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.

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.

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

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.

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.

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.

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.

Síndrome nefrótico por enfermedad de cambios mínimos asociado a enfermedad de Graves y uso de metimazol

Introduction: Graves' disease causes kidney injury through a series of multiple mechanisms, including the treatment for this condition. Nephrotic syndrome due to minimal change disease (MCD) is an unusual form of such kidney injury; the association between methimazole use and MCD is also rare. Case presentation: A 36-year-old woman with a history of Graves' disease in use of methimazole for several months, who presents edematous syndrome due to nephrotic syndrome associated with a KDIGO stage 3 acute kidney injury. Thionamide-induced hypothyroidism and the need of thyroid hormone replacement therapy was evidenced at the time of consultation. Based on a renal biopsy, the patient was diagnosed with MCD, her condition worsened as she experienced oliguria and hypervolemia, therefore, renal replacement therapy with hemodialysis was temporarily required. Methimazole administration was suspended, and treatment consisting of prednisolone administration and levothyroxine supplementation was started, achieving hemodialysis suspension, gradual improvement of proteinuria until remission and a full-maintained recovery of renal clearance. Radioiodine therapy was implemented as definitive treatment for Graves' disease, obtaining a successful outcome. Conclusions: Graves' disease and methimazole use are possible causes of minimal change disease; systemic corticosteroid therapy is a possible management. However, further basic, clinical and epidemiological research on this subject is required.

Introducción: La enfermedad de Graves genera daño renal por múltiples mecanismos, incluyendo sus tratamientos. El síndrome nefrótico por enfermedad de cambios mínimos, es una forma inusual de dicho daño renal en la enfermedad de Graves; la asociación de esta condición renal con el metimazol también es anómalo. Presentación del caso: Una mujer de 36 años con antecedente de enfermedad de Graves en uso de metimazol hacía meses, quien debutó con síndrome edematoso por síndrome nefrótico asociado a una lesión renal aguda KDIGO etapa 3. Se evidenció hipotiroidismo inducido por la tionamida con necesidad de suplencia al momento de la consulta. Asimismo, se realizó biopsia renal que concluyó en enfermedad de cambios mínimos. La paciente progresó a oliguria con hipervolemia sin respuesta a diurético del asa por lo que requirió terapia de reemplazo renal con hemodiálisis de forma transitoria. Se retiró el metimazol, se dio manejo con prednisolona y con suplencia tiroidea, lográndose el retiro de la hemodiálisis con mejoría gradual de la proteinuria hasta la remisión y recuperación de la depuración renal de forma plena y mantenida. Se dio manejo definitivo a la enfermedad de Graves con yodo radioactivo con éxito terapéutico. Discusión y conclusiones: La enfermedad de Graves y el metimazol son causas posibles de enfermedad de cambios mínimos; el tratamiento con corticoide sistémico se postula como una posible estrategia de manejo. Se requiere más investigación básica, clínica y epidemiológica en el tema.

Graves' disease, myxedema, and papillary thyroid carcinoma / Doença de Graves, mixedema e carcinoma papilífero de tireoide

Graves' disease (GD) is the leading cause of hyperthyroidism and diffuse toxic goiter in iodine-sufficient geographi-cal areas. GD is associated with classical manifestations such as ophthalmopathy and thyroid dermopathy, in addi-tion to diffuse goiter, which may be the site of carcinomas, as a complication. Case report: A 52-year-old woman presented with goiter and symptoms compatible with hyperthyroidism, such as heat intolerance, weight loss, fati-gue, increased sweat, tachycardia, fine tremors, increased intestinal transit, anxiety, emotional lability, insomnia, exophthalmos, and pretibial myxedema. A complementary investigation confirmed the diagnosis of hyperthyroidism (high free T4 and total T3 levels and low thyroid-stimulating hormone - TSH levels). Ultrasound images showed dif-fuse enlargement of the thyroid lobes by approximately 10 times and the presence of three thyroid nodules, one of which was larger than 2 cm with heterogeneous echogenicity and vascularization throughout the nodule; ultrasoun-d-guided fine needle aspiration revealed cytology compatible with Bethesda IV; scintigraphy revealed a low uptake area (cold nodule) amid a diffuse high-uptake goiter. A thyroidectomy was performed, and the anatomical specimen diagnosis revealed papillary thyroid carcinoma in the right lobe, with adjacent parenchyma compatible with GD. Histopathological examination of the skin showed the presence of myxedema compatible with Graves' dermopathy. The patient evolved with the normalization of TSH levels and a reduction of cutaneous manifestations. Conclusion:GD abnormalities may not be restricted to the classic clinical manifestations, and a careful investigation may reveal the coexistence of carcinomas. (AU)

A doença de Graves (DG) é a principal causa de hipertireoidismo e bócio difuso tóxico em áreas geográficas com iodo suficiente. DG está associada a manifestações clínicas clássicas como oftalmopatia e dermopatia da tireoide, além do bócio difuso, que pode ser sítio de carcinomas, como uma complicação. Relato de caso: Mulher de 52 anos apresentou bócio e sintomas compatíveis com hipertireoidismo como intolerância ao calor, emagrecimento, fadiga, sudorese aumentada, taquicardia, tremores finos, trânsito intestinal aumentado, ansiedade, labilidade emocional, insônia, exoftalmia e mixedema pré-tibial. A investigação complementar confirmou o diagnóstico de hipertireoidis-mo (níveis elevados de T4 livre e T3 total; níveis baixos de hormônio estimulante da tireoide - TSH). As imagens ultrassonográficas mostraram aumento difuso dos lobos tireoidianos em aproximadamente 10 vezes e a presença de três nódulos tireoidianos, um dos quais, maior que 2 cm, com ecogenicidade e vascularização heterogêneas em todo o nódulo, cuja punção aspirativa por agulha fina guiada por ultrassom revelou citologia compatível com Bethesda IV; e a cintilografia evidenciou uma área de baixa captação (nódulo frio) em meio a um bócio difuso de alta captação. Foi realizada tireoidectomia e o diagnóstico da peça anatômica revelou carcinoma papilífero de tir-eoide em lobo direito, com parênquima adjacente compatível com DG. O exame histopatológico da pele mostrou a presença de mixedema compatível com dermopatia de Graves. A paciente evoluiu com normalização dos níveis de TSH e redução das manifestações cutâneas. Conclusão: As anormalidades da DG podem não estar restritas às manifestações clínicas clássicas, e uma investigação criteriosa pode revelar a coexistência de carcinomas, (AU)

Asymptomatic course of overt primary hypothyroidism with a very high peak systolic velocity of the superior thyroid arteries: A case report

This study reports the case of a 59-year-old woman with asymptomatic overt hypothyroidism who presented with signs of increased thyroid exertion involving the autonomic nervous system. These signs included significantly increased peak systolic velocity (PSV) of the superior thyroid arteries (STA) and moderately increased blood flow intensity. The findings suggest an increase in the rate of thyroxine deiodination and the sufficiency of free triiodothyronine (FT3) for the functional needs of the body. The absence of typical symptoms of hypothyroidism may depend on the sufficiency of FT3 in the serum and additional nonhormonal circumstances. Hence, FT3 should always be measured in addition to thyroid-stimulating hormone and free thyroxine levels. When Doppler ultrasound is used, the intensity of blood flow and PSV-STA from both sides should be determined to assess the magnitude of thyroid exertion. Probably, PSV-STA may not be an absolute criterion for the diagnosis of Graves� disease

Congestive hepatopathy secondary to graves� disease: acase report

Graves� disease is a common cause of hyperthyroidism in iodine-sufficient parts of the world. Excessive thyroid hormone is known to have multiple effects on various organs, including the liver. We reported a case of 49-year old male patient with worsening jaundice, ascites, tremor, and palpitation, with previous history of uncontrolled Graves� disease. Findings from examination reveals signs of congestive hepatopathy, such as positive hepatojugular reflux and dilated hepatic vein. Treatment options for hyperthyroidism in patients with liver dysfunction includes methimazole and radioactive iodine-131. Liver dysfunction in patients with thyrotoxicosis is commonly found in daily practice, but establishing the cause of liver dysfunction can be a challenge because of the multiple cause of liver injury in hyperthyroidism.

Hipertiroidismo en niños y adolescentes: experiencia en un hospital universitario en Colombia / Hyperthyroidism in children and adolescents: Experience in a university hospital in Colombia

Introducción. El hipertiroidismo es una condición heterogénea caracterizada por la producción excesiva de hormonas tiroideas. Su aparición en la edad pediátrica representa un reto diagnóstico y terapéutico. Objetivo. Describir las características clínicas y paraclínicas, así como la evolución y las diferencias entre las principales causas etiológicas de los pacientes con hipertiroidismo atendidos por el Servicio de Endocrinología Pediátrica del Hospital Universitario San Vicente Fundación en Medellín, Colombia, entre el 1° de julio de 2015 y el 30 de junio de 2020. Materiales y métodos. Se hizo un estudio observacional transversal con recolección retrospectiva de la información. Resultados. Se incluyeron 54 pacientes con una edad media de 11,9 años, 72,2 % de ellos mujeres. El 11,1 % tenía antecedentes familiares de enfermedad de Graves y 29,6 % de otras enfermedades tiroideas. El bocio fue la manifestación clínica más frecuente (83,3 %). El 92,6 % había recibido terapia con metimazol, el 79,6 % requirió betabloqueador y el 11,2 % necesitó una terapia farmacológica adicional. Se presentaron reacciones adversas a la medicación en el 16,7 %. En el 20,4 % de los pacientes hubo resolución del hipertiroidismo (espontánea: 9,3 %; posterior a la ablación con yodo radiactivo: 9,3 %, y después de la cirugía: 1,9 %). Conclusión. El hipertiroidismo es una enfermedad con manifestaciones clínicas diversas. La causa más frecuente es la enfermedad de Graves, seguida por la hashitoxicosis. En este estudio, la hashitoxicosis fue más frecuente que en estudios previos. La duración y los efectos secundarios del tratamiento farmacológico fueron similares a los reportados previamente, pero es de resaltar la mayor frecuencia de agranulocitosis en nuestra población.

Introduction: Hyperthyroidism is a heterogeneous condition characterized by the excessive production of thyroid hormones. It represents a diagnostic and therapeutic challenge. Objective: To describe the clinical and paraclinical characteristics and the evolution and differences between the main etiologies in patients with hyperthyroidism treated by the Pediatric Endocrinology Service at the Hospital Universitario San Vicente Fundación in Medellín, Colombia, between July 1st., 2015, and June 30th., 2020. Materials and methods: We conducted a cross-sectional observational study with retrospective data collection. Results: We included 54 patients with a mean age of 11.9 years, 72.2% of whom were female; 85.2% had no history of comorbidities related to autoimmunity; 11.1% had a family history of Graves' disease, and 29.6% of other thyroid diseases. Goiter was the most frequent clinical manifestation (83.3%) and 92.6% of the patients received treatment with methimazole, 79.6% required beta-blockers, and 11.2% additional drug therapy. Adverse drug reactions occurred in 16.7% of the patients and in 20.4% there was a resolution of hyperthyroidism (spontaneous: 9.3%; after radio-iodine ablation: 9.3%, and after surgery: 1.9%). Conclusion: Hyperthyroidism is a disease with diverse clinical manifestations. Its most frequent cause is Graves' disease followed by hashitoxicosis, which in this study had a higher frequency than that reported in the literature. The duration and side effects of pharmacological treatment were similar to those previously reported, but the higher frequency of agranulocytosis is noteworthy.

Depresión psicótica secundaria a hipertiroidismo y desenlace letal por tormenta tirotóxica: a propósito de un caso / Psychotic depression secondary to hyperthyroidism and lethal outcome by thyrotoxic storm: case report

RESUMEN El rol de exceso y déficit de hormona tiroidea en la patogenia de trastornos del ánimo se ha registrado desde hace casi dos siglos. Las patologías tiroideas, las más numerosas dentro de las enfermedades endocrinas, se asocian causalmente a patología psiquiátrica en un importante porcentaje de casos. Específicamente, el hipertiroidismo produce múltiples manifestaciones psicopatológicas de tipo ansioso y depresivo, episodios de manía e, infrecuentemente, psicosis. Aunque el influjo del eje tiroideo sobre las vías neurales de noradrenalina, dopamina, y serotonina juega un rol neurobiológico fundamental en estos fenómenos, existen todavía múltiples mecanismos subyacentes por dilucidar. Dada la necesidad de un diagnóstico diferencial amplio y abarcador entre patologías psiquiátricas primarias y secundarias, reportamos el caso de una paciente de 52 años con depresión psicótica, en la que el diagnóstico tardío de hipertiroidismo acarreó consecuencias penosas y letales. La valoración clínica y laboratorial de la función tiroidea, debe ser parte de la evaluación psiquiátrica de cualquier persona con trastornos afectivos y ansiosos.

SUMMARY The role of excess and deficit of thyroid hormone in the pathogenesis of mood disorders has been recorded for almost two centuries. Thyroid pathologies, the most numerous among endocrine diseases, are causally associated with psychiatric pathology in a significant percentage of cases. Specifically, hyperthyroidism produces multiple psychopathological manifestations of anxious and depressive type, manic episodes and, infrequently, psychosis. Although the influence of the thyroid axis on the neural pathways of norepinephrine, dopamine, and serotonin plays a fundamental neurobiological role in these phenomena, there are still multiple underlying mechanisms to be elucidated. Given the need for a broad and comprehensive differential diagnosis between primary and secondary psychiatric pathologies, we report the case of a 52-year-old patient with psychotic depression in whom the late diagnosis of hyperthyroidism had painful and lethal consequences. Clinical and laboratory-based evaluations of thyroid function should be part of the psychiatric evaluation of any person with affective and anxiety disorders.