Thyroid Hyperplasia and Neoplasm Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists in the Food and Drug Administration Adverse Event Reporting System: Retrospective Analysis.

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are one of the most commonly used drugs for type 2 diabetes mellitus. Clinical guidelines recommend GLP-1 RAs as an adjunct to diabetes therapy in patients with chronic kidney disease, presence or risk of atherosclerotic cardiovascular disease, and obesity. The weight loss observed in clinical trials has been explored further in healthy individuals, putting GLP-1 RAs on track to be the next weight loss treatment. Objective: Although the adverse event profile is relatively safe, most GLP-1 RAs come with a labeled boxed warning for the risk of thyroid cancers, based on animal models and some postmarketing case reports in humans. Considering the increasing popularity of this drug class and its expansion into a new popular indication, a further review of the most recent postmarketing safety data was warranted to quantify thyroid hyperplasia and neoplasm instances. Methods: GLP-1 RA patient reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System database were analyzed using reporting odds ratios and 95% CIs. Results: In this study, we analyzed over 18 million reports from the US FDA Adverse Event Reporting System and provided evidence of significantly increased propensity for thyroid hyperplasias and neoplasms in patients taking GLP-1 RA monotherapy when compared to patients taking sodium-glucose cotransporter-2 (SGLT-2) inhibitor monotherapy. Conclusions: GLP-1 RAs, regardless of indication, are associated with an over 10-fold increase in thyroid neoplasm and hyperplasia adverse event reporting when compared to SGLT-2 inhibitors.

Thyroid neoplasia associated with nutritional deficiency in cultured jade perch in Hong Kong.

Non-neoplastic thyroid hyperplasia is common in terrestrial animals, secondary to nutritional imbalances or other goitrogenic compounds. Thyroid hyperplasia is relatively common in teleost fish; however, malignant thyroid neoplasia is rarely reported. We diagnosed cases of thyroid neoplasia in a population of jade perch (Scortum barcoo). The 3,000 affected fish had grossly apparent, bilateral pharyngeal swellings. Histologic examination confirmed proliferative thyroid lesions ranging from hyperplasia to well-differentiated follicular cell carcinoma. In addition, the younger population of animals on the farm also had bacterial septicemia and mild Dactylogyrus sp. gill infections. Feed analysis revealed a severe deficiency of iodine and vitamin C in the homemade fish diet used on the farm. The concentrations of other minerals, such as zinc, were also on the lower end of the recommended requirements for freshwater fish. The farm was using surface water in its recirculating aquaculture system. We recommended a switch to a commercial aquaculture diet, as well as to use well water rather than surface water to avoid any contaminants, and to treat the younger fish with an antibiotic for bacterial septicemia. Our case provides evidence of progression from nutritional-associated thyroid hyperplasia to neoplasia in farmed teleost fish.

Expression of SMOC2 in papillary thyroid carcinoma and its clinicopathological significance / 临床与实验病理学杂志

Purpose To investigate the expression of SMOC2 in papillary thyroid carcinomas(PTC)and its efficacy in joint diagnosis with CK19,Galectin-3,MC and BRAF V600E.Methods Bioinformatics was uesd to analyze the mR-NA expression differences of SMOC2 in PTC and benign thyroid tissues in the Gene Expression Omnibus database and The Canc-er Genome Atlas database.Detection of SMOC2 protein expres-sion in paraffin tissue of 75 cases of PTC and 45 cases of papilla-ry thyroid hyperplasia(PTH)was used by using EnVision meth-od,combined with CK19,Galectin-3,and MC and BRAF V600E for sensitivity and specificity analysis.Results The bioinformatics analysis results showed that the mRNA expression level of SMOC2 in PTC tissue was significantly lower than that in benign thyroid tissue(P<0.05),and the area under the curve(AUC)predicted by SMOC2 for PTC diagnosis was 0.910(P<0.001).The immunohistochemical results showed that the ex-pression of SMOC2 in PTC was significantly lower than that in PTH tissue(P<0.001),and the AUC of SMOC2 for PTC diag-nosis was 0.898(P<0.001).The AUC of SMOC2 combined with CK19,Galectin-3,MC and BRAF V600E in the diagnosis of PTC was 1.000(P<0.001),and the AUC values of the combination of other markers were lower than 1.000.Conclu-sion The expression of SMOC2 in PTC is significantly de-creased,which can be used as an important marker for the diag-nosis and differential diagnosis of PTC.Combined with CK19,Galectin-3,MC and BRAF V600E,the sensitivity and specifici-ty of PTC can be improved to a certain extent.

PARAMETERS OF CENTRAL AND INTRACARDIAC HAEMODYNAMICS IN WOMEN WITH THYROID HYPERPLASIA AND ACALCULOUS CHOLECYSTITIS.

OBJECTIVE: Aim: The study aimed to investigate some parameters of functional status of central and intracardiac haemodynamics in women with thyroid hyperplasia and acalculous cholecystitis. PATIENTS AND METHODS: Materials and Methods: Functional changes of haemodynamic status in women with thyroid hyperplasia and acalculous cholecystitis were investigated. All data are obtained through general and special clinical methods, standard and special laboratory methods of examination, physiological, biochemical and statistical methods. Parameters of central and intracardiac haemodynamics have been recorded by the method of two-dimensional M-mode echocardiography in the echo chamber "Toshiba-140" (Japan) at the resting state. RESULTS: Results: An increase in heart rate (by 45.6%) was observed in patients, which led to decreased duration of cardiac cycle and ejection time. Statistically significant (p<0.05, 11.7% on average) increase in total peripheral vascular resistance was indicated. Dynamics of changes of parameters of central and intracardiac haemodynamics indicates different parallel existing pathways of secondary disturbances in the part of cardiovascular system. A significant increase in peripheral vascular resistance associated with decreased elasticity (increased vascular rigidity) of the arteries is the element of concentric type of left ventricular hypertrophy. The increase in volume in the absence of vasospastic reactions and increasing venous tone is an element of eccentric hypertrophy. CONCLUSION: Conclusions: It is possible to talk about the presence of systolic dysfunction in patients, which, however, is predominantly of functional character. The revealed specific changes in homeostatic haemodynamic characteristics in the women's body with thyroid hyperplasia and acalculous cholecystitis require the development of new, more effective and preferably drug-free (due to liver pathology and detoxification dysfunction) approaches to medical treatment of such patients.

A case of papillary hyperplasia of thyroid misdiagnosed as papillary thyroid carcinoma: Case report and review of literature.

Overdiagnosis of papillary thyroid hyperplasia which may mimic papillary thyroid carcinoma in fine-needle aspiration and frozen section has a serious impact on the patient. Therefore, it is important to know the difference between them to avoid over or undertreatment.

Effects of chronic exposure to nonylphenol at environmental concentration on thyroid function and thyroid hyperplasia disease in male rats.

The aim of this work was to determine whether chronic exposure to nonylphenol (NP), a representative substance of environmental endocrine disruptors (EEDs), at environmental concentration would have toxic effects on thyroid function and thyroid hyperplasia disease. Two hundred SPF Sprague-Dawley rats were divided into five groups (n = 40 per group): blank control group (corn oil), low-dose NP exposure group (0.4 mg/kg/d), medium-dose NP exposure group (4 mg/kg/d), high-dose NP exposure group (40 mg/kg/d), and estradiol control group (E2: 30 µg/kg/d). The rats were treated by gavage for 34 weeks, which were sampled twice (17 weeks and 34 weeks respectively). NP accumulation in the thyroid tissue (F = 52.93, P < 0.001) and serum (F = 5.54, P = 0.00) continuously increased in a significant dose-effect relationship. After NP exposure, the serum FT3 levels exhibited a dose-dependent increasing trend (F = 4.68, P = 0.01), while the serum FT4 level showed an opposite trend (F = 3.93, P= 0.01). Compared with the control group, hyperechoic areas (i.e., calcification points) were observed in the high-dose group. Follicular epithelial stratification was extremely severe, the monolayer cubic epithelial cells became flat, and the area of single follicles was even smaller in the high-dose group. In the high-dose NP group, there were numerous mitochondria that were severely swollen. The rough endoplasmic reticulum was abundant, with obvious expansion and vesiculation. The relative expression of ERα (F = 5.29, P = 0.00), ERß (F = 10.17, P = 0.00), TRα (F = 7.71, P = 0.00), TRß (F = 3.52.17, P = 0.02) and HMGB1 (F = 10.16, P = 0.01) proteins in the thyroid tissue in each NP exposure group was increased compared with the control group, and the relative expression of proteins increased if the exposure time was prolonged under the same exposure dose. Chronic exposure to NP at environmental concentration could have toxic effects on thyroid function, and induce thyroid hyperplasia disease in male rats.

Bócio em bovinos / Goiter in cattle

Bócio é o aumento não inflamatório e não neoplásico da glândula tireoide em animais adultos e recém-nascidos. Uma das principais causas envolvidas é a deficiência nutricional de iodo. Relata-se neste trabalho, a ocorrência de três surtos de bócio em bovinos. Na primeira propriedade (Propriedade A), 60 bezerros foram afetados, sendo que 20 morreram logo após o nascimento, 30 recuperaram-se e 10 permaneceram doentes e tiveram remissão dos sinais apenas após tratamento parenteral com iodo. Na segunda propriedade (Propriedade B) uma vaca e seu feto foram acometidos e na terceira (Propriedade C) dois bezerros foram afetados. Os principais sinais clínicos observados nos bezerros foram aumento de volume bilateral na região cervical ventral, emagrecimento, dificuldade respiratória, hipotricose e desenvolvimento corpóreo retardado. Na propriedade A foi relatada ainda a ocorrência de abortamentos. Macroscopicamente, os bezerros e o feto apresentavam tireoide aumentada, vermelho-escura, com vascularização evidente e edema subcutâneo cervical. No surto dois também foi observado, à necropsia, aumento de volume da glândula tireoide da vaca. Microscopicamente, a tiroide dos bezerros e do feto apresentava folículos tireoidianos hiperplásicos, heterogêneos, destituídos de coloide e com interstício acentuadamente vascularizado. A tireoide da vaca era semelhante à dos bezerros, no entanto, possuía quantidade maior de coloide. Em todos os casos a suplementação mineral era realizada por meio da mistura de sal mineral com sal branco. Na Propriedade A o sal branco era não iodado e misturado em partes iguais com o sal mineral. Na Propriedade B o sal também era misturado a um sal branco não iodado na proporção e 1:2, respectivamente. Na Propriedade C o sal mineral e o sal branco não iodado eram ofertados em cochos separados no campo e, segundo relato do proprietário, os animais priorizavam o consumo do sal branco. Em todas as propriedades acompanhadas foi recomendada a interrupção da adição de sal branco na mistura mineral e a administração de iodo aos bezerros acometidos. Após essas medidas não foram observados novos casos nas propriedades. Apesar de ser uma enfermidade bem conhecida, ainda são poucos os relatados de casos de bócios em bovinos no Brasil. Além disso, pouco se sabe sobre as reais deficiências minerais de cada região, e que simples orientações de manejo nutricional ainda são necessárias.(AU)

Goiter is a non-inflammatory and non-neoplastic enlargement of the thyroid gland in adults and neonates. One of the main causes involved is the nutritional deficiency of iodine. In this study three outbreaks of goiter in cattle are reported. In the first outbreak (Farm A) 60 calves were affected, of which 20 died soon after birth, 30 recovered and 10 remained sick. In the second outbreak (Farm B) a cow and its fetus were affected and in the third outbreak (Farm C) two calves were affected. The main clinical signs observed were bilaterally enlarged thyroid glands, weight loss, respiratory distress, hypotrichosis and myxedema. Additionally in the Farm A abortions were reported. Macroscopically the thyroid of the calves and fetus was enlarged, dark red with evident vascularization and cervical subcutaneous edema. In the Farm B the cow showed enlarged thyroid gland as well. Microscopically the calves and the fetus had hyperplastic and heterogeneous thyroid follicles with absence of colloid and vascularized interstitium. The thyroid of the cow was also hyperplastic, but had higher amount of colloid. In all outbreaks the mineral supplementation was performed by mixing non-iodized white salt with the mineral mixture. On the property A the white salt was non-iodized and mixed in equal parts with the mineral salt. At property B the salt was also mixed to a non-iodized white salt in ratio and 1:2, respectively. In the property C, mineral salt and non-iodized white salt were offered in separate troughs in the field, and according to the owner's report the animals prioritized the consumption of white salt. In all the monitored properties it was recommended to stop the addition of white salt in the mineral mixture and the administration of iodine to the affected calves. After these measurements no new cases were observed in the properties. Despite being a well-known disease, there are still few reported cases of goiter in cattle in Brazil. Moreover, little is known about the actual mineral deficiencies of each region, and that simple nutritional management guidelines are still needed.(AU)

Thyroid Follicular Hyperplasia Associated With Massive Extracellular Mucin Deposition.

Extensive extracellular mucin deposition is a rare pathological thyroid condition with 6 cases described in literature so far. We report another case of a 67-year-old woman, discussing histopathological features, and review the literature. Our findings showed a diffuse mucin deposition in the stromal compartment of thyroid parenchyma. Histochemical stainings showed positivity for Alcian blue staining, but not for periodic acid-Shiff staining. Our case is peculiar because this mucin deposition was associated with benign nodular hyperplasia, in contrast with the other 6 reports, which described the same stromal alterations associated with benign or malignant thyroid tumors.

Difference expression of CK19, CD56, p53 and its significance in PMC and papillary hyperplasia / 中国现代普通外科进展

Objective:To investigate the difference expression of CK19,CD56,p53 and its significance in PMC and papillary hyperplasia.Methods:112 cases of papillary thyroid microcarcinoma and papillary thyroid hyperplasia were selected as the experimental materials from 2013 to 2015 years,compare the expression of CK19,CD56 and p53in the tissues of PMC and PTC;To analyze the relationship between the expression of CD56 and p53 in PMC tissue and pathological parameters.The efficacy analyzed of CK19,CD56 and p53 in the differential diagnosis of PMC and PTH.Result:Expression positive rate of CK19 and p53 in PMC(100％ and 65.33％) was higher than that of PTH (32.43％ and 13.51％),CD56 expression positive rate in PMC (6.67％) was lower than that of PTH (62.16％),and the difference was statistically significant (P＜0.05).The positive rate of CK19 expression in PMC was not statistically significant difference in gender,age,lesion size,lymph node metastasis,TNM stage and differentiation degree(P＞0.05).TNM stage Ⅲll+ⅣV patients with p53 positive expression rate(79.31％) was higher than that of stage I+Ⅱ patients(26.52％)(P＜0.05),the positive rates of p53 expression in the high,middle and low differentiation degree respectively were 46.43％,72.73％,85.71％,and the positive rate of p53 expression in patients with different degree of differentiation was statistically significant (P＜0.05).The sensitivity of CK19,CD56 and p53 in the differential diagnosis of PMC and PTH were 100％,93.33％,65.33％,The specificity respectively was 67.57％,62.16％,86.49％,and the accuracy respectively was 89.29％,83.04％,72.32％;The sensitivity of CK19 was the highest,and the specificity of p53 was the highest,and the accuracy of CK19 was highest.Conlusions:The high expression of CK19 and p53 in PMC tissue,but also positive expression in PTH tissues,CD56 showed negative expression in PMC,which can be used as auxiliary indexes of CK19 and p53 in the differential diagnosis of PMC and PTH.

An outbreak of thyroid hyperplasia (goiter) with high mortality in budgerigars (Melopsittacus undulatus).

An outbreak of goiter with high morbidity and mortality in a flock of budgerigars (Melopsittacus undulatus) in California is described. Forty-five out of 400 adult birds exhibited signs of illness, weight loss, and enlargement in the crop area; 15 of the 45 birds died over a 2-3-month period. Diet consisted of a commercial mixture with the addition of broccoli, whole oats, and carrots, but no minerals or supplements. Six budgerigars were subjected to necropsy; all 6 birds had severely enlarged thyroid glands. Thyroid follicular hyperplasia was histologically observed in all birds examined, while granulomatous thyroiditis and microfollicular adenoma were observed in 2 birds, respectively. Virological, bacteriological, parasitological, and heavy metal analyses were negative or within normal limits. The total iodine in the thyroid glands of affected birds was measured by inductively coupled plasma-mass spectrometry. Following iodine supplementation and removal of broccoli from the diet, the owner reported weight gain and a reduced death rate among clinically affected birds; no additional birds became sick. The presence of broccoli with its iodine-binding ability and the complete lack of added minerals in the diet of these animals were thought to be the predisposing factors for the outbreak in the present study. Outbreaks of goiter accompanied by high mortality are rare in any species and, to the best of the authors' knowledge, have not been described previously in any avian species. Recognition of this condition may help improve medical, welfare, and trade standards concerning this species.

Pathological study of papillary thyroid carcinoma and papillary thyroid hyperplasia / 肿瘤研究与临床

Objective To study the expression of Galectin-3,CK19 and Ki-67 in the papillary thyroid carcinoma and papillary thyroid hyperplasia and to find the differential diagnostic makers. Methods A total of 200 cases, including 100 with papillary thyroid carcinoma and 100 papillary thyroid hyperplasia by Immunohistochemistry. Results The positive rates for Galectin-3,CK19 and Ki-67 in the papillary thyroid carcinoma were 100 %, 97 % and 93 %, which were significantly higher than those in the papillary thyroid hyperplasia (13 %, 31 %, 1 %) (P

Thyroid Hemiagenesis

Thyroid anomaly are rare embryological condition. The failure of the development of one lobe leading to unilateral agenesis is the rarest of all the thyroid anomalies, The cause of unilateral agenesis is unknown. Thyroid hemiagenes is common in females (3: 1) with the left lobe being absent. The common disease in the remaining lobe is a benign adenoma, a multinodular goiter, hyperthyroidism, chronic thyroiditis, and rarely carcinoma. The most common pathology involved in thyroid hemiagenesis is hyperthyroidism. This report the case of a 57-year-old woman with a right thyroid hemiagenesis.