Insulin Autoimmune Syndrome - An After-Meal Roller Coaster Ride.

Hypoglycemic disorders are rare in persons without diabetes, and clinical evaluation to identify its etiology can be challenging. We present a case of insulin autoimmune syndrome induced by carbimazole in a middle-aged Chinese man with underlying Graves' disease, which was managed conservatively with a combination of dietary modification and alpha-glucosidase inhibitor.

Neutropenia Occurs More Often Under Carbimazole than Under Methimazole Treatment in Pediatric Graves' Disease Patients.

Background: Agranulocytosis is a rare antithyroid drug treatment (ATD) side effect seen in children suffering from Graves' disease (GD). Neutropenia is a recognized adverse event associated with ATD but has also been reported as pre-treatment neutropenia in GD. Methods: We performed a retrospective cohort study to analyze the longitudinal clinical and biochemical data of 161 pediatric patients with GD who received either methimazole (MMI) or carbimazole (CBZ) as ATD. The inclusion criteria were elevated free thyroxine (fT4 >25 pmol/L), suppressed thyrotropin (TSH <0.05 mlU/mL), and elevated thyrotropin receptor antibodies (TSHRAbs >2.5 IU/L). Absolute neutrophil count (ANC) was used to define neutropenia (ANC <1800/µL) and agranulocytosis (ANC <500/µL). Results: Nine of the 161 patients had neutropenia at diagnosis (ANC: 1348/µL ± 250) without further deterioration under ATD. In this subgroup, we found higher levels of free triiodothyronine (fT3: 31.45 pmol/L ± 3.99) at diagnosis in comparison with those who developed neutropenia (26.29 pmol/L ± 12.96; p = 0.07) and those without neutropenia before and during therapy (23.12 pmol/L ± 13.7; p = 0.003). Thirty-eight patients (23.6%) became neutropenic (ANC: 1479/µL ± 262) while receiving ATD. Neutropenia occurred after a mean of 551.8 (range: 10-1376) days, mostly without further deterioration. Two of these 38 patients developed agranulocytosis and underwent emergency thyroidectomy. The patients with neutropenia were significantly younger (p = 0.031). Neutropenia occurred significantly more often in patients receiving CBZ (50%; n = 20/40) than in those receiving MMI (16.5%; n = 18/110; p = 0.001). The minimum ANC was significantly lower in the CBZ (1971/µL ± 1008) than in the MMI group (2546 ± 959); p = 0.004. Conclusions: Neutropenia occurred significantly more often under CBZ than MMI. As this is potentially due to higher immunogenicity, we suggest that children with GD should be treated with MMI. Frequent measurements of ANC may be needed to detect severe agranulocytosis, although low pre-treatment ANC may not necessarily be a contraindication to ATD treatment. Young age may be potentially associated with an increased risk of reduced ANC. Further investigation is necessary to fully understand risk factors for neutropenia in children with GD.

Impact of carbimazole combined with vitamin E on testicular injury induced by experimental hyperthyroidism in adult albino rats: oxidative/inflammatory/apoptotic pathways.

Thyroid hormones play essential roles in spermatogenesis, but their effects on infertile males remain poorly understood. This study aimed to evaluate the impact of combining carbimazole (CBZ) with vitamin E (VE) on testicular injury induced by experimental hyperthyroidism in adult albino rats, focusing on oxidative, inflammatory, and apoptotic pathways. In this experimental study, 64 adult male albino Wistar rats were divided into eight groups: Group I (control-untreated), Group II (CBZ-control), Group III (VE-control), Group IV (CBZ + VE-control), Group V (levothyroxine-induced testicular injury), Group VI (levothyroxine + CBZ-treated), Group VII (levothyroxine + VE-treated), and Group VIII (levothyroxine + CBZ + VE-treated). The study was conducted in the Faculty of Medicine, Suez Canal University (Ismailia, Egypt). After cervical decapitation, both testes and epididymis were examined histopathologically and immunohistochemically. Significant differences were observed among groups concerning malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT; all P < 0.001). Polymerase chain reaction analysis showed significant differences in tumor necrosis factor-α (TNF- α ), interleukin-10 (IL-10), Bcl-2-associated X protein (BAX), B-cell lymphoma 2 protein (Bcl2), p53, Caspase-3, Caspase-8, Caspase-9, and nuclear factor-kappa B (NF- κ B) mRNA levels (all P < 0.001). Hyperthyroid group treated with CBZ alone (Group VI) exhibited testicular side effects, affecting seminiferous tubules and spermatogenesis. However, the Group VIII showed improved spermatogenesis and a decrease in testicular side effects. The addition of VE to the treatment of hyperthyroid rats with CBZ reduced testicular side effects and seminiferous tubular affection when potentially improving spermatogenesis. Further research is needed to elucidate the underlying mechanisms fully.

The influence of thionamides on intra-thyroidal uptake of 131I during radioiodine-131 treatment of Graves' disease.

Graves' disease is one of the most common causes of hyperthyroidism. Guideline recommendations advocate the intake of thionamides for at least 1 year. If hyperthyroidism persists, subsequent radioiodine-131 treatment (RIT) is a therapeutic option. Thionamides are known to influence intra-thyroidal bio-kinetics of iodine and should therefore be discontinued at least 3 days prior to RIT if possible. However, the required therapeutic activity has to be calculated individually by pre-therapeutic measurement of the uptake prior to RIT [radioiodine-131 uptake test (RIUT)] in Germany according to national guidelines. Therefore, the aim of this study was to quantify the influence of thionamides on intra-therapeutic uptake. A cohort of 829 patients with Graves' disease undergoing RIUT and RIT was analysed. Patients were subdivided into three groups. Group A: patients with carbimazole medication (n = 312), group B: patients with methimazole medication (n = 252) and group C: patients without thionamides (n = 265). Group A and B were further subdivided depending on the reduction of dosage of thionamides. In order to analyse the influence of thionamides, the variance of the determined individual extrapolated maximum intra-thyroidal uptake (EMU) between RIUT and RIT within the single groups and within the subgroups was statistically evaluated. When administering an equal dose of thionamides or no thionamides in RIUT and RIT (groups A1, B1 and C) no significant differences were detected when comparing EMU in RIT to EMU in RIUT (p > 0.05). In the subgroups A2-A4 (reduced dosage of carbimazole prior to RIT) EMU was significantly increased in RIT compared to RIUT [21% for a reduction of 0 to < 10 mg/d (A2), 39% for a reduction of 10-15 mg/d (A3) and 80% for a reduction of > 15 mg/d (A4)]. In the subgroups B2-B4 (reduced dosage of methimazole prior to RIT) EMU was as well significantly increased in RIT compared to RIUT [26% for a reduction of 0 to < 10 mg/d (B2), 36% for a reduction of 10-15 mg/d (B3) and 59% for a reduction of > 15 mg/d (B4)]. A significant dose-dependent increase of EMU in RIT compared to EMU in RIUT in patients discontinuing or reducing thionamides was detected. Therefore, thionamides should be discontinued at least 2 days prior to RIUT in order to achieve the designated target dose more precisely and to minimize radiation exposure of organs at risk.

Hypercalcaemia as the initial presentation of Graves' disease.

Hypercalcaemia in patients with hyperthyroidism is usually asymptomatic. It occurs due to increased bone turnover and demineralisation. There are only a few case reports where symptomatic hypercalcaemia was the presenting complaint of hyperthyroidism. An Asian man in his 40s presented to us with intractable vomiting for the last 6 months which was not controlled despite multiple antiemetic medications. On routine biochemistry performed at our institute, he was found to have hypercalcaemia and concomitant hyperthyroidism. Classical symptoms suggestive of hyperthyroidism were not present in our patient thus delaying the diagnosis. His symptoms resolved after the correction of hypercalcaemia. Hypercalcaemia did not recur after achieving an euthyroid status on treatment with carbimazole. Other common and more sinister causes for hypercalcaemia like malignancy were ruled out. This case highlights that symptomatic hypercalcaemia could be the initial presentation of hyperthyroidism and amelioration of hyperthyroidism corrects the hypercalcaemia.

Carbimazole-Resistant Graves' Disease Responding to Oral Prednisolone: A Case Report.

Conventional management of Graves' disease includes antithyroid drugs, radioactive iodine and thyroidectomy. Patients rarely may be resistant to antithyroid drugs and may require additional management, including corticosteroids. We treated an 18-year-old girl with Graves' thyrotoxicosis and resistance to Carbimazole. She was clinically and biochemically hyperthyroid despite getting 75mg Carbimazole and 120mg Propranolol daily. We added tablet Prednisolone (20mg for 15 days, then 10mg for the next 15 days) to Carbimazole (75mg/day). Four weeks later, she was free from thyrotoxic symptoms and her free T4 and total T3 levels normalized. The dose of tablet Prednisolone was lowered to 5mg/day for the next 15 days and Carbimazole was continued at 45mg/day. She received 10mCi Iodine-131 (131¹) at this stage and Carbimazole was discontinued. She remained clinically and biochemically euthyroid when she was followed up at 7th and 24th weeks after radioiodine ablation.

Brain functional connectivity in patients with hyperthyroidism after anti-thyroid treatment.

Thyroid disease is known to affect brain metabolism and cognitive function, although the recovery of thyroid-induced brain functional changes after treatment remains unclear. We aimed to investigate the alteration in brain functional connectivity and its correlation with neuropsychological variables in hyperthyroid patients before and after anti-thyroid treatment using a resting-state functional magnetic resonance imaging (rsfMRI) technique. This is a follow-up rsfMRI study of previous work that showed impaired brain functional connectivity in hyperthyroid patients compared to healthy controls. We included rsfMRI and neuropsychological data from 21 hyperthyroid patients out of an original cohort of 28 patients, before and after anti-thyroid treatment for 30 weeks. Functional connectivity analysis and neuropsychological scores were compared using paired t tests in patients at baseline and at follow-up. Patients showed an improvement in some of the memory (p < .05) and executive, visuospatial and motor (p < .001) functions after treatment, and also showed increased functional connectivity in the regions of the right fronto-parietal network, left fronto-parietal network, and default mode network (DMN) (p < .05). At follow-up, the functional connectivity of the right fronto-parietal network showed a significantly positive correlation with the recognition of objects memory score. The overall findings suggest that anti-thyroid treatment with carbimazole improves the functional connectivity within some of the resting state networks in the hyperthyroid patients, whereas the remaining networks still show impairment.

Notes for the general paediatrician: managing thyrotoxicosis in children and young people.

Thyrotoxicosis due to hyperthyroidism is a serious disorder in childhood often presenting to general paediatricians with a range of clinical manifestations. The commonest cause is Graves' disease, an autoimmune disorder resulting from thyrotropin receptor stimulation by autoantibodies. Early recognition and accurate interpretation of investigations are essential to achieve and maintain a euthyroid state. This will not only optimise growth, development and transition from childhood to young adult life but also avoid the potentially severe and life-threatening complications of acute thyrotoxicosis. In this review, we have focussed on the general paediatrician's perspective of the presentation and management of thyrotoxicosis and the need to network with specialist paediatric endocrine centres to optimise patient care. We have discussed nuances of therapy, side effects and long-term outcomes, while recognising that limited remission rates in this age group often necessitate more definitive management. While carbimazole is usually used as first-line medical therapy, we have provided useful information to guide paediatricians in the discussion of individualised safe and effective treatment plans for both short-term and long-term management.

Graves' disease associated with cholestatic jaundice and persistent diarrhoea.

Liver involvement in Graves' disease can be seen as a part of autoimmune process or rarely, due to the direct effects of thyrotoxicosis on liver. Hyperthyroidism can also have gastrointestinal manifestations like frequent bowel movements, diarrhoea, even malabsorption with steatorrhoea. We report a 36-year-old man with hyperthyroidism, presenting with cholestatic jaundice and persistent small bowel diarrhoea. He was diagnosed to have Graves' disease and after ruling out more common causes, the cause of cholestatic jaundice was supposed to be Graves' disease. Considering this possibility, the patient was started on treatment with carbimazole. As patient's thyroid function tests started improving, he showed significant clinical and biochemical improvement from liver point of view as well.

[Graves' Disease]. / Morbus Basedow.

DIAGNOSIS: The diagnosis of Graves' disease is mainly based on ultrasonography and laboratory diagnostics. This includes the determination of the TSH value and the peripheral thyroid hormones. TSH receptor antibody (TRAb) measurement is highly sensitive and specific for the detection of Graves' disease (GD) and helps to distinguish from autoimmune thyroiditis (AIT). However, as recent studies show, some may AIT patients may also reveal TRAb. THERAPY: Current guidelines recommend primarily the use of thiamazol/carbimazole in GD. Due to the comparatively higher hepatotoxicity, propylthiouracil is not recommended as first line therapy. In case of relapse during 12 up to 18 months of antithyroid drug therapy or after a frustrating attempt at cessation, definitive therapy should be considered. Alternatively, in accordance with the current recommendations of the European Thyroid Association, drug therapy may be continued for up to 12 months after initial diagnosis. PREGNANCY: The treatment of active GD during pregnancy is problematic due to diaplacental crossing of peripheral thyroid hormones, TSH receptor stimulating antibodies and antithyroid drugs. According to current guidelines, PTU is recommended during the first 16 weeks of pregnancy, whereas for the 2nd and 3 rd trimester no special recommendations are given. After that, you can choose which antithyroid drug might be used. The aim of antithyroid drug therapy during pregnancy is to achieve a suppressed TSH value together with normal or slightly increased fT4 while using lowest effective dose of antithyroid drug. IMMUNE CHECKPOINT INHIBITORS (ICI): The most common endocrine side effect with this therapy is thyroid dysfunction. Hyperthyroidism; occur most frequently in combination therapy (CTLA-4 / anti-PD-1 therapy) ICI mainly causes destructive thyroiditis with lymphocytic infiltration; GD is absolutely rare in this context and only few cases are described.

Metabolic effects of brown fat in transitioning from hyperthyroidism to euthyroidism.

OBJECTIVE: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. DESIGN: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. RESULTS: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). CONCLUSION: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.

The adjunctive use of carbimazole during radioactive iodine treatment reduces the cure rate of Graves' disease.

BACKGROUND: Radioactive iodine (RAI) is widely used in the treatment of hyperthyroidism. Adjunctive antithyroid drugs (ATDs) are commonly prescribed to treat the hyperthyroid state before the RAI has taken effect. However, there is no consensus on the use of or timing of adjunctive ATD treatment with RAI. OBJECTIVES: To determine the influence of the ATD carbimazole on the cure rate of RAI treatment for Graves' disease. METHODS: A retrospective chart review was conducted in the Department of Nuclear Medicine of the Steve Biko Academic Hospital in Pretoria. The cure rate of patients treated with RAI for Graves' disease was analysed. The effect of adjunctive carbimazole treatment with regard to its use and timing with RAI dosing was analysed. The cure rate was determined in patients treated with carbimazole either before RAI or before and after RAI administration. Cure rate was defined by the biochemical thyroid function status (thyroxine (T4), thyroid-stimulating hormone (TSH)) as euthyroid or hypothyroid from 3 months and sustained at 12 months. The need for a second dose of RAI was recorded. RESULTS: RAI treatment was administered to 171 patients with Graves' disease. The cure rate was higher in patients receiving a higher dose of RAI. The overall cure rate increased progressively from 3 months and was 91% at 12 months. The cure rate in 97 patients not receiving carbimazole was 98%. The cure rate of the 27 patients on carbimazole treatment given before RAI administration was 81%, and 73% in the 37 patients in whom it was resumed after RAI administration. The overall cure rate was lower in patients who received carbimazole (p<0.001), but especially in patients in whom carbimazole was continued after RAI administration (p<0.001). CONCLUSIONS: Adjunctive carbimazole treatment decreased the RAI cure rate of Graves' disease significantly.

Graves' disease presenting with hypomania and paranoia to the acute psychiatry service.

This manuscript describes the case of a young woman, with no prior psychiatric history, who developed hypomania and paranoia as the principal presenting features of Graves' disease. After starting treatment with carbimazole and propranolol, symptoms resolved without the use of antipsychotic drugs. Close liaison between psychiatry and endocrinology services was essential. This demonstrates that treating underlying thyrotoxicosis in patients presenting with psychiatric symptoms may lead to recovery without the use of antipsychotic medication. While agitation, irritability and mood lability are well-recognised thyrotoxic symptoms, psychosis is a rare presenting feature of Graves' disease. All patients with agitation, delirium or psychiatric symptoms should have thyroid function checked as part of initial tests screening for organic disease. In new or relapsing psychiatric conditions, it is important to ask patients, their carers or relatives about symptoms of hypothyroidism or thyrotoxicosis.

Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations.

Hereditary haemorrhagic telangiectasia (HHT) also known as Osler-Weber-Rendu syndrome is an autosomal dominant disorder affecting 1 in 8000 individuals. The eponym recognises the 19th-century physicians William Osler, Henri Jules Louis Marie Rendu and Frederick Parkes Weber who each independently described the disease. It is characterised by epistaxis, telangiectasia and visceral arteriovenous malformations. Individuals with HHT have been found to have abnormal plasma concentrations of transforming growth factor beta and vascular endothelial growth factor secondary to mutations in ENG, ACVRL1 and MADH4. Pulmonary artery malformations (PAVMs) are abnormal communications between pulmonary arteries and veins and are found in up to 50% of individuals with HHT. The clinical features suggestive of PAVMs are stigmata of right to left shunting such as dyspnoea, hypoxaemia, cyanosis, cerebral embolism and unexplained haemoptysis or haemothorax. The authors present the case of a 33-year-old woman presenting with progressive dyspnoea during the COVID-19 pandemic. She had a typical presentation of HHT with recurrent epistaxis, telangiectasia and pulmonary arteriovenous malformations. Although rare, PAVM should be considered in individuals presenting to the emergency department with dyspnoea and hypoxaemia. Delayed diagnosis can result in fatal embolic and haemorrhagic complications.

Hyperthyroidism treatment by alternative therapies based on cupping and dietary-herbal supplementation: a case report.

OBJECTIVES: Hyperthyroidism is characterized by increasing production of thyroid hormone (TH) and decreasing of thyroid stimulation hormone (TSH) secretion. The treatment of hyperthyroidism includes such as anti-thyroid drugs, radioiodine, and thyroidectomy have many side effects without complete curing results. We described a successful treatment of hyperthyroidism patient with dietary-herbal supplementation with wet cupping without any medicine. CASE PRESENTATION: A 29-years female, blood analysis showed that she had low TSH (0.012 mlU/mL), and normal levels of T3 and T4. After completing 16 weeks on Carbimazole, TSH value still low (0.024 mlU/mL) and urticaria was appeared. She decided to stop Carbimazole and try alternative therapy choices. She received wet cupping and dietary-herbal supplementations (including royal jelly, green barley grass and Taraxaf®) for two months. Notably, TSH values was increased during-after intervention and urticaria was disappeared. CONCLUSIONS: Alternative therapy could be a beneficial choice for hyperthyroidism treatment without any side effects or complications under physician supervision.

Hyperthyroidism in Cats: Considering the Impact of Treatment Modality on Quality of Life for Cats and Their Owners.

In cats, hyperthyroidism can be treated in 4 ways: medical management with methimazole or carbimazole, nutritional management (low-iodine diet), surgical thyroidectomy, and radioactive iodine (131I). Each form of treatment has advantages and disadvantages that should be considered when formulating a treatment plan for the individual hyperthyroid cat. Medical and nutritional managements are considered "reversible" or palliative treatments, whereas surgical thyroidectomy and 131I are "permanent" or curative treatments. The author discusses how each treatment modality could be the optimal choice for a specific cat-owner combination and reviews the advantages and disadvantages of each treatment option.

Long-term outcome of cats with acquired myasthenia gravis without evidence of a cranial mediastinal mass.

BACKGROUND: Acquired myasthenia gravis (AMG) is increasingly recognized in cats, yet information regarding the natural history of the disease, treatment, and outcome including occurrence of immune and spontaneous remission remains limited. OBJECTIVE: To determine the long-term outcome of cats with AMG without evidence of a cranial mediastinal mass (CMM). ANIMALS: Eight cats diagnosed with AMG without evidence of a CMM. METHODS: Retrospective case series. The medical records of cats diagnosed with AMG between 2005 and 2018 from 2 veterinary referral hospitals were reviewed for inclusion. Inclusion criteria consisted of a diagnosis of AMG, thoracic imaging, serum biochemistry including measurement of creatine kinase, and a CBC. Exclusion criteria were the presence of an identifiable CMM, or administration of methimazole or carbimazole. RESULTS: All cats had an excellent long-term outcome, achieving immune remission within 6 months of diagnosis, including 4 cats that did not receive any treatment and whose natural course of disease involved spontaneous remission. Clinical presentation was heterogeneous, and skeletal muscle weakness and fatigability induced or exacerbated by the wheelbarrow exercise stress test were the most consistent abnormalities associated with AMG. CONCLUSION AND CLINICAL IMPORTANCE: Cats diagnosed with AMG without evidence a CMM have a favorable outcome and frequently achieve immune remission. Moreover, the natural history of AMG in cats includes spontaneous remission when there is no evidence of a CMM. Attempting to rule out the presence of a CMM therefore refines prognosis, and treatment is not always necessary in this disease population.

A Case of Polyautoimmunity: Celiac Hepatitis, Grave's Disease and Autoimmune Hemolytic Anemia.

Celiac disease (CD) is an autoimmune disorder with high incidence of multi organ involvement; especially, gastrointestinal manifestations and an increased risk of malignancies. Here we report a case of CD with celiac hepatitis, autoimmune hemolytic anemia (AIHA) and Grave's disease (GD) with their complications. Polyautoimmunity requires comprehensive analysis. While CD and GD were previously diagnosed, AIHA and cirrhosis were diagnosed during admission upon extensive work-up. Similarly, other autoimmune etiologies, such as autoimmune hepatitis (AIH), and/or primary biliary cholangitis were ruled out. All three diseases were treated afresh with strict adherence to a gluten-free diet (GFD) and carbimazole along with addition of medications for cirrhosis complicated by ascites. This was a rare case where non-adherence to a GFD led to such severe adverse events. A case of celiac hepatitis presenting with such a wide array of signs and symptoms has rarely been reported in the literature and the management of this patient was unique and challenging.

Case study of thyrotoxic cardiomyopathy.

We present the case of a 65-year-old woman who was referred urgently from primary care with worsening breathlessness for 3 weeks, associated with tachycardia and left bundle branch block (LBBB). She had a background of type 2 diabetes, asthma and hypertension. Initial ECG revealed atrial fibrillation with the fast ventricular rate on the background of LBBB. ECHO findings were consistent with systolic impairment. Initial testing including checking thyroid function test revealed hyperthyroidism. It became evident that this patient had thyrotoxic cardiomyopathy. Early advice from the endocrine team was sought and the patient was treated with a combination of carbimazole and ivabradine. After a hospital stay, she made a remarkable recovery.