Riedel's thyroiditis - a case report with genes' expression studies

<p>Abstract</p> <p>Background</p> <p>Genetic background of Riedel's thyroiditis remains unknown. Herein, we describe our results of studies on genes expression levels in Riedel's thyroiditis.</p> <p>Case report and genetic findings</p> <p>We report the case of 48-year old woman with Riedel's thyroiditis who has presented unusual course of disease with non-specific cervical discomfort, though as with no pain and/or no compression symptoms. After surgery, thyroid specimens were quantitatively evaluated, regarding <it>PIK3CA, PIK3CD, PIK3CG, Tg, TGFB1, THRB, COL1, CDKN1C, CDH3 </it>and <it>CACNA2D2 </it>genes expression levels, by real-time PCR in the ABI PRISM^®7500 Sequence Detection System. Out of 10 above genes, in 2 cases the expression was higher than in respective Controls of unchanged thyroid tissue. In the remaining 8 cases, expression in question became comparable or lower as in Controls.</p> <p>Discussion</p> <p>The association between increased expression levels of <it>PIK3CA </it>and <it>CDH3 </it>genes and Riedel's thyroiditis is not well-defined. However, the increased expression of <it>PIK3CA </it>and <it>CDH3 </it>genes in our case report and in previous studies of other authors on various malignancies may suggest possible molecular relation between Riedel's thyroiditis and certain neoplastic processes, the relation of which requires further genetic evaluation. It is to be stressed that gene expression studies in Riedel's thyroiditis are difficult to perform, mainly due to fibrosis, resulting in scarce thyroid specimens and - in consequence - small amount of genetic material.</p

COX-2 expression in papillary thyroid carcinoma (PTC) in cytological material obtained by fine needle aspiration biopsy (FNAB)

<p>Abstract</p> <p>Background</p> <p>COX-2 is an enzyme isoform that catalyses the formation of prostanoids from arachidonic acid. An increased <it>COX-2 </it>gene expression is believed to participate in carcinogenesis. Recent studies have shown that <it>COX-2 </it>up-regulation is associated with the development of numerous neoplasms, including skin, colorectal, breast, lung, stomach, pancreas and liver cancers. <it>COX-2 </it>products stimulate endothelial cell proliferation and their overexpression has been demonstrated to be involved in the mechanism of decreased resistance to apoptosis. Suppressed angiogenesis was found in experimental animal studies as a consequence of null mutation of <it>COX-2 </it>gene in mice. Despite the role of <it>COX-2 </it>expression remains a subject of numerous studies, its participation in carcinogenesis or the thyroid cancer progression remains unclear.</p> <p>Methods</p> <p>Twenty three (23) patients with cytological diagnosis of PTC were evaluated. After FNAB examination, the needle was washed out with a lysis buffer and the obtained material was used for <it>COX-2 </it>expression estimation. Total RNA was isolated (RNeasy Micro Kit), and RT reactions were performed. β-actin was used as endogenous control. Relative <it>COX-2 </it>expression was assessed in real-time PCR reactions by an ABI PRISM 7500 Sequence Detection System, using the ΔΔC_Tmethod.</p> <p>Results</p> <p><it>COX-2 </it>gene expression was higher in patients with PTC, when compared to specimens from patients with non-toxic nodular goitre (NTG).</p> <p>Conclusions</p> <p>The preliminary results may indicate <it>COX-2 </it>role in thyroid cancer pathogenesis, however the observed variability in results among particular subjects requires additional clinical data and tumor progression analysis.</p

Wpływ chirurgicznego leczenia rozejścia linii szwu mechanicznego u chorych po zabiegu ominięcia żołądka sposobem Roux na gospodarkę węglowodanową oraz stężenia hormonów jelitowych &#8212; badanie wstępne

Introduction: Staple-line disruption (SLD) following Roux-en-Y gastric bypass (RYGB) results in weight regain. This study evaluated glucose homeostasis and gut hormonal changes following surgical repair of gastrogastric fistula. Material and methods: Three patients with SLD underwent an oral 75 g glucose tolerance test (OGTT) before (baseline) and one week after gastric pouch restoration. Plasma glucose, insulin and glucagon glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide&#8211;1 (GLP-1) were measured in the OGTT samples. Fasting plasma levels of ghrelin and leptin were assessed. Results: Restoration of gastric pouch provided moderate amelioration of glucose metabolism and gut hormones, yet without complete normalisation of glucose homeostasis at one week after surgery. Duodenal passage exclusion resulted in early improvement of control fasting plasma glucose with decrease of glucagon from 18.5 to 15 (ng/mL, by 19%), relatively stable insulin and decline of incretin hormones (GIP and GLP-1). Post-challenge measurements confirmed amelioration of glycaemic control with decrease of plasma glucose from 182 to 158 mg/dL at 60 minutes. Surgical re-intervention resulted in exacerbation of GIP response with brisk rise in plasma level, accompanied by considerable increase of peak insulin concentration. The overall post-challenge glucagon and GLP-1 responses were decreased. Marked decrease in fasting plasma ghrelin and leptin were observed. Conclusions: Our report gives further insight into the hormonal mechanisms underlying the effects of surgically altered anatomy of different parts of the small intestine on glucose homeostasis that is highly important, since it may facilitate novel conservative therapies of diabetes without the need for surgery.Wstęp: Rozejście linii szwu mechanicznego (SLD) po operacji ominięcia żołądka sposobem Roux (RYGB) skutkuje nawrotem otyłości. W badaniu poddano ocenie zmiany gospodarki węglowodanowej oraz stężeń hormonów jelitowych po chirurgicznym leczeniu przetoki żołądkowo-żołądkowej. Materiały i metody: Trzech chorych z SLD poddano doustnemu testowi obciążenia 75 g glukozy (DTOG) przed oraz jeden tydzień po zabiegu odtworzenia proksymalnego zbiornika żołądkowego. W próbkach krwi pobranych podczas DTOG oceniano osoczowe stężenie glukozy, insuliny, glukagonu, insulinotropowego peptydu zależnego od glukozy (GIP) oraz glukagonopodobnego peptydu 1 (GLP-1). We krwi pobranej na czczo oceniano dodatkowo stężenie greliny oraz leptyny. Wyniki: Odtworzenie proksymalnego zbiornika żołądkowego prowadzi do umiarkowanej poprawy metabolizmu glukozy oraz stężeń hormonów jelitowych, jednakże bez całkowitej normalizacji homeostazy węglowodanowej w jeden tydzień od zabiegu operacyjnego. Wyłączenie pasażu dwunastniczego skutkowało wczesną poprawą kontroli stężenia glukozy na czczo, ze spadkiem stężenia glukagonu z 18,5 do 15 (ng/ml, o 19%), względnie stałym stężeniem insuliny oraz spadkiem stężeń hormonów inkretynowych (GIP i GLP-1). Pomiary dokonane po obciążeniu glukozą potwierdziły poprawę kontroli glikemii ze spadkiem osoczowego stężenia glukozy z 182 do 158 mg/dl w 60 minucie testu. Zabieg chirurgiczny skutkował nasileniem sekrecji GIP z wyraźnym wzrostem osoczowego stężenia tego hormonu po obciążeniu glukozą, z towarzyszącym znacznym wzrostem najwyższego stężenia insuliny. Całkowite stężenie glukagonu oraz GLP-1 po obciążeniu glukozą malało. Zaobserwowano znaczny spadek stężenia greliny oraz leptyny na czczo. Wnioski: Praca pozwala na dalsze poznanie mechanizmów hormonalnych leżących u podstaw wpływu chirurgicznie zmienionej anatomii różnych części jelita cienkiego na homeostazę węglowodanową. Poznanie tych mechanizmów jest bardzo istotne z punktu widzenia klinicznego, gdyż w przyszłości może przyczynić się do wprowadzenia nowych metod leczenia zachowawczego cukrzycy, bez konieczności wykonywania operacji bariatrycznych

Relative quantification of PIK3CA gene expression level in fine-needle aspiration biopsy thyroid specimens collected from patients with papillary thyroid carcinoma and non-toxic goitre by real-time RT-PCR

<p>Abstract</p> <p>Background</p> <p>Recent studies have shown that the phosphatidylinositol 3-kinase (PI3K) signaling pathway is important regulator of many cellular events, including apoptosis, proliferation and motility. PI3K pathway alterations (<it>PIK3CA </it>gene mutations and/or amplification) have been observed in various human tumours. In the majority of diagnosed cases, mutations are localized in one of the three "hot spots" in the gene, responsible for coding catalytic subunit α of class I PI3K (<it>PIK3CA</it>). Mutations and amplification of <it>PIK3CA </it>gene are characteristic for thyroid cancer, as well.</p> <p>Methods</p> <p>The aim of our study was to examine a gene expression level of <it>PIK3CA </it>in fine-needle aspiration biopsy (FNAB) thyroid specimens in two types of thyroid lesions, papillary thyroid carcinoma (PTC) and non-toxic goitre (NTG). Following conventional cytological examination, 42 thyroid FNAB specimens, received from patients with PTC (n = 20) and NTG (n = 22), were quantitatively evaluated regarding <it>PIK3CA </it>expression level by real-time PCR in the ABI PRISM^®7500 Sequence Detection System.</p> <p>Results</p> <p>Significantly higher expression level (RQ) of <it>PIK3CA </it>in PTC group has been noted in comparison with NTG group (p < 0.05).</p> <p>Conclusion</p> <p>These observations may suggest role of <it>PIK3CA </it>alterations in PTC carcinogenesis.</p

Novel Insight into Non-Genetic Risk Factors of Graves&rsquo; Orbitopathy

An assessment of the risk of Graves&rsquo; orbitopathy (GO) is an important challenge in Graves&rsquo; disease (GD) management. The purpose of this study was to compare non-genetic parameters in GD patients with and without GO in order to find novel risk factors and to verify the factors already reported. A total number of 161 people, 70 with GO and 91 non-GO patients were included in this study. GO was confirmed to be associated with smoking, older age, higher TSH receptor antibodies (TRAb) and lower thyroglobulin antibody (TgAb) levels and hypercholesterolemia. We demonstrated the latter correlation even for only a mild increase in LDL cholesterol. Importantly, our study provides novel potential GO risk factors, including higher serum creatinine levels, higher MCV and lower PLT. If further confirmed, these new, simple and easily accessible potential GO markers may constitute valuable auxiliary markers in GO risk assessments. We additionally proved that in moderate to severe GO, gender-related differences attenuate. No impact of vitamin D deficiency in GO development in patients with 25-hydroxyvitamin D [25(OH)D] &gt; 20 ng/mL was found. The present report provides a set of GO risk factors, which can be used as a precise tool for an individual GO risk assessment

Assessment of <it>RET/PTC1 </it>and <it>RET/PTC3 </it>rearrangements in fine-needle aspiration biopsy specimens collected from patients with Hashimoto's thyroiditis

<p>Abstract</p> <p>Background</p> <p><it>RET/PTC </it>rearrangements are the most frequent molecular changes in papillary thyroid carcinoma (PTC). So far, 15 main <it>RET/PTC </it>rearrangements have been described, among which <it>RET/PTC1 </it>and <it>RET/PTC3 </it>are the most common in PTC - especially in radiation-induced tumours. <it>RET/PTC1 </it>and <it>RET/PTC3 </it>are the result of intrachromosomal paracentric inversions in chromosome 10, where <it>RET </it>and the activating genes (<it>H4 </it>and <it>ELE1</it>, respectively) are located. Recently, <it>RET/PTC </it>rearrangements have been shown not only in PTC but also in benign thyroid lesions, including Hashimoto's thyroiditis (HT). The aim of study was an assessment of <it>RET/PTC1 </it>and <it>RET/PTC3 </it>rearrangements in patients with Hashimoto's thyroiditis.</p> <p>Materials and methods</p> <p>Thyroid aspirates, eligible for the study, were obtained from 26 patients with Hashimoto's thyroiditis by fine-needle aspiration biopsy (FNAB). Each aspirate was smeared for conventional cytology, while its remaining part was immediately washed out of the needle. The cells, obtained from the needle, were used in further investigation. Total RNA from FNAB was extracted by use of an RNeasy Micro Kit, based on modified Chomczynski and Sacchi's method and reverse transcription (RT-PCR) was done. Quantitative evaluation of <it>RET/PTC1 </it>and <it>RET/PTC3 </it>rearrangements by real-time PCR was performed by an ABI PRISM^®7500 Sequence Detection System. In the study, PTC tissues with known <it>RET/PTC1 </it>and <it>RET/PTC3 </it>rearrangements served as a reference standard (calibrator), while <it>β-actin </it>gene was used as endogenous control.</p> <p>Results</p> <p>Amplification reactions were done in triplicate for each examined sample. No <it>RET/PTC1 </it>and <it>RET/PTC3 </it>rearrangements were found in the examined samples.</p> <p>Conclusions</p> <p>Our results indicate that <it>RET/PTC1 </it>and <it>RET/PTC3 </it>rearrangements in Hashimoto's thyroiditis, if any, are rather rare events and further investigations should be conducted in order to determine molecular changes, connecting Hashimoto's thyroiditis with PTC.</p

The Effect of Recombinant Human TSH on Sclerostin and Other Selected Bone Markers in Patients after Total Thyroidectomy for Differentiated Thyroid Cancer

The direct effect of TSH on bone metabolism in vivo is difficult to capture as the changes of its concentrations are followed by respective alterations of thyroid hormone levels. We evaluated the effect of recombinant human TSH (rhTSH) on sclerostin and other bone markers in 29 patients after total thyroidectomy for differentiated thyroid cancer (DTC), without any signs of disease recurrence, who received L-thyroxine, most at non-suppressive doses. For two consecutive days, the patients were administered a standard dose of 0.9 mg rhTSH, i.m. Concentrations of sclerostin, osteocalcin, β-CrossLaps, PTH, and some other parameters, were measured before and five days after the first rhTSH administration. The greater the increase in TSH concentration (∆TSH), the greater the decrease in: ∆sclerostin (r = −0.672; p &lt; 0.001), ∆β-CrossLaps (r = −0.580; p &lt; 0.001) and ∆osteocalcin (r = −0.405; p = 0.029) levels, were recorded. The degree of TSH increase depended on the baseline PTH (r = 0.651; p &lt; 0.001), age, and creatinine concentrations. rhTSH strongly inhibited bone turnover, thus, TSH—independently of thyroid hormones—exerted a direct protective effect on bone metabolism. Baseline PTH affected the magnitude of TSH increase and the degree of lowering in sclerostin and β-CrossLaps that suggest factors affecting PTH may play a role in the effect of TSH on the bone

Gruczolak somatotropowy przysadki w przebiegu zespołu McCune-Albrighta u 21-letniego pacjenta, powikłany wystąpieniem raka wątrobowokomórkowego

Not required for Clinical Vignette.Pacjenci z zespołem McCune-Albrighta charakteryzują się występowaniem dysplazji włóknistej kości, plamami na skórze typu café-au-lait i/lub obwodowym przedwczesnym dojrzewaniem płciowym. Rzadziej obserwuje się nadmierne wydzielanie hormonów przysadki, tarczycy, przytarczyc czy nadnerczy. Gruczolak przysadki produkujący GH zdarza się w około 30% przypadków. W przypadku niemożliwości przeprowadzenia doszczętnego zabiegu operacyjnego, stosuje się leczenie farmakologiczne analogami somatostatyny, jednak ich skuteczność w zespole McCune-Albright nie jest optymalna. W pracy został opisany przypadek obecnie 21-letniego mężczyzny z zespołem McCune-Albrighta i gruczolakiem somatotropowym przysadki, rozpoznanym w 11 rż. Całkowite wycięcie gruczolaka nie było możliwe z powodu jego lokalizacji anatomicznej i masywnych zmian dysplazji włóknistej w kościach czaszki. Pomimo stosowania analogów somatostatyny i pegwisomantu nie udało się uzyskać kontroli wydzielania GH i IGF-1. W 21 roku życia u pacjenta stwierdzono 3,5 cm ognisko raka wątrobowo komórkowego, tj. nowotworu niezwykle rzadko spotykanego w tej grupie wiekowej. Pojawienie się tego guza może być związane z przewlekle podwyższonym stężeniem IGF-1. Przedstawiony przypadek pokazuje trudności w uzyskaniu kontroli akromegalii u osób z zespołem McCune-Albrighta i podkreśla potrzebę wzmożonej czujności onkologicznej u tych pacjentów