Methimazole Treatment Research Articles

The effect of radioactive iodine treatment on 14C urea breath test results in patients with hyperthyroidism.

Radioactive Iodine therapy (RAIT) plays a major role in the treatment of hyperthyroidism. In addition to the thyroid gland, significant amounts of radioactive iodine are maintained in the stomach. The aim of this study was to determine if RAIT has any effect on Helicobacter pylori infection, based on the C urea breath test (UBT). The study included 85 patients with hyperthyroidism scheduled to undergo RAIT and 69 hyperthyroid subjects in whom methimazole treatment was planned. All subjects had pretreatment-positive UBT results, and the test was repeated on the first and third months after RAIT and methimazole treatment. After a mean RAIT dose of 15 mCi (range, 10-20 mCi), UBT became negative in 13 (15.3%) of 85 patients on the first month and 18 (21.2%) of 85 patients on the third month. All subjects treated with methimazole remained UBT positive on the first and third months of methimazole treatment (100%). Reduction in the number of UBT-positive patients on both the first and the third months after RAIT was statistically significant (P < 0.001). Distribution of hyperthyroidism etiologies and thyroid autoantibody levels in subjects with UBT that became negative and in subjects with UBT that remained positive were similar in the RAIT group (P > 0.05). Urea breath test negativity rates did not differ according to the radioiodine dose. Our findings indirectly showed that RAIT might have an antimicrobial effect on H. pylori. Clinical applications of this beneficial effect of RAIT on H. pylori should be further evaluated.

Olfactory ensheathing cells are the main phagocytic cells that remove axon debris during early development of the olfactory system.

During development of the primary olfactory system, axon targeting is inaccurate and axons inappropriately project within the target layer or overproject into the deeper layers of the olfactory bulb. As a consequence there is considerable apoptosis of primary olfactory neurons during embryonic and postnatal development and axons of the degraded neurons need to be removed. Olfactory ensheathing cells (OECs) are the glia of the primary olfactory nerve and are known to phagocytose axon debris in the adult and postnatal animal. However, it is unclear when phagocytosis by OECs first commences. We investigated the onset of phagocytosis by OECs in the developing mouse olfactory system by utilizing two transgenic reporter lines: OMP-ZsGreen mice which express bright green fluorescent protein in primary olfactory neurons, and S100β-DsRed mice which express red fluorescent protein in OECs. In crosses of these mice, the fate of the degraded axon debris is easily visualized. We found evidence of axon degradation at embryonic day (E)13.5. Phagocytosis of the primary olfactory axon debris by OECs was first detected at E14.5. Phagocytosis of axon debris continued into the postnatal animal during the period when there was extensive mistargeting of olfactory axons. Macrophages were often present in close proximity to OECs but they contributed only a minor role to clearing the axon debris, even after widespread degeneration of olfactory neurons by unilateral bulbectomy and methimazole treatment. These results demonstrate that from early in embryonic development OECs are the primary phagocytic cells of the primary olfactory nerve.

Methimazole-Induced Goitrogenesis in an Adult Patient With the Syndrome of Resistance to Thyroid Hormone.

Patients with the syndrome of resistance to thyroid hormone (RTH) have clinical (tachycardia and anxiety) and biochemical (elevated thyroid hormones level) features of hyperthyroidism. Based on previous reports in pediatric patients with the RTH, antithyroid treatment in these patients is not indicated. Clinical and biochemical sequel of antithyroid therapy in an adult patient with RTH was not previously reported. A 63-year-old African American female with history of RTH was treated with a therapy consisting of methimazole 15 mg daily and atenolol. Methimazole treatment resulted in reduction in thyroid hormone level while the patient’s TSH increased with a peak of 24.88 mIU/L. Having achieved biochemical euthyroidism, the patient developed thyroid gland enlargement associated with progressive symptoms of dysphagia and dyspnea. Examination demonstrated globally enlarged firm thyroid gland with areas of nodularity in both lobes. A computed tomography of the neck showed enlarged thyroid gland with extension around bilateral sternocleidomastoid muscles and compression onto the trachea. Methimazole therapy was discontinued and patient was treated just on atenolol. Over 12 months following discontinuation of methimazole, the patient experienced marked clinical and radiographic improvement of the goiter size associated with TSH reduction to 1.26 mIU/L and modest free thyroxine increase as expected in RTH. It seems appealing to treat patients with the RTH with antithyroid medications. However, in these patients decrease in thyroid hormone levels will stimulate TSH production, which can, in turn, predispose to goiter formation. Our report supports prior observations in children with RTH that treatment with methimazole is not indicated in adult patients with RTH.

Hypoglycemic coma due to insulin autoimmune syndrome induced by methimazole: A rare case report.

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by the presence of insulin-binding autoantibodies and fasting or late postprandial hypoglycemia. The number of reports on the association of human leukocyte antigen (HLA) genotype with this disease in adolescents in China is limited. This is the case report of a 17-year-old female patient with Graves’ disease who was treated with methimazole (MTZ). After 4 weeks of continuous MTZ treatment, the patient suffered an episode of unconsciousness during the late postprandial phase and was admitted to the hospital, where the blood glucose level was found to be 2.88 mmol/l. The symptoms were relieved following intravenous glucose administration. Imaging studies of the pancreas were unremarkable, but the laboratory investigations on admission revealed high serum levels of total insulin, associated with relatively low levels of free insulin and markedly elevated insulin autoantibody (IAB) levels. HLA testing revealed DRB1*0406/0901 and the patient discontinued MTZ and was prescribed propylthiouracil. During the long-term follow-up, the total insulin and IAB levels gradually declined. There was no other episode of hypoglycemia. Therefore, in adolescents with Graves’ disease receiving antithyroid treatment with MTZ who experience hypoglycemia, the IAB levels should be assessed to exclude or confirm IAS as the underlying cause.

Failure of radioactive iodine in the treatment of hyperthyroidism.

Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common and many patients require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism. We conducted a retrospective review of patients treated with RAI from 2007 to 2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidectomy. Using a Cox proportional hazards model, we conducted univariate analysis to identify factors associated with failure of RAI. A final multivariate model was then constructed with significant (p < 0.05) variables from the univariate analysis. Of the 325 patients analyzed, 74 patients (22.8 %) failed initial RAI treatment, 53 (71.6 %) received additional RAI, 13 (17.6 %) received additional RAI followed by surgery, and the remaining 8 (10.8 %) were cured after thyroidectomy. The percentage of patients who failed decreased in a stepwise fashion as RAI dose increased. Similarly, the incidence of failure increased as the presenting T3 level increased. Sensitivity analysis revealed that RAI doses <12.5 mCi were associated with failure while initial T3 and free T4 levels of at least 4.5 pg/mL and 2.3 ng/dL, respectively, were associated with failure. In the final multivariate analysis, higher T4 (hazard ratio [HR] 1.13; 95 % confidence interval [CI] 1.02-1.26; p = 0.02) and methimazole treatment (HR 2.55; 95 % CI 1.22-5.33; p = 0.01) were associated with failure. Laboratory values at presentation can predict which patients with hyperthyroidism are at risk for failing RAI treatment. Higher doses of RAI or surgical referral may prevent the need for repeat RAI in selected patients.

A patient with agranulocytosis following the discontinuation of methimazole treatment for 4 months: A case report.

Agranulocytosis is a rare and serious adverse effect of antithyroid drugs (ATD), in particular methimazole (MMI), and usually develops within 3 months following the start of uninterrupted ATD treatment. Agranulocytosis may also develop for the first time following interruption and subsequent resumption of the same ATD treatment. In this case report, a 27-year-old female, who was treated for thyrotoxicosis with MMI, developed agranulocytosis following the discontinuation of MMI treatment for four months. To the best of our knowledge, this is the first study to report this. The aim of this report is to increase the awareness of physicians of the onset of agranulocytosis when MMI is discontinued, and to demonstrate that MMI should be used with caution.

Transdermal application of methimazole in hyperthyroid cats: a long-term follow-up study.

Transdermal methimazole is suggested as an alternative to oral therapy for hyperthyroid cats that are difficult to pill. However, no information on long-term management with this treatment is available. Our objective was therefore to retrospectively evaluate the efficacy and safety of long-term transdermal methimazole treatment in hyperthyroid cats. Sixty cats with newly diagnosed hyperthyroidism and available long-term follow-up information were included. Methimazole was formulated in a pluronic lecithin organogel-based vehicle and was applied to the pinna of the inner ear. Cats were re-evaluated at regular intervals. Median (range) follow-up was 22.6 months (3.6-88.4 months). Clinical improvement was observed in all cats and side effects were rare (mild transient gastrointestinal signs: n = 3; erythema of the pinna: n = 2, necessitating a switch to oral medication). Despite a significant decrease, with median T4 concentrations within the reference interval during the follow-up period, several cats repeatedly had T4 concentrations in the thyrotoxic and hypothyroid range. Maximal and minimal daily doses during the follow-up period were 15.0 and 1.0 mg, respectively; they were significantly higher than the starting dose after 24-36 months of therapy. Although the majority of owners were highly satisfied with the treatment, several admitted not treating their cat regularly. Transdermal methimazole is a safe option for the long-term management of feline hyperthyroidism. However, it seems difficult to keep the T4 concentrations constantly within the reference interval. Higher doses can be expected after prolonged treatment and, despite the convenience of transdermal application, owner compliance should be assessed regularly.

Increase of Interferon-γ Inducible CXCL9 and CXCL11 Serum Levels in Patients with Active Graves' Disease and Modulation by Methimazole Therapy

Chemokine (C-X-C motif) ligand (CXCL)9 and CXCL11 play an important role in the initial phases of autoimmune thyroiditis (AT); however, their serum levels in patients with Graves' disease (GD) have never been evaluated in relation to thyroid function and treatment. To evaluate CXCL9 and CXCL11 serum levels in GD and to relate these parameters to the clinical phenotype, we measured CXCL9 and CXCL11 serum levels in 91 GD patients; 91 AT, 34 nontoxic multinodular goiters (MNGs), 31 toxic nodular goiters (TNGs), respectively; and 91 healthy controls (age- and sex-matched). Mean CXCL9 and CXCL11 levels were higher in GD in comparison with controls, euthyroid AT, MNG, or TNG (p < 0.05, ANOVA; CXCL9: 274 ± 265, 76 ± 33, 132 ± 78, 87 ± 48, and 112 ± 56 pg/mL; CXCL11: 140 ± 92, 64 ± 20, 108 ± 48, 76 ± 33, 91 ± 41 pg/mL, respectively). Hyperthyroid GD patients had significantly higher CXCL9 or CXCL11 than euthyroid or hypothyroid GD patients. GD patients with untreated hyperthyroidism had higher CXCL9 or CXCL11 than hyperthyroid or euthyroid GD patients under methimazole (MMI) treatment. Comparable CXCL9 and CXCL11 levels were observed in newly diagnosed untreated hyperthyroid GD versus untreated patients with relapse of hyperthyroidism after a previous MMI course. Serum CXCL9 and CXCL11 levels are associated with the active phase of GD both in newly diagnosed and relapsing hyperthyroid patients. The reduction of serum CXCL9 and CXCL11 levels in treated patients with GD may be related to the immunomodulatory effects of MMI.

Impact of Methimazole Treatment on Magnesium Concentration and Lymphocytes Activation in Adolescents with Graves’ Disease

The aim of this research was to assess plasma magnesium (Mg) concentration, the frequencies of activated T CD4+ and T CD8+ lymphocytes and B lymphocytes in adolescents with hyperthyroidism due to Graves’ disease (GD), and to assess changes in the above-mentioned parameters during methimazole (MMI) treatment. The frequencies of activated T and B cells were measured by flow cytometry method and plasma Mg concentration was determined by spectrophotometry method in 60 adolescents at the time of GD diagnosis and after receiving the normalisation of the thyroid hormones levels. The control group consisted of 20 healthy volunteers. We observed lower plasma Mg concentration, and higher frequencies of activated T and B lymphocytes in the study group before the treatment in comparison with healthy controls, and with study group in MMI-induced euthyreosis (p < 0.01).Statistically significant negative correlations between the percentages of activated T CD3+, T CD4+, T CD8+ and B CD19+ lymphocytes, and plasma Mg concentration before the treatment were found (r < −0.335, p < 0.002). After the treatment no vital differences in plasma Mg concentration, and in percentages of activated cells between GD patients and controls were found, except CD8+CD25+ cells (p = 0.03). The present study demonstrates that both activated T and B cells might play an important role in the pathogenesis of GD, and activation is related to Mg plasma level. The use of MMI in treatment of hyperthyroidism due to GD leads to decrease the frequencies of activated lymphocytes and normalisation of Mg levels.

Duration of T4 Suppression in Hyperthyroid Cats Treated Once and Twice Daily with Transdermal Methimazole

Transdermal methimazole is an acceptable alternative to oral treatment for hyperthyroid cats. There are, however, no studies evaluating the duration of T4 suppression after transdermal methimazole application. Such information would be valuable for therapeutic monitoring. To assess variation in serum T4 concentration in hyperthyroid cats after once- and twice-daily transdermal methimazole administration. Twenty client-owned cats with newly diagnosed hyperthyroidism. Methimazole was formulated in a pluronic lecithin organogel-based vehicle and applied to the pinna of the inner ear at a starting dose of 2.5mg/cat q12h (BID group, 10 cats) and 5mg/cat q24h (SID group, 10 cats). One and 3weeks after starting treatment, T4 concentrations were measured immediately before and every 2hours after gel application over a period of up to 10hours. Significantly decreased T4 concentrations were observed in week 1 and 3 compared with pretreatment concentrations in both groups. All cats showed sustained suppression of T4 concentration during the 10-hour period, and T4 concentrations immediately before the next methimazole treatment were not significantly different compared with any time point after application, either in the BID or SID groups. Because transdermal methimazole application led to prolonged T4 suppression in both the BID and SID groups, timing of blood sampling does not seem to be critical when assessing treatment response.

A Case of Elevation of Serum Creatine Kinase With Antithyroid Medications for Graves’ Disease

We describe a female patient with Graves ’ disease (GD) who had abnormal increases of serum creatine kinase (CK) concentration during treatment with antithyroid medications. She experienced myalgia and manifested increased serum CK levels, with a maximum of 7,925 U / L, 2 - 4 months after initiation of methimazole (MMI) treatment at a dose of 10 - 15 mg / day. After MMI was exchanged for potassium iodide (KI), serum CK levels decreased and the myalgia resolved. However, after KI was exchanged for propylthiouracil (PTU), the myalgia recurred and serum CK levels increased with a maximum of 521 U / L. PTU was discontinued and serum CK levels returned to normal, but hyperthyroidism recurred and the patient did not consent to the alteration of treatment from antithyroid drugs to radioiodine therapy or surgical treatment. PTU was restarted and increased gradually from 50 to 300 mg / day. Serum CK levels did not increase, but the hyperthyroidism persisted. After we exchanged PTU for MMI (20 mg / day) and levothyroxine (25 u g / day), serum CK levels did not increase and the hyperthyroidism diminished. While the mechanisms for this process are not clearly defined, a rapid reduction in thyroid hormones in tissues following chronic hyperthyroidism may result in relative hypothyroid states and subsequent alterations in CK concentration. doi: http://dx.doi.org/10.4021/jem130w

Neural crest-derived horizontal basal cells as tissue stem cells in the adult olfactory epithelium

Horizontal basal cells (HBCs) have garnered attention as tissue stem cells of the olfactory epithelium (OE); however, these cells’ exact lineage and their contributions to OE regeneration remain unknown. Neural crest-derived cells (NCDCs) have been shown to possess stem cell properties and to participate in the normal development of the OE. However, the contributions of NCDCs to both normal and regenerating adult OE remain unclear. In this study, we investigated the contribution of NCDCs to the OE, focusing particularly on HBCs. Using immunohistochemistry, we observed the OE of P0-Cre/EGFP mice expressing EGFP-tagged NCDCs at several stages of normal development along with regenerated OE following methimazole treatment. We observed EGFP expression in the HBCs, sustentacular cells (SUSs), Bowman's glands, olfactory receptor neurons (ORNs), and olfactory ensheathing cells of 6-week-old mice. No ectopic Cre expression was identified. Although HBCs at late embryonic stages were placode-derived (i.e., EGFP-negative), we found that EGFP+ HBCs alternatively increased with the decrease of placode-derived HBCs during maturation. In regenerated OE, the percentages of neural crest-derived ORNs and SUSs significantly increased compared with normal OE. These results suggest that NCDCs contribute greatly to the adult HBC population and that they are important for the maintenance of the OE.

Effects of adult dysthyroidism on the morphology of hippocampal granular cells in rats.

Thyroid hormones are essential for normal brain development and very important in the normal functioning of the brain. Thyroid hormones action in the adult brain has not been widely studied. The effects of adult hyperthyroidism are not as well understood as adult hypothyroidism, mainly in hippocampal granular cells. The purpose of the present study is to assess the consequences of adult hormone dysthyroidism (excess/deficiency of TH) on the morphology of dentate granule cells in the hippocampus by performing a quantitative study of dendritic arborizations and dendritic spines using Golgi impregnated material. Hypo-and hyperthyroidism were induced in rats by adding 0.02 percent methimazole and 1 percent L-thyroxine, respectively, to drinking water from 40 days of age. At 89 days, the animals' brains were removed and stained by a modified Golgi method and blood samples were collected in order to measure T4 serum levels. Neurons were selected and drawn using a camera lucida. Our results show that both methimazole and thyroxine treatment affect granule cell morphology. Treatments provoke alterations in the same direction, namely, reduction of certain dendritic-branching parameters that are more evident in the methimazole than in the thyroxine group. We also observe a decrease in spine density in both the methimazole and thyroxine groups.

Hypoglycemia due to insulin binding antibodies in a patient with insulin-treated type 2 diabetes and Graves’ disease

To the Editor, Insulin autoimmune syndrome (IAS) showed hypoglycemia, hyperinsulinemia, positive insulin antibodies without insulin injection history. Some patients with diabetes, treated with insulin, also showed these signs. The first case of IAS was reported in 1970s. [1, 2]. IAS can be induced by autoimmune diseases, some drugs, such as methimazole [3]. Here we report one case of special IAS, who suffered from type 2 diabetes concomitant with Graves’ disease. This an 85-year-old woman diagnosed with type 2 diabetes 30 years ago. She accepted oral antidiabetic drugs initially, and switched to insulin injection therapy (Novolin 30R 12 u/day) 5 years ago. About 1 year ago, she began to experiencing recurrent cold sweat, hunger, palpitation, and other symptoms of hypoglycemia, with her peripheral blood glucose ranged from 3.0–4.0 mmol/L during the night and morning. Hypoglycemia episodes still occurred after insulin treatment was suspended. Meanwhile she appeared weight loss, palpitation, chest tightness, fatigue, and lower extremity edema. One month prior to admission, the patient began to appearing eyelid edema, proptosis, photophobia, tearing, redness and pain of eye, polyphagia, heat intolerance, sweating, irritability, and stool frequency. She has hypertension and dyslipidemia history. Physical examination revealed a thinly built woman, BMI 20.7 kg/m, BP 160/70 mmHg, pulse 106/min. Her skin appeared sweeting and hot. She appeared wider palpebral fissures, proptosis, limited eye movements, conjunctival edema, and hyperemia. The movements of the lids were jerky and spasmodic, and the lightly closed lids tremor. Thyroid examination revealed II degrees of goiter with marked tremor and vascular murmur. Thyroid function tests revealed that TSH 0.01 lU/mL, T4 223.18 nmol/l, FT4 34.8 pmol/l, rT3 0.58 ng/ml, thyroglobulin 27.73 ng/ml, Anti-Tg 906.1 IU/ml, TPO [ 600 IU/ml, TRAB 20.8 IU/ml, ESR 64 mm/h. Serum total insulin concentration was 552.3 uU/ml, free insulin concentration 394.4 uU/ml, and Iab binding rate 70.6 %. Scatchard analysis revealed that the serum Iab constituted by two types binding sites which were high-affinity with low capacity (k1 = 3.125 9 10 mol/l, b1 = 37.5 9 10 mol/l) and low-affinity with high capacity (k2 = 1.0 9 10 mol/l, b2 = 5.918 9 10 mol/l), (Fig. 1). Insulin binding antibodies analysis suggested that it was IgG with k light chains. Ultrasound showed bilateral thyroid swelling, diffuse lesions. Abdominal magnetic resonance imaging revealed no abnormalities. The patient was diagnosed with Grave’s diseases, Grave’s ophthalmopathy and IAS, and start receiving prednisone (20 mg/day) and methimazole (10 mg qd) treatment. The insulin injection treatment (Novolin 30R) continued and the dose increased along with blood glucose change. After treatment for 1 month, symptoms including palpitation, heat intolerance, fatigue relieved, photophobia and tearing relieved, meanwhile hypoglycemia attack disappeared. After 2 months of treatment, her serum insulin levels returned to normal range and insulin antibody became X. Wang X. Xu X. Zhao X. Ma H. Yu H. Gong F. Chen (&) No. 3 People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China 280# MoHe Road, Shanghai 201900, People’s Republic of China e-mail: 903561138@qq.com; fengling_chen@hotmail.com

Outcomes of Children with Hashitoxicosis

Aim: To investigate hashitoxicosis outcome in 14 children with persistent absence of thyrotropin receptor autoantibodies who were followed for 1.3-8.8 years (mean 3.5 ± 2.5). Due to a more severe presentation, 4 patients required methimazole (subgroup A1), whilst in the remaining 10 cas es (subgroup A2) no treatment was given. Results: A definitive resolution of hyperthyroidism was recorded 8.3 ± 6.3 months after diagnosis, even though there was a wide variability between subjects (3-23 months). In subgroup A2, hyperthyroidism resolution occurred spontaneously and earlier with respect to subgroup A1 (4.8 ± 2.0 months after diagnosis vs. 17.0 ± 4.5, p = 0.00001). After hyperthyroidism resolution, no relapses were recorded in any patients. Hyperthyroidism duration positively correlated with thyroid peroxidase autoantibody (TPOAb) levels at presentation (r = 0.729, p = 0.002). Conclusions: In all the 14 hashitoxicosis children with persistently absent thyrotropin receptor autoantibodies, the hyperthyroid phase was widely variable and always followed by definitive resolution with no relapses and persistent euthyroidism or hypothyroidism. In the few patients with a more severe presentation, methimazole treatment was required, and definitive hyperthyroidism resolution was delayed. In this subgroup, TPOAb levels at diagnosis were higher than in the subgroup with less severe presentation and earlier hyperthyroidism resolution, suggesting a relationship between TPOAb levels and severity of the disease.

Peripheral blood lymphocyte apoptosis and its relationship with thyroid function tests in adolescents with hyperthyroidism due to Graves' disease

IntroductionFailures in apoptotic pathways can contribute to various autoimmune diseases, including autoimmune hyperthyroidism due to Graves’ disease (GD). The aim of the present research was to assess changes in the degree of peripheral blood (PB) lymphocyte apoptosis during methimazole (MMI) treatment in the group of teenage children, and to describe its relationship with thyroid function tests.Material and methodsThe percentage of PB apoptotic lymphocytes, assessed by the decrease in mitochondrial transmembrane potential (CMXRos staining), was measured in 30 adolescents at the time of diagnosis and after obtaining normalization of the thyroid hormone levels.ResultsThe percentage of apoptotic lymphocytes in previously untreated patients with GD (5.16 ±2.81%) was significantly lower (p = 0.000001) than the percentage of apoptotic cells in the same group of patients after obtaining methimazole-induced euthyroidism (10.72 ±4.66%). There was a correlation between the increase of the mean percentages of apoptotic lymphocytes and the reduction of FT4 levels (R = 0.63, p < 0.0001), as well as the reduction of TT3 levels (R = 0.95, p < 0.0001). The more signs and symptoms accompanying the diagnosis of GD, the higher was the increment of the degree of lymphocyte apoptosis observed during the MMI-treatment (R = 0.74, p < 0.0000001). The methimazole dosage correlated (R = 0.85, p < 0.0001) with the percentage of apoptotic cells.ConclusionsThe use of methimazole in treatment of hyperthyroidism due to GD leads to an increment of apoptotic cells in PB. Higher doses of methimazole cause a higher increase of apoptotic lymphocytes. Apoptosis induction of human PB lymphocytes seems to be one of the indicators of proper hyperthyroidism treatment.

Expression of prostanoid receptors (EP1, 2, 3, and 4) in normal and methimazole-treated mouse olfactory epithelium

Conclusion: Prostanoid receptors (EP1, EP2, EP3, and EP4) are expressed in the olfactory epithelium (OE), and the EP4 prostanoid receptor may play an important role in the OE. Objective: The purpose of the present study was to investigate the expression and localization of the four types of prostanoid receptors (EP1, EP2, EP3, and EP4) in the OE of normal and methimazole-treated mice to gain more complete knowledge about the functional significance of the prostanoid receptors in OE. Methods: CBA/J mice were used in this study. The localization of the prostanoid receptors (EP1, EP2, EP3, and EP4) in the OE was investigated by immunohistochemistry. The changes in expression of prostanoid receptors were studied in methimazole-treated mice. Furthermore, the effect of EP agonists on the methimazole-induced degeneration of OE was assessed by morphological analysis and by assessment of apoptosis. Results: All four types of EP receptors were recognized in mouse OE. Expression of EP4 in the OE was significantly reduced after methimazole treatment. In the methimazole-treated mice, an EP4 agonist reduced OE damage and apoptosis.

A Case of Elevation of Serum Creatine Kinase With Antithyroid Medications for Graves’ Disease

We describe a female patient with Graves ’ disease (GD) who had abnormal increases of serum creatine kinase (CK) concentration during treatment with antithyroid medications. She experienced myalgia and manifested increased serum CK levels, with a maximum of 7,925 U / L, 2 - 4 months after initiation of methimazole (MMI) treatment at a dose of 10 - 15 mg / day. After MMI was exchanged for potassium iodide (KI), serum CK levels decreased and the myalgia resolved. However, after KI was exchanged for propylthiouracil (PTU), the myalgia recurred and serum CK levels increased with a maximum of 521 U / L. PTU was discontinued and serum CK levels returned to normal, but hyperthyroidism recurred and the patient did not consent to the alteration of treatment from antithyroid drugs to radioiodine therapy or surgical treatment. PTU was restarted and increased gradually from 50 to 300 mg / day. Serum CK levels did not increase, but the hyperthyroidism persisted. After we exchanged PTU for MMI (20 mg / day) and levothyroxine (25 u g / day), serum CK levels did not increase and the hyperthyroidism diminished. While the mechanisms for this process are not clearly defined, a rapid reduction in thyroid hormones in tissues following chronic hyperthyroidism may result in relative hypothyroid states and subsequent alterations in CK concentration. J Endocrinol Metab. 2012;2(6):244-247 doi: https://doi.org/10.4021/jem130w

Recurrent Drug-Induced Insulin Autoimmune Syndrome in a Patient with Premature Ovarian Failure

Insulin autoimmune syndrome (IAS) is characterized by hypoglycemic attacks, very high insulin levels and the presence of circulating autoantibodies to insulin in patients who have not been treated with exogenous insulin. Approximately half of patients with insulin autoimmune syndrome have a medication history preceding hypoglycemic events. We present the case of a young woman with premature ovarian failure who developed IAS initially after treatment with methimazole and several years later after captopril, and because of coexistent premature ovarian failure was classified as having autoimmune polyglandular syndrome (APS) type 3. Termination of methimazole and Captopril treatment resulted in the disappearance of hypoglycemic episodes. We discuss diagnostic and treatment dilemmas associated with discovering and management of IAS and APS in this patient.

The Treatment of Pernicious Anemia in Children with Graves' Disease

Organ specific autoimmune diseases may occur in the same individual. Type III polyglandular autoimmune disease is defined by the occurrence in the same individual of two or more of the following: autoimmune thyroid disease, pernicious anemia, insulin dependent diabetes, and other organ specific autoimmune diseases not falling into class I or class II categories. A 16-year-old girl developed pernicious anemia during the treatment of Graves' disease. She was diagnosed with Graves' disease 5 years ago and had received methimazole 20 mg/day, but the medication was not well tolerated. Bone marrow findings were compatible with pernicious anemia as macrocytic normochromic red blood cell (RBC) and increased megakaryocyte. The serum value of vitamin B12 was low, and the serum titer of antibody to gastric parietal cell was high. After diagnosis of pernicious anemia, she had treatment by monthly intramuscular vitamin B12 and methimazole (20 mg/day). The values of hemoglobin and RBC indices as well as thyroid function were normalized after 2 months. Vitamin B12 therapy was maintained for 1 year with normal RBC indices. At present, she dose not receive treatment with vitamin B12 but she does receive methimazole treatment. We report a case of treatment of pernicious anemia in a 16 year-old girl during treatment for Graves disease.