Clinical and genetic analysis of a case of Gitelman syndrome accompanied with Graves disease and adrenocortical adenoma: A case report.

RATIONALE: Gitelman syndrome (GS), also known as familial hypokalemia and hypomagnesemia, is a rare autosomal recessive inherited disease caused by primary renal desalinization caused by impaired reabsorption of sodium and chloride ions in the distal renal tubules. We report a case of clinical and genetic characteristics of GS accompanied with Graves disease and adrenocorticotrophic hormone (ACTH)-independent adrenocortical adenoma. PATIENT CONCERNS: The patient is a 45 year old female, was admitted to our hospital, due to a left adrenal gland occupying lesion as the chief complaint. DIAGNOSIS: The patient was finally diagnosed as GS with Graves disease and adrenocortical adenoma. INTERVENTIONS: Potassium magnesium aspartate (1788 mg/d, taken orally 3 times a day (supplement a few times a day, intake method, treatment duration). Contains 217.2 mg of potassium and 70.8 mg of magnesium, and potassium chloride (4.5 g/d, taken orally 3 times a day (supplement a few times a day, intake method, and treatment duration); Potassium 2356 mg), spironolactone (20 mg/d, taken orally once a day (supplement a few times a day, intake method, treatment duration). After 3 months of treatment, the patient's blood potassium fluctuated between 3.3-3.6 mmol/L, and blood magnesium fluctuated between 0.5-0.7 mmol/L, indicating a relief of fatigue symptoms. OUTCOMES: On the day 6 of hospitalization, the symptoms of dizziness, limb fatigue, fatigue and pain were completely relieved on patient. In the follow-up of the following year, no recurrence of the condition was found. LESSONS: The novel c.1444-10(IVS11)G > A variation may be a splicing mutation. The compound heterozygous mutations of the SLC12A3 gene may be the pathogenic cause of this GS pedigree.

Successful guselkumab treatment of a refractory psoriasis patient with Graves' disease: a case report.

Psoriasis is a chronic inflammatory skin disease. It is associated with many autoimmune diseases such as rheumatoid arthritis, Crohn's disease and thyroid diseases. Graves' disease (GD) is a common organ-specific autoimmune disease characterized by diffuse goitre and thyrotoxicosis. Management of psoriasis patients with GD is challenging. This current report presents the case of a 34-year-old female patient with refractory psoriasis with GD who was hospitalized for drug eruption and then experienced new-onset erythema and scaling following treatment with adalimumab and secukinumab. Despite the sequential move to phototherapy, tofacitinib and ustekinumab, the erythema and scaling continued unabated and exacerbated. Finally, switching to guselkumab resulted in the psoriasis lesions significantly improving. These findings suggest that guselkumab might be an effective treatment option for refractory psoriasis combined with GD.

Thyrotoxic periodic paralysis presenting with quadriparesis and hyperreflexia.

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism that manifests as painless flaccid paralysis. An East Asian man in his late 20s presented to the emergency department with an acute onset of quadriparesis associated with hypertonia and hyperreflexia. His initial symptoms and signs suggested involvement of the brain and spinal cord; however, MRI of the neuroaxis was normal. His serum potassium concentration was low, and thyroid test results were consistent with hyperthyroidism. The patient was diagnosed with TPP associated with Graves' disease and was treated with potassium supplementation, propranolol and methimazole. Motor strength improved to his baseline level of power; bulk was normal, and tone was increased. Although flaccid paralysis is a typical presentation of TPP, brisk reflexes and muscle spasticity cannot rule out this condition. This case highlights the importance of considering TPP as a possible diagnosis in patients presenting with acute quadriparesis.

Mapping the path towards novel treatment strategies: a bibliometric analysis of Hashimoto's thyroiditis research from 1990 to 2023.

Background: Hashimoto's thyroiditis (HT), a common form of thyroid autoimmunity, is strongly associated with deteriorating clinical status and impaired quality of life. The escalating global prevalence, coupled with the complexity of disease mechanisms, necessitates a comprehensive, bibliometric analysis to elucidate the trajectory, hotspots, and future trends in HT research. Objective: This study aims to illuminate the development, hotspots, and future directions in HT research through systematic analysis of publications, institutions, authors, journals, references, and keywords. Particular emphasis is placed on novel treatment strategies for HT and its complications, highlighting the potential role of genetic profiling and immunomodulatory therapies. Methods: We retrieved 8,726 relevant documents from the Web of Science Core Collection database spanning from 1 January 1990 to 7 March 2023. Following the selection of document type, 7,624 articles were included for bibliometric analysis using CiteSpace, VOSviewer, and R software. Results: The temporal evolution of HT research is categorized into three distinct phases: exploration (1990-1999), rapid development (1999-2000), and steady growth (2000-present). Notably, the United States, China, Italy, and Japan collectively contributed over half (54.77%) of global publications. Among the top 10 research institutions, four were from Italy (4/10), followed by China (2/10) and the United States (2/10). Recent hotspots, such as the roles of gut microbiota, genetic profiling, and nutritional factors in HT management, the diagnostic dilemmas between HT and Grave's disease, as well as the challenges in managing HT complicated by papillary thyroid carcinoma and type 1 diabetes mellitus, are discussed. Conclusion: Although North America and Europe have a considerable academic impact, institutions from emerging countries like China are demonstrating promising potential in HT research. Future studies are anticipated to delve deeper into the differential diagnosis of HT and Grave's disease, the intricate relationship between gut microbiota and HT pathogenesis, clinical management of HT with papillary thyroid carcinoma or type 1 diabetes, and the beneficial effects of dietary modifications and micronutrients supplementation in HT. Furthermore, the advent of genetic profiling and advanced immunotherapies for managing HT offers promising avenues for future research.

Elevated free thyroxine and free triiodothyronine probably caused by high-dose biotin intake in a patient with Graves' disease: a case report.

Biotin is a water-soluble vitamin that acts as a cofactor for carboxylase, and is often used as a component in several immunoassays. We present a case of a 46-year-old male with Graves' disease (GD) who revealed elevated free thyroxine (FT4) and free triiodothyronine (FT3) levels after high-dose biotin intake. Levels of these hormones had been within the reference range when he was on thiamazole 5 mg/day for 7 years; however, the levels increased from 1.04 to 2.20 ng/dL and from 3.05 to 9.84 pg/mL for FT4 and FT3, respectively, after he started taking biotin 72 mg/day. Despite these high levels, his symptoms and the other laboratory results, including the thyroid-stimulating hormone level, did not suggest GD relapse. His thyroid hormone data was decreased and returned within the reference range immediately after the laboratory assays for FT3 and FT4 had been coincidentally changed from those containing streptavidin-biotin complexes to biotin-free ones. Biotin interference, which is caused by high-dose biotin intake and immunoassays using some form of streptavidin-biotin complex, is sometimes clinically problematic, giving high or low results. To our knowledge, this is the first case report of a patient with GD on high-dose biotin receiving high thyroid hormone level results that were initially misunderstood as an aggravation of the disease; there are some reports of misdiagnosis of hyperthyroidism due to biotin administration. Unexpected fluctuations in thyroid function test results in patients with GD should be checked for biotin intake, immunoassays and the limiting concentration of biotin to avoid misdiagnosis of relapse.

Postoperative Hypocalcemia in Hyperthyroid Patients: The Parathyroids Aren't Always to Blame.

INTRODUCTION: Hypocalcemia is commonly reported after thyroidectomy and has multiple possible etiologies including: parathyroid devascularization, reactive hypoparathyroidism from relative hypercalcemia in thyrotoxicosis, and abrupt reversal of thyrotoxic osteodystrophy. In patients that are actively hyperthyroid and undergoing thyroidectomy, it is not known how many experience hypocalcemia from nonhypoparathyroidism etiologies. Therefore, our aim was to examine the relationship among thyrotoxicosis, hypocalcemia, and hypoparathyroidism. METHODS: A retrospective review was performed of prospectively-collected data from all patients undergoing thyroidectomy for hyperthyroidism by 4 surgeons from 2016 to 2020. All patients carried a diagnosis of Graves' disease or toxic multinodular goiter. Patient demographics, preoperative medications, laboratory reports, and postoperative medications were reviewed. Hypocalcemia within the first month of surgery despite a normal parathyroid hormone (PTH) level was the primary outcome of interest and was compared between patients with and without thyrotoxicosis. Secondary outcomes were duration of postoperative calcium use and the relationship between preoperative calcium supplementation and postoperative calcium supplementation. Descriptive statistics, Wilcoxon rank-sum, and chi-square tests were used for bivariate analysis, as appropriate. RESULTS: A total of 191 patients were identified, with mean age of 40.5 y (range 6-86). Most patients were female (80%) and had Graves' disease (80%). At the time of surgery, 116 (61%) had uncontrolled hyperthyroidism (thyrotoxic group, Free Thyroxine >1.64 ng/dL or Free Triiodothyronine > 4.4 ng/dL), with the remaining 75 (39%) considered euthyroid. Postoperative hypocalcemia (calcium < 8.4 mg/dL) developed in 27 (14%), while hypoparathyroidism (PTH < 12 pg/mL) was observed in 39 (26%). Thyrotoxic patients comprised a majority of those with hypocalcemia (n = 22, 81%, P = 0.01) and hypoparathyroidism immediately following surgery (n = 14, 77%, P = 0.04). However, a majority of initially hypocalcemic, thyrotoxic patients had normal PTH values within the first month after surgery (n = 17, 85%), pointing to a potential nonparathyroid etiology. On bivariate analysis, no significant relationship was found for thyrotoxic patients with initial postoperative hypocalcemia (18%) and hypoparathyroidism <1-month after surgery (29%, P = 0.29) or between 1 and 6 mo after surgery (2%, P = 0.24). Of the 19 patients in the nonhypoparathyroidism group, 17 (89%) were off all calcium supplements by 6 mo postop. CONCLUSIONS: In patients with hyperthyroidism, those in active thyrotoxicosis at time of surgery have a higher rate of postoperative hypocalcemia compared to euthyroid patients. When hypocalcemia lasts >1 mo postoperatively, data from this study suggest that hypoparathyroidism may not be the primary etiology in many of these patients, who typically require calcium supplementation no more than 6 mo postoperatively.

Graves' Disease in Children Presenting With Fragility Fracture: A Case Report.

Background: Adults with hyperthyroidism have been found to have decreased bone mineral density (BMD) and higher fracture risk. The most typical cause of hyperthyroidism is Graves' disease. However, there are limited studies on how hyperthyroidism affects bone metabolism and fractures in children. We describe a unique instance of a patient who initially displayed a fragility fracture and was ultimately identified with Graves' disease after biochemical evaluations. Case Summary: A 2-year-8-month-old female presented with fragility fractures three times in only 7 months. A series of examinations were performed to evaluate any possible malformations or abnormalities of bone metabolism. Graves' disease was found, and drug therapies were employed (methimazole, propranolol, calcium carbonate, vitamin D). Since children with Graves' disease and fragility fractures have been uncommonly described in the past, a stringent and thorough long-term follow-up was initiated. Conclusions: Children with undiagnosed Graves' disease had a higher risk of fractures and osteoporosis. This case suggests that BMD measurement may be necessary for the initial evaluation of Graves' disease in children.

What we know about the relationship between autoimmune thyroid diseases and gut microbiota: a perspective on the role of probiotics on pediatric endocrinology.

INTRODUCTION: Autoimmune diseases account for a cumulative overall prevalence of about 3-5% worldwide. Among them, autoimmune thyroid diseases (ATDs) are the most common and comprise two main entities: Hashimoto's thyroiditis (HT) and Graves-Basedow disease (GD). The pathogenesis of ATDs remains not fully elucidated, however the role of microbioma has been proposed. Gut microbiota exert an important influence on the intestinal barrier, nutrient metabolism and immune system development and functions. EVIDENCE ACQUISITION: In this review, we describe on the main features of ATDs in pediatrics, focusing on the reciprocal influence between gut microbiota, thyroid hormone metabolism and thyroid autoimmunity and consider the role of probiotics and other microbiota-targeted therapies in thyroid diseases with a perspective on pediatric endocrinology. EVIDENCE SYNTHESIS: Microbiome affects both endogenous and exogenous thyroid hormone metabolism and influences the absorption of minerals important to the thyroid function, which are iodine, selenium, zinc and iron. The alteration of the gut microbiota, with the consequent modifications in the barrier function and the increased gut permeability, seems involved in the development of autoimmune and chronic inflammatory diseases, including ATDs. The supplementation with probiotics showed beneficial effects on the thyroid hormone and thyroid function because this strategy could restore the intestinal eubiosis and the good strain microorganism proliferation. CONCLUSIONS: Even though the evidence about the interaction between microbiota and ATDs in pediatric patients is limited, the promising results obtained in the adult population, and in other autoimmune disorders affecting children, highlight the need of for further research in the pediatric field.

[Multimodal anesthesia in a patient with Graves' disease and thyrotoxicosis: A case report]. / Anestesia multimodal en paciente con enfermedad de Graves y tirotoxicosis: reporte de caso.

Background: Hyperthyroidism is the increase in the synthesis and secretion of thyroid hormones. It is rare but serious in children and constitutes approximately 5% of all cases; 15% manifests before 10 years of age. The peak of presentation and the majority of cases (80%) are diagnosed around 10-15 years of age. Adolescence is usually the stage with the highest incidence and it is more frequent in women (5:1). Acute thyrotoxic crisis or thyroid storm is rare and only occurs in a poorly controlled hyperthyroid patient or in a hyperthyroid patient undergoing emergency surgery. It is manifested by fever, extreme tachycardia, tachyarrhythmia with atrial fibrillation, vomiting, diarrhea, agitation and mental confusion. Clinical case: 17-year-old adolescent with Graves' disease with uncontrolled clinical manifestations that did not respond to medical treatment and was scheduled for radical thyroidectomy. 35 points were obtained on the Burch and Wartofsky Scale. It was managed with general anesthesia, reducing stimuli for airway and regional control to reduce surgical stimuli. Adjuvant medications such as magnesium sulfate for intraoperative stability were used. Conclusion: Multimodal anesthesia managed to avoid thyroid storm, postoperative pain, as well as other complications.

Introducción: el hipertiroidismo es el incremento en la síntesis y secreción de hormonas tiroideas. Es raro pero grave en la edad pediátrica y constituye aproximadamente el 5% de todos los casos; el 15% se presenta antes de los 10 años. El pico de presentación y la mayoría de los casos (80%) se diagnostican hacia los 10-15 años. La adolescencia es la etapa de mayor incidencia y más frecuente en mujeres (5:1). La crisis tirotóxica aguda o tormenta tiroidea es rara y solo se presenta en un hipertiroideo mal controlado o en un paciente hipertiroideo intervenido de urgencia. Se manifiesta con fiebre, taquicardia extrema, taquiarritmia con fibrilación auricular, vómito, diarrea, agitación y confusión mental. Caso clínico: adolescente de 17 años con enfermedad de Graves con manifestaciones clínicas descontroladas, la cual no respondió a tratamiento médico y se programó para tiroidectomia radical. Se obtuvieron 35 puntos en la Escala de Burch y Wartofsky. Se manejó con anestesia general y fueron disminuyendo los estímulos para control de vía aérea y regional a fin de disminuir los estímulos quirúrgicos. Se usaron medicamentos adyuvantes como sulfato de magnesio para la estabilidad transoperatoria. Conclusión: la anestesia multimodal logró evitar la tormenta tiroidea, el dolor postoperatorio, así como otras complicaciones.

Actual prevalence of hypoparathyroidism after total thyroidectomy: a health insurance claims-database study.

PURPOSE: Persistent hypoparathyroidism (hypoPT) is a major complication of total thyroidectomy. Nonetheless, previous reports may have underestimated the prevalence of hypoPT due to patient selection bias. We aimed to estimate the actual prevalence of persistent hypoPT after total thyroidectomy and to find predictive factors for postoperative hypoPT. METHODS: This study retrospectively reviewed data from a health insurance claims-based database provided by the Japan Medical Data Center Co., Ltd. From 2009 to 2019, 2388 patients who underwent total thyroidectomy were identified using the medical procedure codes. Persistent hypoPT was defined as the prescription of active vitamin D supplements for >1 year postoperatively and the assignment of hypoPT codes. The prevalence of persistent hypoPT was estimated at two different levels: minimum and maximum estimations with or without postoperative osteoporosis and/or renal failure codes. Correlates for persistent hypoPT were investigated among several demographic and clinical variables. RESULTS: Of the 2388 patients, 1752 (73.4%) were women with a mean age of 45 years. The types of diseases were: benign thyroid disease (n = 235), malignant thyroid tumors (n = 1570), Graves ' disease (n = 558), and malignancy combined with Graves' disease (n = 25). The minimum and the maximum estimation of the prevalence of persistent hypoPT were 15.0 and 20.3%, respectively. Multivariate logistic regression analysis showed that the malignant tumor (odds ratio, 1.8) independently correlated with persistent hypoPT. CONCLUSIONS: The prevalence of persistent hypoPT after total thyroidectomy estimated by the claims-based database was higher than previously recognized. Comprehensive attempts to preserve parathyroid function, especially in malignant diseases, are essential.

Follow-Up of Thyroid Function in Children With Neonatal Hyperthyroidism.

Introduction: Neonatal hyperthyroidism mainly occurring in the children born to mothers with Graves' disease (GD). The influence of maternal GD on the newborn's thyroid function includes not only hyperthyroidism, but also various forms of hypothyroidism. Maternally transferred thyrotropin receptor antibodies (TRAb), the antithyroid drug (ATD) administration during pregnancy and previous definitive treatment of GD (radioactive iodine therapy or thyroidectomy) in the mother impact the function of the fetal/neonatal thyroid. Some newborns born to mothers with GD may present central hypothyroidism (CeH) due to impaired regulation of the fetal hypothalamic-pituitary-thyroid axis. The aim of this study was to evaluate different types of thyroid dysfunction in babies with neonatal hyperthyroidism. Materials and Methods: Medical records of 14 infants with neonatal hyperthyroidism (13 born to mothers with GD, and one born to mother with Hashimoto thyroiditis) were analyzed. Results: Transient hyperthyroidism was the main thyroid dysfunction in our study group. Overt hyperthyroidism with highly increased TRAb levels (mean 13.0 ± 7.0 IU/L) was diagnosed in 6 (43%) neonates. Another 6 (43%) babies presented hyperthyroidism with slightly increased fT4 and/or fT3 levels and TSH levels in the lower limit of the normal range coinciding with positive TRAb levels (mean 3.8 ± 1.6 IU/L). Normal thyroid hormone levels with TSH levels below the lower limit of the range were observed in 2 (14%) neonates. Four babies in the study group (28.5%) required further levothyroxine (L-T4) supplementation due to CeH or, in one case, due to primary hypothyroidism. Conclusion: Our study highlights the need for prolonged monitoring of thyroid function in children born to mothers with GD. Diagnosis of CeH could be delayed due to its masking by transient hyperthyroidism. Prolonged thyroid-stimulating hormone suppression after TRAb elimination should be considered as a signal announcing CeH.

[LIFESTYLE ADJUSTMENT AS THERAPEUTIC TOOL IN THYROID EYE DISEASE].

OBJECTIVES: Thyroid Eye Disease (TED), also known as Graves' ophthalmopathy, is the most frequent extrathyroidal manifestation of autoimmune dysthyroidism. The most common ocular signs are eyelid retraction, proptosis, and strabismus, alongside specific dermatopathies. This article aims to review the options to improve TED manifestation by lifestyle adjustment. RESULTS: Tobacco smoking is the strongest risk factor for the development of TED and is associated with increased incidence and severity of TED and reduction in response to treatment. Smoking cessation decreases the incidence of TED and compares the risk level of ex-smokers to the risk level of the general population. Selenium is a chemical element with anti-oxidative properties. Selenium levels were significantly lower in Graves' disease patients with TED compared with those without TED. A double-blinded, randomized-control trial demonstrated that supplementation of selenium was associated with improved quality of life, decreased ocular involvement, and slowed TED progression while taken for a limited period. Statins administration to thyroid patients is associated with a reduced risk of TED. Recently, a few studies have shown an increased risk of developing TED and increased severity depending on the level of lipids in the blood, which suggests that balancing blood lipid levels by statins or by low-fat diet can help prevent TED. CONCLUSIONS: Lifestyle adjustment might be critical for a significant portion of patients. By supporting smoking cessation, the recommendation of selenium supplementation for a limited period and reducing serum cholesterol levels can prevent the development of TED, reduce its severity, and improve the patient's quality of life.

IMPACT OF GRAVES' DISEASE AND ANTITHYROID DRUG THERAPY ON BONE MINERAL DENSITY - PATHOPHYSIOLOGICAL MECHANISMS AND CLINICAL RELEVANCE.

Graves' disease is an autoimmune disease characterized by excessive thyroid hormone production. One of the consequences of that state can be a decrease in bone mineral density (BMD). Graves' disease is often treated with antithyroid drugs (ATD) as first line therapy, which can lead to disease remission. Moreover, recent data show that improvement in BMD can be expected. However, vitamin D deficiency can coexist along with Graves' disease, which is also involved in the process of bone remodeling. It is still not known whether lower values of vitamin D can contribute to onset of Graves' disease and if its supplementation might be helpful in therapy for hyperthyroidism. In the past couple of decades, osteopenia and osteoporosis have become a major health burden not only in post-menopausal women but also as a result of other diseases, leading to extensive research into various pathophysiological mechanisms responsible for bone remodeling. The Wnt (wingless integrated) signaling pathway is a very important factor in bone homeostasis, especially the canonical pathway. Present data indicate that stimulation of the Wnt pathway leads to bone mass increase and, in contrast, its inhibition leads to bone mass decrease. Hence, inhibitors of the canonical Wnt pathway became the focus of interest, in particular sclerostin and dickkopf 1 (DKK1). Hyperthyroidism and osteopenia/osteoporosis are quite common today and can coexist together or as separate entities. In this article, we aimed to give an overview of possible associations and potential mutual pathophysiological mechanisms.

Prevalence of hyperthyroidism with hypercalcemia in Xindu district and the efficacy of vitamin D3 treatment in these patients: a randomized trial.

BACKGROUND: This trial aimed to analyze the relationship between hyperthyroidism and the morbidity rate of hypercalcemia in the Xindu district, Chengdu, Sichuan province. We observed the level of serum calcium, the bone metabolic and thyroid autoimmune-related antibodies index during vitamin D3 treatment combined with traditional antithyroid drugs (ATD). METHODS: Our research included hyperthyroid patients with a first-time diagnosis of Graves diseases (GD) combined with hypercalcemia on the basis of conventional anti-hyperthyroidism therapy, which were randomized into a vitamin D3 group (vitamin D3, 800-1,200 IU/day) and an ATD group (methimazole, 15-30 mg/day). All hyperthyroidism patients with hypercalcemia were analyzed, and changes in serum calcium (Ca2+), parathyroid hormone (PTH), thyroid function, thyroid autoimmune-related antibodies, and 25-dihydroxyvitamin D (25-OHVit D) levels during treatment of thyrotoxicosis with added vitamin D3 were explored. RESULTS: In total, 184 patients with hyperthyroidism were observed, including 36 (19.57%) patients associated with hypercalcemia, with an age of onset of (56.39±5.80) years old. Twelve (6.52%) of these 36 cases reported digestive symptoms as the first manifestation, and four (2.17%) patients presented with a hypercalcemia crisis as the first manifestation. Serum Ca2+, free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin hormone receptor antibody (TRAb) levels increased in patients with hypercalcemia. Following the addition of vitamin D3 treatment, serum Ca2+, FT3, FT4, and TRAb levels were significantly decreased relative to the ATD group, while the thyroid-stimulating hormone (TSH), PTH, and 25-OHVit D levels were normalized. CONCLUSIONS: Our study highlighted the importance of taking functional digestive disturbance into consideration in hyperthyroidism diagnosis, even in the absence of the typical symptoms. The level of thyroid related antibodies, thyroid function, and bone metabolism in hyperthyroidism patients combined with hypercalcemia could be improved by vitamin D3 adjuvant therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100047870.

Identification of Two Different Phenotypes of Patients with Amiodarone-Induced Thyrotoxicosis and Positive Thyrotropin Receptor Antibody Tests.

Introduction: Serum thyrotropin (TSH) receptor antibodies (TRAbs) are occasionally found in patients with amiodarone-induced thyrotoxicosis (AIT), and usually point to a diagnosis of type 1 AIT (AIT1) due to Graves' disease (GD). However, the TRAb role and function in AIT have not been clarified. Methods: A retrospective cohort study of 309 AIT patients followed at a single academic center over a 30-year period. AIT TRAb-positive patients (n = 21, 7% of all cases) constituted the study group; control groups consisted of type 2 AIT (AIT2) TRAb-negative patients (n = 233), and 100 non-AIT patients with GD. Clinical and biochemical data at diagnosis and during the course of disease were compared. Histological samples of patients who had total thyroidectomy were reviewed. Stored serum samples were used for a functional assay of TRAb class G immunoglobulins (IgGs) in Chinese hamster ovary (CHO) cells stably transfected with complementary DNA encoding for the TSH receptor. Results: TRAb-positive patients were grouped according to color flow Doppler sonography, radioactive iodine thyroid uptake, and duration of amiodarone therapy before thyrotoxicosis in type 1 (n = 9, 43%; TRAb1) or type 2 (n = 12, 57%; TRAb2) AIT. TRAb1 patients had clinical and biochemical features indistinguishable from GD controls, and were responsive to methimazole. Conversely, TRAb2 patients had clinical features similar to AIT2 controls, and were responsive to glucocorticoids, but not to methimazole. The CHO cell functional assay demonstrated that TRAb1 IgGs had a stimulatory effect on cyclic AMP production, which was absent in TRAb2 IgGs. Pathology in TRAb1 showed hyperplastic thyroid follicles and mild lymphocyte infiltration, reflecting thyroid stimulation. On the contrary, TRAb2 samples revealed follicle destruction, macrophage infiltration, and sometimes fibrosis, consistent with a destructive process. Conclusions: Almost 60% of TRAb-positive AIT patients had a destructive thyroiditis. TRAb-positive tests in AIT patients do thus not necessarily imply a diagnosis of GD and AIT1, and should be evaluated in the clinical and biochemical setting of each AIT patient and confirmed by measuring thyroid-stimulating immunoglobulins.

Graves disease and metastatic hormonal-active Hürthle cell thyroid cancer: A case report.

RATIONALE: A hormone-active metastatic Hürthle cell thyroid carcinoma (HCTC) and Graves disease (GD) present a therapeutic challenge and is rarely reported. PATIENT CONCERNS: We present a 64-year-old male patient, who had dyspnea and left hip pain lasting 4 months. He had clinical signs of hyperthyroidism and a tumor measuring 9 cm in diameter of the left thyroid lobe, metastatic neck lymph node and metastases in the lungs, mediastinum, and bones. DIAGNOSIS: Laboratory findings confirmed hyperthyroidism and GD. Fine-needle aspiration biopsy and cytological investigation revealed metastases of HCTC in the skull and in the 8th right rib. A CT examination showed a thyroid tumor, metastatic neck lymph node, metastases in the lungs, mediastinum and in the 8th right rib measuring 20 × 5.6 × 4.5 cm, in the left acetabulum measuring 9 × 9 × 3 cm and parietooccipitally in the skull measuring 5 × 4 × 2 cm. Histology after total thyroidectomy and resection of the 8th right rib confirmed metastatic HCTC. INTERVENTIONS: The region of the left hip had been irradiated with concomitant doxorubicin 20 mg once weekly. When hyperthyroidism was controlled with thiamazole, a total thyroidectomy was performed. Persistent T3 hyperthyroidism, most likely caused by TSH-R-stimulated T3 production in large metastasis in the 8th right rib, was eliminated by rib resection. Thereafter, the patient was treated with 3 radioactive iodine-131 (RAI) therapies (cumulative dose of 515 mCi). Unfortunately, the tumor rapidly progressed after treatment with RAI and progressed 10 months after therapy with sorafenib. OUTCOMES: Despite treatment, the disease rapidly progressed and patient died due to distant metastases. He survived for 28 months from diagnosis. LESSONS: Simultaneous hormone-active HCTC and GD is extremely rare and prognosis is dismal. Concomitant external beam radiotherapy and doxorubicin chemotherapy, followed by RAI therapy, prevented the growth of a large metastasis in the left hip in our patient. However, a large metastasis in the 8th right rib presented an unresolved problem. Treatment with rib resection and RAI did not prevent tumor recurrence. External beam radiotherapy and sorafenib treatment failed to prevent tumor growth.

Successful intervention with Chinese herbal medicine for hyperthyroidism: Two case reports and a literature review.

BACKGROUND: Hyperthyroidism, the excessive production of thyroid hormones, is most commonly attributed to autoimmune dysfunction such as Graves' disease. Western medical treatment of hyperthyroidism includes antithyroid medications, radioiodine, and thyroidectomy, all of which are associated with side effects. We describe the successful treatment of two patients with Graves' disease who used Chinese herbal medicine (CHM) with or without Western medicine. CASE PRESENTATION: Both cases (a 50-year-old female [case 1] and a 56-year-old male [case 2]) received the Chinese herbal formula Jia Wei Xiao Yao San (JWXYS) as well as Prunella vulgaris, Fritillaria thunbergii, and Crassostrea gigas. Elevated thyroid hormone levels were restored to normal after 10 months of treatment in case 1 and 8 months in case 2. Neither patient experienced any complications or side effects during CHM treatment. Notably, symptoms and thyroid hormone levels have remained well controlled in both patients over 1 year of follow-up until the time of this report. To explore the possible mechanisms involved in CHM treatment of hyperthyroidism, we searched biomedical literature databases and reviewed the literature up to June 2020. CONCLUSIONS: As for the hyperthyroidism almost was controlled by Western medicine instead of CHM, we report that JWXYS as well as Prunella vulgaris, Fritillaria thunbergii, and Crassostrea gigas was a safe and effective formula and we propose that CHM may be considered as either a first choice or combination therapy to control hyperthyroidism.

Thyrotoxic Hypokalemic Periodic Paralysis Triggered by Dexamethasone Administration.

Thyrotoxic hypokalemic periodic paralysis (THPP) is a disease characterized by recurrent episodes of muscle weakness due to intracellular potassium shifting in the presence of high levels of thyroid hormone. It occurs more commonly amongst young Asian men with underlying Graves' disease. Attacks are commonly precipitated by ingestion of carbohydrate-rich meals or alcohols, stress or strenuous exercise. Herein, we describe an adult Thai man suffering from a hypokalemic periodic paralysis attack after receiving a dexamethasone injection. The diagnosis of Graves' disease was confirmed by his thyroid function test and a presence of thyrotropin-receptor antibody. His weakness and hypokalemia responded well to potassium supplement and a non-selective beta blocker, while his thyrotoxicosis was initially controlled by an anti-thyroid medication and subsequently with a subtotal thyroidectomy. Clinicians should beware of this manifestation when administering steroids in the thyrotoxic patients, especially of Asian male descent.

Predictors of euthyreosis in hyperthyroid patients treated with radioiodine 131I-: a retrospective study.

BACKGROUND: Radioiodine (RAI) treatment for hyperthyroidism is a very common modality, chosen by physicians worldwide. The outcome of the therapy, however, is not always predictable. While rendering a patient hypo- or euthyroid is meant as a therapeutic success, the latter does not require lifelong hormonal supplementation. The aim of our study is to determine predictors of euthyreosis in patients who underwent RAI treatment. METHODS: Medical records of 144 patients who had undergone RAI therapy were examined. Laboratory and clinical data were analyzed statistically. Ultrasonography findings, such as thyroid volume, nodules' size and characteristics had been collected at the beginning of treatment and 6 months after the administration of radioiodine 131I-. Moreover, scintigraphy results were taken into account. Multivariate logistic regression analysis model has been used to find predictors of euthyroidism after 12 months of follow-up. The predictors of normal thyroid function have also been analyzed separately for patients with GD (Graves' disease) and TMNG (toxic multinodular goiter). RESULTS: The analysis showed that age (OR 1,06; 95%CI 1.025-1.096, p = 0,001), thyroid gland volume (OR 1,04; 95%CI 1,02-1,06; p < 0.001) and iodine uptake level (OR 0,952; 95%CI 0,91-0,98; p = 0,004) were significant factors of achieving normal thyroid function after RAI therapy. According to multivariate logistic regression analysis, in GD patients only age has been shown to be a significant factor (OR 1,06; 95%CI 1,001-1,13; p = 0.047), while in TMNG patients' age (OR 1,04; 95%CI 1-1,09; p = 0.048), thyroid gland volume (OR 1.038; 95%CI 1.009-1.068; p = 0.009) and iodine uptake level (OR 0.95; 95%CI 0.9-0.99; p = 0.02) all have been proven to be significant predictors of achieving euthyroidism. CONCLUSIONS: The more advanced age, larger volume of thyroid gland and lower iodine uptake level are predictors of euthyreosis after RAI treatment.

[Thyrotoxic hypokalemic periodic paralysis in two African black women]. / Paralysie périodique hypokaliémique thyrotoxique chez deux femmes noires africaines.

Thyrotoxic hypokalemic periodic paralysis is a rare complication of hyperthyroidism. It has been most often reported in Asian subjects while it has been little described in the black population. Its mechanism has been little elucidated, but it would be caused by hyperactivity of the Na+/K+pump. We here report two cases of thyrotoxic hypokalemic periodic paralysis in black African subjects. The clinical manifestation was identical in both patients: proximal muscle paralysis of the lower limbs. Paralysis was associated with severe hypokalemia and occurred in female patients treated for Graves' disease without any other associated disease. Outcome was immediately favorable under potassium supplementation. Treatment of hyperthyroidism prevented recurrences. This study highlights the importance of suspecting the diagnosis of thyrotoxic hypokalemic periodic paralysis despite its rarity in the black African population.