Mapping Thyroid Changes in Size and Position During Enlargement in Adult Mice With Hyperthyroidism.

The thyroid in Graves' disease undergoes a considerable divergence in size and position from the normal anatomy. However, knowledge of the pathological anatomy related to the change, which is required before planned surgical or local intervention, or diagnosis, is neglected. To investigate Graves' disease, we established a model of mice that successfully mimicked all the signs presented in the clinic. Under a long-term immunization (35 weeks), the animals displayed large heterogeneity in thyroid size, such as the cases of natural occurrence. These thyroids in the model were sized into various phases and registered. A blend of the registered thyroids and the thyroid and tracheal cartilage landmarks led to the production of site-dependent incidence graphs of thyroid in the front view and on the section for each phase. The merger of the incidence graphs of all the phases resulted in thyroid phase-dependent topography. The depicted graphs illustrate the fine localization of the thyroid in various sizes and their dynamic changes during enlargement, which may facilitate currently used fine-needle aspiration biopsy and ultrasonography-guided biopsy techniques. Familiarity with this knowledge might avoid misclassifying an abnormality as normal, or vice versa, and be helpful for imaging diagnosis and local surgery therapy in Graves' disease.

Canine follicular cell and medullary thyroid carcinomas: Immunohistochemical characterization.

Research on modulation of iodine uptake by thyroid cells could help improve radioiodine treatment of dogs with thyroid tumors. The aim of this study was to characterize the immunohistochemical expression of thyroid transcription factor-1 (TTF-1), thyroglobulin, thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, thyroid peroxidase (TPO), vimentin, and Ki-67 in follicular cell thyroid carcinomas (FTCs) and medullary thyroid carcinomas (MTCs), and to compare protein expression between FTC causing hyperthyroidism and FTC of euthyroid dogs. Immunohistochemistry was performed in 25 FTCs (9 follicular, 8 follicular-compact, and 8 compact) and 8 MTCs. FTCs and MTCs were positive for TTF-1, and expression was higher in FTCs of euthyroid dogs compared with FTCs of hyperthyroid dogs (P= .041). Immunolabeling for thyroglobulin was higher in follicular and follicular-compact FTCs compared with compact FTCs (P = .001), while vimentin expression was higher in follicular-compact FTCs compared with follicular FTCs (P = .011). The expression of TSHR, NIS, pendrin, and TPO was not significantly different among the different subtypes of FTCs or between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. TSHR, NIS, pendrin, and TPO were also expressed in MTCs. Ki-67 labeling index was comparable between FTCs and MTCs, and between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. Proteins of iodine transport were also expressed in canine MTCs, which could have implications for diagnosis and treatment. The different expression of thyroglobulin and vimentin between FTC histological subtypes could reflect variations in tumor differentiation.

Incidence and Risk Factors of Thyroid Malignancy in Patients with Toxic Nodular Goiter.

Background: Although hyperfunctioning thyroid disorders were thought to be protective against malignancy, some recent studies reported a high incidence of incidentally discovered cancer in patients with hyperfunctioning benign thyroid disorders. We performed this study to estimate the incidence and predictors of malignant thyroid disease in patients with toxic nodular goiter (TNG). Patients and Methods. The data of 98 patients diagnosed with TNG were reviewed (including toxic multinodular goiter SMNG and single toxic nodule STN). The collected data included patients age, gender, systemic comorbidities, family history of thyroid malignancy, previous neck radiation, type of disease (multinodular or single), size of the dominant nodule by the US, operative time, and detection of significant lymph nodes during operation. Based on the histopathological analysis, the cases were allocated into benign and malignant groups. Results: Malignancy was detected in 21 patients (21.43%). Although age distribution was comparable between the two groups, males showed a significant increase in association with malignancy. Medical comorbidities and family history of cancer did not differ between the two groups. However, TMNG showed a statistically higher prevalence in the malignant group. Operative data, including operative time and lymph node detection, were comparable between the two groups. On regression analysis, both male gender and TMNG were significant predictors of malignancy. Conclusion: The presence of thyroid hyperfunction is not a protective factor against malignancy, as malignancy was detected in about 1/5 of cases. Male gender and TMNG were significant risk factors of malignancy in such patients.

N-Acetylcysteine and Safranal prevented the brain damage induced by hyperthyroidism in adult male rats.

Background: Hyperthyroidism is associated with impairment in the neurotransmission and severe tissue damage in the brain. The present study explored the potential deleterious effects of experimentally-induced hyperthyroidism on the neurotransmitters, oxidative homeostasis, apoptosis and DNA fragmentation in cerebral cortex, thalamus & hypothalamus, and hippocampus in rats.Methods and Results: The ameliorative effects of N-acetylcysteine (NAC; 50 mg/kg, oral) and safranal (50 mg/kg, intraperitoneal) against hyperthyroidism (L-T4 500 µg/kg, subcutaneous) were investigated. All treatments continued daily over three weeks. Hyperthyroidism was manifested by significant elevations in serum fT3 and fT4 levels and a decline in serum TSH level and body weight. It was also characterized by significant elevations in the levels of dopamine, serotonin, and 5-hydroxyindole acetic acid, and monoamine oxidase activity to varying degrees in the brain regions examined and a significant reduction in norepinephrine in hippocampus only. Hyperthyroidism resulted in a significant oxidative stress in brain typified by elevations in malondialdehyde and nitric oxide content and reductions in glutathione level and SOD and catalase activities. This led to elevations in Caspases 9 and 3 and a reduction in Bcl2 resulting in DNA damage and confirmed by the histopathology of brain tissue. The administration of NAC or safranal with L-T4 prevented these deleterious effects by reducing the oxidative load and improving the brain antioxidant status.Conclusions: Hyperthyroidism disrupted the neurotransmitters in the brain which aggravated the oxidative stress and resulted in apoptosis. N-Acetylcysteine and safranal prevented these deleterious effects by enhancing the poor antioxidant milieu of the brain.

Relapse of Human Chorionic Gonadotropin-Induced Hyperthyroidism and Severe Hyperemesis Gravidarum Secondary to Twin-Twin Transfusion Syndrome, With Rapid Recovery Following Fetoscopic Laser Coagulation: Case Report.

Background: Limited data have shown that, compared to uncomplicated twin pregnancies, pregnancies complicated by twin-twin transfusion syndrome (TTTS), a life-threatening condition, are associated with higher maternal serum levels of both human chorionic gonadotropin (hCG) and thyroid hormones. With the continuing expansion of assisted reproductive technologies, the rate of twin pregnancies, including those complicated by TTTS and associated hyperemesis gravidarum, is expected to increase further. Therefore, detailed descriptions of the maternal and fetal clinical outcomes of maternal thyrotoxicosis linked to TTTS can be useful for timely diagnosis and management. However, such descriptions are currently lacking in the literature. Case Presentation: We report the case of a 30-year-old woman carrying a monochorionic twin pregnancy complicated by TTTS that induced a relapse of severe hyperemesis gravidarum with overt non-autoimmune hyperthyroidism at 17 weeks of gestation. Following fetoscopic laser coagulation (FLC), both hyperemesis and hyperthyroidism improved within 1 week. Conclusions: The present experience contributes to the knowledge base on maternal thyrotoxicosis linked to TTTS and can be useful in the diagnosis and treatment of future cases; it also emphasizes the need for a high degree of clinical suspicion and for close collaboration between endocrinologists and obstetricians. Another key point is that TTTS-associated hyperemesis gravidarum and maternal hyperthyroidism should be considered in the differential diagnosis of refractory or relapsing hyperemesis gravidarum in women with monochorionic twin pregnancy, because this condition may require more stringent supportive treatment before and during the FLC procedure when the mother is overtly hyperthyroid.

Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Because subclinical hyperthyroidism increases the risk of osteoporosis and fractures, concerns are growing about the long-term skeletal safety of TSH suppression therapy after total thyroidectomy in patients with differentiated thyroid cancer (DTC). OBJECTIVE: We aimed to determine the effect of TSH suppression therapy on bone mineral density (BMD) in DTC patients. METHODS: We searched PubMed, Embase, the Cochrane library, and other sources. Eligible observational studies included DTC patients who underwent TSH suppression therapy and BMD measurement. Two independent reviewers extracted data on the studies' characteristics and outcomes and determined their risk of bias. Data were extracted from each study for postmenopausal/premenopausal women's and men's lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD and summed using a random-effects meta-analysis model. The weighted mean differences with 95% CIs are expressed for the differences in outcome measurements between groups. RESULTS: Seventeen studies (739 patients and 1085 controls) were included for quantitative analysis. In postmenopausal women, TSH suppression therapy showed a significant decrease in LS BMD (-0.03; -0.05, -0.02), and a similar trend was seen in TH. In premenopausal women, TSH suppression therapy significantly increased LS BMD (0.04; 0.02, 0.06) and FN BMD (0.02; 0.01, 0.04). In men, there was no significant association between TSH suppression therapy and BMD at any site compared with the controls. CONCLUSION: Evidence from observational studies suggests that postmenopausal women treated with TSH suppression therapy are at risk for lower BMD. Attention should be paid to long-term skeletal safety in DTC survivors.

Hyperthyroidism is associated with breast cancer risk and mammographic and genetic risk predictors.

BACKGROUND: Despite the biological link between thyroid hormones and breast cancer cell proliferation shown in experimental studies, little is known about the association between hyperthyroidism and breast cancer, as well as its association with the most common mammographic and genetic risk predictors for breast cancer. METHODS: This study estimates the incidence rate ratios (IRRs) of breast cancer among women diagnosed with hyperthyroidism, compared to those who are not, using two cohorts: a Swedish national cohort of the general female population (n = 3,793,492, 2002-2011) and the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA, n = 69,598, 2002-2017). We used logistic regression to estimate the odds ratios (ORs) of hyperthyroidism according to the mammographic and genetic risk predictors for breast cancer. RESULTS: An increased risk of breast cancer was observed in patients in the national cohort with hyperthyroidism (IRR = 1.23, 95% CI = 1.12-1.36), particularly for toxic nodular goiter (IRR = 1.38, 95% CI = 1.16-1.63). Hyperthyroidism was associated with higher body mass index, early age at first birth, and lower breastfeeding duration. Higher mammographic density was observed in women with toxic nodular goiter, compared to women without hyperthyroidism. Additionally, among genotyped women without breast cancer in the KARMA cohort (N = 11,991), hyperthyroidism was associated with a high polygenic risk score (PRS) for breast cancer overall (OR = 1.98, 95% CI = 1.09-3.60) and for estrogen receptor-positive specific PRS (OR = 1.90, 95% CI = 1.04-3.43). CONCLUSION: Hyperthyroidism is associated with an increased risk of breast cancer, particularly for patients with toxic nodular goiter. The association could be explained by higher mammographic density among these women, as well as pleiotropic genetic variants determining shared hormonal/endocrine factors leading to the pathology of both diseases.

Evaluating Hyperthyroidism-Induced Liver Injury Based on In Situ Fluorescence Imaging of Glutathione and Phosphate via Nano-MOFs Sensor.

Hyperthyroidism-induced liver injury is quite common in clinical settings. Therefore, developing rapid and simple methods for the assessment of hyperthyroid liver injury is of great significance. Considering phosphorus metabolism is disordered because of hyperthyroidism, and the hyperthyroid liver injury is closely related to the abnormal level of glutathione (GSH). Thus, development of a new method that can simultaneously detect changes in blood phosphorus and GSH levels of serum, liver, kidney, and other organs to assess the degree of hyperthyroid liver injury is necessary for clinical medical research. Herein, a novel fluorescent metal-organic frameworks (MOFs) nanoprobe using the UiO-66(OH)2 as core and Cu-MOFs as shell was designed and synthesized. Through the specific action between Zr (IV) and phosphate, and the combine interaction of MOFs active center Cu (II) and GSH, high sensitivity and specific fluorescence detection of phosphate and GSH were achieved, respectively. Finally, the nanosensor was applied for evaluating different degrees of hyperthyroid liver injury in mice models and realized the monitoring of serum, liver, kidney, and other organs' blood phosphorus and GSH levels, and found that the levels of phosphate and GSH in serum were negatively correlated with the degree of hyperthyroid liver injury, while the changes of phosphate and GSH levels in the liver and kidney organs were positively correlated with the degree of hyperthyroid liver injury. In general, the present works provide a new way to effectively evaluate liver injury induced by hyperthyroidism in the early clinical stage.

[Hereditary predispositions to follicular thyroid tumors]. / Prédispositions héréditaires aux tumeurs thyroïdiennes de souche folliculaire.

Familial thyroid cancers of follicular origin are rare and include syndromic and non-syndromic tumours. In familial adenomatous polyposis, the prevalence of papillary thyroid cancer is 2-12% and in 20-40% of cases it is a cribriform-morular papillary thyroid carcinoma. Morules and cribriform pattern are the two main typical criteria, associated with a nuclear and cytoplasmic immunopositivity for beta catenin. DICER1 syndrome is associated with pleuropneumoblastoma, ovarian tumors and thyroid pathology (multinodular goiter and less frequently a well-differentiated thyroid cancer without microscopic particularity). Cowden syndrome is characterized by multiple hamartomas and two-thirds of patients develop thyroid pathology, including multinodular goiter (50-67%) and cancer (35%), the latter being one of the major diagnostic criteria of the syndrome. Classic triad of Carney complex associates lentiginosis, myxoid tumors, and various endocrine abnormalities; thyroid pathology occurs in 10% of cases and may be benign or malignant. In Werner's syndrome, thyroid cancer is present in 18% of cases. McCune-Albright syndrome is characterized by fibrous dysplasia, café-au-lait spots and various endocrinopathies including hyperthyroidism and nodular hyperplasia. Non-syndromic thyroid cancers, which represent the majority of familial cancers, are most often papillary carcinomas. In daily practice, in the presence of multiple benign thyroid nodules and/or thyroid cancer in a young person, or with family thyroid diseases, the pathologist should be aware about hereditary predispositions to propose an oncogenetic consultation.

Quercetin alleviates hyperthyroidism-induced liver damage via Nrf2 Signaling pathway.

Quercetin is a plant flavonoid and has antioxidative properties. In this study, we evaluated the therapeutic effect of quercetin on thyroid dysfunction in L-thyroxin (LT4)-induced hyperthyroidism rats. LT4 was used to prepare the experimental hyperthyroidism model via the intraperitoneal injection. Quercetin was injected at a series doses (5, 50, and 100 mg/kg) to LT4-induced hypothyroidism rats once a day for 14 days. The body weight and food intake were measured once a week. The levels of thyroid hormones, liver function, oxidative stress markers, and antioxidant markers were measured using commercial enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the thyroid tissue histological changes. The levels of nuclear and total nuclear factor erythroid 2-related factor 2 (Nrf2) were determined by western blot. The liver oxidative stress markers in LT4-induced hyperthyroidism Nrf2 knockout rats were determined to evaluate the role of Nrf2 on quercetin induced protective effects. LT4 administration increased the levels of serum triiodothyronine and thyroxine, activity of oxidative stress markers with a parallel decrease in antioxidant markers and Nrf2. However, the simultaneous administration of quercetin, reversed all these effects indicating its potential in the regulation of hyperthyroidism. Furthermore, the loss function of Nrf2 diminished these effects resulting from the quercetin application, indicating the inhibitory effects caused by the quercetin may be involved in Nrf2 signaling pathway. These results indicate that quercetin could be used to protect against experimental hyperthyroidism-induced liver damage via Nrf2 signaling pathway.

Radioiodine therapy and Graves' disease - Myths and reality.

INTRODUCTION: Autoimmune reactions in Graves' disease (GD) occur not only in the thyroid gland, but also in the orbital connective tissue, eyelids, extraocular muscles. The occurrence of orbitopathy in the course of GD is influenced by environmental factors, e.g. cigarette smoking. OBJECTIVES: The aim of the study was to analyze the effect of cigarette smoking on the efficacy of activity of radioiodine(131I) therapy in patients with GD. We also studied the influence of cigarette smoking and the efficacy of prednisone prophylaxis on the risk of thyroid-associated ophthalmopathy (TAO) development after radioiodine therapy (RIT) during two years of follow-up. PATIENTS AND METHODS: Medical records of hyperthyroid patients treated with radioiodine had been included. Patients were scheduled to visit outpatient clinics at baseline and 1, 3, 6, 9, 12, 18, and 24 months after RIT. RESULTS: The studied group consisted of 336 patients (274 women, 62 men) diagnosed with GD and treated with RIT; 130 patients received second therapeutic dose of 131I due to recurrent hyperthyroidism. Among all studied patients, 220 (65.5%) were smokers and 116 (34.5%) non-smokers. In the group of smokers 115 (52.2%) of patients received single RIT, 105 (47.8%) received second dose of RAI due to recurrent hyperthyroidism. In non-smokers 91 (78.6%) received single activity of RAI, while 25 (21.4%) patients required second RIT due to recurrent hyperthyroidism. The ophthalmic symptoms in the group of smokers after RIT were less frequent, if the patient received preventative treatment in the form of oral prednisone (P = 0.0088). CONCLUSIONS: The results of our study suggest that cigarette smoking reduces the efficacy of treatment with 131I in patients with GD. The study also confirmed the effectiveness of steroid prophylaxis against TAO development or exacerbation after RIT.

Immune checkpoint inhibitor-associated thyroid dysfunction: a disproportionality analysis using the WHO Adverse Drug Reaction Database, VigiBase.

OBJECTIVE: Our study aimed to identify and characterize thyroid dysfunctions associated with immune checkpoint inhibitors (ICIs). DESIGN: Data were obtained from VigiBase, between January 1, 2011 to March 6, 2019. METHODS: All thyroid drug-adverse events are classified by group queries according to the Medical Dictionary for Regulatory Activities. Information component (IC) and reporting odds ratio (ROR) were considered as measures of disproportionality for the assessment of association between ICIs and thyroid dysfunctions. We used IC to identify meaningful drug-adverse events while using ROR to compare differences in the reporting of drug-adverse events caused by different ICI subgroups. Positive IC values are deemed significant. RESULTS: Compared with the full database, the following ICI-associated thyroid dysfunctions were over-reported: hypothyroidism (1125 reports for ICIs vs 12495 for all drugs; Information Component 4.28 (95% CI: 4.18-4.35)), hyperthyroidism (926 vs 7538; 4.66 (95% CI: 4.55-4.74)), thyroiditis (294 vs 1237; 5.40 (95% CI: 5.21-5.54)), thyrotoxic crisis (11 vs 288; 3.55 (95% CI: 2.61-4.20)). Hypothyroidism was over-reported for patients treated with ICI combination therapy versus those treated with ICI monotherapy (ROR 1.3 (95% CI: 1.1-1.7)), and the same was observed for hyperthyroidism (ROR: 1.9 (95% CI: 1.5-2.4)), thyroiditis (ROR: 3.3 (95% CI: 2.3-4.8)), thyrotoxic crisis (ROR: 11.5 (95% CI: 2.4-53.8)). All 11 thyrotoxic crisis cases were malignant melanoma patients, of which seven occurred under ICI combination therapy. CONCLUSIONS: Thyroid dysfunction may occur after ICI therapies, and severe thyrotoxic crisis may even occur. Raising awareness of ICI-associated thyroid dysfunction can improve the detection and treatment of these diseases.

Evaluation of ultrasonographical and cytological features of thyroid nodules in patients treated with radioactive iodine for hyperthyroidism.

BACKGROUND: In this study, we aimed to evaluate ultrasonographical and cytological features of thyroid nodules in patients who were treated with radioactive iodine (RAI) for hyperthyroidism years ago. METHODS: Patients who had a history of RAI treatment for hyperthyroidism and had thyroid nodules that were evaluated with fine-needle aspiration biopsy (FNAB) were included in the study. RESULTS: There were 27 patients (22 female and 5 male) with a mean age of 59.3 ± 13.5. The indication for RAI treatment was Graves in 5 (18.6%), toxic nodular or multinodular goiter in 16 (69.2%), and unknown in 6 (22.2%) patients. A total of 48 thyroid nodules were evaluated with FNAB and cytological diagnosis were benign in 24 (50.0%), nondiagnostic in 15 (31.2%), atypia of undetermined significance in 5 (10.4%), suspicous for malignancy in 2 (4.2%), and malignant in 2 (4.2%) nodules. Thyroidectomy was performed in 10 patients, 5 were benign (50.0%), and 5 (50.0%) were malignant histopathologically. Ultrasonography features of 31 cytologically/histopathologically benign and five cytologically/histopathologically malignant nodules were compared. Prevalence of isoechoic nodules was higher in benign nodules (P = .025). Macrocalcification was observed in 4 (80.0%) of malignant and 10 (32.3%) of benign nodules (P = .042). CONCLUSION: In patients with a history of RAI treatment for hyperthyroidism, thyroid nodules with suspicious ultrasonography features, particulary hypoechoic appearence and macrocalcification, should be evaluated with FNAB irrespective of the time elapsed after RAI treatment.

Can we predict expected adenoma weight preoperatively with reference to the correlation of preoperative biochemical tests with parathyroid adenoma weight?

BACKGROUND: Primary hyperparathyroidism is a prevalent disease with proven benefits for appropriately selected patients who undergo parathyroidectomy. The ability to accurately predict expected single adenoma gland weight as the cause based on preoperative biochemical tests could improve cure rates in a minimally invasive approach. OBJECTIVE: To assess the correlation between parathyroid weight and preoperative parathyroid hormone and calcium levels in patients with primary hyperparathyroidism with a solitary adenoma and determine if these could be used to predict expected parathyroid weight. METHODS: Patients with primary hyperparathyroidism who underwent curative parathyroidectomy from 2013 to 2018 was retrospectively analysed. RESULTS: There is a strong positive correlation r = 0.602 between preoperative PTH levels with respect to parathyroid weight (p < 0.001). There was a moderate correlation r = 0.474 between preoperative adjusted Calcium and PTH weight (p < 0.001). An algorithm was developed to calculate predicted weight of a single adenoma but when tested against cases with hyperplasia and double adenomas during the period, the variability of predicted weight meant it was impossible to differentiate between the causes. Hyperplasia was excluded and 95% of double adenomas excluded however, when parathyroid weight exceeded 1200 mg CONCLUSION: There is a strong correlation between preoperative PTH levels and calcium levels with parathyroid weight. The large variability of predicted parathyroid weight however, precludes the use of biochemical tests alone preoperatively in being able to differentiate between a single adenoma, double adenoma or hyperplasia as the cause in primary hyperparathyroidism. At parathyroid predicted weights above 1200 mg however, all cases of hyperplasia, and 95% of double adenomas excluded.

The impact of thyroid diseases starting from birth on reproductive function.

The aim of this review is to provide relevant information regarding the impact of thyroid disease, starting from birth and mainly concerning hyperthyroidism and hypothyroidism, on reproduction. Hyperthyroidism occurs much less commonly in children than hypothyroidism, with Graves' disease (GD) being the most common cause of thyrotoxicosis in children. Children born with neonatal GD have no defects in the reproductive system that could be related to hyperthyroidism. Current treatment options include antithyroid drugs (ATD), surgery, and radioactive iodine (RAI). In males, normal thyroid function seems important, at least in some parameters, for maintenance of semen quality via genomic or non-genomic mechanisms, either by locally acting on Sertoli cells, Leydig cells, or germ cells, or by affecting crosstalk between the HPT axis and the HPG axis. Sexual behavior may also be affected in thyroxic men, although many of these patients may have normal free testosterone levels. In women, menstrual irregularities are the most common reproduction-related symptoms in thyrotoxicosis, while this disorder is also associated with reduced fertility, although most women remain ovulatory. An increase in sex hormone-binding globulin (SHBG) and androgens, thyroid autoimmunity, and an impact on uterine oxidative stress are the main pathophysiological mechanisms which may influence female fertility. Thyroid hormones are responsible for normal growth and development during pre- and postnatal life, congenital hypothyroidism (CH) being the most common cause of neonatal thyroid disorders, affecting about one newborn infant in 3500. The reproductive tract appears to develop normally in cretins. Today, CH-screening programs allow for early identification and treatment, and, as a result, affected children now achieve normal or near-normal development. Hypothyroidism in males is associated with decreased libido or impotence. Although little is currently known about the effects of hypothyroidism on spermatogenesis and fertility, it has been established that sperm morphology and motility are mainly affected. In women of reproductive age, hypothyroidism results in changes in cycle length and amount of bleeding. Moreover, a negative effect on fertility and higher miscarriage rates has also been described.

[Hyperthyroidism as a diagnostic key to advanced choriocarcinoma. An unusual association]. / Hipertiroidismo como clave diagnóstica de un coriocarcinoma avanzado. Una asociación inusual.

Hyperthyroidism is a relatively frequent condition with multiple causes. The most common cause is Graves' disease; followed by hyperthyroid multinodular goiter and toxic adenoma. Association between hyperthyroidism and cancer is infrequent in daily practice. We present the case of a 42-year-old man who developed severe symptoms of hyperthyroidism within a period of two months. Physical examination revealed significant hepatomegaly. Testicular examination proved normal. Imaging studies showed the presence of multiple hepatic solid lesions consistent with metastases. After discarding the most common causes of hyperthyroidism and primary thyroid gland neoplasm, the possibility of molecular mimicry was considered through human chorionic gonadotrophin production. Critical high values of this hormone were found and choriocarcinoma histological diagnosis was confirmed through a liver biopsy. We consider that the recognition of this rare mechanism of hyperthyroidism may be a clue permitting a faster diagnosis, particularly when extragonadal tumors are present.

El hipertiroidismo es una condición relativamente frecuente con múltiples etiologías. La más común es la enfermedad de Graves, seguida del bocio multinodular y el adenoma tóxico. La asociación entre hipertiroidismo y cáncer es infrecuente en la práctica clínica. Presentamos el caso de un varón de 42 años con síntomas de hipertiroidismo de dos meses de evolución. Al examen físico se constató una marcada hepatomegalia de consistencia duro pétrea. El examen de testículos se reveló normal. Se llevó a cabo el diagnóstico de hipertiroidismo a través del dosaje hormonal. Los estudios por imágenes mostraron la presencia de múltiples lesiones sólidas compatibles con metástasis hepáticas. Luego de descartar las causas habituales de hipertiroidismo y las neoplasias primarias de la glándula tiroides, se consideró la posibilidad de mimetismo molecular a través de la producción ectópica de gonadotrofina coriónica humana. Se obtuvieron valores críticamente elevados de esta hormona y en un segundo tiempo se confirmó el diagnóstico histológico de coriocarcinoma a través de una biopsia hepática. Consideramos que el reconocimiento de este mecanismo poco frecuente de hipertiroidismo, puede ser una clave diagnóstica para arribar rápidamente al diagnóstico correcto, particularmente en los tumores extragonadales.

Hipertiroidismo como clave diagnóstica de un coriocarcinoma avanzado: Una asociación inusual / Hyperthyroidism as a diagnostic key to advanced choriocarcinoma. An unusual association

El hipertiroidismo es una condición relativamente frecuente con múltiples etiologías. La más común es la enfermedad de Graves, seguida del bocio multinodular y el adenoma tóxico. La asociación entre hipertiroidismo y cáncer es infrecuente en la práctica clínica. Presentamos el caso de un varón de 42 años con síntomas de hipertiroidismo de dos meses de evolución. Al examen físico se constató una marcada hepatomegalia de consistencia duro pétrea. El examen de testículos se reveló normal. Se llevó a cabo el diagnóstico de hipertiroidismo a través del dosaje hormonal. Los estudios por imágenes mostraron la presencia de múltiples lesiones sólidas compatibles con metástasis hepáticas. Luego de descartar las causas habituales de hipertiroidismo y las neoplasias primarias de la glándula tiroides, se consideró la posibilidad de mimetismo molecular a través de la producción ectópica de gonadotrofina coriónica humana. Se obtuvieron valores críticamente elevados de esta hormona y en un segundo tiempo se confirmó el diagnóstico histológico de coriocarcinoma a través de una biopsia hepática. Consideramos que el reconocimiento de este mecanismo poco frecuente de hipertiroidismo, puede ser una clave diagnóstica para arribar rápidamente al diagnóstico correcto, particularmente en los tumores extragonadales.

Hyperthyroidism is a relatively frequent condition with multiple causes. The most common cause is Graves' disease; followed by hyperthyroid multinodular goiter and toxic adenoma. Association between hyperthyroidism and cancer is infrequent in daily practice. We present the case of a 42-year-old man who developed severe symptoms of hyperthyroidism within a period of two months. Physical examination revealed significant hepatomegaly. Testicular examination proved normal. Imaging studies showed the presence of multiple hepatic solid lesions consistent with metastases. After discarding the most common causes of hyperthyroidism and primary thyroid gland neoplasm, the possibility of molecular mimicry was considered through human chorionic gonadotrophin production. Critical high values of this hormone were found and choriocarcinoma histological diagnosis was confirmed through a liver biopsy. We consider that the recognition of this rare mechanism of hyperthyroidism may be a clue permitting a faster diagnosis, particularly when extragonadal tumors are present.

Diagnosis, pathology, and management of TSH-secreting pituitary tumors. A single-center retrospective study of 20 patients from 1981 to 2014.

TSH (thyroid-stimulating hormone)-secreting tumors are the rarest type of pituitary tumor. The objective of this study was to describe initial presentation and follow-up in patients presenting TSH-secreting tumors and to characterize the pathological features, based on a cohort of 20 patients treated in our referral center, between 1981 and 2014. Most of the patients (75%) were female, aged around 50 years (mean: 50±13 years). Initial symptoms were hyperthyroidism (8/20) and/or tumor mass-related symptoms. Median time to diagnosis was 18 months. Biochemical hyperthyroidism was found in 15 patients. Most of the tumors were macroadenomas (75%) and 30% were invasive. Seventeen patients underwent transsphenoidal surgery. All tumors expressed TSH, with>50% positive cells. Eleven were monohormonal and 6 plurihormonal, expressing ßTSH plus growth hormone (GH) and/or prolactin (PRL). Both subtypes showed high expression of Pit-1 and SSTR2A somatostatin receptors. SSTR5 was slightly expressed in the plurihormonal subtype. Ki-67 index was elevated (≥3%) in only one tumor. Signs of hyperthyroidism were more frequent in the plurihormonal than in the monohormonal subtype. At final follow-up (median: 34.79±66.7 months), 75% of the patients were in complete remission after surgery; persistent hyperthyroidism was controlled by somatostatin analogs, alone (n=3) or associated to radiotherapy (n=1). The multidisciplinary approach promoted early diagnosis and control of hyperthyroidism by neurosurgical treatment, associated to somatostatin analogs or not. Clinical/pathological correlations highlighted the variations in immune profiles and in clinical and biological symptoms.

Surgical Outcome and Treatment of Thyrotropin-Secreting Pituitary Tumors in a Tertiary Referral Center.

OBJECTIVE: Thyrotropin (TSH)-secreting pituitary tumors are rare and typically present with hyperthyroidism. Here we report the diagnosis, treatment, and surgical outcomes in a series of patients with TSH-secreting pituitary tumors in a tertiary referral center. METHODS: Descriptive retrospective study that included all patients with TSH-secreting pituitary tumors who underwent transsphenoidal surgery in the endocrinology and nutrition unit of the Virgen del Rocío University Hospital (Seville, Spain) between 2004 and 2016. RESULTS: The mean age at diagnosis was 42.8 ± 17 years. The mean time from onset of symptoms to diagnosis was 13 ± 10 months. Four patients displayed symptoms indicating hyperthyroidism (1 suffered from tachycardia); 3 patients showed symptoms because of mass effect (visual impairment and headache) and 3 patients were diagnosed based on incidental findings after routine blood tests (high free thyroxine levels). Eight patients had macroadenomas, and 2 patients had microadenomas. Five patients underwent conventional pituitary surgery, and 5 patients underwent expanded endoscopic transsphenoidal surgery. Six patients achieved cure after surgery. The other patients received radiotherapy and/or treatment with somatostatin analogs. Analysis of somatostatin receptor (SSTR) expression by immunohistochemistry could be performed in 6 tumors. CONCLUSIONS: Our results confirm the clinical and hormonal heterogeneity caused by TSH-secreting pituitary adenomas. Surgery is considered the first choice of treatment for these tumors. We observed surgical cure rates similar to those reported in recent published series. SSTR2 and SSTR3 are highly expressed in TSH-secreting pituitary adenomas. Our results suggest that somatostatin analog treatment may be also helpful in the treatment of TSH-secreting pituitary adenomas.

An improved mouse model of Graves disease by once immunization with Ad-TSHR289.

The novel Graves disease (GD) model was established in BALB/c mice with recombinant adenovirus expressing the full-length human TSHR (Ad-TSHR289) by three times immunizations for nearly three months. Reducing the frequency of immunizations may shorten the modeling time to improve the efficiency of the study. In this study, female BALB/c mice were immunized one time with an adenovirus expressing the autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). At the 3, 6, 12, 17 weeks after the immunization, mice were sacrificed. The blood was collected and thyroids were removed. T3, T4, TRAB and thyroid weight/body weight (TW/BW) were tested. Compared with the Normal control (NC) group, the incidence of hyperthyroidism at 3, 6, 12 and 17 weeks after immunization were about 66.67%, 100%, 100%, and 100%. Meanwhile, the incidences of goiter were nearly 50%, 83.33%, 100% and 100% at the same stages. Therefore, modeling rates of GD were about 50%, 83.33%, 100%, 100% at 3, 6, 12 and 17 weeks after immunization. T3 in serum continues to increase from 3 weeks to 17 weeks after immunization. Serum TRAb reached to peak at 6 weeks and remained from 12 weeks after immunization, while T4 and TW/BW had kept steady from 6 weeks. There are positive correlations between T3, T4 and TRAb, TRAb and TW/BW, as well as T3, T4 and TW/BW. GD model can be constructed by primary immunization with Ad-TSHR289, which could be detected at 3 weeks and at least until the 17 weeks after primary immunization. It would improve the efficiency of GD research.