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Hyperthyroidism is a rare clinical entity in paediatric age. In most cases the etiology is autoimmune and goiter represents the typical presentation. Ophthalmopathy is rare and can precede the diagnosis of autoimmune hyperthyroidism. Thyrotoxicosis caused by the hyperthyroid phase of Hashimoto’s thyroiditis must be carefully distinguished from Graves’ disease (GD), since the first condition has a better prognosis for spontaneous remission. Three treatment options are currently available for the management of paediatric GD. First-line therapy is antithyroid drugs, while thyroidectomy and radioiodine are considered on relapse. A lower remission rate and a higher risk of adverse events are observed after the first course of methimazole in childhood with respect to adulthood. Children and adolescents may require a prolonged antithyroid treatment, but an overall consensus regarding the optimal regimen is lacking.

The majority of agranulocytosis cases are caused by drugs, including nonsteroidal anti-inflammatory drugs, antibiotics, antithyroid agents, etc. Here, we report a case of severe agranulocytosis in a 67-year-old woman following nonsteroidal anti-inflammatory therapy which was successfully managed using recombinant human granulocyte colony-stimulating factor. Although metamizole, has been in use since 1922 in the management of postoperative pain, colic pain, cancer pain and migraine, agranulocytosis as a direct side effect of metamizole therapy has been rarely reported. It is important to keep in mind this rare but potentially life-threatening adverse effect of metamizole, when initiating therapy.

Graves' disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through inhibition of thyroid hormone synthesis or destruction of the thyroid gland. Recurrence after antithyroid drug (ATD) treatment is common. Recent studies have shown that the longer is the duration of use of ATD, the higher is the remission rate. Considering the relationship between clinical outcomes and iodine intake, recurrence of Graves' disease is more common in iodine-deficient areas than in iodine-sufficient areas. Iodine restriction in an iodine-excessive area does not improve the effectiveness of ATD or increase remission rates. Recently, Danish and Korean nationwide studies noted significantly higher prevalence of birth defects in newborns exposed to ATD during the first trimester compared to that of those who did not have such exposure. The prevalence of birth defects was lowest when propylthiouracil (PTU) was used and decreased by only 0.15% when methimazole was changed to PTU in the first trimester. Therefore, it is best not to use ATD in the first trimester or to change to PTU before pregnancy.

Background The aim of this study was to investigate the changes in vital signs and hemodynamic status that occur in patients during the intraoperative course of thyroidectomy in Graves- Disease (GD). Methods A total of 71 patients were included in the study. Patients were directed to surgery when they had large goiters with compressive symptoms or suspicious nodules, were pregnant or lactating, were unresponsive or intolerant to antithyroid drugs (ATDs), or expressed a preference to have surgery. All patients scheduled for operations underwent surgery while in the euthyroid state. Results Hemodynamic instability was observed in 18 patients during thyroidectomy. Disease duration, sample weight, and thyroid-stimulating hormone receptor antibodies (TRAb) levels were found to be effective on hemodynamic instability. Logistic regression analysis revealed an 11-fold increase in the instability risk in patients with a period of disease shorter than 21 months (P = 0.037). A TRAb value >11.5 increased the risk by 235fold (p < 0.001). Conclusion High levels of TRAb values and new onset of disease with shorter periods of ATDs use may be risk factors for hemodynamic instability during thyroidectomy. Patients with larger thyroid glands are at greater risk for instability during surgery. Those risks should be taken into account during surgery, and the surgical and anesthetic management of the patient should be made more carefully in concordance with the anesthesia team.

Current literature suggests 12–18 months of antithyroid drug (ATD) treatment for patients with Graves’ disease, but the risk of relapse is high. Although some studies reported better outcomes of long-term ATD treatment, recent data that suggest the optimal treatment duration are limited. We performed a multicenter retrospective cohort study of 908 patients newly diagnosed with Graves’ disease between 2006 and 2013. The relapse rate according to ATD treatment duration was analyzed. After initial ATD treatment, 338 patients (37.2%) had relapsed. The relapse rate according to ATD treatment duration was 42.4% at 1 year, 38.5% at 2 years, 33.8% at 3 years, 31.7% at 4 years, 30.2% at 5 years, 27.8% at 6 years, and 19.1% at more than 6 years, respectively, demonstrating a significant decreasing trend (p = 0.003). In a multivariable Cox regression analysis, ATD treatment duration was an independent risk factor for relapse (p = 0.043). The longer that ATD therapy is used, the lower the relapse rate is in patients with Graves’ disease. Long-term ATD treatment may be considered in Graves’ patients who do not show complications or an economic burden from hyperthyroidism.

Maternal and fetal complications may occur because of pathologic or immunologic changes during pregnancy. The American Thyroid Association (ATA) suggests an optimal thyroid stimulating hormone (TSH) reference range of 0.50-4.00 mU/L in pregnant women. Based on Korean data, the same range may be applied to Korean pregnant women. According to the ATA guideline, levothyroxine therapy is recommended for thyroid peroxidase antibody (TPOAb)-positive women with a TSH greater than the pregnancy-specific reference range (approximately ＞4.0 mU/L in Korea) and TPOAb-negative women with a TSH ＞10.0 mU/L. The presence of TPOAb may be a sign of hypothyroidism due to damage to the thyroid. Because the titer of TPOAb decreases as gestation progresses, its measurement should be performed as early as possible during pregnancy. Although the mechanism is unknown, the association between thyroid autoimmunity and miscarriage/premature delivery is clear. Selenium may reduce the development of postpartum thyroiditis and permanent hypothyroidism; however, routine prescription of selenium is not recommended as it may increase the risk of type 2 diabetes. According to Korean nationwide data, birth defects in antithyroid drug (ATD)-exposed offspring in early pregnancy increased by 1.1 to 2.2% compared with non-exposed offspring. Avoidance of ATD in early pregnancy is the best option, otherwise, it is preferable to switch to propylthiouracil before pregnancy. When methimazole use is unavoidable in early pregnancy, it is recommended to use less than 5 mg per day.

The protolytic properties and reactions with molecular iodine and blood serum proteins of 5,7-dimethyltetrahydro-1H-imidazo[4,5-e]-1,2,4-triazine-3,6(2H,4H)-dithione and (R)-1,3-dialkyl-4-[(2-hydroxybenzylidene)amino]-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-ones were studied. These compounds exhibit different chemical reactivities towards molecular iodine. The binding constants between these compounds and serum albumin attest to a considerable protein affinity of the compounds. The properties of the thiones make them promising as antithyroid agents.

To investigate the long-term outcomes of radioiodine therapy (RIT) for juvenile Graves disease (GD) and the ultrasonographic changes of the thyroid gland.All of 117 juvenile patients (25 males and 92 females, aged 10 to 18lsqb;median 16] years) who had undergone RIT for GD at our clinic between 1999 and 2018 were retrospectively reviewed. Each RIT session was delivered on an outpatient basis. The maximumAt the latest follow-up more than 12 months after RIT (n = 111), the patients' thyroid functions were overt hypothyroidism (91%), subclinical hypothyroidism (2%), normal (5%), or subclinical hyperthyroidism (2%). New thyroid nodules were detected in 9 patients, 4 to 17 years after initial RIT. Patients with newly detected thyroid nodules underwent RIT with lower doses ofOver a median follow-up period of 95 months (range, 4 to 226 months), RIT was found to be effective and safe in juvenile GD. However, cumulative evidence from further studies is required to confirm the long-term safety of RIT for juvenile GD.ATD = antithyroid drug; GD = Graves disease; KI = potassium iodide; LT4 = levothyroxine; MMI = methimazole; PTU = propylthiouracil; RAIU = radio-active iodine uptake; RIT = radioiodine therapy

Objective: To analyze the effects of methimazole (MMI)-containing combination regimens on the thyroid status and relapse rates in patients with Graves hyperthyroidism (GH) using a network meta-analysis to provide guidance for clinical application. Methods: We conducted a literature review, which identified 21 trials for inclusion. The major outcomes were serum free triiodothyronine (FT3) and free thyroxine (FT4) concentrations. The secondary outcome was relapse rate. A network meta-analysis was used to compare multiple regimens to identify the most advantageous regimen. Results: The types of combined drugs included anti-oxidant complexes, selenium, vitamin D3, cholestyramine, risedronate, iodine, potassium bromide, immunosuppressants, and β-adrenergic antagonists. Regarding the FT3 results, the rank probability of the best result showed that potassium bromide (0.897) and vitamin D3 (0.833) had relative advantages in reducing FT3 at the 1-month time point. According to the time trend analysis, compared with the control treatment, cholestyramine and iodine showed advantages in reducing FT3 during the early stage (0 to 3 months). The immunosuppressants showed advantages in reducing FT3 during the late stage (>9 months) but not the early stage. Regarding the FT4 results, potassium bromide had the highest P-score (.965) at the 1-month time point. Iodine and cholestyramine had advantages in reducing FT4 during the early stage. The immunosuppressants had advantages during both the early and late stages. Conclusion: MMI combined with cholestyramine or iodine was shown to regulate serum FT3 and FT4 during the early stage of GH. MMI combined with immunosuppressants had a long-term advantage in FT3/FT4 regulation and reduced the relapse rate. Abbreviations: ATD = antithyroid drug; CI = confidence interval; FT3 = free triiodothyronine; FT4 = free thyroxine; GH = Graves hyperthyroidism; MMI = methimazole; OR = odds ratio; RCT = randomized controlled trial; SMD = standard mean difference; TCM = traditional Chinese medicine.

Before us is the story of young woman who actively monitored the condition of the thyroid gland, due to the accidental detection of antibodies to the thyroid tissue. After the detection of a tumor (7 mm), hemi thyroidectomy was conducted. For two years after the operation she has been under the care of oncologist and endocrinologist. However, despite explanations about a good prognosis of the disease, she is extremely alarmed and unjustifiably often conducts laboratory tests, ignoring the fact that both the reference range and the evaluation methods are different. It should be said that similar problems exist in all countries (Nedman C. et al., 2017) fear of relapse of the disease worries the vast majority of patients even years after its been diagnosed. People are concerned not only about the risks of thyroid cancer recurrence, but also about the risks of development of other cancers, the risks of being not able to get access to skilled care. The obvious task of a doctor is to correct a pattern of patient behavior that increases anxiety.

Graves’ disease is the most common cause of hyperthyroidism, which is characterized by thyroid antibodies and the following clinical manifestations: goiter, ophthalmopathy, and pretibial myxedema. On the other hand, Henoch–Schönlein purpura is an IgA-mediated small-vessel vasculitis. Review of the literature showed a relationship between propylthiouracil overdose and the following Henoch–Schönlein purpura (IgA vasculitis) as a side effect. The patient was a 31-year-old woman with a chief complaint of tremor and significant weight loss who contracted pruritic palpable purpura during her disease course. Then, she underwent the treatment of hyperthyroidism by methimazole which intensified her cutaneous lesions. The diagnosis of Henoch–Schönlein purpura (IgA vasculitis) was confirmed after skin biopsy. Finally, she was treated with colchicine, prednisolone, and radioiodine ablation, which caused her lesions to disappear. The temporal priority of pruritic palpable skin lesions to hyperthyroidism treatment with methimazole suggested that Henoch–Schönlein purpura (IgA vasculitis) was related to hyperthyroidism and was intensified by antithyroid agents in this patient.

Radioactive iodine (RAI) is widely used to treat patients with Graves’ disease, as either initial therapy or following failure of thionamides, and thyroid nodular autonomy. The recent publication of a study from Kitahara and colleagues, indicating a slightly higher relative risk of breast cancer in hyperthyroid patients receiving RAI therapy, started a large debate that is mainly focused on methodological limitations. Quite surprisingly, two of Kitahara’s study co-authors showed, using data from the same cohort, that the standardized mortality ratio (SMR) for breast cancer is higher for patients treated with antithyroid drugs compared with patients treated with RAI.

A 34-year-old Filipino with Graves’ disease on methimazole came in due to fever, sore throat and jaundice. Patient was initially diagnosed with methimazole induced agranulocytosis and drug induced liver injury. She was treated with intravenous broad spectrum antibiotic and granulocyte colony stimulating factor. On day 4 of admission, patient had pancytopenia and was managed as methimazole induced aplastic anemia and was started on steroid therapy and 1 unit of packed red blood cell was transfused. The jaundice also increased hence she was given ursodeoxycholic acid. On day 9 of admission, with the consideration of “lineage steal phenomenon,” biopsy was done and eltrompobag was started. Patient was discharged stable at 12th day of hospital admission. This case presents the 3 rarest, life threatening complication of methimazole: agranulocytosis, aplastic anemia and hepatitis. .

The study was primarily aimed at investigating the effect of brassica sprout consumption, namely rutabaga (Brassica napus L. var. napobrassica) sprouts (R) generally recognized as antithyroid agent due to its goitrogenic substance content, on hematological, biochemical, and immunological parameters in rats. Sprouts were tested alone and in a combination with other antithyroid factors, such as iodine deficiency (RDI) and sulfadimethoxine (RS). The expression of the heme oxygenase-1 (HO-1) gene in the thyroid as a stress-inducible protein was determined. The thermographic analysis was also estimated. The intake of rutabaga sprouts by healthy rats did not reveal any significant, harmful effect on the thyroid function. Both body temperature and expression of HO-1 remained unchanged in response to the consumed sprouts. In animals with hypothyroidism, rutabaga sprouts enhanced the negative effect of iodine deficiency or sulfadimethoxine ingestion on the organism by increasing the WBC (RDI), TNF-α (RS), creatinine (RS), and triglyceride (RDI and RS) levels, as well as decreasing PLT (RS) level. Moreover, rutabaga sprout consumption by rats with iodine deficiency and sulfadimethoxine decreased their body temperature. Additionally, the concomitant administration of sprouts and iodine depletion significantly reduced the expression of HO-1 in the thyroid. The results may prove useful in confirming rutabaga sprout consumption to be safe, though the seeds of this vegetable provide a well-known antithyroid agent. Our results have shown that rutabaga sprout consumption may be also a factor that enhances the negative clinical features only when combined with iodine deficiency and sulfadimethoxine ingestion.

Whether or not Graves’ hyperthyroidism can be really cured, depends on the definition of “cure.” If eradication of thyroid hormone excess suffices for the label “cure,” then all patients can be cured because total thyroidectomy or high doses of 131I will abolish hy perthyroidism albeit at the expense of creating another disease (hypothyroidism) requiring lifelong medication with levothyroxine. I would not call this a “cure,” which I would like to define as a state with stable thyroid stimulating hormone (TSH), free thyroxine, and triiodothyronine serum concentrations in the normal range in the absence of any thyroid medication. Surgery and radioiodine are unlikely to result in so-defined cures, as their preferable aim as stated in guidelines is to cause permanent hypothyroidism. Discon tinuation of antithyroid drugs is followed by 50% recurrences within 4 years; before starting therapy the risk of recurrences can be estimated with the Graves’ Recurrent Events After Therapy (GREAT) score. At 20-year follow-up about 62% had developed recur rent hyperthyroidism, 8% had subclinical hypothyroidism, and 3% overt hypothyroidism related to TSH receptor blocking antibod ies and thyroid peroxidase antibodies. Only 27% was in remission, and might be considered cured. If the definition of “cure” would also include the disappearance of thyroid antibodies in serum, the proportion of cured patients would become even lower.

The functional role of thyroid hormone (TH) in the cortex and hippocampus of mouse during neuronal development was investigated in this study. TH insufficiency showed a decrease in the expression of parvalbumin (PV) in the cortex and hippocampus of pups at postnatal day (PD) 14, while treatment with thyroxine from PD 0 to PD 14 ameliorated the PV loss. On the other hand, treatment with antithyroid agents in adulthood did not result in a decrease in the expression of PV in these areas. These results indicate the existence of a critical period of TH action during the early postnatal period. A decrease in MeCP2-positive neuronal nuclei was also observed in the cortical layers II–IV of the cerebral cortex. The brains were then stained with CUX1, a marker for cortical layers II–IV. In comparison with normal mice, CUX1 signals were decreased in the somatosensory cortex of the hypothyroid mice, and the total thickness of cortical layers II–IV of the mice was lower than that of normal mice. These results suggest that TH insufficiency during the perinatal period strongly and broadly affects neuronal development.

Hypothyroidism is the most frequent thyroid dysfunction. It is the consequence of a decrease in the biological activity of thyroid hormones in target tissues. The aim of this paper is to review and update acquired hypothyroidism in childhood and adolescence with emphasis on primary hypothyroidism due to its greater frequency. Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, is the most common cause of primary acquired hypothyroidism. The distinctive feature is the profound impact on skeletal growth, maturation, and pubertal development, with potential implications on adult height. Signs and symptoms of acquired hypothyroidism are similar to those reported in adults and are generally not associated with neurodevelopmental impairment. Biochemical confirmation of primary hypothyroidism requires the finding of elevated thyrophine and decreased free thyroxine levels. Treatment goals are to achieve normal growth and maturation as well as cognitive development. In most of the patients, replacement treatment reverses symptoms and signs of hypothyroidism and may decrease goiter size.

Graves’ orbitopathy (GO) is the main extrathyroidal manifestation of Graves’ disease (GD). Choice of treatment should be based on the assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments, and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight-threatening GO, antithyroid drugs are preferred when managing Graves’ hyperthyroidism. In moderate-to-severe and active GO i.v. glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness, and patient choice after extensive counseling, a combination of i.v. methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 g of i.v. methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include (a) the second course of i.v. methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, (b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; (c) orbital radiotherapy combined with oral or i.v. glucocorticoids, (d) teprotumumab; (e) rituximab and (f) tocilizumab. Sight-threatening GO is treated with several high single doses of i.v. methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint, and eyelid surgery) is indicated for inactive residual GO manifestations.

Background. The shift of Graves’ disease (GD) to Hashimoto’s disease- (HD-) related hypothyroidism is well established. However, the opposite is rare. This is likely to the loss of critical thyroid mass available for stimulation by thyroid hormone receptor stimulating antibody, making this shift unusual. Herein, we report a young lady with a late shift from HD into GD and present a scoping literature review. Case presentation. We report a twenty-five-year-old lady with a sixteen-year-history of Hashimoto’s-related hypothyroidism stable on levothyroxine. While following in the clinic, she started developing thyrotoxic symptoms in the form of anxiety, weight loss, and palpitation. Physical examination was remarkable for mild exophthalmos. The thyroid function test confirmed hyperthyroidism. Levothyroxine-induced hyperthyroidism was initially suspected; however, the symptoms did not improve despite reducing and stopping levothyroxine. Subsequent workup confirmed the diagnosis of GD. Discussion and Conclusion. This case highlights a unique association that has significant diagnostic and management implications. This shift should be considered when hyperthyroidism persists despite reducing or stopping levothyroxine. The diagnosis is made utilizing antibody titers and radioiodine update scan. While the management depends on the disease’s stage and the treating physician preference, antithyroid agents can be used initially. Following up these patients is essential as the shift can be transient.

Le traitement de la maladie de Basedow repose sur trois thérapies: le traitement médical par les antithyroïdiens de synthèse, la chirurgie et l´irathérapie. L´objectif de notre étude était d´étudier la place et l´efficacité du traitement à l´iode radioactif dans le traitement de la maladie de Basedow. Une étude rétrospective portant sur 54 patients suivis pour une maladie de Basedow et traités par iode 131. On a mené en une étude descriptive des aspects épidémiologiques, cliniques, para cliniques et thérapeutiques et du le taux de rémission à court et à moyen terme. Le sex-ratio était de 0,45. L´âge moyen est de 38,33 ± 12,7 ans. Les signes fonctionnels les plus fréquemment retrouvés étaient l´amaigrissement, les tremblements et les palpitations. La FT4 moyenne est de 54,51 ± 19,56ng/dl (extrêmes: 8,90-100). La TSHus moyenne de nos patients était égale 0,074 ± 0,29 µUI/ml. Les antithyroïdiens de synthèse ont été prescrits chez 49 patients avec une persistance d´une hyperthyroïdie dans 83,67% des cas. L´irathérapie a été prescrite en première intention dans 9,3% et en 2ème intention dans 90,7% des cas. L´activité moyenne était égale à 13,29 mCi ± 1,46 avec des extrêmes allant de 10 à 15 mCi. Le premier contrôle hormonal post-irathérapie, réalisé après un délai moyen de 1,91 mois, a montré une rémission (eu- ou hypo-thyroïdie) chez 29 patients soit 53,7%. Après 12 mois de suivi, l´évolution était marquée par une rémission dans 88,88% (euthyroïdie chez 14,8% et l´hypothyroïdie chez 74%). L´irathérapie est un traitement efficace de la maladie de Basedow. Une dose forfaitaire forte d´iode radioactif permet d´obtenir un taux de rémission élevé.

Context: Graves’ disease is an autoimmune disease caused by thyrotropin receptor antibodies (TRAb). These antibodies can be measured and used for the diagnosis, prediction of remission, and risk of Graves’ orbitopathy development. There are three treatments for Graves’ disease that have remained unchanged for the last 75 years: Antithyroid drugs, radioiodine, and surgery. Antithyroid drugs are the first treatment option worldwide and are usually used for 12 - 18 months. Recent reports suggest the use of antithyroid drugs for more than 18 months with better outcomes. This review focuses on two aspects of treatment with antithyroid drugs: The impact of using antithyroid drugs for more than 12 - 18 months on remission rates and the trend of TRAb during prolonged antithyroid drug treatment. Evidence Acquisition: A review was performed in Medline on the published work regarding the duration of ATD treatment and remission of Graves' disease and also ATD treatment and TRAb status during the 1990 - 2019 period. Results: Remission rates are variable (30% - 80%), and many clinical and genetic factors serve as predictors. The long-term use of antithyroid drugs appears to increase remission rates. TRAb values usually decline during ATD treatment, but the trend could occur in two ways: Becoming negative or showing a fluctuating pattern. However, approximately 10% of the patients will remain TRAb-positive after five years of treatment with antithyroid drugs. Conclusions: Antithyroid drugs can be used for long periods with an increase in remission rates, and a gradual decrease in TRAb levels, with the disappearance of TRAb in 90% of the patients after 60 months.

Despite its’ life-threatening potential due to cardiac severe dysrhythmia in the context of severe hypokalemia, thyrotoxic periodic paralysis (TPP) often goes unrecognized. Although classically confined to young Asian men, it can occur irrespective of age, sex, and race. We report a short series of three cases of TPP as first presentation of Graves’ disease in a young Caucasian male and in two Caucasian elderly and middle-aged women, respectively. The first patient developed malignant ventricular arrhythmias due to severe hypokalemia and was defibrillated, with recovery after prompt potassium correction and administration of antithyroid agents and propranolol. The other two cases developed persistent hypokalemia despite adequate potassium chloride (KCl) repletion, with slow recovery of motor deficit and serum potassium normalization up to day 5. In the first case, long-term euthyroid state was achieved via total thyroidectomy due to the presence of a suspicious nodule that proved to be malignant. In the other two cases, medical treatment was the choice of therapy for thyrotoxicosis. None experienced recurrent TPP. Thyroid hormone evaluation is mandatory in the presence of hypokalemic paralysis, even in the absence of clinical signs of thyrotoxicosis. If TPP is confirmed, initial therapy should comprise antithyroid drugs and propranolol, besides hypokalemia correction.

Elbuken, Gulsah/0000-0002-0920-6895; Kadioglu, Pinar/0000-0002-8329-140X WOS:000562953800001 PubMed ID: 32154572 Introduction: The outcome of medical treatment in patients with Graves' disease (GD) is generally difficult to predict. In this study, we examined the hypothesis that gender may affect the outcome of treatment with antithyroid drugs (ATDs). Material and methods: This is a retrospective multicentre study including 717 (514 female and 203 male) patients with the first episode of GD treated for at least 12 months. Patients were classified as relapse, poorly controlled (several episodes of hyperthyroidism followed by euthyroidism and rarely hypothyroidism, occurring after titration of ATDs), and remission. Results: During the mean follow-up time of 26.75 +/- 21.25 months (between 1 and 120 months), 269 (37.5%),176 (24.5%), and 272 (37.9%) patients experienced a relapse, a poorly controlled disease, and remained in remission, respectively. During the follow-up time, 223 (43.4%) of the female and only 49 (24%) of the male patients remained in remission. Relapse and poorly controlled disease (non-remitting GD) were more common in male compared to female patients with GD (hazard ratio 1.26, 95% CI: 1.03-133, p - 0.025). Graves' disease in male patients tended to relapse earlier, and male patients tended to have larger goiter sizes at diagnosis as well. The smoking habit was also significantly inure frequent in males compared to female patients with GD. Conclusion: Male patients with GD have a markedly higher frequency of relapse and poorly controlled disease, as compared to female patients. Larger goiter sizes and higher frequency of smoking may contribute to the higher frequency of relapse and poorly controlled disease in male patients.

Thyroid hormone (TH) is critical for many aspects of neurodevelopment and can be disrupted by a variety of environmental contaminants. Sensory systems, including audition and vision are vulnerable to TH insufficiencies, but little data are available on visual system development at less than severe levels of TH deprivation. The goal of the current experiments was to explore dose-response relations between graded levels of TH insufficiency during development and the visual function of adult offspring. Pregnant Long Evans rats received 0 or 3 ppm (Experiment 1), or 0, 1, 2, or 3 ppm (Experiment 2) of propylthiouracil (PTU), an inhibitor of thyroid hormone synthesis, in drinking water from gestation day (GD) 6 to postnatal day (PN) 21. Treatment with PTU caused dose-related reductions of serum T4, with recovery on termination of exposure, and euthyroidism by the time of visual function testing. Tests of retinal (electroretinograms; ERGs) and visual cortex (visual evoked potentials; VEPs) function were assessed in adult offspring. Dark-adapted ERG a-waves, reflecting rod photoreceptors, were increased in amplitude by PTU. Light-adapted green flicker ERGs, reflecting M-cone photoreceptors, were reduced by PTU exposure. UV-flicker ERGs, reflecting S-cones, were not altered. Pattern-elicited VEPs were significantly reduced by 2 and 3 ppm PTU across a range of stimulus contrast values. The slope of VEP amplitude-log contrast functions was reduced by PTU, suggesting impaired visual contrast gain. Visual contrast gain primarily reflects function of visual cortex, and is responsible for adjusting sensitivity of perceptual mechanisms in response to changing visual scenes. The results indicate that moderate levels of pre-and post-natal TH insufficiency led to alterations in visual function of adult rats, including both retinal and visual cortex sites of dysfunction.

Objective: The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating hyperthyroidism. Methods: Qualitative analysis was performed for studies identified in a literature search up to April 20, 2019, and 30 studies were selected for meta-analysis. The study designs included case-control, randomized controlled, and retrospective cohort. Patients were in four age groups: childhood, gestating mothers, older adults, and other ages, and all were receiving PTU or MMI/CMZ. Adverse reactions to MMI/CMZ and PTU were evaluated and compared. Results: Odds of liver function injury were higher in the PTU group than in the MMI/CMZ group (odds ratio lOR], 2.40; 95% confidence interval lCI], 1.16 to 4.96; P = .02). Odds of elevated transaminase were much higher in the PTU group than in the MMI/CMZ group (OR, 3.96; 95% CI, 2.49 to 6.28; P Conclusion: The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children. In treating pregnancy-related hyperthyroidism, PTU should be used in the first trimester and MMI reserved for use in late pregnancy. Abbreviations: ALT = alanine aminotransferase; ATD = antithyroid drug; CI = confidence interval; CMZ = carbimazole; GD = Graves disease; MMI = methimazole; MTU = methylthiouracil; NOS = Newcastle-Ottawa Scale; OR = odds ratio; PTU = propylthiouracil; RAI = radioactive iodine

Moringa leaves and spinach used as vegetables containing cyanogens and polyphenols having suspected antithyroidal activity; however, detailed studies in this aspect found unavailable. Goitrogenic/antithyroid potentiality of those plant foods of Indian origin was evaluated. To explore the goitrogenic/antithyroid effect of those plant foods cyanogenic glucosides, glucosinolates, thiocyanate and polyphenol content were measured. These plant foods were fed with diet regularly to adult male albino rats for 30 and 60 days respectively, followed by evaluation of morphological and functional status of thyroid,as thyroid gland weight, the activity status of thyroid hormone synthesizing enzymes viz. TPO, Na+ -K+ -ATPase, deiodinase I, thyroid hormone profiles, thyroid histoarchitecture as well as urinary iodine and thiocyanate. In moringa leaves and spinach fed diet, there was a significant increase in urinary excretion of thiocyanate and iodine, enlargement of thyroid gland along with hypertrophy of thyroid follicles and altered in the activities of thyroid hormone synthesizing enzymes with concomitant changes of thyroid hormone profiles. Effects were more severe in moringa leaves treated group than that of spinach. Biochemical analysis moringa leaves and spinach reveal that those are rich sources of goitrogens and their prolonged consumption gradually developed a relative state of biochemical and morphological hypothyroidism.

Background The approach to the clinical management of Graves’ disease (GD) is debatable. This study aimed to identify predictors of remission in pediatric GD. Methods A longitudinal study of 36 children and adolescents with GD followed from 1997 to 2017 at a single tertiary hospital was performed. Clinical and biochemical parameters, including comorbidities, treatment with anti-thyroid drugs (ATD) or definitive therapy (radioiodine [RIT] and thyroidectomy), and remission as the main outcome were collected. We performed a multivariable logistic regression analysis to identify likely predictors of remission. Results Among patients, most were female, in late puberty, with exuberant symptoms at onset. Eleven also suffered from Down syndrome (DS). Thirty-four patients (94%) started on methimazole from disease onset, and 25 (69%) received it as the only therapy, with a mean duration of 2.7±1.8 years. Six changed to RIT and three underwent thyroidectomy; no DS patient received definitive therapy. Remission was higher in DS patients (45% vs. 25%, p=0.24), but afterwards (3.9±2.5 vs. 2.3±1.4 years, p Conclusions Males were more likely to achieve remission. TSI values may normalize in GD, notably from the second year of treatment. DS children may benefit with conservative management in GD.

Background: Antithyroid drugs (ATDs) are first-line treatment for Graves’ hyperthyroidism worldwide, but relapses are frequent. The reliability of individual risk factors to predict at baseline subsequent relapse is poor. Predictive scores grouping single risk factors might help to select the best treatment (pharmacological vs. ablative). Objective: To assess the predictivity of a recently developed score (Clinical Severity Score, CSS) and to compare it with another score (GREAT score). Patients: A retrospective observational, single-center study was conducted of 387 consecutive, newly diagnosed Graves’ patients, who completed an 18–24 months ATD course and were followed for at least 2 years. Results: Hyperthyroidism relapsed in 185 patients (48%). At diagnosis and before treatment, the relapse group had higher serum TSH-receptor antibody and free thyroxine levels and larger goiters than the remission group, with no differences in Graves’ orbitopathy prevalence and severity. In the multivariate analyses, only large goiter size was significantly associated with an increased recurrence hazard ratio. Using CSS, the risk of relapse increased from 36% in the mild category and 49% in the moderate category to 59% in the severe category, with quite a good area under the curve (AUC) (0.60; 95% CI: 0.55; 0.66). GREAT score showed an increase in relapse from 34% for class I (mild) and 49% for class II (moderate) to 64% for class III (severe) (AUC, 0.63; CI: 0.58; 0.68). Conclusions: Both CSS and GREAT score are useful, although imperfect, tools to predict at baseline relapse of hyperthyroidism after treatment. In real life they may help the clinician to tailor a treatment for newly diagnosed Graves’ hyperthyroidism.

Concurrent presentation of acute hepatitis A virus (HAV) infection and Graves' disease has not been reported in literature worldwide. Although there is no well-established mechanism that explains the induction of Graves' disease by HAV to date, our case suggests that HAV infection may be responsible for inducing Graves' disease. A healthy 27-year-old female presented fever, palpitation, and diarrhea, and she was subsequently diagnosed as acute HAV infection. Concurrently, she showed hyperthyroidism, and the diagnosis was made as Graves' disease. She had never had symptoms that suggested hyperthyroidism, and previous thyroid function test was normal. Acute HAV infection was recovered by conservative management, however, thyroid dysfunction was maintained even after normalization of liver enzymes. Methimazole was used to treat Graves' disease. We report a case of concurrent acute HAV infection and Graves' disease in a patient without preexisting thyroid disease. This suggests that HAV infection may be a trigger for an autoimmune thyroid disease in susceptible individuals.

Thyroid cancer in children, the most common endocrine malignancy, shows aggressive behavior and has a high recurrence rate after surgical ablation. Radioactive iodine (RAI) treatment is the most effective primary modality for medical ablation of juvenile thyroid cancer, and leads to intentional hypothyroidism. Although several negative impacts of hypothyroidism have been reported in children in response to other antithyroid agents, the combined effects of RAI exposure and hypothyroidism, on growing bones specifically, are unknown. In this study, we investigated the effect of RAI-induced hypothyroidism on the long bones during the pubertal growth spurt using immature female rats. Female Sprague-Dawley rats were randomly divided into a control group, and an RAI-treated group fed with RAI (0.37 MBq/g body weight) twice via gavage. After 4 weeks, we observed a significantly-reduced serum free thyroxine level in the RAI group. The latter group also displayed decreased body weight gain compared to the control. In addition, the lengths of long bones, such as the leg bones and vertebral column, as well as bone mineral content, were reduced in the RAI-treated animals. Our results confirm the negative impacts of RAI-induced thyroid deficiency during puberty on longitudinal bone growth and bone mineralization.

Importance The incidence of Graves disease (GD) is rising in children, and adequate care of these patients requires a multidisciplinary approach. Whether patients are seen in the context of endocrinology, nuclear medicine, or surgery, it is important to know the nuances of the therapeutic options in children. Observations Given the rarity of GD in children, it is important to recognize its various clinical presenting signs and symptoms, as well as the tests that may be important for diagnosis. The diagnosis is typically suspected clinically and then confirmed biochemically. Imaging tests, including thyroid ultrasonography and/or nuclear scintigraphy, may also be used as indicated during care. It is important to understand the indications for and interpretation of laboratory and imaging tools so that a diagnosis is made efficiently and unnecessary tests are not ordered. Clinicians should be well-versed in treatment options to appropriately counsel families. There are specific scenarios in which medical therapy, radioactive iodine therapy, or surgery should be offered. Conclusions and Relevance The diagnosis and treatment of pediatric patients with GD requires a multidisciplinary approach, involving pediatric specialists in the fields of endocrinology, ophthalmology, radiology, nuclear medicine, and surgery/otolaryngology. Antithyroid drugs are typically the first-line treatment, but sustained remission rates with medical management are low in the pediatric population. Consequently, definitive treatment is often necessary, either with radioactive iodine or with surgery, ideally performed by experienced, high-volume pediatric experts. Specific clinical characteristics, such as patients younger than 5 years or the presence of a thyroid nodule, may make surgery the optimal treatment for certain patients.

This study sought to investigate the clinical characteristics and outcomes of propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in patients with Graves' disease.Sixteen patients diagnosed with PTU-induced ANCA-associated vasculitis at the authors' hospital from January 2010 to June 2017 were analyzed retrospectively.All 16 patients with PTU-induced ANCA-associated vasculitis were female. The mean age ± standard deviation of the patients was 39.4 ± 15.3 years (range 19-69 years), and the median time of onset was 36 months (range 1-193 months) post-PTU initiation. The median dose at the onset of PTU-induced ANCA-associated vasculitis was 150 mg/day (range 50-300 mg/day). All patients had a positive serum perinuclear staining pattern (p-ANCA) and antibodies directed against myeloperoxidase (anti-MPO). Six patients tested positive for both anti-MPO antibodies and antibodies directed against proteinase-3. Seven (43.8%) patients presented with involvement of a single organ. The kidney was the organ most commonly affected, as 12 (75%) patients were found to have disease involving this organ. PTU was stopped in all patients, corticosteroids were administered to two patients, and immunosuppressive agents and corticosteroids were administered to five patients. Three patients were lost to follow-up. However, the remaining patients achieved remission after a median follow-up period of 38 months (range 6-76 months). Patients who were positive for pANCA and displayed cytoplasmic staining showed negative findings at rates of approximately 53.8% (7/13) and 100% (6/6), respectively, following treatment.PTU-induced ANCA-positive vasculitis occurs at varying times and after exposure to various doses of PTU. The condition has a milder course and has a better prognosis after PTU cessation.

A 49-year-old woman, G8P7, presented with 1 week of worsening vaginal bleeding and abdominal cramps in the setting of a recently discovered unplanned pregnancy. Vaginal ultrasound findings and a significantly elevated human chorionic gonadotropin (hCG) level were concerning for molar pregnancy. She developed signs of hyperthyroidism on the night of admission, for which the endocrinology team was consulted. Laboratory data were consistent with hyperthyroidism. The patient was believed to have thyrotoxicosis secondary to molar pregnancy with concern for impending thyroid storm. Her mental health disorder and bacteraemia made taking care of her further challenging. She was started on a beta-blocker, antithyroid agent and intravenous corticosteroids. She underwent an uncomplicated suction dilation and curettage (D&C), with resolution of her symptoms a few days after. At a follow-up appointment, the patient continued to be asymptomatic and was feeling well.

Objectives Radioiodine (131I) dose determination using radiotracer kinetic studies or scoring systems, and fixed relatively high 131I dose (ie, 4 or 5 mCi) administration, are effective and associated with prolonged survival times for hyperthyroid cats. The latter method is less complicated but could expose patients and veterinary personnel to unnecessary levels of radiation. The aim of this study was to retrospectively evaluate the efficacy of a fixed 3.35 mCi 131I dose for the treatment of 96 hyperthyroid cats with no length estimation for any palpated goitre ⩾20 mm, assess outcome and identify factors associated with survival. Methods Serum total thyroxine concentrations at diagnosis and at follow-up times, survival times and cause of death were recorded. Multivariable Cox regression analysis was used to identify factors associated with time to any cause of death from 131I therapy initiation. Results Administration of a median (interquartile range) dose of 3.35 mCi (3.27–3.44 mCi) radioiodine was an effective treatment in 94/96 cats, but two cats remained hyperthyroid. No death related to hyperthyroidism was recorded. Median survival time was 3.0 years; the 1 and 2 year survival rates after 131I therapy were 90% and 78%, respectively. Low body weight (⩽3.1 kg; adjusted hazard ratio [aHR] 5.88; 95% confidence interval [CI] 2.22–16.67; P Conclusions and relevance This study suggests that a fixed 3.35 mCi 131I dose treatment is effective for hyperthyroid cats with goitre(s) with a maximal length estimation

Antithyroid drug (ATD) is a widely used treatment for Graves' disease (GD). However, its long-term efficiency remains unclear. This study investigated the long-term disease prognosis and predictive factors for relapse in ATD-treated GD patients.Newly diagnosed, ATD-treated GD patients with at least four years of follow-up were recruited (n = 187). Remission was defined as maintaining a euthyroid status for more than one year after ATD withdrawal.During 11.1 years (range 4.0-23.7 years) of median follow-up, overall, 51.9% of the newly diagnosed ATD-treated GD patients achieved remission, 32.1% continued ATD treatment, and 13.4% underwent other ablation treatments. The 10-year remission rates were higher in the first (34.2%) and second (25.5%) ATD courses than in any of the other subsequent ATD courses, and decreased as ATD treatments were repeated. The 10-year relapse rate was the highest after the third ATD treatment (71.4%) compared with that after the first (60.5%) and second (58.3%) courses. Longer duration of ATD treatment (odds ratio [OR] = 1.4 [confidence interval (CI) 1.2-1.7], p 0.001), higher number of relapses (OR = 4.7 [CI 2.3-9.8], p 0.001), and moderate to severe Graves' ophthalmopathy (OR = 4.1 [CI 1.1-15.2], p = 0.032) were associated with persistent disease status.A second course of ATD can be considered for GD patients after the first relapse because the chance of remission and the relapse rate are similar to the one after the first ATD treatment course. For GD patients with more than two relapses, or with an ATD treatment duration of more than four to five years, low-dose maintenance of ATD or ablative treatment needs to be considered.

Perinatal hypothyroidism causes serious damage to auditory functions that are essential for vocalization development. In rat pups, perinatal hypothyroidism potentially affects the development of ultrasonic vocalization (USV) as a result of hearing deficits. This study examined the effect of perinatal hypothyroidism on the development of USVs in rat pups. Twelve pregnant rats were divided into three groups and treated with the anti-thyroid drug methimazole (MMI) via drinking water, from gestational day 15 to postnatal day (PND) 21. The MMI concentration (w/v) was 0% (control group), 0.01% (low-dose group), or 0.015% (high-dose group). After birth, the pups were individually separated from the dam and littermates on PNDs 5, 10, 15, and 20, and their USVs were recorded for 5 min. On PNDs 5 and 10, compared with the control group, the low- and high-dose groups exhibited reductions of both frequency modulated and downward USVs. On PND 15, however, the low- and high-dose groups displayed increases in number, duration, and amplitude of USVs compared with those in the control group. Lower body weights were observed for the low- and high-dose groups than for the control group. Total thyroxine concentrations in plasma were dose-dependently reduced. The onset of auditory functions appeared on PNDs 11-14. Thus, the rat pups were unable to hear externally produced USVs before PND 11. USVs emitted on PNDs 5 and 10 might have been spontaneous and independent of the pups' own or littermate-emitted USVs. The developmental retardation of vocalization-related organs or muscles might underlie the acoustic alterations of USVs on PNDs 5 and 10. The greater number, duration, and amplitude of USVs on PND 15, after which the hearing onset occurred, suggested that the elevation of auditory thresholds occurred as a result of hearing deficits in the low- and high-dose groups. Perinatal hypothyroidism appears to have caused acoustic alterations in the USV development. (C) 2016 Elsevier B.V. All rights reserved.

Neuromuscular disorders associated with hyperthyroidism have several variations in their clinical phenotype, such as ophthalmopathy, periodic paralysis, and thyrotoxic myopathy. We herein report an unusual case of thyrotoxic myopathy presenting as unilateral drop foot. Histopathological examinations of the left tibialis anterior muscle showed marked variation in the fiber size, mild inflammatory cell infiltration, and necrotic and regenerated muscle fibers with predominantly type 1 fiber atrophy. Medical treatment with propylthiouracil resulted in complete improvement of the left drop foot. This case expands the phenotype of thyrotoxicosis and suggests that thyrotoxicosis be considered as a possible cause of unilateral drop foot.

Inhaled corticosteroids (ICSs) are used as first-line drugs for asthma, and various novel antiasthma drugs targeting type 2 immune mediators are now under development. However, molecularly targeted drugs are expensive, creating an economic burden on patients. We and others previously found pendrin/SLC26A4 as a downstream molecule of IL-13, a signature type 2 cytokine critical for asthma, and showed its significance in the pathogenesis of asthma using model mice. However, the molecular mechanism of how pendrin causes airway inflammation remained elusive. We have recently demonstrated that hypothiocyanite (OSCN−) produced by the pendrin/DUOX/peroxidase pathway has the potential to cause airway inflammation. Pendrin transports thiocyanate (SCN−) into pulmonary lumens at the apical side. Peroxidases catalyze SCN− and H2O2 generated by DUOX into OSCN−. Low doses of OSCN− activate NF-κB in airway epithelial cells, whereas OSCN− in high doses causes necrosis of the cells, inducing the release of IL-33 and accelerating inflammation. OSCN− production is augmented in asthma model mice and possibly in some asthma patients. Heme peroxidase inhibitors, widely used as antithyroid agents, diminish asthma-like phenotypes in mice, indicating the significance of this pathway. These findings suggest the possibility of repositioning antithyroid agents as antiasthma drugs.

Agranulocytosis is a rare and serious adverse effect of antithyroid drugs, with unknown etiology. The present study aimed to uncover genetic susceptibility and underlying mechanisms of antithyroid drug-induced agranulocytosis (ATDAC). We studied two independent families with familial Graves' disease, of which several members developed ATDAC. In addition, six sporadic ATDAC patients with Graves' disease were investigated. Whole exome sequencing analysis of affected and unaffected family members was performed to identify genetic susceptibility variants for ATDAC, followed by functional characterization of primary granulocytes from patients and unrelated healthy controls. Whole exome sequencing, cosegregation analysis, and stringent selection criteria of candidate gene variants identified NOX3 as a genetic factor related to ATDAC. Functional studies revealed increased apoptosis of methimazole-treated granulocytes from patients carrying NOX3 variants. In conclusion, genetic variants in NOX3 may confer susceptibility to antithyroid drug-induced apoptosis of granulocytes. These findings contribute to the understanding of the mechanisms underlying ATDAC. Refereed/Peer-reviewed

We herein report the case of a Japanese woman with familial dysalbuminemic hyperthyroxinemia (FDH) who was initially diagnosed with Graves' disease. Direct genomic sequencing revealed a guanine to cytosine transition in the second nucleotide of codon 218 in exon 7 of the albumin gene, which then caused a proline to arginine substitution. She was finally diagnosed with FDH, which did not require treatment. FDH is - superficially - an uncommon cause of syndrome of inappropriate secretion of thyrotropin (SITSH) in Japan. A misdiagnosis of pseudo-hyperthyroidism will lead to inappropriate treatment. Thus, physicians should strongly note the possibility of FDH as a differential diagnosis of SITSH.

Hyperthyroidism is the most common feline endocrinopathy; thyroid computed tomography (CT) may improve disease detection and methimazole dose selection. Objectives of this experimental pre-post with historical case-control study were to perform thyroid CT imaging in awake or mildly sedated hyperthyroid cats, compare thyroid gland CT appearance in euthyroid and hyperthyroid cats pre- and postmethimazole treatment, and determine whether thyroid size or attenuation correlate with methimazole dose needed for euthyroidism. Premethimazole treatment, eight hyperthyroid cats received CT scans from the head to heart, which were compared to CT of seven euthyroid cats. Total thyroxine levels were monitored every 3-4 weeks. Postmethimazole CT was performed 30 days after achieving euthyroid status. Computed tomography parameters recorded included thyroid length, width, height, attenuation, and heterogeneity. Median time between CT was 70 days (53-213 days). Mild sedation was needed in five hyperthyroid cats premethimazole, and none postmethimazole. Thyroid volume was significantly larger in hyperthyroid cats compared to euthyroid cats (785.0 mm3 vs. 154.9 mm3 ; P = 0.002) and remained unchanged by methimazole treatment (-4.5 mm3; P = 0.50). Thyroid attenuation and heterogeneity decreased with methimazole treatment (96.1 HU vs. 85.9 HU; P = 0.02. 12.4 HU vs. 8.1 HU; P = 0.009). Methimazole dose ranged from 2.5 to 10 mg daily with a positive correlation between pretreatment thyroid gland volume and dose needed to achieve euthyroidism (P = 0.03). Euthyroid and hyperthyroid cats are easily imaged awake or mildly sedated with CT. Methimazole in hyperthyroid cats significantly lowers thyroid attenuation and heterogeneity, but not size.

We report the case of a 40-year-old Greek female with symptoms of polyarthritis, pruritic rash and positive p-ANCA antibodies, undergoing treatment with Methimazole therapy for Graves’ disease. The rash and the arthritis symptoms promptly disappeared after withdrawal of methimazole, but p-ANCA antibodies remained positive for 6 weeks. By the time that p-ANCA became negative, anti-dsDNA antibodies presented and remained at high titers for 3 months, with no clinical or specific organ disease symptoms. The patient was under close monitoring for the case of potentially life-threating vasculitis of the lung or the kidney and was treated with methylprednisolone. We diagnosed the patient with Antithyroid drug Syndrome, which in our patient presented with arthritis symptoms and had serological features which are commonly found to Antithyroid drug pANCA vasculitis and Antithyroid drug lupus-like syndrome. Physician’s awareness is essential for the diagnosis and treatment of this syndrome in clinical practice, taking into consideration the high frequency of the use of antithyroid agents.

usc Background: Thyrotoxicosis is a clinical state that results from inappropriately high thyroid hormone action in tissues. Although it is one of the common endocrine disorders, there is scarcity of data on the management of thyrotoxicosis in Africa, particularly in Ethiopia. The aim of this study was to investigate treatment outcomes and determinants of treatment outcomes among hyperthyroid patients on antithyroid drugs attending a teaching hospital in Ethiopia. Methods: A retrospective cohort study was conducted on medical records of patients with thyrotoxicosis who had attended the medical inpatient ward and chronic ambulatory clinic of the University of Gondar Comprehensive Specialized Hospital in Ethiopia between June 2013 and April 2018. Descriptive statistics were used to summarize socio-demographic and other baseline information. A cox regression method was used to determine factors associated with normalization of thyroid function tests (TFTs). All statistical tests were performed using STATA version 14. Results: Data from a total 211 patients were eventually analyzed. The mean age of the patients was 47.25 ± 14.26 years with female majority (94.31%). The most common etiology was toxic multinodular goiter (54.90%). Because methimazole or carbimazole are not easily available locally, all of the patients included in this study were taking propylthiouracil (PTU). Nearly 9 out of 10 patients (90.38%) had symptom resolution within a mean period of 5.37 (± 6.59) months. Sixty-two (29.81%) and 122 (58.65%) patients achieved normalization of TSH and FT4, respectively during the study period. The mean time to normalization of TSH and FT4 was 13 (±13.28) and 11.53 (±13.39) months, respectively. On the other hand, T3 and all three TFTs were normalized only among 79 (38.16%) and 55 (26.32%) patients, respectively. Older age and higher baseline FT4 levels were shown to modestly reduce the chances of achieving normalization of TSH. Conclusion: Though PTU is not the preferred antithyroid agent in the management of thyrotoxicosis, all patients used PTU for the management of hyperthyroidism. All TFTs were normalized in only less than one-third of the participants. Resolution of symptoms took longer period of time than expected. Refereed/Peer-reviewed

Objective: Previous surveys from different world regions have demonstrated variations in the clinical management of Graves disease (GD). We aimed to investigate the clinical approach to GD relapse among endocrinologists. Methods: Electronic questionnaires were e-mailed to all members of the Israeli Endocrine Society. Questionnaires included demographic data and different scenarios regarding treatment and follow-up of patients with GD relapse. Results: The response rate was 49.4% (98/198). For a young male with GD relapse, 68% would restart antithyroid drug (ATD) (98% methimazole), while 32% would refer to radioactive iodine (RAI) treatment. Endocrinologists who treat >10 thyroid patients a week tended to choose ATDs over RAI (P = .04). In the case of GD relapse with ophthalmopathy, 50% would continue ATDs, whereas 22.4% would recommend RAI treatment and 27.6% surgery. Most endocrinologists (56%) would continue ATDs for 12 to 24 months. Seventy-five percent would monitor complete blood count and liver function (39% for the first month and 36% for 6 months), and 44% would recommend a routine neck ultrasound. In a case of thyrotoxicosis due to a 3-cm hot nodule, most endocrinologists (70%) would refer to RAI ablation, 46.4% without and 23.7% with a previous fine-needle aspiration. No significant differences were found regarding gender, year of board certification, or work environment. Conclusion: Our survey demonstrates diverging patterns in the diagnosis and management of GD relapse that correlate well with previous surveys from other countries on GD-naive patients and a less than optimal adherence to recently published clinical guidelines. Abbreviations: ATA = American Thyroid Association; ATD = antithyroid drug; CBC = complete blood count; GD = Graves disease; GO = Graves ophthalmopathy; LFT = liver function test; MMI = methimazole; PTU = propylthiouracil; RAI = radioactive iodine; TSI = thyroid-stimulating immunoglobulin

Objective: To review the diagnosis and management of thyrotoxicosis in women who are preconception, pregnant, and in the postpartum period. Methods: Literature review of English-language papers published between 1980 and 2018. Results: Overt thyrotoxicosis occurs in 0.2% of pregnancies and subclinical thyrotoxicosis in 2.5%. Hyperthyroidism in women of childbearing age most frequently is caused by Graves disease (GD). Gestational thyrotoxicosis, transient human chorionic gonadotropin (hCG)-mediated hyperthyroidism, may develop in the first trimester. In the first year following delivery, postpartum thyroiditis, which frequently includes a thyrotoxic phase, occurs in 5% of women. Hyperthyroidism from nodular autonomy is uncommon in women of childbearing age. It is essential to understand the underlying etiology for thyrotoxicosis in order to recommend appropriate treatment. Gestational thyrotoxicosis requires supportive care, without antithyroid drug therapy. GD may be treated with antithyroid drugs, radioactive iodine, or thyroidectomy. Pregnancy, plans for pregnancy, and lactation have important implications for the choice of GD treatment. When thyrotoxicosis presents following delivery, postpartum thyroiditis must be differentiated from GD. Conclusion: The diagnosis and management of thyrotoxicosis in the peripregnancy period present specific challenges. In making management decisions, it is essential to weigh the risks and benefits of treatments not just for the mother but also for the fetus and for breastfed infants. A team approach to management is critical, with close collaboration among endocrinologists, maternal-fetal medicine specialists, and neonatologists. Abbreviations: GD = Graves disease; hCG = human chorionic gonadotropin; MMI = methimazole; PPT = postpartum thyroiditis; PTU = propylthiouracil; T3 = triiodothyronine; T4 = thyroxine; TBG = thyroxine-binding globulin; TRAb = TSH receptor antibody; TSH = thyroid-stimulating hormone