Apical bleeding: a rare cause of blindness after orbital decompression / Sangramento apical: uma causa rara de cegueira pós descompressão orbitária

ABSTRACT Orbital decompression is widely performed for the management of proptosis for cosmetic and functional cases of Graves orbitopathy. The main side effects include dry eye, diplopia, and numbness. Blindness after orbital decompression is extremely rare. The mechanisms of vision loss after decompression are not well described in the literature. Considering the devastating effect and rarity of this complication, this study presented two cases of blindness after orbital decompression. In both cases, vision loss was provoked by slight bleeding in the orbital apex.

RESUMO A descompressão orbitária é uma cirurgia amplamente empregada para correção da proptose em casos cosméticos e funcionais da orbitopatia de Graves. Os principais efeitos colaterais induzidos pela descompressão são olho seco, diplopia e parestesias. Amaurose pós descompressão é uma complicação extremamente rara e cujos mecanismos são pouco discutidos na literatura. Considerando o efeito devastador representado pela perda visual e a escassez de relatos dessa complicação, os autores apresentam dois relatos de amaurose após descompressão orbitária. Nos dois casos a perda visual ocorreu devido a sangramento de pequena monta no ápice orbitário.

Características clínico-oftalmológicas y evolución de los pacientes con oftalmopatía tiroidea activa moderada severa tratados con bolos de metilprednisolona que acuden al Hospital Central del Instituto de Previsión Social, Paraguay / Clinical-ophthalmological characteristics and evolution of patients with moderately severe active thyroid ophthalmopathy treated with methylprednisolone boluses who attended the Central Hospital of the Instituto de Previsión Social, Paraguay

Introducción: La oftalmopatía tiroidea (OT) es un trastorno debilitante en pacientes con enfermedad tiroidea autoinmune, principalmente enfermedad de Graves, que se desarrolla entre el 30 a 50% de los casos. Objetivos: Describir las características clínico-oftalmológicas y la evolución de los pacientes con oftalmopatía tiroidea activa moderada severa tratados con bolos de metilprednisolona que acuden al Hospital Central del Instituto de Previsión Social en el tiempo comprendido entre enero de 2018 y setiembre de 2021. Materiales y métodos: Investigación de diseño observacional, con estudio descriptivo, retrospectivo. Resultados: Se revisaron fichas de 34 pacientes con OT activa moderada severa que recibieron bolos de metilprednisolona basado en las guías EUGOGO 2016, de los cuáles se excluyeron 3 pacientes por tener fichas incompletas y otros 3 pacientes ya que requirieron tratamiento de segunda línea previo al término del esquema de 12 sesiones. De los 28 pacientes estudiados, la edad promedio fue de 43,6 ±13,1 años, el 89% de sexo femenino y el 28,5%, fumadores. En cuanto a la función tiroidea de la población previo al tratamiento, se constató hipertiroidismo en el 82%, hipotiroidismo en el 11% y eutiroidismo en el 7%; y posterior al tratamiento, se constató hipertiroidismo en el 78,6% (subclínico), eutiroidismo en el 17,9% e hipotiroidismo en el 3,5%. La mayoría (92.6%) contaba con anticuerpos contra el receptor de TSH positivo, con un promedio de 18 ± 9,9 mIU/Ml. Respecto a la actividad de la oftalmopatía según la escala CAS, se constató un promedio de 4,1 ±1,0 previo al tratamiento y posterior 1,2 ±1,4; de ellos el 46,4% presentó un estado leve según escala de gravedad, 39% sin criterios de gravedad y 14 % persistió en moderada -severa. Se constató mejoría de la agudeza visual tras el tratamiento (57,1%), el promedio de exoftalmía previo al tratamiento fue 22,2 mm y posterior 21,1 mm; se presentó diplopía en el 7,1% previo al tratamiento y en el 3,6% posterior al tratamiento. Conclusión: El tratamiento con glucocorticoides endovenosos en la oftalmopatía de Graves moderada-severa (esquema EUGOGO 2016) fue muy efectivo, revirtiendo la actividad y consecuentemente ayudando a disminuir la gravedad, en la gran mayoría de nuestros pacientes. Esto podría explicarse porque la oftalmopatía era incipiente y por el alto grado de adherencia de los pacientes en el contexto de un manejo multidisciplinar bien protocolizado.

Introduction: Graves' orbitopathy (GO) is a debilitating disorder in patients with autoimmune thyroid disease, mainly Graves' disease, which develops in 30 to 50% of cases. Objectives: To describe the clinical-ophthalmological characteristics and evolution of patients with moderate-to- severe active GO treated with methylprednisolone boluses who attended the Central Hospital of the Institute of Social Security between January 2018 and September 2021. Materials and methods: Observational design research, descriptive, retrospective study. Results: Records of 34 patients with active moderate-to-severe GO who received boluses of methylprednisolone based on the EUGOGO 2016 guidelines, were reviewed, of which 3 patients were excluded due to having incomplete records and another 3 patients since they required second-line treatment prior to end the 12-session scheme. Of the 28 patients studied, the average age was 43.6 ±13.1 years, 89% were female and 28.5% were smokers. Regarding the thyroid function of the population prior to treatment, hyperthyroidism was found in 82%, hypothyroidism in 11% and euthyroidism in 7%; and after treatment, hyperthyroidism was found in 78.6% (subclinical), euthyroidism in 17.9% and hypothyroidism in 3.5%. The majority (92.6%) had positive thyrotropin receptor antibodies, with an average of 18 ± 9.9 mIU/Ml. Regarding the activity of orbitopathy according to the CAS scale, an average of 4.1 ±1.0 was found before treatment and 1.2 ±1.4 after; Of them, 46.4% presented a mild condition according to the severity scale, 39% without severity criteria and 14% persisted in moderate-severe. Improvement in visual acuity was noted after treatment (57.1%), the average exophthalmia before treatment was 22.2 mm and after 21.1 mm; Diplopia occurred in 7.1% before treatment and in 3.6% after treatment. Conclusion: Treatment with intravenous glucocorticoids in moderate-severe Graves' orbitopathy (EUGOGO 2016 scheme) was very effective, reversing the activity and consequently helping to reduce the severity, in the vast majority of our patients. This could be explained because the orbitopathy was incipient and by the high degree of patient adherence in the context of well-protocolized multidisciplinary management.

Una plaga citadina peligrosa: los murciélagos / A dangerous urban pest: bats

Los murciélagos son mamíferos vertebrados presentes en la Ciudad de Buenos Aires, estimándose una población de 4 animales por habitante. Son portadores de varias enfermedades importantes y además empeoran las condiciones respiratorias de enfermos crónicos. En el campo cumplen una interesante función, ya que se alimentan de insectos perjudiciales para las siembras. El guano puede ser útil en el abono de la tierra debido al aporte de carbono y nitrógeno. En las ciudades su presencia tiene consecuencias diferentes. Se encuentran en los taparrollos de las habitaciones, así como también en todas las oquedades de muros, árboles, grietas, etc. Se exponen aquí los peligros y los cuidados que deben tenerse en la Ciudad de Buenos Aires ante la invasión de estos quirópteros. (AU)

Bats are vertebrate mammals present in the City of Buenos Aires, with an estimated population of 4 animals per inhabitant. They are carriers of several important diseases and also worsen the respiratory conditions of the chronically ill. In rural areas they fulfill an interesting function, since they feed on insects harmful to crops. Guano can be useful in soil fertilization due to its contribution of carbon and nitrogen. In cities their presence has different consequences. They are found in the roll covers of the rooms as well as in all the hollows of walls, trees, cracks, etc. The dangers and precautions to be taken in the city of Buenos Aires in the face of the invasion of these chiroptera are described here. (AU)

Manejo del paciente con Hipertiroidismo en consulta externa de la Unidad Técnica de Endocrinología del Hospital Carlos Andrade Marín / Management of the patient with hyperthyroidism in the outpatient clinic of the Technical Unit of Endocrinology of the Endocrinology Technical Unit of the Carlos Andrade Marín Hospital

El hipertiroidismo es un trastorno caracterizado por el exceso de hormonas tiroideas. El déficit de yodo es un factor clave en dicha patología y en lugares con suficiencia del mismo se asocian a au-toinmunidad tiroidea. La prevalencia de hipertiroidismo mani-fiesto varía del 0,2% al 1,3% en áreas con suficiencia de yodo, sin embargo, esto puede variar en cada país por diferencias en umbrales de diagnóstico, sensibilidad de ensayo y población se-leccionada. Un reporte de The Third National Health and Nutri-tion Examination Survey (NHANES III) mostró que el hiperti-roidismo manifiesto se presenta en 0,7% de la población general e hipertiroidismo subclínico en el 1,7%1,2.En incidencia, la patología se asocia con la suplementación de yodo, con la mayor frecuencia en áreas de deficiencias, por au-mento de nódulos tiroideos en la población anciana, teniendo a regiones de áreas montañosas como América del Sur, África Central y suroeste de Asia dentro de este grupo. Un meta aná-lisis de estudios europeos mostró una incidencia general de 50 casos por 100000 personas/años1. En Ecuador, según los datos del Instituto Nacional de Estadísticas y Censos (INEC) del 2017, se reportaron 157 casos de hipertiroidismo, de los cuales la En-fermedad de Graves (EG) fue la causa más común, seguida por el bocio multinodular tóxico (BMNT) y finalmente el adenoma tóxico (AT) con una incidencia de 61 %, 24 % y 14 % respecti-vamente3.Los pacientes con esta patología tienen aumento de riesgo com-plicaciones cardiovasculares y mortalidad por todas las causas, siendo falla cardíaca uno de sus principales desenlaces, así el diagnóstico precoz evita estos eventos, principalmente en pobla-ción de edad avanzada.El presente protocolo se ha realizado para un correcto trata-miento de esta patología en el Hospital de Especialidades Carlos Andrade Marín (HECAM).

Hyperthyroidism is a disorder characterized by an excess of thyroid hormones. Iodine deficiency is a key factor in this pa-thology and in places with iodine deficiency it is associated with thyroid autoimmunity. The prevalence of overt hyperthyroidism varies from 0,2% to 1,3% in iodine-sufficient areas; however, this may vary from country to country due to differences in diag-nostic thresholds, assay sensitivity, and selected population. A report from The Third National Health and Nutrition Examina-tion Survey (NHANES III) showed that overt hyperthyroidism occurs in 0,7% of the general population and subclinical hyper-thyroidism in 1,7%1,2.In incidence, the pathology is associated with iodine supplemen-tation, with the highest frequency in areas of deficiencies, due to increased thyroid nodules in the elderly population, having regions of mountainous areas such as South America, Central Africa and Southwest Asia within this group. A meta-analysis of European studies showed an overall incidence of 50 cases per 100000 person/years1. In Ecuador, according to data from the National Institute of Statistics and Census (INEC) in 2017, 157 cases of hyperthyroidism were reported, of which, Graves' di-sease (GD) was the most common cause, followed by toxic mul-tinodular goiter (BMNT) and finally toxic adenoma (TA) with an incidence of 61 %, 24 % and 14 % respectively3.Patients with this pathology have an increased risk of cardiovas-cular complications and all-cause mortality, with heart failure being one of the main outcomes, so early diagnosis avoids these events, mainly in the elderly population.The present protocol has been carried out for the correct treat-ment of this pathology at the Carlos Andrade Marín Specialties Hospital (HECAM).

Dolor y edema de miembros inferiores por dermopatía tiroidea: presentación inusual de la enfermedad de Graves en una paciente adolescente / Lower limb pain and edema due to thyroid dermopathy: an unusual presentation of Graves disease in an adolescent patient

La enfermedad de Graves es un proceso inmunomediado en el que autoanticuerpos se dirigen contra el receptor de tirotrofina. Por su acción estimulante sobre la glándula tiroides, se genera crecimiento glandular difuso y aumento de la hormonogénesis. Se caracteriza por el comienzo subagudo de síntomas constitucionales, neuromusculares, cardiovasculares, gastrointestinales y oculares, seguidos en algunos casos de la aparición de manifestaciones cutáneas como la dermopatía tiroidea o mixedema. En pediatría la enfermedad de Graves es infrecuente (aunque es la causa más frecuente de hipertiroidismo), pero la cronología de aparición de los síntomas está bien descrita; es rara la aparición de dermopatía en ausencia de otros síntomas de hipertiroidismo y sin afectación ocular. Se presenta el caso de una paciente de 15 años con dermopatía tiroidea por enfermedad de Graves sin oftalmopatía ni otros síntomas de hipertiroidismo clínico asociados.

Graves disease is an immune-mediated process characterized by the presence of autoantibodies to thyrotropin receptors. Its stimulating action on the thyroid gland causes diffuse glandular growth and increased hormone production. Graves disease is characterized by a subacute onset of non-specific, neuromuscular, cardiovascular, gastrointestinal, and eye symptoms, sometimes followed by skin manifestations, such as thyroid dermopathy or myxedema. In pediatrics, Graves disease is rare (although it is the most frequent cause of hyperthyroidism). However, the chronology of symptom onset has been well described; the development of dermopathy in the absence of other symptoms of hyperthyroidism and without eye involvement is rare. Here we describe the case of a 15-year-old female patient with thyroid dermopathy due to Graves disease without eye disease or other associated clinical symptoms of hyperthyroidism.

Treatment of Graves' disease in Brazil: results of a survey among endocrinologists

ABSTRACT Objective: The objective of the study was to determine how physicians in Brazil manage Graves' disease in different scenarios including extrathyroidal manifestations. Materials and methods: This study was conducted via a digital survey. The respondents (n = 573) answered multiple-choice questions based on a clinical case and variations of the case regarding laboratory and imaging evaluation, treatment choice, and follow-up. Results: The preferred initial treatment chosen by 95% of the respondents was ATD with a preferred treatment duration of 18-24 months. For 5% of the respondents, RAI was the initial treatment of choice. None of the respondents chose thyroidectomy. When presented with a patient with a desire for pregnancy in the near future, most respondents (69%) opted for ATD as the initial treatment. For a patient with signs of mild to moderate Graves' orbitopathy, ATD remained the initial therapy for 93.9% of the respondents. For patients initially treated with ATD with disease recurrence after ATD interruption, most respondents (60%) chose definitive treatment with RAI. A similar survey published in 2011 by Burch and cols. had results comparable to those of the present survey but with a higher proportion of respondents choosing RAI (45% in the 2011 survey versus 5% in the present survey). Conclusion: Brazilian endocrinologists choose ATD as the initial management of Graves' disease, and most choose RAI as a definitive treatment for a patient with relapse after ATD therapy.

Efficacy of methimazole before the administration of radioactive iodine in the management of Graves' disease: a systematic review and meta-analysis

ABSTRACT BACKGROUND: The efficacy of anti-thyroid drugs in conjunction with radioactive iodine therapy in the management of Graves' disease is still controversial. OBJECTIVE: To compare the efficacy of pretreatment with methimazole before the administration of radioactive iodine for the treatment of Graves' disease. DESIGN AND SETTING: A systematic review and meta-analysis was conducted at a teaching/tertiary hospital in Ibadan, Nigeria. METHODS: A systematic search of the PubMed, Embase, Cochrane Library, and Web of Science databases was performed from inception to December, 2021. RESULTS: Five studies with 297 participants were included. There was no difference in the risk of persistent hyperthyroidism when radioactive iodine was used in conjunction with methimazole compared with when radioactive iodine was used alone (relative risk: 1.02, 95% confidence interval, CI: 0.62-1.66; P = 0.95, I2 = 0%). Subgroup analysis based on the duration between discontinuation of methimazole and the administration of radioactive iodine showed a lower risk of persistent hyperthyroidism when methimazole was discontinued within 7 days before radioactive iodine use, although this did not reach statistical significance (risk ratio: 0.85, CI: 0.28-2.58). CONCLUSIONS: The use of methimazole before radioactive iodine administration was not associated with an increased risk of persistent hyperthyroidism. Concerns about medication toxicity and adverse effects should be considered when clinicians make decisions on combination therapies for the treatment of Graves' disease. PROSPERO REGISTRATION: CRD42020150013, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150013.

Prediction for recurrence following antithyroid drug therapy for Graves' hyperthyroidism

ABSTRACT Objective: A common problem with antithyroid drugs (ATD) treatment in patients with Graves' disease (GD) is the high recurrence rate after drug withdrawal. Identifying risk factors for recurrence is crucial in clinical practice. We hereby prospectively analyze risk factors for the recurrence of GD in patients treated with ATD in southern China. Subjects and methods: Patients who were newly diagnosed with GD and aged > 18 years were treated with ATD for 18 months and followed up for 1 year after ATD withdrawal. Recurrence of GD during follow-up was assessed. All data were analyzed by Cox regression with P values < 0.05 considered statistically significant. Results: A total of 127 Graves' hyperthyroidism patients were included. During an average follow-up of 25.7 (standard deviation = 8.7) months, 55 (43%) had a recurrence within 1 year after withdraw of anti-thyroid drugs. After adjustment for potential confounding factors, the significant association remained for the presence of insomnia (hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.47-5.88), greater goiter size (HR 3.34, 95% CI 1.11-10.07), higher thyrotrophin receptor antibody (TRAb) titer (HR 2.66, 95% CI 1.12-6.31) and a higher maintenance dose of methimazole (MMI) (HR 2.14, 95% CI 1.14-4.00). Conclusions: Besides conventional risk factors (i.e., goiter size, TRAb and maintenance MMI dose) for recurrent GD after ATD withdraw, insomnia was associated with a 3-fold risk of recurrence. Further clinical trials investigating the beneficial effect of improving sleep quality on prognosis of GD are warranted.

Acute suppurative thyroiditis with Graves disease - A very rare association

SUMMARY Acute suppurative thyroiditis is an uncommon disorder caused by a bacterial infection, usually presenting with normal thyroid function. It is a serious condition that requires a prompt diagnosis and treatment with antibiotics and supportive measures. A 62 years-old female presented with a painful cervical induration and odynophagia a week after a fish bone had been removed from her pharynx. She was febrile, and tachycardic and, on physical examination, a painful thyroid mass was detected. High inflammatory parameters and thyrotoxicosis were confirmed: thyroid stimulating hormone (TSH) < 0.01 mIU/L (normal range [NR] 0.27-4.2); free thyroxine (FT4) 3.86 ng/dL (NR 0.9-1.7) and anti-TSH receptor antibodies (TRABs) 5.3 U/L (NR < 1.5). Thyroid scintigraphy showed a diffuse uptake of the thyroid parenchyma suggesting Graves disease. Cervical ultrasonography revealed an abscess of the left thyroid lobe of 36 × 36 mm and fine needle aspiration biopsy (FNAB) with partial drainage was performed. Staphylococcus aureus and Streptococcus viridans were isolated, and directed antibiotic therapy was started. Clinical improvement was observed as well as a decrease of inflammatory parameters and the patient was discharged after 9 days of hospitalization. Eighteen days after discharge, thiamazole was initiated due to persistent thyrotoxicosis. Complete resolution of the abscess was documented within 6 months and the patient became euthyroid under thiamazole one year after initial presentation. To our knowledge, this is the third case reporting an association between acute thyroiditis and Graves disease. Furthermore, this is the first case detailing the simultaneous diagnosis of acute suppurative thyroiditis caused by a foreign body and Graves disease.

Hipertiroidismo por enfermedad de Graves posterior a vacuna contra SARS-CoV-2: reporte de 2 casos / Graves' disease hyperthyroidism following SARS-CoV-2 vaccination: a two cases report

Luego del inicio de las campañas de vacunación masiva contra la infección por COVID-19, se han publicado una serie de reportes que muestran la posible asociación entre la vacuna y alteraciones de la función tiroidea. Desde entonces, múltiples teorías han intentado explicar este hallazgo, en su mayoría de índole autoinmune. Dentro de estas destaca el síndrome autoinmune-autoinflamatorio secundario a adyuvantes (ASIA), que podría generar desórdenes tiroideos de novo o exacerbar los ya existentes. Presentamos dos casos de enfermedad de Graves Basedow posterior al uso de Coronavac. Ambas pacientes presentaron características similares a las descritas en la literatura y cumplen con los criterios de ASIA. No obstante, los beneficios de las vacunas superan los posibles riesgos asociados.

After the beginning of COVID-19 vaccination campaigns, a number of reports have shown the potential association between vaccines and thyroid disfunction. Since then several theories have tried to explain this finding, mostly autoinmmune. One of them is the autoimmune/inflammatory syndrome induced by adjuvants, that could trigger or exacerbate thyroid disease. We present two cases of Graves' disease post Coronavac vaccination. Both pacients share similar features than cases published previously and meet criteria for ASIA syndrome. Nevertheless, the benefts of vaccination largely outweigh any adverse events associated.

A case of acute cholestatic jaundice after hormone treatment of Graves disease with upper respiratory tract infection / 中国综合临床

Cholestatic jaundice is rare in patients with Graves' disease and is generally considered to be a complication of Graves' disease or an adverse reaction to methimazole. We report a case of acute cholestatic jaundice caused by Graves' disease complicated with upper respiratory tract infection in Jinan Central Hospital. After timely treatment with glucocorticoid, the jaundice quickly subsided and the liver function gradually returned to normal. We believe that Graves' disease combined with upper respiratory tract infection can lead to cholestatic jaundice, the pathogenesis of which may be immune dysfunction, and glucocorticoid therapy is beneficial to the regression of jaundice.

Association of bone resorption marker β-CTX with hypercalcemia in patients with Graves′ disease / 中国医师杂志

Objective:To explore the association of bone resorption marker β carboxyterminal peptide of collagen Ⅰ (β-CTX) with hypercalcemia in patients with Graves′ disease (GD).Methods:287 patients with GD who were hospitalized in the endocrinology department of Fuyang People′s Hospital from January 2021 to December 2021 were divided into control group ( n=251) and hypercalcemia group ( n=36) according to the corrected blood calcium level. The clinical data and serum β-CTX level of the two groups were compared. Logistic regression model was used to analyze the risk factors of hypercalcemia in GD patients. Pearson correlation was used to analyze the correlation between serum β-CTX level and other indexes. Results:Of the 287 GD patients, 36 were diagnosed as hypercalcemia, and the incidence of hypercalcemia was 12.54%. The levels of free triiodothyronine (FT3), free thyroxine (FT4), blood phosphorus (P) and β-CTX in hypercalcemia group were higher than those in control group, and the total parathyroid hormone (iPTH) in hypercalcemia group were lower than those in control group (all P<0.05). Multivariate Logistic regression analysis showed that FT3 ( OR=1.283, 95% CI: 1.049-1.570, P<0.05), iPTH ( OR=0.924, 95% CI: 0.863-0.989, P<0.05), β-CTX ( OR=2.488, 95% CI: 1.193-5.189, P<0.05) were the influencing factors for hypercalcemia in GD patients. Pearson correlation analysis showed that β-CTX was positively correlated with FT3, FT4, blood calcium, P, alkaline phosphatase (ALP), total procollagen type I amino end terminal peptide (PINP), N-bone-gamma-carboxyglutamic-acid-containing proteins (N-MID) and 25(OH)D, and negatively correlated with iPTH (all P<0.05). Conclusions:β-CTX is highly expressed in the serum of GD patients with hypercalcemia, which is a risk factor for the occurrence of hypercalcemia in GD patients.

Correlation of serum 25-hydroxyvitamin D level with Thyrotropin receptor antibody and bone metabolism markers in patients with Graves' disease / 中华临床营养杂志

Objective:To investigate the serum 25-hydroxyvitamin D [25(OH)D] level in patients with Graves' disease (GD) and its correlation with thyrotropin receptor antibody (TRAb) and bone metabolism markers.Methods:A total of 124 patients with newly diagnosed or relapsed GD were selected and divided into three groups according to serum 25(OH)D level, namely vitamin D deficiency group with 25(OH)D <12 μg/L, vitamin D insufficiency group with 25(OH)D of 12 to 20 μg/L, and vitamin D sufficiency group with 25(OH)D ≥ 20 μg/L. The levels of serum 25(OH)D, TRAb, type I procollagen N-terminal pro-peptide (PINP), type I collagen cross-linked C-terminal peptide (S-CTX), parathyroid hormone (PTH), total triiodothyronine (TT 3), total thyroxine (TT 4) and thyroid-stimulating hormone (TSH) were measured in all patients, and the differences of these biochemical indices were compared across groups. Oneway analysis of variance or Kruskal-Wallis test was used for comparison between groups, and Pearson or Spearman correlation analysis was applied for correlation test. Results:The levels of serum TT 3, TT 4, PINP, and S-CTX significantly increased ( P < 0.01) and the level of phosphorus (P) decreased ( P < 0.01) with the decreased vitamin D levels. The levels of PTH and calcium (Ca) were significantly lower in the vitamin D sufficiency group compared with the vitamin D insufficiency group and vitamin D deficiency group ( P < 0.01). Correlation analysis showed that serum 25(OH)D level was negatively correlated with the levels of TT 3, TT 4, PINP, S-CTX, PTH and Ca ( P < 0.01), and positively correlated with the levels of P and TSH ( P < 0.01). Conclusions:Decreased serum 25(OH)D level is closely related with increased bone turnover, PTH, and thyroid hormone levels in patients with GD, but not related with TRAb. Thyroid hormone levels have a certain predictive value regarding vitamin D deficiency in GD patients. It is necessary to monitor the vitamin D levels in patients with GD and provide vitamin D supplementation to reduce the incidence of osteoporosis, improve the effectiveness of antithyroid treatment and reduce the recurrence of GD.

Secretory expression of human thyroid stimulating hormone receptor A subunit in sf9 insect cell system / 西安交通大学学报(医学版)

【Objective】 To construct the secretory expression system of insect cells to express the secretory TSHR A subunit protein in the ovarian cells of Spotoma oryzae (sf9). 【Methods】 A recombinant plasmid containing the target protein was constructed, and then the positive bacmid was screened out by the blue and white spots experiment. The verified bacmid was transfected into SF9 insect cells to obtain recombinant baculovirus. The virus was amplified, and the titer level was detected by virus plaque assay. Finally, Western blotting was used to identify the expression of the recombinant protein and optimize the expression conditions. 【Results】 During the construction of the protein expression system, PCR identification and sequencing results confirmed the correctness of the sequences of the recombinant plasmid and the recombinant bacmid. After the transfection of the bacmid, the signs of virus budding were observed in sf9 cells. The virus was collected and amplified. The titer of P1 generation virus was 2×107 pfu/m according to the plaque assay. The recombinant protein was identified by Western blotting and confirmed to be exogenous into the culture medium. The optimal condition for virus infection and protein expression was 72 h after the infection when the multiplicity of infection (MOI) was 1. 【Conclusion】 We constructed an insect cell expression system secreting TSHR 22-289 (55 ku), and the protein could be successfully glycolyzed. This system provides a preliminary basis for the construction and production of its industrial platform and also provides a useful tool for studies on TSHR protein and prevention of GO in the future.

UR value of thyroid scintigraphy in differential diagnosis of thyrotoxicosis / 中华全科医师杂志

The clinical and imaging data of 99 patients with Graves′ disease, 78 patients with thyroiditis and 28 patients with other diseases (resolving thyroiditis, non thyroid disease and simple goiter) who underwent thyroid scintigraphy in Beijing Shijingshan Hospital from January 2016 to March 2022 were retrospectively reviewed. The UR value of thyroid scintigraphy was calculated and ROC curve was used to assess the UR value in diagnosis of Graves′ disease. The UR value of patients with Graves′ hyperthyroidism was significantly higher than that of patients with thyroiditis and other diseases ( H=163.62, P<0.05). UR>4.84 was taken as optimal cutoff value to diagnose Graves′ hyperthyroidism, with the sensitivity and specificity of 95.0% and 98.1%, respectively.

Inhibitory effect of phloretin on inflammation and oxidative stress in IL-1β induced orbital fibroblasts in Graves orbitopathy and its mechanism / 中华实验眼科杂志

Objective:To investigate the inhibitory effect of phloretin on inflammation and oxidative stress in interleukin (IL)-1β induced orbital fibroblasts (OFs) from Graves orbitopathy (GO) patients and its mechanism.Methods:The orbital fat and connective tissue from 6 eyes of 6 patients diagnosed as inactive GO who underwent orbital decompression in Henan Eye Hospital from January 2019 to December 2020 were collected.Primary OFs were isolated and passaged by explant culture and were identified by cell immunofluorescence assay.OFs were divided into control group, IL-1β induced group, and groups of various phloretin concentrations (25, 50, 75, 100 and 200 μmol/L). The viability of OFs after 24- and 48-hour treatment of the various phloretin concentrations was determined by cell counting kit-8 (CCK-8). OFs were induced by IL-1β to simulate an inflammatory environment of GO in vitro.Intracellular reactive oxygen species (ROS) levels of the normal control group, IL-1β induced group, 50 μmol/L phloretin group and 100 μmol/L phloretin group were detected by fluorescent probe (H 2DCF-DA). The concentrations of pro-inflammatory cytokines IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) in cell culture supernatant of the normal control group, IL-1β induced group and phloretin treated groups (25, 50, 75, and 100 μmol/L) were examined by enzyme-linked immunosorbent assay (ELISA). The expressions of heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor (Nrf2) proteins, as well as P38, extracelluar regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) proteins as well as their phosphorylated proteins in the MAPK signal pathway of the normal control group, IL-1β induced group and 100 μmol/L phloretin group, were detected by Western blot.The purpose and methods of the study were explained to the patients and their family members.Written informed consent was obtained.The study protocol was approved by the Ethics Committee of Henan Provincial People's Hospital (No.HNEECKY-2020[07]). Results:For cultured OFs, the mesenchymal origin was confirmed by positive expression of vimentin and fibroblasts were identified by negative expression of desmin, S-100 and cytokeratin-18.CCK-8 showed that there was no significant difference in absorbance value after 24- and 48-hour treatment between 25 μmol/L, 50 μmol/L, 75 μmol/L and 100 μmol/L phloretin groups and control group (all at P>0.05). The ROS levels of 50 μmol/L and 100 μmol/L phloretin groups were 21.95±1.71 and 10.01±1.03, respectively, which were significantly lower than 39.27±4.01 of IL-1β induced group (both at P<0.01). ELISA showed that IL-6 concentrations in 25 μmol/L, 50 μmol/L, 75 μmol/L and 100 μmol/L phloretin groups were (4 544.25±572.98), (1 000.25±133.96), (724.25±98.63), (519.50±118.02)pg/ml, respectively, which were all significantly lower than (7 581.75±565.93)pg/ml in IL-1β induced group (all at P<0.01). IL-8 concentrations in 50 μmol/L, 75 μmol/L and 100 μmol/L phloretin groups were (3 679.50±676.76), (2 143.75±616.20), (1 174.75±284.18)pg/ml, respectively, which were all significantly lower than (8 411.00±939.67)pg/ml in IL-1β induced group (all at P<0.01). The concentrations of MCP-1 in 50 μmol/L, 75 μmol/L and 100 μmol/L phloretin groups were (3 783.25±610.24), (1 565.75±457.89), (745.75±227.01)pg/ml, respectively, which were all significantly lower than (5 533.00±602.87)pg/ml in IL-1β induced group (all at P<0.01). The relative expression levels of HO-1 and Nrf2 were significantly higher and the relative expression levels of p-P38, p-ERK, and p-JNK were significantly lower in 100 μmol/L phloretin group than IL-1β induced group (all at P<0.01). Conclusions:Phloretin reduces the oxidative stress level of IL-1β induced OFs from GO patients and inhibits the production of pro-inflammatory cytokines.The mechanism is related to the activation of Nrf2/HO-1 and the inhibition of the MAPK signal pathway.

Uso de plasmaféresis en el manejo de colestasis intrahepática grave asociada a enfermedad de Graves: a propósito de un caso / Use of plasmapheresis in the treatment of severe intrahepatic cholestasis associated with Graves' disease: a case report

La tirotoxicosis es la manifestación clínica de una liberación excesiva de hormonas tiroideas, asociada o no a una función glandular autónoma; en este primer escenario, se denomina específicamente hipertiroidismo. Las principales etiologías son la enfermedad de Graves (EG), el adenoma tóxico, el bocio multinodular tóxico y el grupo de tiroiditis, predominando sus formas aguda y subaguda. La EG es la forma más común de hipertiroidismo, representando entre el 60 % y el 80 % de los casos, con una mayor incidencia en personas entre 40 y 60 años. Se ha descrito un compromiso hepático entre 45 % y el 90 % de pacientes con hipertiroidismo. Presentamos el caso de un hombre de 47 años con tirotoxicosis secundaria a enfermedad de Graves con compromiso bioquímico hepático manifestado como colestasis intrahepática refractaria al tratamiento médico en el corto plazo, tratado exitosamente con plasmaféresis como terapia puente a tiroidectomía total, proporcionando un análisis de la respuesta a la terapia a través de un cambio en los niveles de tiroxina libre (T4) y bilirrubina total a lo largo de su evolución.

Thyrotoxicosis is the clinical manifestation of excessive thyroid hormone release, whether or not asso-ciated with autonomous glandular function; in this first scenario, it is specifically termed hyperthyroi-dism. The main etiologies are Graves' disease (GD), toxic adenoma, toxic multinodular goiter ant the group of thyroiditis, predominantly acute and subacute forms. GD is the most common form of hyperthyroidism, accounting for 60% to 80% of cases, with a higher incidence among people aged 40 to 60 years. Liver involvement has been reported in 45% to 90% of patients with hyperthyroi-dism. We present the case of a 47-year-old man with thyrotoxicosis secondary to Graves' disease with hepatic biochemical involvement manifested as intrahepatic cholestasis refractory to medical management in the short term, successfully treated with plasmapheresis as bridge therapy to total thyroidectomy, providing an analysis of the response to therapy through a change in free thyroxine (T4) and total bilirubin levels throughout his evolutio

Adverse effects associated with peribulbar injection of triamcinolone for the treatment of thyroid eye disease: a retrospective case series / Efeitos adversos de injeções peribulbares de triancinolona na doença ocular da tireoide: estudo retrospectivo de uma série de casos

ABSTRACT Purpose: Peribulbar injection of triamcinolone is an alternative treatment for thyroid eye disease; however the safety profile of this therapeutic option remains controversial. The aim of this study was to describe the occurrence of local and systemic adverse effects after peribulbar injection of triamcinolone in patients with thyroid eye disease. Methods: This was a retrospective case series. Medical records of patients with thyroid eye disease treated with peribulbar injections of triamcinolone at a single academic institution between 2007 and 2019 were analyzed. Local and systemic complications were documented. Results: A total of 123 patients were treated. Only 11 patients (8.9%) developed local complications. The most frequent complication was the presence of superficial eyelid ecchymosis (nine patients; 7.3%). Notably, systemic complications (hyperglycemic and suprarenal inhibition after stop treatment) occurred in two patients (1.6%). All complications were transient, and the patients did not have any long-term sequelae. Conclusions: Peribulbar injection of triamcinolone for the treatment of thyroid eye disease is linked to a very low rate of local or systemic complications. Prospective studies are warranted to delve into this topic.

RESUMO Objetivo: A injeção peribulbar de triancinolona é um tratamento alternativo para doenças oculares da tireoide; no entanto, a segurança desse procedimento continua controversa. O objetivo deste artigo é descrever os efeitos adversos locais e sistêmicos de injeções peribulbares de triancinolona em pacientes com doença ocular da tireoide. Métodos: Estudo retrospectivo de uma série de casos. Foram analisados os prontuários médicos dos pacientes com doença ocular da tireoide tratados com injeções de triancinolona peribulbar em uma única instituição acadêmica entre 2007 e 2019. Foram documentadas as complicações locais e sistêmicas. Resultados: Um total de 123 pacientes foram tratados. Apenas 11 (8,9%) pacientes apresentaram complicações locais, sendo a mais frequente a presença de equimoses palpebrais superficiais (7,3%), enquanto 2 (1,6%) pacientes apresentaram complicações sistêmicas (hiperglicemia e inibição da suprarrenal após a interrupção do tratamento). Todas estas complicações foram transitórias e nenhum paciente apresentou sequelas de longo prazo. Conclusões: As injeções peribulbares de triancinolona nas doenças oculares da tireoide têm uma taxa muito baixa de complicações, tanto locais quanto sistêmicas. São necessários estudos prospectivos para aprofundar este tópico.

Caractéristiques épidémio-cliniques et évolutives des dysthyroïdies autoimmunes au centre national hospitalier universitaire Hubert Koudougou Maga (CNHU-HKM) de Cotonou / Epidemiological, clinical and evolutionary characteristics of autoimmune dysthyroidism in the National University Center Hubert Koutoukou Maga (CNHU-HKM) Of Cotonou

Objectif : Etudier les caractéristiques épidémio cliniques et évolutives des dysthyroïdies auto immunes dans le service d'endocrinologie diabétologie du CNHU-HKM. Matériel et méthode d'étude : Il s'agit d'une étude transversale descriptive et analytique ayant porté sur les patients reçus en consultation pour une pathologie thyroïdienne dans le service d'endocrinologie diabétologie sur une période de 10 ans. Ont été inclus les patients ayant au moins une TSH anormale et les anticorps anti thyroïdiens positifs. Résultats : Sur la période d'étude, nous avons enregistré 2883 consultants, 347 avaient une pathologie thyroïdienne, dont 69 cas de dysthyroïdie auto-immune répartis en 54 cas de maladie de Basedow et 15 cas de maladie de Hashimoto. Les dysthyroïdies auto immunes représentaient donc 2,39 % des consultations et 19,89% des thyroïdopathies. Les fréquences de la maladie de Basedow et de la maladie de Hashimoto étaient respectivement de 1,87% (54 cas) et 0,52% (15 cas) parmi les consultations. Les dysthyroïdies auto immunes étaient plus fréquentes dans les tranches d'âge de 30 à 40 et 40 à 50 ans. Les manifestations les plus fréquentes de la maladie de Basedow étaient l'asthénie (94,4%), l'amaigrissement (87,0%) et la tachycardie (85,2%) . Quant à la maladie de Hashimoto les principales manifestations étaient représentées par une asthénie (86,66%), un goitre (66,6%) et une prise de poids (60%). Le titre initial élevé des anticorps anti R-TSH, l'hypothyroïdie iatrogène ont été retrouvés comme des facteurs associés au suivi prolongé de la maladie de Basedow au-delà de 18 mois. Conclusion : Les dysthyroïdies auto-immunes sont des affections fréquentes dominées par la maladie de Basedow. Leur évolution sous traitement est influencée par des facteurs cliniques, biologiques et échographiques.

Objective: To study the epidemiological, clinical and evolutionary characteristics of autoimmune dysthyroidism in the endocrinology-diabetes department of the CNHU-HKM. Material and method: This was a descriptive and analytical cross-sectional study of patients seen for thyroid pathology in the endocrinology diabetology department over a 10-year period. Patients with at least one abnormal TSH and positive anti-thyroid antibodies were included. Results: Over the study period, we recorded 2883 consultants, 347 of them having thyroid diseases, including 69 cases of autoimmune dysthyroidism divided into 54 cases of Graves' disease and 15 cases of Hashimoto's disease. Autoimmune dysthyroidism represented 2.39% of consultations and 19.89% of thyroid disorders. Graves' disease and Hashimoto's disease accounted for 1.87% (54 cases) and 0.52% (15 cases) of consultations respectively. Autoimmune dysthyroidism was more frequent in the 30-40 and 40-50 age groups. The most frequent symptoms of Graves' disease were asthenia (94.4%), weight loss (87.0%) and tachycardia (85.2%). In Hashimoto's disease, the main symptoms were asthenia (86.66%), goiter (66.6%) and weight gain (60%). High initial R-TSH antibody levels and iatrogenic hypothyroidism were found to be factors associated with extended follow-up of Graves' disease beyond 18 months. Conclusion: Autoimmune dysthyroidism is a frequent condition, with Graves' disease predominating. Their evolution under therapy is influenced by clinical, biological and ultrasonographic factors.

Trends in Graves' orbitopathy research in the past two decades: a bibliometric analysis / Tendências na pesquisa da orbitopatia de Graves nas últimas duas décadas: uma análise bibliométrica

ABSTRACT Purpose: This study was conducted to identify trends in Graves' orbitopathy research in the past two decades and to elaborate on hot topics in the field. Methods: The Web of Science database was used to extract articles on Graves' orbitopathy or its synonyms. Full data and references were exported to VOSviewer software to be analyzed. Visualization maps and charts were constructed accordingly. Results: We retrieved 1067 articles on Graves' orbitopathy from the Web of Science database. The United States ranked first in terms of the article count (25), followed by Italy (141) and the People's Republic of China (120). Wiersinga's and the University of Amsterdam's articles received the highest citation count (1509 and 3052, respectively). The University of Pisa and Thyroid published the highest number of articles (65 and 93, respectively). Co-authorship analysis showed four clusters of country collaborations: red cluster, European countries; green cluster, the United States, Brazil, Canada, South Korea, and Taiwan; a yellow cluster, People's Republic of China; and blue cluster, Japan, Australia, and Poland. Keyword analysis revealed five clusters of topics: pathogenesis, management, association, quality of life, and surgery. Analysis of co-cited references also revealed five clusters: pathogenesis, management, risk factors, clinical assessment, and surgical management. Conclusion: Research on Graves' orbitopathy has grown during the past two decades. Hot research topics are pathogenesis, management, risk factors, quality of life, and complications. Research trends have changed in the past two decades. Increasing interest in exploring Graves' orbitopathy mechanisms and associations is evident. European countries are cooperating in this field of research. The United States has established more extensive international cooperation than other countries. We believe that more international collaboration involving developing countries is required.

RESUMO Objetivo: Identificar tendências no campo de pesquisa da orbitopatia de Graves nas últimas duas décadas e analisar os ramos de maior concentração de pesquisas nessa área. Métodos: O banco de dados Web of Science foi usado para extrair artigos com "orbitopatia de Graves" ou seus sinônimos no título. Dados completos e referências foram exportados para o programa VOSviewer para serem analisados. Mapas e gráficos de visualização foram construídos a partir desses dados. Resultados: Foram obtidos 1067 artigos sobre a orbitopatia de Graves a partir do banco de dados Web of Science. Os EUA ficaram em primeiro lugar em termos de número de publicações, seguidos pela Itália e pela República Popular da China. Dentre os autores, os artigos de Wiersinga WM tiveram o maior número de citações. Quanto às instituições, os artigos da Universidade de Amsterdã tiveram o maior número de citações, mas a Universidade de Pisa publicou o maior número de artigos. Dentre os periódicos, a revista Thyroid publicou o maior número de artigos. A análise de coautoria mostrou quatro agrupamentos de colaboração entre países. O primeiro agrupamento engloba países europeus; o segundo engloba os EUA, Brasil, Canadá, Coreia do Sul e Taiwan. A República Popular da China compreende um agrupamento por si só. O quarto agrupamento inclui Japão, Austrália e Polônia. A análise das palavras-chave revelou cinco agrupamentos de tópicos de palavras-chave: patogênese, gerenciamento, associação, qualidade de vida e cirurgia. A análise das referências citadas em conjunto revelou cinco agrupamentos: patogênese, manejo, fatores de risco, avaliação clínica e manejo cirúrgico. Conclusão: A pesquisa no campo da orbitopatia de Graves cresceu nos últimos vinte anos. Os tópicos com a maior concentração de pesquisas são: patogênese, gerenciamento, fatores de risco, qualidade de vida e complicações. As tendências de pesquisa mudaram nas últimas duas décadas. Ficou evidente um aumento do interesse em explorar os mecanismos e associações da orbitopatia de Graves. Observou-se uma cooperação entre países europeus neste campo de pesquisa. Os EUA estabeleceram uma cooperação internacional mais ampla que outros países. Acreditamos que mais colaboração internacional envolvendo países em desenvolvimento seria recomendável.