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Background: Previous studies of fixed-dose radioiodine therapy (RIT) for Graves’ disease (GD) have utilized a variety of techniques and reported differing success rates. This study sought to compare the efficacy of RIT using two fixed-dose protocols and to estimate the optimal radioiodine (RAI) activity for the treatment of GD. Methods: This retrospective trial enrolled 658 patients with GD who received RIT between January 2014 and December 2021. Participants were divided into two groups: protocol 1, which utilized a thyroid size-specific RAI dose, and protocol 2, which employed a modified dose calculation approach. The primary outcome assessed was the presence of euthyroidism or hypothyroidism at the 6-month follow-up. The success rates of RIT were compared between the two protocols. Results: The RIT success rate was marginally lower for protocol 2 than for protocol 1 (63.6% vs. 67.2%); however, the risk of treatment failure did not differ considerably between the groups (relative risk, 1.1089; 95% confidence interval, 0.8937 to 1.3758; P=0.3477). The median RAI activity associated with protocol 2 was lower than that for protocol 1 (10.7 mCi vs. 15.0 mCi, P=0.0079), and the frequency of hypothyroidism was significantly lower in the protocol 2 group (39.0% vs. 48.9%, P=0.0117). Conclusion: The success rate of the modified dose calculation protocol was comparable to that of the thyroid size-specific RAI dose protocol. The former approach reduced RAI activity and the incidence of hypothyroidism following RIT without compromising the success rate. [ABSTRACT FROM AUTHOR]

Objective: The association between autoimmunity-related tissue injury and thyroid cancer development remains an area of interest. Evidence suggests that patients with Graves disease (GD) may have an elevated risk for differentiated thyroid cancer. Multicenter studies are needed to gain insight into the correlates of papillary thyroid carcinoma (PTC) identified in this particular group of patients. This study aimed to investigate the prevalence of PTC and synchronous thyroid nodules in thyroidectomy specimens from GD patients in an endemic goiter region. Material and Methods: A retrospective review of institutional pathology records at two tertiary care centers identified 237 surgically treated patients with GD. Patients were categorized as having nodular Graves disease (N-GD) if synchronous nodular thyroid was identified by ultrasonography, while those without synchronous thyroid nodules were categorized as non-nodular or simple Graves disease (S-GD). The prevalence of PTC, histopathological correlates, and demographic characteristics were recorded and compared between groups N-GD and S-GD. Results: One hundred thirty-one and 106 patients were assigned to N-GD and S-GD, respectively. The mean age was significantly higher in N-GD (mean 45.52 years) compared to S-GD (mean 35.18 years) (p<0.001). The overall frequency of PTC was 36.3% (86/237) in the entire cohort. PTC was identified in 48.1% (63/131) of N-GD and 21.7% (23/106) of S-GD (p<0.001). Subcentimeter tumors constituted the majority of cases in both groups (76.2% in N-GD and 82.6% in S-GD) (p>0.05). The group of S-GD was enriched in BRAF-like PTCs, whereas N-GD had equal distribution for RAS- and BRAF-like tumors. Conclusion: This study underscores that the majority of PTCs encountered in GD were enriched in low-risk subcentimeter PTCs with a prevalence that varies depending on the presence of underlying nodular thyroid tissue. [ABSTRACT FROM AUTHOR]

The frequency of thyrotoxicosis may vary between countries and some laboratory test results may be used in etiology research. This study aimed to evaluate the prevalence of thyrotoxicosis diagnoses and laboratory test results. 3246 patients with overt thyrotoxicosis were included in this study. Laboratory test results, epicrisis, thyroid ultrasonography, thyroid scintigraphy, and radioactive iodine uptake test reports of the patients were examined in the study. Thyrotoxicosis was found due to levothyroxine overdose in 58.1% of the patients. When this group was excluded, 36.1% of the patients were diagnosed with toxic multinodular goiter most frequently. TRab levels were 8.5 times higher in Graves' disease than in other diagnostic groups. Anti-TPO levels were found to be the highest in the Graves' disease and Hashitoxicosis groups compared to other diagnostic groups (p<0.001). Anti-Tg levels were found to be highest in Graves' disease, Postpartum thyroiditis, and Hashitoxicosis patients (p<0.001). The free triiodothyronine / free thyroxine ratio was significantly higher, a cut-off value of >2.94 provided a sensitivity of 66% and specificity of 64% in diagnosing Graves' disease. The causes of thyrotoxicosis show some differences between countries. Patients using levothyroxine should be informed about drug use and dose titration. The free triiodothyronine / free thyroxine ratio can be used in addition to other tests during diagnosis. [ABSTRACT FROM AUTHOR]

Objective: The association between autoimmunity-related tissue injury and thyroid cancer development remains an area of interest. Evidence suggests that patients with Graves disease (GD) may have an elevated risk for differentiated thyroid cancer. Multicenter studies are needed to gain insight into the correlates of papillary thyroid carcinoma (PTC) identified in this particular group of patients. This study aimed to investigate the prevalence of PTC and synchronous thyroid nodules in thyroidectomy specimens from GD patients in an endemic goiter region. Material and Methods: A retrospective review of institutional pathology records at two tertiary care centers identified 237 surgically treated patients with GD. Patients were categorized as having nodular Graves disease (N-GD) if synchronous nodular thyroid was identified by ultrasonography, while those without synchronous thyroid nodules were categorized as non-nodular or simple Graves disease (S-GD). The prevalence of PTC, histopathological correlates, and demographic characteristics were recorded and compared between groups N-GD and S-GD. Results: One hundred thirty-one and 106 patients were assigned to N-GD and S-GD, respectively. The mean age was significantly higher in N-GD (mean 45.52 years) compared to S-GD (mean 35.18 years) (p0.05). The group of S-GD was enriched in BRAF-like PTCs, whereas N-GD had equal distribution for RAS- and BRAF-like tumors. Conclusion: This study underscores that the majority of PTCs encountered in GD were enriched in low-risk subcentimeter PTCs with a prevalence that varies depending on the presence of underlying nodular thyroid tissue.

Treatment patterns and preferences for patients with Graves’ disease (GD) vary across countries. In this study, we assessed the initial therapies and subsequent treatment modalities employed for GD in real-world clinical practice in Korea. We analyzed 452,001 patients with GD from 2004 to 2020, obtained from the Korean National Health Insurance Service database. Initial treatments included antithyroid drug (ATD) therapy (98% of cases), thyroidectomy (1.3%), and radioactive iodine (RAI) therapy (0.7%). The rates of initial treatment failure were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Even among cases of ATD treatment failure or recurrence, the rates of RAI therapy remained low. Regarding initial treatment, the 5-year remission rate was 46.8% among patients administered ATDs versus 91.0% among recipients of RAI therapy; at 10 years, these rates were 59.2% and 94.0%, respectively. Our findings highlight a marked disparity in the use of RAI therapy in Korea compared to Western countries. Further research is required to understand the reasons for these differences in treatment patterns.

Patients with newly diagnosed Graves disease often elect for treatment with the drug methimazole (MMI) over alternative therapies. However, MMI can commonly result in skin allergy that in severe cases can lead to discontinuation of therapy. We present a case of Graves thyrotoxicosis with a delayed hypersensitivity reaction while on MMI. The patient was successfully treated with a novel, individualized, 27-day desensitization protocol that resulted in tolerance of MMI with subsequent improvement in thyroid indices. Previous literature has offered various rapid desensitization protocols to MMI for immediate type hypersensitivity reactions. However, in nonimmediate, delayed hypersensitivity reactions, a slower desensitization protocol can be considered. As demonstrated in this case, desensitization to MMI is a reasonable alternative in patients who wish to avoid definitive therapy who develop an initial adverse reaction to MMI, as this can occur in up to 13% of treated cases. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the significance of etiological basis of thyrotoxicosis in guiding optimal treatment selection and its correlation with age and the presence of goiter. METHODS: This cross-sectional study was conducted at MTI-Hayatabad Medical Complex in Peshawar, Pakistan, from December 2022 to May 2023. Utilizing nonprobability-consecutive sampling, we enrolled 119 participants, focusing on individuals presenting with thyrotoxicosis confirmed by thyroid function tests (TFTs). Those already undergoing treatment for hyperthyroidism were also included. Essential diagnostic assessments, such as radioiodine scans, erythrocyte sedimentation rate (ESR), and thyroid receptor stimulating antibody tests, were performed as needed. Patients with chronic renal disease, chronic liver disease, and pregnant and lactating women were excluded. RESULTS: The mean age of participants was 40.39±13.65 years, with 84.03% having TSH

Myxedema is a rare, cutaneous complication of autoimmune thyroid diseases that most often affects the anterior shins. Herein, we report a patient with a history of Graves disease and Hashimoto thyroiditis who presented with boggy, alopecic patches associated with scalp pruritus. Punch biopsies from these lesions showed increased interstitial mucin in the reticular dermis, consistent with localized myxedema. This report showcases a rare presentation of localized myxedema of the scalp, highlighting the diverse cutaneous manifestations of autoimmune thyroid diseases.

Pretibial myxedema, more generally thyroid dermopathy, results from mucopolysaccharide accumulation in the dermis, typically between the knee and dorsal foot. Thyroid dermopathy presents in Graves disease, but can occur in Hashimoto thyroiditis, primary hypothyroidism, and euthyroid patients. Treatment of thyroid eye disease with teprotumumab is established in the literature, with few case reports also showing improvement in pretibial myxedema. Reported is a 76-year-old man with thyroid eye disease and pretibial myxedema treated with teprotumumab; improvement was demonstrated in both conditions. He developed "muffled" hearing as an adverse effect, a complication not widely published in the dermatology literature. At 18 months post-treatment, his symptoms are stable without recurrence, but hypoacusis persists. Given the long-term efficacy and side-effects, dermatologists should recognize the potential benefits and risks of using teprotumumab for thyroid dermopathy. A baseline audiogram may be considered prior to therapy. Additionally, longitudinal data is needed to document the benefits and risks of this novel therapy.

We present a unique case of hypokalemic thyrotoxic periodic paralysis (TPP) in an adolescent girl in North America. TPP is a rare but dangerous complication seen in thyrotoxic patients characterized by hypokalemia and acute proximal symmetric lower-extremity weakness. It is an especially rare phenomenon in pediatrics, with roughly 20 case reports described in adolescents worldwide; the majority are male. Our patient is a 14-year-old Asian girl with biochemical hyperandrogenism and known Graves disease who presented with an acute episode of lower-extremity weakness after eating a carbohydrate-rich meal. Laboratory workup revealed hypokalemia, hypomagnesemia, an undetectable thyrotropin, and hyperthyroxinemia. Electrolyte derangements responded well to supplementation, and the muscle weakness resolved with electrolyte normalization. Following improvement in thyroid function, the patient underwent thyroidectomy for definitive management of Graves disease. As TPP is potentially exacerbated by higher androgen and insulin levels, we suspect that with increasing rates of obesity and polycystic ovary syndrome, the incidence of TPP among adolescents may increase. It is therefore critically important that there is awareness and recognition of this serious diagnosis among all health care providers. [ABSTRACT FROM AUTHOR]

Introductions: Graves’ disease is the most common cause of hyperthyroidism. Neuropsychiatric manifestations may occur in thyroid disease. As the premier clinical manifestation of Graves disease, psychosis is highly uncommon; it was reported in 1% of cases. The major neuropsychiatric manifestations of hyperthyroidism are acute psychosis, dementia, apathy, agitation, mania, delusional behavior, and hallucinations, especially in older people. Psychosis is highly rare as the first clinical symptom of a grave disease. Case: A 48-year-old female with grave disease symptoms had been taken to the emergency department with psychotic manifestations. She had a three-month history of increasing irritability, increasing irrational talking, staying awake most of the night, muttering, nighttime wandering, and poor personal hygiene. She was admitted to the hospital, and the laboratory investigations showed an elevated FT4 and a decreased thyroid-stimulating hormone (TSH). The patient was started on propanolol 3 x 10 mg, propylthiouracil 3 x 50 mg tab, risperidone 2x2mg, trihexylphenidil 2x2mg, lorazepam 1x2mg, and Zyprexa injection once, which showed improvement in psychotic symptoms. Conclusion: Graves’ disease can present with neuropsychiatric manifestations such as psychosis, mania, or a combination of both. A detailed medical history and physical and psychiatric evaluation are necessary for diagnosing and giving adequate treatment. A detailed clinical evaluation, including thyroid function tests, could be recommended for all patients who showed psychotic symptoms. More research is needed to comprehend the pathophysiology underlying psychosis due to Graves’ disease, so that it is expected that the management can be carried out properly [ABSTRACT FROM AUTHOR]

Introduction and purpose: The gut microbiota is a diverse collection of microorganisms that coexist in the human intestine. Disorders in its structure leads to dysregulation of huge number of organs, including the thyroid. This review summarizes the latest findings regarding the links between gut microbiota and common thyroid diseases: Hashimoto's thyroiditis, Graves' disease and thyroid cancer. Materials and methods: This review was based on the PubMed and Google Scholar databases, using keywords: „gut microbiota AND thyroid/Hashimoto/Graves/thyroid cancer”, „Graves’ disease”, ,,Hashimoto thyroiditis”. Description of knowledge: Gut dysbiosis can contribute to autoimmune thyroid diseases by influencing micronutrient availability and immune regulation. Specific bacterial species may impact Hashimoto's development by regulating neurotransmitters and hormone secretion. In Graves' disease, significant changes in gut microbiota suggest their potential role in autoimmune processes. Research on gut microbiota in thyroid cancer suggests potential diagnostic tools and implicates gut microbiota alterations in tumor development. Conclusions: Significant gut microbiota changes are observed in Hashimoto's thyroiditis, Graves' disease, and thyroid cancer compared to healthy individuals, indicating a possible association. However, the exact mechanisms remain unclear, necessitating further research to understand how microbiota alterations contribute to these diseases.

Purpose: We present a case of rapid improvement in symptoms of thyroid eye disease and amelioration of worsening peripheral edema and acropathy with infusion of teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor. Observations: A 66 year old female with history of Hashimoto thyroiditis developed progressive thyroid eye disease (TED), peripheral edema, and acropathy attributable to acute Graves disease. Her signs and symptoms, refractory to oral steroid and diuretic therapy, rapidly improved following a standard dosing regimen of teprotumumab (one infusion 10 mg/kg then seven infusions 20 mg/kg) to resolution. Conclusions & importance: Teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor, is the first medication approved by the FDA for use in TED. Teprotumumab may contribute to the treatment of extraocular manifestations of Graves disease, chief among these peripheral soft tissue manifestations.

Thyroid hormones are vital in metabolism, growth and development1. Thyroid hormone synthesis is controlled by thyrotropin (TSH), which acts at the thyrotropin receptor (TSHR)2. In patients with Graves' disease, autoantibodies that activate the TSHR pathologically increase thyroid hormone activity3. How autoantibodies mimic thyrotropin function remains unclear. Here we determined cryo-electron microscopy structures of active and inactive TSHR. In inactive TSHR, the extracellular domain lies close to the membrane bilayer. Thyrotropin selects an upright orientation of the extracellular domain owing to steric clashes between a conserved hormone glycan and the membrane bilayer. An activating autoantibody from a patient with Graves' disease selects a similar upright orientation of the extracellular domain. Reorientation of the extracellular domain transduces a conformational change in the seven-transmembrane-segment domain via a conserved hinge domain, a tethered peptide agonist and a phospholipid that binds within the seven-transmembrane-segment domain. Rotation of the TSHR extracellular domain relative to the membrane bilayer is sufficient for receptor activation, revealing a shared mechanism for other glycoprotein hormone receptors that may also extend to other G-protein-coupled receptors with large extracellular domains.

Abstract Background Identification of modifiable risk factors for Alzheimer’s Disease (AD) onset is an important aspect of controlling the burden imposed by this disease on an increasing number of older U.S. adults. Graves disease (GD), the most common cause of hyperthyroidism in the U.S., has been hypothesized to be associated with increased AD risk, but there is no consensus. In this study, we explore the link between GD and risk of clinical AD. Methods Cox and Fine-Grey models were applied to a retrospective propensity-score-matched cohort of 19,798 individuals with GD drawn from a nationally representative 5% sample of U.S. Medicare beneficiaries age 65 + over the 1991–2020 period. Results Results showed that the presence of GD was associated with a higher risk of AD (Hazard Ratio [HR]:1.19; 95% Confidence Interval [CI]:1.13–1.26). Competing risk estimates were consistent with these findings (HR:1.14; CI:1.08–1.20) with the magnitude of associated risk varying across subgroups: Male (HR:1.25; CI:1.07–1.47), Female (HR:1.09; CI:1.02–1.16), White (HR:1.11; CI:1.03–1.19), and Black (HR:1.23; CI:1.02–1.49). Conclusions Our results indicate a robust and consistent association between a diagnosis of GD and a subsequent diagnosis of AD in later stages of life. The precise biological pathways that could potentially connect these two conditions remain unclear as is the role of treatment in this relationship. Replications of these findings on datasets with both biomarkers and laboratory test results, especially in underrepresented groups is vital.