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Background Thyroid eye disease (TED), a common extrathyroidal manifestation of Graves disease, poses significant management challenges due to potential disfigurement, visual impairment, and decreased quality of life. Uncertainties remain about the optimal treatment approach, especially regarding TED duration and its impact on outcomes. Objective This meta-analysis evaluates the effects of various treatments on inflammatory markers and severity endpoints in TED, stratified by disease duration, distinguishing between treatments initiated within the first 6 months (initial phase) and those initiated thereafter (subacute/chronic phase). Methods Following PRISMA guidelines, a systematic search of multiple electronic databases yielded 26 studies meeting predefined inclusion criteria. Methodological quality was assessed, and data were meticulously extracted and analyzed. Results In the initial phase, treatments like corticosteroids and teprotumumab showed significant improvements in clinical activity score, proptosis, and diplopia. In the subacute/chronic phase, the efficacy of methylprednisolone and teprotumumab is reduced. A "critical window" effect was observed, with treatments showing diminished efficacy after 6 months of TED duration. Conclusion This meta-analysis highlights the importance of tailoring treatment strategies based on TED duration, emphasizing early interventions to maximize benefits. The findings guide clinicians in selecting optimal treatments and underscore the need for further research to refine evidence-based approaches, ultimately enhancing patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Context Over the past several decades, there have been indications of potential shifts in the diagnostic strategies, treatment, and monitoring of patients with Graves disease (GD). Objective To evaluate current practices in managing GD and compare them to previous surveys Methods We used a global online survey of endocrinologists to assess shifts in the diagnosis, monitoring, and treatment in a typical patient with GD, as well as treatment variation in 5 different clinical scenarios. Results A total of 1252 respondents from 85 countries completed the survey. Methods used to diagnose an uncomplicated GD case have changed over the past decade, reflecting increased use of thyrotropin receptor antibody (TRAb) and reciprocal decreases in nuclear medicine studies. The preferred mode of therapy for uncomplicated GD was antithyroid drugs (ATDs) by 91.5% of respondents, radioactive iodine (RAI) therapy by 7%, and thyroidectomy by 1.5%. Compared with previous surveys, the use of RAI as a first-line choice decreased in all geographic regions. The United States had the sharpest decline in the selection of initial therapy with RAI, decreasing from 69% in 1990 to 11.1% in 2023. In patients with persistent TRAb positivity after 18 months, 68.7% of respondents would continue the use of ATDs. After a relapse of GD, resumption of ATDs was selected by 59.9% of respondents. In patients with active thyroid eye disease or planning pregnancy, ATDs were the first choice (67.5% and 72.8%, respectively), and thyroidectomy emerged as the second choice (22.9% and 15.6%, respectively). Conclusion Paradigm shifts have occurred in the management of uncomplicated GD and its variants, as well as the response to persistent and recurrent hyperthyroidism. [ABSTRACT FROM AUTHOR]

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]

The autoimmune disorder known as Graves’ disease. The condition is due to the binding of thyroid-stimulating immunoglobulins to the thyrotropin receptor located on the thyroid gland. The result is an excess of thyroidal hormones. symptoms of hyperthyroidism, and the formation of diffuse goiter. This research intends to quantify the levels of CD40L, TSAB in people who suffer from Graves’ disease. It also aims to determine the relationship between TSAB and the duration of the disease, as well as analyze the role of CD40L as a predictive marker for Graves’ disease using medcalc Statistical Software version 16.4.3 and SAS (2018). In a case-control study, randomly selected 90 graves disease patients were included, the randomly selected patients were divided equally and matched into a case group who have graves disease and graves disease-free patients as a control group. For both groups whole blood sample was examined to compare for (TSAB), and (CD40L) levels determination by ELISA technique. The average serum levels of CD40L showed a highly significant correlation (P value < 0.01) among the groups examined for Graves’ disease. The patient group consisted of 13 males (28.89%) and 32 females (71.11%). No significant correlation was identified between TSAB and the duration of the condition. Thyroid stimulating antibody (TSAb) test and ultrasonography of the thyroid gland are valuable diagnostic techniques for autoimmune Graves’ disease (GD). CD40L could potentially serve as a predictive diagnostic marker for Graves’ disease. However, there is no observed link between the duration of the disease and the concentration of TSAB. [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]

miRNA short non-coding RNAs have a function in regulating gene expression at the post-transcriptional level. Dysregulation of miRNA expression and activity in the immune system is associated with a range of illnesses. Evaluate the levels of miRNA-762 in individuals with Graves' ophthalmopathy (GO) and the extent to which it serves as a biomarker. A total of (150) individuals of different genders and ages who were enrolled and distributed into three groups according to symmetrical criteria (50) patients of Graves' disease with Ophthalmopathy (GO) and (50) patients of Graves' disease (GD) and (50) healthy individuals. All patients were diagnosed with GD by TRAB test, miR-762 expression level was determined by one-step qRTPCR. GO is more common in females (76.0%) than males (24.0%), and in the age mean (42.8 ± 14.6). GO patients had a significantly higher TRAB level compared to both GD and controls, 8.32, 5.98 and 0.66, respectively (P < 0.01). miRNA-762 expression was significantly upregulated in GO patients (fold change = 11.2), compared to GD, control group (fold change = 7.4), (fold change = 3.0), respectively, at P < 0.01. ROC curve indicates miRNA-762 Specificity and Sensitivity, cutoff value was 6.5, sensitivity 88.0%, specificity 76.0%, AUC 0.87. Pearson correlation shows that miRNA-762 was positively associated with TRAb in the GO group (r = 0.689, p < 0.001). miRNA-762 expression is higher in Graves' ophthalmopathy. When the ROC curve was done for serum miRNA-762 for prediction of the diagnosis of GO, gave good sensitivity and specificity. These results indicated good validity of miRNA-762 as a diagnostic marker for GO. [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]

Background: The optimal treatment strategy for radioiodine (RAI) treatment protocols for benign hyperthyroidism remains elusive. Although individualised activities are recommended in European Law, many centres continue to provide fixed activities. Our institution implemented a dosimetry protocol in 2016 following years of fixed dosing which facilitates the calculation of individualised activities based on thyroid volume and radioiodine uptake. Methods: This was a retrospective study comparing success rates using a dosimetry protocol targeting an absorbed dose of 150 Gy for Graves' disease (GD) and 125 Gy for Toxic Multinodular Goiter (TMNG) with fixed dosing (200MBq for GD and 400MBq for TMNG) among 204 patients with hyperthyroidism. Success was defined as a non‐hyperthyroid state at 1 year for both disease states. Results were analysed for disease specific or patient specific modulators of response. Results: This study included 204 patients; 74% (n = 151) received fixed activities and 26% (n = 53) of activities administered were calculated using dosimetry. A dosimetry‐based protocol was successful in 80.5% of patients with GD and 100% of patients with TMNG. Differences in success rates and median activity administered between the fixed (204Mbq) and dosimetry (246MBq) cohort were not statistically significant (p =.64) however 44% of patients with GD and 70% of patients with TMNG received lower activities following treatment with dosimetry as opposed to fixed activities. Use of dosimetry resulted in successful treatment and reduced RAI exposure for 36% of patients with GD, 70% of patients with TMNG, and 44% of patients overall. Conclusion: This retrospective clinical study demonstrated that treatment with a dosimetry‐based protocol for TMNG and GD achieved comparable success rates to fixed protocols while reducing RAI exposure for over a third of patients with GD and most patients with TMNG. This study also highlighted that RAI can successfully treat hyperthyroidism for some patients with activities lower than commonplace in clinical practise. No patient or disease specific modulators of treatment response were established in this study; however, the data supports a future prospective trial which further scrutinises the individual patient factors governing treatment response to RAI. [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]

Thymomas are benign thymic epithelial neoplasms, rarely found outside the anterior mediastinum. Although hyperthyroid states have been associated with thymic hyperplasia, only 3 thymoma cases have been previously reported in patients with Graves disease (GD), all within the anterior mediastinum. Here, we report a case of ectopic cervical thymoma in a 22-year-old female patient previously treated for GD. The patient underwent ultrasonography, computed tomography, inconclusive fine-needle aspiration, and ultimately gross dissection for diagnostic workup and definitive treatment of an anterior neck mass, producing a 2.5 × 2.3 × 1.5-cm entity consistent with Masaoka stage I and type B2 thymoma per World Health Organization classification. The patient underwent an uncomplicated subsequent clinical course, with no adjuvant radiotherapy administered. After conducting a systematic literature review, we conclude that of the 109 cases of ectopic cervical thymoma reported, this is the first to describe a case of ectopic cervical thymoma in a patient with a past medical history of GD. For GD patients in stable euthyroid remission with the persistent or recurrent presence of an anterior neck mass, the extrathyroidal origin of the mass should always be considered, including the exceptional presence of a cervical ectopic thymoma. [ABSTRACT FROM AUTHOR]

Purpose: Hashimoto thyroiditis and Graves's disease are two related autoimmune disorders, representing the leading causes of hypothyroidism and hyperthyroidism. Autoimmune hypothyroidism is generally irreversible but very rarely, some patients would shift to hyperthyroidism. The aim of the study was to seek for possible clinical predictors of the transition from hypo to hyperthyroidism in patients with Hashimoto thyroiditis and to outline their clinical phenotype. Methods: Twelve patients with overt autoimmune hypothyroidism who had at least one transition from hypothyroidism to autoimmune hyperthyroidism were compared with 294 consecutive patients with autoimmune hypothyroidism and 69 consecutive patients with autoimmune hyperthyroidism that accessed the outpatient clinic over six months. Demographic, hormonal data and autoantibodies titers were compared. Results: Prevalence of smoking habit was significantly higher in switchers compared to controls. Switchers showed a significantly higher prevalence of personal and familial history of non-thyroidal autoimmune disorders. TSH levels were significantly lower in the switcher group during the hypothyroid phase and levothyroxine dose required was lower. TSH concentrations were significantly lower while free fT4 and free fT3 values were higher in GD patients compared to switchers during the hyperthyroid phase despite comparable TRAb levels. Prevalence and type of hyperthyroid symptoms and orbitopathy were similar between switchers and GD group. Mean dose of anti-thyroid drugs was significantly higher in GD patients compared to switchers. No differences were observed in the remission rate from hyperthyroidism between the two groups, despite switchers showed a significantly lower time-to-remission. Conclusions: Conversion of Hashimoto Thyroiditis towards Graves' disease is a rare phenomenon which can occur almost at any time after the development of autoimmune hypothyroidism. Our findings suggest active surveillance of hypothyroid patients who require frequent reduction of levothyroxine during follow up and testing for TSHR antibodies in these patients. [ABSTRACT FROM AUTHOR]

There is an association between hyperthyroidism and pulmonary hypertension. However, the prevalence of pulmonary hypertension in hyperthyroidism and the underlying mechanisms are incompletely defined. Consecutive patients with severe hyperthyroidism, mostly due to Graves disease, were included in this single-center study. Echocardiographic assessment of pulmonary hemodynamics was performed at the time of hyperthyroidism diagnosis (baseline) and after normalization of thyroid hormones (follow-up; median 11 months). In a subset of patients, right heart catheterization and noninvasive assessment of central hemodynamics was performed. Among all 99 patients, 31% had pulmonary hypertension at baseline. The estimated systolic pulmonary artery pressure correlated significantly with the estimated left ventricular filling pressure (E/e′). The invasively measured systolic pulmonary artery pressure correlated well with the estimated systolic pulmonary artery pressure. Cardiac output, E/e′, left and right ventricular dimensions were significantly reduced from baseline to follow-up, whereas the estimated pulmonary vascular resistance did not differ. Diastolic blood pressure was significantly higher at follow-up, with no change in systolic blood pressure. The central systolic blood pressure, however, exhibited a trend for a reduction at follow-up, while the pulse wave velocity was significantly lower at follow-up. Approximately one-third of patients with hyperthyroidism have evidence of pulmonary hypertension. Our data suggest that an increased cardiac output and left ventricular filling pressure are the main mechanisms underlying the elevated systolic pulmonary artery pressure in hyperthyroidism, whereas there is no evidence of significant pulmonary vascular disease. [ABSTRACT FROM AUTHOR]