in Kayseri. Perchlorate doses were higher in the study population (median 0.13 µg/kg/day), compared with a reference population (median 0.059 µg/kg/day), but lower than the U.S. EPA reference dose (0.7 µg/kg/day). Urinary thiocyanate levels increased with increasing exposure to tobacco smoke, with non-smokers (268 µg/L) significantly lower than light smokers (1110 µg/L), who were significantly lower than heavy smokers (2410 µg/L). This pilot study provides novel data indicating that study participants were moderately iodine deficient and had higher intakes of the iodide uptake inhibitor perchlorate compared with a reference population. Further investigation is needed to characterize the thyroid impact resulting from iodine deficiency coupled with exposure to iodide uptake inhibitors such as perchlorate, thiocyanate and nitrate.

Sublingual epidermoid cyst: a case report.

Epidermoid and dermoid cysts represent less than 0.01% of all oral cavity cysts. The cysts can be defined as epidermoid when the lining presents only epithelium, dermoid cysts when skin adnexa are found, and teratoid cysts when other tissue such as muscle, cartilage, and bone are present.In this article, we present the case of an epidermoid cyst, with an oral as well as a submental component, in an 11 year old boy who presented with complaints of a mass in the oral cavity, difficulty chewing and swallowing of solid foods for about 3 years. He was admitted to the otolaryngology department. On examination, a mass displacing the tongue superiorly and posteriorly was noticed. An MRI scan was done and showed a 40 x 35 mm well-circumscribed non-enhancing cystic mass extending from the sublingual area to the level of the thyroid notch. The content of the cyst was homogenous. On examining the neck, a firm swelling was also noticed in the submental area, extending down to the thyroid notch. Under general anesthesia and with nasotracheal intubation, the patient underwent surgical removal of the mass. Extraorally, a midline submental horizontal incision was performed through the mucosa overlying the swelling and the cyst was dissected from the surrounding tissues and removed. On histological examination, acidophilic stratum corneum and basophilic dot like staining of stratum granulosum, which is the hallmark of an epidermoid cyst, were seen. The patient did well postoperatively, and no recurrence was noticed at the 6-months follow-up.

Mucopyocele of the maxillary sinus: a case report.

Mucoceles are defined as chronic, cystic lesions in the paranasal sinuses. When the mucocele content becomes infected, the lesion is defined as mucopyocele. Involvement of the maxillary sinus is rare. A 26-year-old male patient presented with left-sided facial swelling and nasal obstruction that had a history of six months. He had several episodes of sinus infections treated with antibiotics. His visual acuity was not affected. A computed tomography scan showed complete opacification of the left maxillary sinus with expansion through the medial wall of the antrum and hard palate, and thinning and destruction of the adjacent bony structures. The lesion was excised via a sublabial approach. During surgery, the cystic mass had yellowish color with foul-smelling mucopurulent material. In light microscopy, the cystic mass was diagnosed as mucopyocele.

[Iatrogenic nasal meningocele: a cause of recurrent meningitis]. / Iyatrojenik nazal meningosel: Bir reküren menenjit nedeni.

We present a 35-year-old male patient with an eight-year history of endoscopic nasal polypectomy followed by five episodes of meningitis (4 episodes in the past 3 years). His major complaints were right-sided nasal obstruction, frequent watery nasal discharge, headache, and fever. Physical examination revealed a mass in the right nasal cavity. Computed tomography and magnetic resonance imaging demonstrated a defect in the cribriform plate and an ethmoidal meningocele. The patient was referred to the neurosurgery department for surgical reparation.

Two novel mutations in the sixth transmembrane segment of the thyrotropin receptor gene causing hyperfunctioning thyroid nodules.

Autonomously functioning thyroid nodules (AFTNs) can present as hyperfunctioning adenomas or toxic multinodular goiters. In the last decade, a large number of activating mutations have been identified in the thyrotropin receptor (TSHR) gene in autonomously functioning thyroid nodules. Most have been situated close to, or within the sixth transmembrane segment and third intracellular loop of the TSHR where the receptor interacts with the Gs protein. In this study we describe two novel mutations in the sixth transmembrane segment of the TSHR causing hyperfunctioning thyroid nodules. Genomic DNAs were isolated from four hyperfunctioning thyroid nodules, normal tissues and peripheral leukocytes of two patients with toxic multinodular goiter. After amplifying the related regions, TSHR and G(s)alpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. Functional studies were done by site-directed mutagenesis and transfection of a mutant construct into COS-7 cells. We identified two novel TSHR mutations in two hyperfunctioning thyroid nodules: Phe631Val in the first patient and Iso630Met in the second patient. Both mutant receptors display an increase in constitutive stimulation of basal cyclic adenosine monophosphate (cAMP) levels compared to the wild-type receptor. This confirms that these mutant receptors cause hyperfunctioning thyroid nodules.

Endothelial function, insulin sensitivity and inflammatory markers in hyperprolactinemic pre-menopausal women.

BACKGROUND: Hyperprolactinemia has been reported to be associated with abnormalities of carbohydrate metabolism. The aim of this study was to evaluate the effects of hyperprolactinemia and bromocriptine (Brc) treatment on endothelial function, insulin sensitivity and inflammatory markers in pre-menopausal women. METHODS: Sixteen hyperprolactinemic pre-menopausal women with pituitary adenomas were recruited and 20 healthy subjects were included as controls. Patients were given Brc in doses of 2.5-20 mg/dl until normal levels of prolactin were reached. Prior to treatment and 2 months after prolactin levels were normalized, the following tests were performed. Insulin sensitivity was determined by an oral glucose tolerance test based on a formula named the insulin sensitivity index (ISI composite). Endothelial function was measured as flow-mediated dilatation (FMD) on a brachial artery using high resolution ultrasound. RESULTS: Serum glucose, insulin, estrogen, highly sensitive C-reactive protein (hsCRP), fibrinogen, homocysteine and uric acid levels were measured. Calculated ISI composite and FMD were significantly lower in the hyperprolactinemic group in comparison with the controls and improved after Brc treatment. Serum homocysteine, hsCRP and uric acid levels were significantly higher in hyperprolactinemic patients than in the controls and returned to normal levels with Brc treatment. Serum prolactin concentrations were inversely correlated with FMD measurements (r=-0.68; P<0.0001), ISI composite (r=-0.48; P<0.005) and serum estrogen (r=-0.54; P<0.005), and positively correlated with serum homocysteine concentrations (r=0.55; P<0.0001) in the hyperprolactinemic group. CONCLUSIONS: The hyperprolactinemic state is associated with impaired endothelial function and decreased insulin sensitivity, which are early markers of atherosclerosis. These alterations may predispose to the development of atherosclerosis in non-treated cases. Correction of the hyperprolactinemic state is associated with improved endothelial function and insulin sensitivity.