Antithyroid Research Articles

Comparison of agranulocytosis and anti-neutrophil cytoplasmic antibody-associated vasculitis caused by two antithyroid drugs: A pharmacovigilance study using the WHO international database.

Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real-world large pharmacovigilance database. We searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non-case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non-cases). We further analyzed information for the cases of agranulocytosis and AAV. Among 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake. This is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real-world setting.

Identifying the Transients and Transformation Products in Hydroxyl Radical-Methimazole Reactions Using DFT and UPLC-Q-TOF MS/MS Approaches.

Oxidative reactions of the hydroxyl radical (·OH) with methimazole (MMI), an antithyroid drug, are crucial for understanding its fate in oxidizing environments. By synergistically integrating density functional theory and ultraperformance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF MS/MS) techniques, we elucidated the transients and transformation products (TPs) arising from the ·OH-MMI reactions. We probed two hydrogen-atom abstraction (HA) reactions, three radical adduct formation reactions, and single electron transfer (SET) at the M06-2X/6-311++G(d,p)/SMD(water) level. All proposed reaction channels, except for HA from the methyl group and SET, were found to be barrier-free. SET is the dominant oxidation pathway, accounting for 44% of oxidations, as determined by branching ratio analysis. The selenium analogue, MSeI, exhibited minor reactivity differences compared to MMI, yet its overall patterns resembled those of ·OH-MMI reactions. TPs were generated experimentally by reacting MMI with ·OH produced by UV-photolysis of H2O2. Eight TPs were identified from an approximately 24% degradation of MMI using UPLC-Q-TOF MS/MS analysis, and an additional two TPs were identified from the approximately 52% degraded MMI sample. The exact identities of all of the TPs were established through their corresponding fragmentation patterns. This study elucidates the drug's susceptibility to free radical species under physiologically relevant conditions.

Understanding and approach of Ayurveda management towards a unique case of Hashimoto Thyroiditis - A Case Report

Hashimoto thyroiditis is also known as chronic autoimmune thyroiditis and chronic lymphocytic thyroiditis, is an autoimmune disease in which thyroid cells are destroyed via cell and antibody-mediated immune processes. It is the most common cause of hypothyroidism in developed countries. The Pathophysiology of Hashimoto Thyroiditis involves the formation of antithyroid antibodies that attack the thyroid tissue, causing progressive fibrosis. The condition is sometimes not diagnosed until late in the disease process. The most common laboratory findings demonstrate elevated Thyroid-Stimulating Hormone (TSH) and low Thyroxine (T4) levels, coupled with increased anti thyroid peroxidase (anti-TPO) antibodies. In Ayurveda, it can be correlated with Rasavaha Sroto Vikara, Dhatwagnimandya, Vataja Pandu, Pittavruta Vata based on symptoms. Case Report: In this present study a female patient aged 37 years, known case of Hashimoto Thyroiditis since 8 years was treated with Shiro Takradhara, Sarvanga Abhynaga, Virechana and specific Shamanaushadhi’s as per signs and symptoms. Results: After 2 months of treatment there was a significant reduction in the signs and symptoms of the disease with 70% improvement in the condition.

Fe single atoms encapsulated in N, P-codoped carbon nanosheets with enhanced peroxidase-like activity for colorimetric detection of methimazole

Excessive use of antithyroid drug methimazole (MMI) in pharmaceutical samples can cause hypothyroidism and symptoms of metabolic decline. Hence, it is urgent to develop rapid, low cost and accurate colorimetric method with peroxidase-like nanozymes for determination of MMI in medical, nutrition and pharmaceutical studies. Herein, Fe single atoms were facilely encapsulated into N, P-codoped carbon nanosheets (Fe SAs/NP-CSs) by a simple pyrolysis strategy, as certified by a series of characterizations. UV–vis absorption spectroscopy was employed to illustrate the high peroxidase-mimicking activity of the resultant Fe SAs/NP-CSs nanozyme through the typical catalysis of 3,3′,5,5′-tetramethylbenzidine (TMB) oxidation. The catalytic mechanism was scrutionously investigated by the fluorescence spectroscopy and electron paramagnetic resonance (EPR) tests. Additionally, the introduced MMI had the ability to reduce the oxidation of TMB (termed oxTMB) as a peroxidase inhibitor, coupled by fading the blue color. By virtue of the above findings, a visual colorimetric sensor was established for dual detection of methimazole (MMI) with a linear scope of 5–50 mM and a LOD of 1.57 mM, coupled by assay of H2O2 at a linear range of 3–50 mM. According to the irreversible oxidation of the drug, its screening with acceptable results was achieved on the sensing platform even in commercial tablets The Fe SAs/NP-CSs nanozyme holds great potential for clinical diagnosis and drug analysis.

Cardiac Thyrotoxicosis Mimicking an Acute Coronary Syndrome

This case report details the clinical presentation, diagnosis, and multidisciplinary management of a 68-year-old man with cardiac thyrotoxicosis mimicking an acute coronary syndrome (ACS). The patient presented with persistent anginal chest pain, systemic symptoms, and electrocardiographic abnormalities suggestive of ACS. Despite presenting with persistent chest pain and ACS-like symptoms, a thorough examination, including the calculation of the thyrotoxicosis storm (StPRM) score, revealed thyrotoxicosis-induced dilated cardiomyopathy, challenging the initial diagnosis. This specific scoring for thyrotoxicosis severity played a crucial role in accurately identifying the thyrotoxic crisis. The case highlights the intricate relationship between thyroid dysfunction and cardiovascular manifestations, emphasizing the need for a multidisciplinary approach. Management included standard ACS protocols, careful titration of antithyroid medications, and the transition from intravenous to oral heart failure medications. Follow-up assessments demonstrated the success of personalized treatment strategies, with the normalization of thyroid function and complete resolution of the patient's symptoms. Nevertheless, the enduring impairment of left ventricular function following treatment prompts intriguing inquiries into the lasting impact of cardiac thyrotoxicosis on myocardial recovery. However, the persistence of impaired left ventricular function post-treatment raises intriguing questions about the lingering effects of cardiac thyrotoxicosis on myocardial recovery. This case underscores the importance of considering diverse cardiac presentations in hyperthyroid patients and the effectiveness of individualized management approaches in navigating the complexities of thyroid-cardiac interactions.

A comparison of cardiovascular disease, cancer, mortality, and Graves' ophthalmopathy following treatment for hyperthyroidism: A Bayesian network meta-analysis.

This network meta-analysis aimed to evaluate the association of anti-thyroid drugs (ATD), radioactive iodine (RAI), and thyroidectomy with subsequent outcomes in patients with newly-diagnosed hyperthyroidism. The Ovid Medline, Ovid Embase, and Cochrane Library databases were searched for observational studies and randomized controlled trials. Included studies were published on or before 1st May 2022 involving at least two of the treatments among ATD, RAI, and thyroidectomy for hyperthyroidism. Pairwise comparisons and Bayesian network meta-analysis were used to estimate hazard ratios (HRs) and their credible interval (CrI) of outcomes, including cardiovascular disease (CVD), cancer, overall mortality, and Graves' ophthalmopathy (GO). A total of 22 cohort studies with 131,297 hyperthyroidism patients were included. Thyroidectomy was associated with lower risks of mortality and GO than ATD (HR=0.54, 95% CrI: 0.31, 0.96; HR=0.31, 95% CrI: 0.12, 0.64) and RAI (HR=0.62, 95% CrI: 0.41, 0.95; HR=0.18, 95% CrI: 0.07, 0.35). RAI had a higher risk of GO (HR=1.70, 95% CrI: 1.02, 2.99) than ATD treatment. This Bayesian network meta-analysis indicated that thyroidectomy was associated with lower risks of mortality and GO in newly-diagnosed hyperthyroid patients compared to ATD and RAI. Relative to ATD, RAI therapy increased the risk of GO.

P-79 Graves’ Disease associated with alemtuzumab use for multiple sclerosis

Abstract Introduction Alemtuzumab was the first humanized monoclonal antibody to be created and is directed against CD52, a lymphocyte cell surface marker of unknown function. It has been used to treat leukemia and organ transplant rejection. More recently, alemtuzumab has been demonstrated to be highly effective in treating relapsing-remitting multiple sclerosis (MS) disease. Thyroid disease develops in approximately 20% of patients using alemtuzumab for MS, and Graves’ disease is the most common among them. Graves’ disease has not been reported in the use of alemtuzumab for reasons other than MS. Clinical Case A 28-year-old female patient with a 10 year history of MS had been treated with pulse corticosteroid, β-interferon and fingolimod. She received alemtuzumab in May 2019 due to increased relapse rates. After the first dose of alemtuzumab, she could not continue her treatment program due to the COVID-19 pandemic. Thyrotoxic thyroid functions (TSH: <0.015 uIU/mL, free T4: 24.79 pmol/L) were detected in the laboratory examination of the patient who was admitted to the endocrinology outpatient clinic with the complaint of palpitation in April 2021. The review of the patient's past laboratory test results determined she was euthyroid before alemtuzumab treatment. She had no personal or family history of thyroid disease. She had no signs and symptoms of thyroid ophthalmopathy. Ultrasonographic examination of her thyroid gland revealed normal size gland and pseudonodular appearance in the parenchyma. Subsequent thyroid scintigraphy showed diffuse uptake of the radioisotope and reduced counting time of the examination. These results were consistent with Graves’ disease. The patient was started on 5 mg methimazole twice a day. Since the etiology of Graves’ disease was thought to be primarily related to alemtuzumab, the patient's MS treatment was continued with ocrelizumab. She stopped the methimazole treatment within 3 months and did not regularly show up to her follow-up visit. In November 2022, she was admitted to the outpatient department with palpitation, sweating, and irritability symptoms. Thyrotoxic thyroid functions were detected again (TSH:<0,015 uIU/mL, free T4: 26,82 pmol/L). She was restarted on 5 mg methimazole treatment twice a day. In June 2023, she was euthyroid (TSH: 0,496 uIU/mL, free T4: 5,42 pmol/L, free T4: 10,45 pmol/L) and her TSI level was undetectable. The methimazole was reduced to 5 mg once a day. She continues to her treatment and follow-up in our center. Conclusion Graves’ disease is a common complication of alemtuzumab use in MS. Alemtuzumab-associated Graves’ disease follows an atypical course compared to the classical form of the disease. The spontaneous remission rate is less than in the classical form of the disease, and medical treatment is often required. Thyroidectomy may be necessary in cases that do not respond to antithyroid agents. Close monitoring of thyroid function tests is essential in alemtuzumab-associated Graves’ disease.

Pemeriksaan Imunologi Terhadap Kadar Hormon Thyroid Stimulating Hormone (TSH) Pada Pasien Gangguan Tiroid Di RSUD Panembahan Senopati Periode 2020-2022

Thyroid disorders are conditions of abnormalities in thyroid gland. According to function, thyroid disorders are divided into three, hyperthyroidism, hypothyroidism and euthyroidism. To detect thyroid disorders, can use laboratory test examination of TSH (Thyroid Stimulating Hormone) hormone. The aim is to determine the description of TSH levels checked periodically in patients with thyroid disorders using immunological methods. Research method is a case series method or case-by-case using secondary data from TSH hormone examination results in 2020-2022. The results were from 93 respondents based on age showed that 20-30 years old 11.8%, 31-40 years old 26.9%, 41-50 years old 26.9% and 51-60 years old 34.4%. Based on gender, 20.4% were male and 79.6% were female. Then we looked at changes in TSH hormone in patients with thyroid disorders by randomization 10 respondents. It was found that the changes were caused by consumption of anti-thyroid drugs, Thiamazole, Propranolol, Thyrozol, Propylthiouracil, Levothyroxine. Respondents with thyroid disorders were mostly found in 51-60 years and were female. There are changes in TSH hormone levels in patients with thyroid disorders were anti-thyroid drugs. The immunological method used ECLIA (Electrochemiluminescence Immunoassay) method. Factors that influence examination are the condition of sample and patient.

Sustained Euthyroidism during Thionamide Antithyroid Drug Treatment: Comparison of Short- and Long-term Methimazole Therapy

Background: Extended low serum thyrotropin (TSH) levels may increase the risk of cardiovascular events in patients with hyperthyroidism. Objectives: This study aimed to compare the time spent with sustained normal TSH concentration following short- and long-term methimazole treatment. Methods: A total of 258 patients with Graves’ hyperthyroidism completed 18 - 24 months of methimazole therapy and were randomized to discontinue treatment (n = 128, short-term group) or continue an additional 36 - 102 months of methimazole therapy (n = 130, long-term group). Clinical and laboratory evaluations were performed every 6 months for 132 months after randomization. Results: There was no difference in serum-free thyroxine, triiodothyronine, and TSH concentrations between the 2 groups at the time of randomization. Of 128 patients in the short-term group, 5 left in follow-up, 2 became hypothyroid, 67 (54%) had a relapse of hyperthyroidism, and only 54 (44%) were euthyroid at the end of the study. Among 130 patients on the long-term methimazole therapy, 4 were left in follow-up, 24 developed hyperthyroidism, 4 developed hypothyroidism, and 98 (78%) were euthyroid 132 months post-randomization. Total time spent on euthyroidism was 90.4% ± 8.1% of the study period in the short-term and 95.8% ± 7.0% in the long-term treatment groups (P < 0.001). The lowest time spent in euthyroidism (74.6% ± 6.4% of the study period) belonged to 29 (24%) patients in the short-term group under levothyroxine therapy because of fluctuation in serum TSH. Patients in both groups with hyperthyroidism relapse who chose methimazole therapy spent >90% of the study time in euthyroidism. Conclusions: In patients with Graves' hyperthyroidism, sustained normal serum TSH levels were more common in the long term as compared to the short-term methimazole treatment.

The Effects of Anti-thyroid Drugs on Lipoproteins and Insulin Resistance in Graves' Disease: A Randomized Clinical Trial.

Graves' disease (GD) is characterized by thyroid overactivity. Anti-thyroid drugs (ATDs), such as propylthiouracil (PTU) and methimazole (MMI), are commonly used for GD treatment, and studies have suggested a link between these drugs and elevated lipoprotein levels. However, data on their effects on lipoproteins, insulin resistance, or low-density lipoprotein receptor (LDL-R) levels are lacking, both in Indonesia and in other countries. This study investigated changes in lipoproteins, LDL-R, and insulin resistance markers with ATD treatment. This study is a secondary analysis of a randomized clinical trial entitled "The Differential Effects of Propylthiouracil and Methimazole as Graves' Disease Treatment on Vascular Atherosclerosis Markers" conducted in Jakarta, Indonesia. Thirty-seven newly diagnosed GD patients received MMI or PTU for 3 months. After 3 months of ATD treatment, LDL-R levels significantly decreased compared to baseline (197 vs. 144 ng/mL, p<0.001), while most lipoproteins, including TC, LDL-C, HDL-C, non-HDL-C, the cholesterol ratio, and the LDL-C/HDL-C ratio, increased. Unexpectedly, neither the PTU nor MMI groups showed an increased dyslipidemia prevalence. Although body mass index increased significantly and fasting plasma glucose decreased slightly, no significant post-treatment change in insulin resistance was observed. The study received ethical approval from the Ethics Committee of the Faculty of Medicine, Universitas Indonesia (ref KET-784/UN.2.F1/ETIK/PPM.00.02/2019) and was registered on clinicaltrials.gov (NCT05118542). ATD treatment for GD led to a significant increase in total cholesterol, LDL-cholesterol, and high-density lipoprotein-cholesterol levels, along with a reduction in LDL-R levels. Both PTU and MMI showed similar effects. These findings provide valuable insights into the effects of ATDs on lipoproteins and insulin resistance in GD patients. ClinicalTrials.gov Identifier: NCT05118542.

Preoperative Preparation in Hyperthyroidism and Surgery in the Hyperthyroid State.

Hyperthyroidism is a clinical condition that develops due to the excessive production and secretion of thyroid hormones by the thyroid gland, leading to an elevated concentration of thyroid hormones in tissues. Hyperthyroidism is characterized by low TSH and elevated T3 and/or T4, with the most common causes being Graves' disease, toxic multinodular goiter, and solitary toxic adenoma. T3 is the peripherally active form of thyroid hormone, affecting nearly each tissue and system. The most prominent aspects of hyperthyroidism are related to the cardiovascular system. The treatment of hyperthyroidism includes three options: antithyroid drugs (ATDs), radioactive iodine therapy (RAI), and surgery. Among these treatment modalities, surgery is considered as the most effective one. For patients who are candidates for surgery, preoperative preparation is required to ensure that the thyroidectomy can be performed under optimal conditions. Preoperative preparation should be a combination therapy aimed at preventing the synthesis, secretion, and peripheral effects of thyroid hormones from the thyroid gland. Medications that can be used in this treatment include thionamides, beta-blockers, iodine, corticosteroids, cholestyramine, perchlorate, lithium, and therapeutic plasma exchange. These treatment options can be combined based on the patient's condition. While it is recommended that patients be made euthyroid through preoperative antithyroid treatment to prevent the feared complication, which is the thyroid storm, the supporting evidence is limited. Preoperative treatment does not prevent against thyroid storm whether the patient is euthyroid or hyperthyroid during surgery. Whether surgery should be delayed until biochemical euthyroidism is achieved in hyperthyroid patients remains a topic of debate. Recent studies suggest that thyroidectomy can be safely performed during the hyperthyroid phase by experienced anesthesiologists and surgeons without precipitating thyroid storm or increasing intraoperative and postoperative complications. Although achieving the euthyroid state before surgery is ideal in hyperthyroid patients, it is not always possible. Factors such as allergies to medications, drug side effects, treatment-resistant disease, patient noncompliance, and the urgency of definitive treatment are critical in determining whether hyperthyroidism can be controlled preoperatively. When surgery is necessary in hyperthyroid patients without achieving euthyroidism, the patient's overall condition and comorbidities should be evaluated together by the anesthesiologist, surgeon and endocrinologist, with particular attention to stabilizing the cardiovascular system. We believe that in hyperthyroid patients who are cardiovascularly stable during the hyperthyroid phase, thyroid surgery may not need to be delayed and can be performed safely.

Clinical features of neonatal hyperthyroidism: a retrospective analysis in southwestern China.

This study aimed to explore the clinical characteristics and evaluate the different types of thyroid dysfunction in babies with neonatal hyperthyroidism. The clinical data of 19 neonates with hyperthyroidism admitted to the Children's Hospital of Chongqing Medical University between January 2012 and April 2021 were retrospectively analyzed. Fifteen (78.9%) infants were born to mothers with Graves' disease. Eleven (57.9%) infants were premature; two babies were born at small for gestational age. The age at diagnosis ranged from 3 to 34 days, with a mean of 18.53 ± 6.85 days. The majority of the babies presented with goiter (84.2%) and tachycardia (94.7%) after birth. Nine (47.4%) of them presented with abnormal weight gain, seven (36.8%) presented with stare or ocular protrusion, six (31.6%) presented with hyperexcitability, four (21.1%) presented with jaundice and liver dysfunction, two (10.5%) presented with sweating, one (5.3%) presented with fever, and one case presented without any symptoms. Transient hyperthyroidism was the main thyroid dysfunction in our study. Overt hyperthyroidism was diagnosed in 13 (68.4%) neonates. Another three babies (15.8%) presented with hyperthyroidism with slightly elevated free triiodothyronine levels, normal thyroxine (T4) levels, and low thyroid-stimulating hormone (TSH) levels. Normal thyroid hormone levels with low TSH levels were observed in three (15.8%) neonates. Ten children were treated with antithyroid drugs. Eighteen children recovered normal thyroid function at 1-3 months of age; one baby in the study group required further levothyroxine supplementation due to primary hypothyroidism (HT). One child was found to have developmental delay at 2 years of age during follow-up. Our study highlights the need for prolonged monitoring of thyroid function in suspected patients. A single normal screening for hyperthyroidism or the absence of a maternal history of hyperthyroidism cannot exclude this disease.

Novel Association of KLRC4-KLRK1 Gene Polymorphisms with Susceptibility and Progression of Antithyroid Drug-Induced Agranulocytosis.

Antithyroid drug (ATD)-induced agranulocytosis (TIA) is the most serious adverse effect during ATD treatment of Graves' disease (GD). Previously, the MICA gene was reported to be associated with TIA. MICA protein is an important ligand for the NKG2D protein, which is encoded by the KLRK1 gene and KLRC4-KLRK1 read-through transcription. This study further investigated the association between KLRC4-KLRK1 gene polymorphisms and susceptibility to TIA. Twenty-eight candidate single nucleotide polymorphisms (SNPs) on KLRC4-KLRK1 read-through transcription were evaluated by the iPLEX MassARRAY system in 209 GD control patients and 38 TIA cases. A significant association of rs2734565 polymorphism with TIA was found (p=0.02, OR=1.80, 95% CI=1.09-2.96). The haplotype C-A-A-C-G, including rs2734565-C, was associated with a significantly higher risk of TIA (p=4.79E-09, OR=8.361, 95% CI=3.737-18.707). In addition, the interval time from hyperthyroidism to agranulocytosis onset was shorter in patients carrying the rs2734565-C allele than in non-carrying groups (45.00 (14.00-6570.00) d vs. 1080.00 (30.00-3600.00) d, p=0.046), and the interval from ATD treatment to agranulocytosis onset was also shorter in patients carrying rs2734565-C allele (29.00 (13.00-75.00) d vs. 57.50 (21.00-240.00) d, p=0.023). The findings suggest that the KLRC4-KLRK1 gene polymorphism is associated with susceptibility and progression of ATD-induced agranulocytosis. Patients carrying the rs2734565-C allele had a higher susceptibility and faster onset time of TIA.

An Autopsy Case of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Induced by Propylthiouracil.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a complication caused by antithyroid drugs, particularly propylthiouracil (PTU). Most patients experience organ failure due to the affects of the treatment regimen. We herein report the case of an 89-year-old woman whose severe AAV induced by PTU resulted in various instances of organ failure that eventually led to death after 9 years of PTU therapy. During autopsy, we identified five types of organ failure. As AAV is a potentially fatal disease, the development of various vasculitis symptoms during PTU therapy should therefore be carefully monitored.

Ni(II)-MOF based hypersensitive dual-function luminescent sensor towards 3-nitrotyrosine biomarker and 6-Propyl-2-thiouracil antithyroid drug in Urine

Trace detection of bioactive small molecules (BSMs) in body fluids is of great importance for disease diagnosis, drug discovery, and health monitoring. Based on the chiral ligand of 4,4′-(1,2-dihydroxyethane-1,2-diyl)dibenzoic acid...

Graves Eye Disease Medical and Surgical Management: A Review

Graves’ disease (GD) is the most frequent cause of hyperthyroidism, where iodine levels are abundant. One of the extrathyroidal symptoms is Graves’ ophthalmopathy (GO) which presents with ophthalmic symptoms that can range from minor (e.g., dry eye) to sight-threatening (e.g., corneal ulceration and compressive optic neuropathy) features. About 79% of Graves’ disease cases can be attributed to genetic predispositions, while the remaining 21% are due to environmental factors. Acute stress, active or passive smoking, and past radioactive iodine therapy have all been linked to the development or aggravation of thyroid eye disease (TED). The devastating effects of GO or TED might include diplopia, ocular hypertension, optic nerve degeneration, and glaucoma. A low basal serum Thyroid Stimulating hormone (TSH) level has the highest sensitivity and specificity for diagnosing hyperthyroidism. Moreover, the appearance of Thyroid Stimulating hormone receptors (TSHR) autoantibodies (TRAbs) is presumed to be highly specific for the diagnosis of Graves’ disease. Imaging studies of the orbit that use ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI), for example, can confirm the diagnosis of TED. In order to treat Graves’s eye disease optimally, a multidisciplinary approach must be applied involving primary care physicians, ophthalmologists, internists and endocrinologists. Therefore, it is essential to restore the euthyroid state and this can be obtained by either antithyroid medications, radioactive iodine or surgical thyroidectomy. Treatment of GO ranges from supportive treatment (lubricants and moisturizer drops), to medical intervention, preferably corticosteroid, and variable surgical interventions. Key words: Graves’ disease, Medical and surgical management

RARE ASSOCIATION BETWEEN HASHITOXICOSIS, BASEDOW DISEASE AND PAPILLARY THYROID CARCINOMA.

We present the case of a 32 yeas old male, diagnosed 7 years ago with Graves disease, with numerous recidives which needed anti-thyroid medication, with poor response (hypo to hyper-thyroid status, with high variations of TSH and FT4) whom after a period of remission (8 months, no treatment) came in for a polymorphic symptomatology sugestive for hyperthyroidism. The hyperthyroid state was confirmed he had high TRAb (31 UI/ml vs. <1.75 UI/ml) - on his last check in the detection rate of TRAb was under 0.3 UI/ml. The thyroid ultrasound revels on the left lobe a small mass of 0.8/0.8 cm, with EU-TIRADS score of 4, that was newly diagnosed. Postoperative histopathology revealed papillary microcarcinoma developed on Hashitoxicosis- pT1aN0, of 1 mm in the middle of left thyroid lobe. The particularity of this case consists in a long evolution of Graves disease with numerous relapses, the appearance of a thyroid nodule after 7 years in which they identified a papillary microcacinoma associated with Hashimoto thyroiditis and also the postoperative recovery that was slowed by the parathyreoprive tetany.

Block-and-replace regimen versus titration of antithyroid drugs: a recent meta-analysis.

Drug therapy for Graves' disease (GD) is the first-line treatment in Europe. The use of a specific regimen for the administration of anti-thyroid drugs (ATDs) is still controversial. The objective was to compare block-and-replace therapy (BRT) with a titration (T) regimen in terms of incidence of overt hypothyroidism and development of Graves' orbitopathy (GO) over 18 months of treatment. Two databases (PubMed, Cochrane Library) and reference lists were searched. Prospective and retrospective observational cohort studies were included. Data collection and analysis were performed independently by 2 authors. Two studies with 716 GD patients (40.36% treated with BRT, 59.64% with T regimen) were included. No statistically significant differences were observed between the ATDs regimens used in terms of incidence of overt hypothyroidism during 18 months of treatment [Mantel-Haenszel (M-H) odds ratio (OR): 1.54, 95% confidence interval (CI): 0.75-3.16, p-value = 0.24]. GD patients who followed BRT were less likely to achieve control of thyroid function than patients on T regimen (M-H OR: 0.55, 95% CI: 0.34-0.88, p = 0.01). One study reported fewer thyroid function tests (TFT) during BRT than during the T regimen. The other study included patients without GO at baseline and reported a lower incidence of GO during BRT than in the T regimen (9.1% versus 17.8%), with no statistical difference between the 2 regimens (M-H OR: 0.47, 95% CI: 0.19-1.14, p = 0.10). BRT may be more useful than the T regimen for patients with complicated GD or for those who required fewer TFTs.

Relationship between Anti Tumour Necrosis factor and Thyroid Functions in Patients with Rheumatological Diseases

Relationship between Anti Tumour Necrosis factor and Thyroid Functions in Patients with Rheumatological Diseases

Current Therapeutic Approaches for Graves' Orbitopathy - are Targeted Therapies the Future?

Graves' orbitopathy is an autoimmune disease of the orbit that most frequently occurs with Graves' hyperthyroidism. The occurrence of autoantibodies directed against the TSH receptor (TRAb) is of central importance for the diagnosis and pathogenesis. These autoantibodies are mostly stimulating, and induce uncontrolled hyperthyroidism and tissue remodelling in the orbit and more or less pronounced inflammation. Consequently, patients suffer to a variable extent from periocular swelling, exophthalmos, and fibrosis of the eye muscles and thus restrictive motility impairment with double vision. In recent decades, therapeutic approaches have mainly comprised immunosuppressive treatments and antithyroid drug therapy for hyperthyroidism to inhibit thyroid hormone production. With the recognition that TRAb also activates an important growth factor receptor, IGF1R (insulin-like growth factor 1 receptor), biological agents have been developed. Teprotumumab (an inhibitory IGF1R antibody) has already been approved in the USA and the therapeutic effects are enormous, especially with regard to the reduction of exophthalmos. Side effects are to be considered, especially hyperglycaemia and hearing loss. It is not yet clear whether the autoimmune reaction (development of the TRAb/attraction of immunocompetent cells) is also influenced by anti-IGF1R inhibiting agents. Recurrences after therapy show that the inhibition of antibody development must be included in the therapeutic concept, especially in severe cases.