Antioxidant effects of α-lipoic acid against epididymal oxidative damage in adult offspring rats exposed to maternal hypothyroidism stress.

It is well known that the epididymis promotes post-testicular sperm maturation events. However, its malfunction during congenital hypothyroidism is relatively less understood as compared to the testis. The present study evaluated the probable effect of α-lipoic acid on epididymal oxidative stress parameters in rats exposed to antithyroid drug, carbimazole during fetal period. Time-mated pregnant rats in unexposed and carbimazole (1.35 mg/Kg body weight exposed were allowed to deliver pups and weaned. At postnatal day 100, the F1 male pups were assessed for epididymal endpoints. Among the epididymal regions, significant elevation of lipid peroxidation levels, superoxide anion, and hydrogen peroxide contents with a concomitant reduction in the activity levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and reduced glutathione levels were observed in cauda epididymis of carbimazole exposed rats over controls. Significant elevation in sperm DNA fragmentation (comet assay), accelerated cauda epididymal sperm transit time and reduction in epididymal sialic acid content was observed in carbimazole exposed rats. RT-qPCR studies revealed that embryonic exposure to carbimazole resulted in down regulation of androgen receptor, nuclear factor eryrthoid 2 like 2, 5α-reducatse 1 mRNA levels, while up regulation of caspase 3 mRNA was observed in epididymal regions of rats. In addition, fetal exposure to carbimazole resulted in disorganization of cauda epididymal architecture in rats. Conversely, supplementation of α-lipoic acid (70 mg/Kg bodyweight) during PND 3 to 14 restored epididymal functions in carbimazole exposed rats and the ameliorative effects of lipoic acid could be attributed to its antioxidant and steroidogenic effects.

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.

Carbimazole-induced atypia - A mimicker of malignancy in fine-needle aspiration cytology.

A 20-year-old female presented with complaints of thyroid swelling and showed signs and symptoms of thyrotoxicosis and fine-needle aspiration cytology (FNAC) was requested by the surgeon. On examination of FNAC smear, it showed thyroid follicular cells with atypical features like bizarre giant cells, pseudo nuclear inclusions, and mitotic figure. Correlation between clinical history and cytomorphologic features was done and it was reported as atypical changes in thyroid probably due to carbimazole-induced changes. It helped the patient, as radical surgery and its untoward complications were avoided.

Azathioprine as an adjuvant therapy in severe Graves' disease: a randomized controlled open-label clinical trial.

Introduction: Azathioprine (AZA) interferes with the activation of T and B lymphocytes, which are the main cells involved in the pathogenesis of Graves' disease (GD). The aim of this study was to investigate the effectiveness of AZA as an adjuvant therapy to antithyroid drugs (ATDs) for moderate and severe GD. In addition, we conducted an incremental cost-effectiveness analysis of AZA to determine its cost-effectiveness. Methods: We conducted a randomized, open-label, and parallel-group clinical trial. We randomized untreated hyperthyroid patients with severe GD into three groups. All patients received 45-mg carbimazole (CM) as the starting dose and propranolol 40-120 mg daily. The first group (AZA1) received an additional 1 mg/kg/day AZA, the second group (AZA2) received an additional 2 mg/kg/day AZA, and the third group (control group) received only CM and propranolol. We measured thyroid-stimulating hormone (TSH) and TSH-receptor antibody (TRAb) levels at baseline and every 3 months, while free triiodothyronine (FT3) and free thyroxine (FT4) levels were measured at the time of diagnosis, 1 month after initiation of therapy, and every 3 months thereafter until 2 years after remission. Thyroid volume (TV) was assessed by ultrasound at baseline and 1 year after remission. Results: A total of 270 patients were included in this trial. By the end of follow-up, there was higher remission rate in the AZA1 and AZA2 groups compared with controls (87.5% and 87.5% vs. 33.4%, p = 0.002). Throughout the course of follow-up, FT3, FT4, TSH, and TRAb were significantly different between the AZA groups and the control group, but there was no significant difference regarding TV. The decline in the concentrations of FT4, FT3, and TRAb was significantly faster in the AZA2 group than in the AZA1 group. The relapse rate during the 12-month follow-up was insignificantly higher in the control group than in either the AZA1 or AZA2 group (10, 4.4, and 4.4%, p = 0.05, respectively). The median relapse time was 18 months for the control group and 24 months for the AZA1 and AZA2 groups. The incremental cost-effectiveness ratio for the AZA group compared with the conventional group was 27,220.4 Egyptian pounds per remission reduction for patients using AZA as an adjuvant for ATDs. Conclusion: AZA could be a novel, affordable, cost-effective, and safe drug offering hope for patients with GD to achieve early and long-lasting medical remission. Trial registry: The trial is registered at the Pan African Clinical Trial Registry (Registration number: PACTR201912487382180).

Preconception Management of Hyperthyroidism and Thyroid Status in Subsequent Pregnancy: A Population-Based Cohort Study.

CONTEXT: Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy. OBJECTIVE: We aimed to determine trends in the management of hyperthyroidism before and during pregnancy and to assess the impact of different preconception treatment strategies on maternal thyroid status. METHODS: We utilized the Clinical Practice Research Datalink database to evaluate all females aged 15-45 years with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset. RESULTS: Our study cohort comprised 4712 pregnancies. Thyrotropin (TSH) was measured in only 53.1% of pregnancies, of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH <0.1 mU/L plus FT4 >reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared with pregnancies starting during antithyroid drug treatment (odds ratio 4.72, 95% CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000 to 2017. One-third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole. CONCLUSION: The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counseling are needed to optimize thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes.

Severe Neutropenia and Hepatotoxicity After Carbimazole Drug Therapy for Hyperthyroidism in a Pediatric Patient: A Case Report.

BACKGROUND Hyperthyroidism is an overproduction of thyroid hormones. Carbimazole is an anti-thyroid medication used to treat hyperthyroidism in adults and children. It is a thionamide associated with rare adverse effects such as neutropenia, leukopenia, agranulocytosis, and hepatotoxicity. Severe neutropenia is a life-threatening event characterized by a sharp drop in absolute neutrophil count. Severe neutropenia can be treated by discontinuation of the precipitating medication. Administration of granulocyte colony-stimulating factor provides longer protection against neutropenia. Elevated liver enzymes indicate hepatotoxicity, which usually normalize after discontinuation of the offending medication. CASE REPORT A 17-year-old girl was treated with carbimazole since the age of 15 for hyperthyroidism secondary to Graves' disease. She initially received 10 mg of carbimazole orally twice daily. After 3 months, the patient's thyroid function reflected residual hyperthyroidism and was then up-titrated to 15 mg orally in the morning and 10 mg orally in the evening. She presented to the emergency department reporting fever, body aches, headache, nausea, and abdominal pain for 3 days. She was diagnosed with severe neutropenia and hepatotoxicity induced by carbimazole after 18 months of dose modification. CONCLUSIONS In hyperthyroidism, it is important to maintain patients in a euthyroid state for a long period to minimize the autoimmunity and hyperthyroid relapse, which often requires long-term use of carbimazole. However, severe neutropenia and hepatotoxicity are rare and serious adverse effects of carbimazole. Clinicians should be aware of the importance to discontinuation of carbimazole, administration of granulocyte colony-stimulating factors, and supportive treatment to reverse the consequences.

The protective impact of hesperidin against carbimazole-induced hypothyroidism, via enhancement of inflammatory cytokines, histopathological alterations, and Nrf2/HO-1.

The aim of this study was to evaluate the anti-inflammatory, antioxidant, and antiproliferative effects of hesperidin (HSP) and eltroxin (ELT) on hypothyroidism (HPO) induced by carbimazole (CBZ) in white male albino rats. Thirty-two adult rats were categorized into four groups: Group 1, no treatment (control); Group II, treated with CBZ (20 mg/kg); Group III, treated with HSP (200 mg/kg) + CBZ; and Group IV, treated with ELT (0.045 mg/kg) + CBZ. All treatments were provided as oral daily doses for 90 days. Thyroid hypofunction was significantly manifested in Group II. However, increased levels of thyroid hormones, antioxidant enzymes, nuclear factor erythroid 2-related factor 2, heme oxygenase 1, and interleukin (IL)-10, and a decrease in the level of the thyroid-stimulating hormone were observed in Groups III and IV. On the contrary, decreased levels of lipid peroxidation, inducible nitric oxide synthase, tumor necrosis factor α, IL-17, and cyclooxygenase 2 were detected in groups III and IV. The histopathological and ultrastructural findings were ameliorated in Groups III and IV; on the contrary, Group II presented with significant increases in the height and number of layers of the follicular cells. Immunohistochemistry demonstrated a marked increase in thyroglobulin and significant decreases in the levels of nuclear factor kappa B and proliferating cell nuclear antigen in Groups III and IV. These results confirmed the effectiveness of HSP as an anti-inflammatory, antioxidant, and antiproliferative agent in rats with hypothyroidism. Additional studies are required to assess its potential as a novel agent against HPO.

Transcriptomic profiling identified altered expression of genes associated with testicular functions in adult F1 rats exposed to carbimazole during fetal period.

The central goal of this study was to investigate the alterations in transcriptome of testis in F1 generation adult rats exposed to carbimazole prenatally. At post-natal day 100, the testis of rats delivered to carbimazole exposed (time-mated pregnant rats orally administered with carbimazole from gestation day 9 to 21) and control (untreated pregnant rats) groups were subjected to transcriptomic analysis using NGS platform. A total of 187 differentially expressed (up regulated: 49 genes; down regulated: 138) genes were identified in carbimazole exposed rats over controls and the major processes associated with these altered testicular transcripts were examined. Functional clustering analysis suggest that the involvement of identified DEGs were linked to intrinsic and extrinsic apoptotic pathways, mitochondrial solute carriers slc25a members, nuclear receptors/zinc family members, steroidogenic pathway and cholesterol synthesis, and growth factors and protein kinases and thus represent potential mediators of the developmental toxic effects of carbimazole in F1 generation rats. Based on the findings, it can be concluded that prenatal exposure to carbimazole prominently affects expression of multiple transcripts implicating key regulatory events associated with testicular functions, spermatogenesis and steroidogenesis in rats at their adulthood. These results support our earlier findings and hypothesis. This background information obtained at the testicular transcriptome during gestational hypothyroidism might be helpful for future studies and experiments to gain additional in-depth analysis and to develop strategies to protect F1 generation male reproductive health. SIGNIFICANCE: The rationale for the paper described thyroid gland changes in the off springs. Antithyroid drugs are widely used to control thyroid disorders and used to control thyroid hormone levels during surgeries. Carbimazole is one of the antithyroid drugs and is a parent molecule of methimazole. Both the drugs can able to cross placenta. During fetal period, the development of thyroid gland is not completely formed and hence, the fetus entirely depends on the maternal thyroid hormones. Therefore, it is conceivable that the disturbances at the level of maternal thyroid hormones could interfere with the development of vital organs such as testis and glands including thyroid gland (Kala et al., 2012). To address this notion, the present study was designed and executed.

Acute pancreatitis caused by methimazole/carbimazole assumption: a case-series.

The World Health Organization (WHO) has listed 525 different drugs, that can lead to acute pancreatitis cases, as a medication side-effect. Among them, methimazole (MMI also known as thiamazole, the active form of carbimazole [CBZ]) was included. We reported case reports of patients with overall features compatible with acute pancreatitis episodes following and presumably triggered by the exposure to MMI and its prodrug CBZ. A systematic search was performed on MEDLINE (PubMed). We included case reports of patients with overall features compatible with acute pancreatitis episodes following and presumably triggered by the exposure to MMI and its prodrug CBZ Data extraction and analysis were undertaken in duplicate. We identified 7 case reports. Most patients were female, and one patient was male. Mean age at baseline ranged from 18 to 80 years old. The average time, that elapses between the initiation of the therapy with MMI/CBZ and the onset of typical clinical signs and symptoms pathognomonic of acute pancreatitis, was 2-3 weeks. Based on the data derived from these case reports, it could be considered the possibility of a potential association between MMI/CBZ exposure. Evidence is, however, limited and requires more studies of high quality to confirm this association.

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.

Metformin alleviates the dysregulated testicular steroidogenesis and spermatogenesis induced by carbimazole in levothyroxine-primed rats.

Most of the published experiments about carbimazole (CMZ)-induced testicular injury are constructed in normal healthy animals, which lakes the translational identification. Despite metformin (MET) having advantageous effects on injured testicles, its impact on thyroid function is arguable. In the current levothyroxine (LT4)/CMZ model, Wistar rats were primed by LT4 for sixty days. CMZ was then given individually or simultaneously with different doses of MET, 100, 200, and 400 mg, daily for thirty days. Serum was assessed for thyroid profile panel, sex hormones, and gonadotropin levels. Testicular tissues were examined for steroidogenesis, spermatogenesis, inflammation, and apoptosis. Histopathology of thyroid and testes were examined, besides thyroidal nuclear factor (NF)-kB expression. MET in a dose-response manner improved the LT4/CMZ-induced testicular toxicity by increasing the steroidogenic acute regulatory protein (StAR), and 17-ß-hydroxysteroid dehydrogenase (17ßHSD) activities, the proliferating cell nuclear antigen (PCNA), sperm count and motility, sex hormones, and gonadotropin levels. MET-400 mg markedly decreased the elevated NF-kB expressions, tumour necrosis factor (TNF)-α, caspase-3, and BAX, and increased BCL-2. LT4/CMZ could be used as translational animal modelling. MET displayed a dose-dependent ameliorative effect on the LT4/CMZ model without significant harmful effects on thyroid functions. MET-testicular protective roles in diabetics with thyroidal diseases should be explored.

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.

Possible protective role of L-thyroxin on the parotid gland of adult male albino rat in carbimazole induced hypothyroidism: histological, histomorphometry, and ultrastructural study.

BACKGROUND: Thyroid disorders are among the most common metabolic disorders worldwide. Thyroid dysfunction affects salivary glands function, causing hyposalivation. It also provokes physiological and histological changes in parotid, submandibular, and in particular the sublingual gland. THE AIM OF THIS WORK: The aim of this work was to clarify the histological and ultrastructural changes that occur in the parotid gland following carbimazole-induced hypothyroidism in adult male albino rats. The study also aims to investigate the possible protective role of L-thyroxin supplementation on the rat parotid glands after long and short duration of hypothyroidism. MATERIAL AND METHODS: Fifty-five adult male albino rats of Sprague Dawley strain; were divided into four groups and eleven subgroups, five rats each. G І received nothing. G П given normal saline orally daily. G Ш (medical Hypothyroidism, short duration - long duration - recovery group) given Carbimazole orally by gastric tube in a dose of 0.05 mg/kg daily for 3,6 successive weeks for group (a, b) and for 6 successive weeks then were left without any medication for another 3 weeks in recovery group c. G IV-b, c (L-Thyroxine supplemented group, short duration-long duration) given Carbimazole orally daily for 3,6 successive weeks then L-thyroxine was given orally in a dose of (10 µg/100 g/B.W) daily for another 3 successive weeks. Animals were sacrificed 24 hours after the last dose of Carbimazole in G III-a, b and 3 weeks after stoppage the drug in G III-c. Animals were sacrificed 24 hours after the last dose of L- Thyroxine in G IV-b, c. The parotid specimens were processed for histopathological examination by light and electron microscopy. The medically induced Hypothyroidism resulted in significant parotid gland damage which was more obvious with longer duration; as follow: a) most of the acini had irregular outlines and were widely separated with narrow lumen and cytoplasmic vacuoles. b) some acinar cells contained ill defined, irregular, pyknotic or hyperchromatic nuclei. c)Vascular changes: dilated and engorged with blood. d) the interlobular and striated ducts appeared disrupted and dilated. e) extravasated blood with cellular infiltration were seen in the interstitial space. IN CONCLUSION: Thyroid hormones (THs) had a significant effect in protection of parotid gland against damage induced by carbimazole, as it preserved the normal histological architecture of the parotid gland. This beneficial effect of THs was mostly related to its antioxidant properties. The expression of BCL-2 has certain regularity in apoptosis after drug administration. Regulation of glandular atrophy and apoptosis are closely related. The molecular mechanism of the apoptosis of the gland is not clear, and further study is needed in the future.

The Protective Effect of Turmeric against Carbimazole Induced Toxicity in Male Rats.

Carbimazole is a widespread drug utilized for treating hyperthyroidism. However, carbimazole usage could be associated with adverse effects such as liver damage and nephritis in rats. At the same time, turmeric, as a medical plant, has many antioxidant effects against liver and kidney toxicity. This study aimed to explore the protective effect of turmeric against carbimazole-induced toxicity in rats. The experiment was carried out on 24 male Wistar rats. They were separated into four groups, each with six animals, as follows: 1. Control group: represents a healthy animal, and each rat is only given standard food and distilled water for 30 days. 2. Carbimazole group: drenched orally 0.5 mg carbimazole daily for 30 days. 3. Turmeric group: drenched orally 100 mg turmeric powder daily for 30 days. 4. Carbimazole and turmeric group: drenched orally carbimazole 0.5 mg and turmeric 100 mg daily for 30 days. The study demonstrated a significant effect of turmeric powder in reducing the toxicity of carbimazole in both the kidney and liver biochemical parameters, in addition to the evidence of histological sections. Turmeric powder has the ability to reduce and prevent renal and hepatic toxicity induced by carbimazole overdose, which gives turmeric medical value.

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.

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.

Antithyroid drug therapy in pregnancy and risk of congenital anomalies: Systematic review and meta-analysis.

OBJECTIVES: The risk of congenital anomalies following in utero exposure to thionamide antithyroid drugs (ATDs) is unresolved. Observational studies are contradictory and existing meta-analyses predate and preclude more recent studies. We undertook an updated meta-analysis of congenital anomaly risk in women exposed to carbimazole or methimazole (CMZ/MMI), propylthiouracil (PTU), or untreated hyperthyroidism in pregnancy. METHODS: We searched Medline, Embase, and the Cochrane database for articles published up till August 2021. We pooled separate crude and adjusted risk estimates using random effects models and subgroup analyses to address heterogeneity. RESULTS: We identified 16 cohort studies comprising 5957, 15,785, and 15,666 exposures to CMZ/MMI, PTU, and untreated hyperthyroidism, respectively. Compared to nondisease controls, adjusted risk ratio (RR) and 95% confidence intervals (95% CIs) for congenital anomalies was increased for CMZ/MMI (RR, 1.28; 95% CI, 1.06-1.54) and PTU (RR, 1.16; 95% CI, 1.08-1.25). Crude risk for CMZ/MMI was increased relative to PTU (RR, 1.20; 95% CI, 1.01-1.43). Increased risk was also seen with exposure to both CMZ/MMI and PTU, that is, women who switched ATDs in pregnancy (RR, 1.51; 95% CI, 1.14-1.99). However, the timing of ATD switch was highly variable and included prepregnancy switches in some studies. The excess number of anomalies per 1000 live births was 17.2 for patients exposed to CMZ/MMI, 9.8, for PTU exposure, and 31.4 for exposure to both CMZ/MMI and PTU. Risk in the untreated group did not differ from control or ATD groups. The untreated group was however highly heterogeneous in terms of thyroid status. Subgroup analysis showed more positive associations in studies with >500 exposures and up to 1-year follow-up. CONCLUSIONS: ATD therapy carries a small risk of congenital anomalies which is higher for CMZ/MMI than for PTU and does not appear to be reduced by switching ATDs in pregnancy. Due to key limitations in the available data, further studies will be required to clarify the risks associated with untreated hyperthyroidism and with switching ATDs in pregnancy.

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.