Graves' Disease in Hypopituitarism Due to Pituitary Apoplexy.

BACKGROUND: Central hypothyroidism and autoimmune hyperthyroidism are contrasting pathologies requiring careful hormone monitoring for restoring euthyroidism. Their coexistence is rare and challenging for clinicians [1, 2]. CASE REPORT: We have, herein, presented the case of a 41-year-old female patient with an unremarkable clinical history except for chronic autoimmune thyroiditis in euthyroidism. At the 21st week of gestation, she experienced a spontaneous abortion. The patient underwent an assessment of the uterine cavity, which was complicated by bleeding and hypotensive shock. In the postoperative course, the patient presented worsening headache, and after an MRI, the diagnosis of pituitary apoplexy due to an ischemic-hemorrhagic base was made. Laboratory tests showed anterior panhypopituitarism. Multiaxial replacement therapy was initiated with hydrocortisone, levothyroxine (LT4), and subsequently estrogen-progestin and GH. After two years of good recovery with stable LT4 dosage, the patient experienced palpitations and fine tremors; blood tests showed hyperthyroidism with suppressed Thyroid-stimulating Hormone (TSH) levels and elevated free thyroid fractions and anti-TSH receptor antibodies. Diagnosis of Graves' disease was made, and therapy with methimazole was initiated. During antithyroid therapy, TSH remained persistently suppressed, consistent with the underlying central hypothyroidism. This condition required close follow-up, with monitoring based solely on free thyroid hormone levels. After six months of antithyroid therapy, disease remission was achieved, with negative antibodies and mild hypothyroxinemia. Therefore, methimazole was discontinued and replacement therapy gradually resumed until optimal hormone levels were reached. CONCLUSION: This case is unique demonstrating autoimmune hyperthyroidism to coexist with central hypothyroidism, rendering TSH a misleading disease progression indicator. Consequently, managing Graves' disease has become more complex and challenging.

Comparison of survival times of cats with hyperthyroidism treated with thyroidectomy or methimazole at a primary care hospital in Japan.

OBJECTIVE: We identified the associated factors and compared the survival times of feline hyperthyroidism (FHT) between thyroidectomy and methimazole alone. METHODS: The medical records of 41 cats diagnosed with new-onset hyperthyroidism were retrospectively reviewed. The cats were categorized into the thyroidectomy (n = 15) and methimazole (26) treatment groups. Survival analyses using the Kaplan-Meier method, log-rank test, and Cox proportional hazards models were conducted to compare the time to the selected outcomes. RESULTS: Univariate analysis revealed that survival time was significantly longer with thyroidectomy than with methimazole (P < .001). Multivariate analyses revealed thyroidectomy as an independent prognostic factor for good outcomes (hazard ratio, 0.209; 95% CI, 0.073 to 0.601; P = .004). The recurrence rate was significantly lower in cats that underwent thyroidectomy than in those that received methimazole alone (P = .011). CLINICAL RELEVANCE: Compared with methimazole alone, thyroidectomy was associated with a longer survival time in FHT and can be considered an irreversible treatment modality in settings where radioisotopes are not available.

Lower proportion of intra-thyroidal B lymphocytes CD20+ associated to methimazole and lack of influence of iodide on lymphocyte subpopulations in Graves' disease.

Graves' disease (GD), an autoimmune thyroid disease, is one of the main autoimmune diseases in the general population. It is known that the pathophysiology of this disease may be related to immunological mechanisms dysregulation. These mechanisms can be influenced by GD therapies, such as iodide or antithyroid drugs (ATD). OBJECTIVE: Verify relation between clinical, biochemical and treatment modalities used prior to surgery and histopathological characteristics observed in total thyroidectomy products from patients previously diagnosed with Graves' disease. Furthermore, these data were related to composition of lymphocytic infiltrate in terms of proportions of lymphocytes CD4+, CD8+, CD25+ and CD20+. We aim to contribute to the understanding of the evolution pattern of GD, whose pathophysiology is not yet completely understood. METHODS: Cross-sectional study assessing thyroidectomy products for the presence of lymphocytic infiltrate, as well as the proportion and intensity of CD4+, CD8+, CD25+ and CD20+ markers. We selected 50 patients who underwent total or partial thyroidectomy in a tertiary service between 1996 and 2013 due to GD with histopathological confirmation. The control group (non-autoimmune disease group) consisted of 12 patients with histopathological data compatible with normal perilesional thyroid parenchyma. The intensity of lymphocytic infiltrate and immunohistochemical expression of the markers CD4+ (helper T lymphocytes), CD8+ (cytotoxic T lymphocytes), CD25+ (regulatory T lymphocytes) and CD20+ (B lymphocytes) were retrospectively evaluated and relationship with ultrasound, laboratory and clinical data was assessed. RESULTS: No differences were found in intensity, presence of lymphoid follicles, and expression of CD4+/CD8+/CD25+ in patients with GD who did or did not use ATD or iodide. In the group that did not use ATD, a higher proportion of CD20+ expression was found. The GD group was associated with hyperplastic epithelium and the control group was associated with simple epithelium. There was no difference in ultrasound thyroid volume between the groups. In GD patients with mild lymphocytic infiltrate, higher free thyroxin (FT4) levels were observed than those in patients with no infiltrate or moderate infiltrate. CONCLUSION: We found a lower proportion of intrathyroidal CD20+ B lymphocytes in patients under use of methimazole. However, no difference was observed in intrathyroidal lymphocyte subpopulations related to the short-term use of iodide. The understanding of thyroid autoimmunity, as well as identifying points of pharmacological modulation, are very important for advancement and improvement in treatments for these diseases.

Approach to the Patient Considering Long-term Antithyroid Drug Therapy for Graves' Disease.

Antithyroid drugs (ATD) are the treatment of choice for the majority of patients with Graves' hyperthyroidism worldwide. However, relapse of hyperthyroidism after withdrawal of arbitrarily chosen conventional 12 to 18 months of therapy is very common. In the last 2 decades, many studies have shown that treatment with long-term ATD (LT-ATD) is effective and safe in the maintenance of euthyroidism. In addition, it has been reported that serum TSH receptor antibody may not decrease permanently before 5 to 6 years of ATD treatment, and clinical trials have shown that ≥5 years of ATD treatment is accompanied by remission in the majority of patients with Graves' hyperthyroidism. The objective of this article is to discuss the optimal time to withdraw of conventional ATD therapy, to illustrate the decision-making of the management of recurrent hyperthyroidism, to review the proper management of LT-ATD, and to generate suggestions for lifelong ATD treatment by discussing 4 scenarios of decision-making in patients with Graves' disease.

Late gestation fetal hypothyroidism alters cell cycle regulation across multiple organ systems.

BACKGROUND: Hypothyroidism is a common endocrine disruption observed in utero that adversely affects fetal growth and maturation leading to long-term impacts on health; however, the exact molecular mechanisms by which these deleterious effects occur are unknown. We hypothesize that fetal hypothyroidism during late gestation will disrupt cell cycle regulation in a tissue-specific manner. To evaluate this, eight pregnant gilts were dosed with either methimazole or an equivalent negative control during days 85-106 out of 114 days of gestation (n = 4/group). Following treatment, the gilts were humanely euthanized, and tissue samples of fetal heart, ileum, kidney, lung, liver, muscle, spleen, and thymus taken from two male and two female fetuses (n = 32) from each gilt. RESULTS: The relative expression of three cell cycle promoters (CDK1, CDK2, and CDK4), and one cell cycle inhibitor (CDKN1A) was compared in each tissue to determine the effect of hypothyroidism on the developing fetus. All of the eight tissues examined experienced at least one significant up- or downregulation in the expression of the aforementioned genes as a result of treatment with methimazole. Substantial changes were observed in the liver and muscle, with the latter experiencing significant downregulations of CDK1, CDK2, and CDK4 as a result of treatment. In addition, all tissues were examined for changes in protein content, which further elucidated the impact of hypothyroidism on the fetal liver by the observation of a marked increase in protein content in the methimazole-treated group. Finally, the heart and liver were histologically examined for evidence of cellular hyperplasia and hypertrophy by measuring average nuclei density and size in each tissue, with the results showing a significant decrease in average nuclei size in the liver of hypothyroid fetuses. CONCLUSIONS: Collectively, these findings indicate the occurrence of organ-specific disruptions in cell cycle progression as a result of in utero hypothyroidism, which may explain the long term and widespread effects of hypothyroidism on fetal development.

Rare Presentation of Thyrotoxicosis Defying Methimazole Treatment: A Case Series.

Thyrotoxicosis, also known as hyperthyroidism, is a condition characterized by the excessive production of thyroid hormones by the thyroid gland. Besides Graves' disease, other common causes of thyrotoxicosis include toxic multinodular goiter, toxic adenoma, and subacute thyroiditis. The treatment of thyrotoxicosis depends on the underlying cause and may include medications (e.g., antithyroid drugs, beta-blockers), radioactive iodine therapy, or surgical removal of the thyroid gland (thyroidectomy). In this report, we present two instances of thyrotoxicosis where conventional high doses of antithyroid treatment failed to control the condition effectively. This failure prompted the exploration of alternative therapeutic interventions. These cases highlight the intricacies involved in managing thyrotoxic crises that do not respond to methimazole (MMI), emphasizing the necessity for innovative approaches such as plasmapheresis and thyroidectomy. Understanding such scenarios is vital for enhancing the care provided to patients encountering resistance to standard treatments. The distinct clinical pathways and treatment strategies adopted in these cases offer valuable insights into this disease management, particularly concerning resistance to MMI.

Methimazole Desensitization in a Patient Experiencing a Thionamide-induced Hypersensitivity Reaction.

Patients with newly diagnosed Graves disease often elect for treatment with the drug methimazole (MMI) over alternative therapies. However, MMI can commonly result in skin allergy that in severe cases can lead to discontinuation of therapy. We present a case of Graves thyrotoxicosis with a delayed hypersensitivity reaction while on MMI. The patient was successfully treated with a novel, individualized, 27-day desensitization protocol that resulted in tolerance of MMI with subsequent improvement in thyroid indices. Previous literature has offered various rapid desensitization protocols to MMI for immediate type hypersensitivity reactions. However, in nonimmediate, delayed hypersensitivity reactions, a slower desensitization protocol can be considered. As demonstrated in this case, desensitization to MMI is a reasonable alternative in patients who wish to avoid definitive therapy who develop an initial adverse reaction to MMI, as this can occur in up to 13% of treated cases.

Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil.

Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the evidence has not been conclusive. The objective of our study was to determine whether the incidences of agranulocytosis induced by MMI and PTU exhibit dose-dependency. The subjects were 27,784 patients with untreated Graves' disease, 22,993 of whom were on an antithyroid drug treatment regimen for more than 90 days. Within this subset, 18,259 patients had been treated with MMI, and 4,734 had been treated with PTU. The incidence of agranulocytosis according to dose in the MMI group was 0.13% at 10 mg/day, 0.20% at 15 mg/day, 0.32% at 20 mg/day, and 0.47% at 30 mg/day, revealing a significant dose-dependent increase. In the PTU group, there were 0 cases of agranulocytosis at doses of 125 mg/day and below, 0.33% at 150 mg/day, 0.31% at 200 mg/day, and 0.81% at 300 mg/day, also revealing a significant dose-dependent increase. The incidence of agranulocytosis at MMI 15 mg and PTU 300 mg, i.e., at the same potency in terms of hormone synthesis inhibition, was 0.20% and 0.81%, respectively, and significantly higher in the PTU group. Our findings confirm a dose-dependent increase in the incidence of agranulocytosis with both drugs, but that at comparable thyroid hormone synthesis inhibitory doses PTU has a considerably higher propensity to induce agranulocytosis than MMI does.

Important Counteranion Effect on Adsorption Efficacity of Hydrogen Sulfide by Silver(I)-Dithione Coordination Polymers.

Four new coordination polymers (CPs) have been prepared and evaluated for their efficacy in adsorbing hydrogen sulfide. The reactions of the structurally flexible assembling dithione ligand, L, with different silver(I) salts lead to four new metal-organic coordination architectures (CPs I, III, V, and VIII) exhibiting either one- or two-dimensional networks. CP I, 2D-[(Ag2Cl2)L]n, exhibits a linear series of rhomboid (S)2Ag(µ2-Cl)2Ag(S)2 secondary building units (SBUs) where S is one of the thione functions of L, altogether forming a 2D-network. CP III, 2D-[(AgI)L]n, is built upon parallel staircase-shaped 1D-[Ag2(µ3-I)2]n SBUs bridged by S atoms of L that form a 2D-grid. CP V, 2D-[(AgL)(NO3)]n, presents parallel 1D-folded S-shaped [AgL]n+ chains linked by strong argentophilic Ag···Ag interactions, forming a 2D-scaffolding. CP VIII, 1D-[(Ag2L3)(Cr2O7)]n, shows 1D-zigzag [{Ag(η2-µ2,η-µ,µ-L)}2]n2n+ chains accompanied by Cr2O72- counteranions. The adsorption isotherms of H2S gas by these new CPs were examined and compared to those of related CPs [(Ag2Br2)L]n (II), [(AgCN)4L]n (IV), [(Ag2L)(CF3SO3)2]n (VI), and [(Ag2L)(NO3)(ClO4)]n (VII). Among the tested polymers, the 3D-CP IV featuring cyanide anions exhibits the highest adsorption capacity of the CPs studied in this work. In order to determine the reason for this marked difference, density functional theory (DFT) computations were used. All in all, it turns out that the electrostatic interactions (CN-···H-SH) are significantly stronger than the O-···H-SH ones. This investigation provides a valuable conceptual tool for other designs of CPs and MOFs having the purpose of capturing toxic gases.

Toxic Epidermal Necrolysis Secondary to Iodine Versus Methimazole in a Pediatric Patient With Complex Autoimmune Disease.

We report a case of a 17-year-old girl who developed toxic epidermal necrolysis (TEN) secondary to preoperative iodine administration before thyroidectomy for Graves' disease. Past medical history was significant for COVID-19 and multisystem inflammatory syndrome in Children (MISC-C), with subsequent diagnoses of type 1 diabetes mellitus (T1DM), Addison disease, and Graves' disease. Her Graves disease was initially managed with methimazole. While there are reported cases of Stevens-Johnson syndrome (SJS) and TEN due to methimazole, the patient had discontinued methimazole over one month prior. Therefore, she likely represents the first case of TEN reported secondary to potassium iodide solution in a pediatric patient. Given the rarity of TEN in pediatric patients, our case highlights the challenges in managing complex autoimmune conditions and underscores the importance of careful medication choices in such cases.

Influence of propranolol plus methimazole on curative efficacy and thyroid function of patients with hyperthyroidism.

PURPOSE: To analyze the influence of propranolol (Prop) plus methimazole (MMI) on curative efficacy and thyroid function (TF) of patients with hyperthyroidism (HT). METHODS: In this retrospective study, 107 cases of HT presented between August 2019 and August 2021 were grouped according to different therapeutic regimens: a control group (the Con) with 53 cases treated with MMI, and a research group (the Res) with 54 cases treated with Prop + MMI. Inter-group comparisons were performed in terms of the following domains: heart rate (HR), efficacy, adverse reactions (ARs), TF parameters (free triiodothyronine, FT3; free thyroxine, FT4; thyroid stimulating hormone, TSH), hepatic function indicators (alanine aminotransferase, ALT; aspartate aminotransferase, AST), and quality of life (Short-Form 36 Item Health Survey, SF-36). Finally, multivariate analysis was performed by Logistic regression to determine the risk factors leading to the ineffectiveness of treatment. RESULTS: The analysis showed an obviously higher total effective rate and an evidently lower AR rate in the Res compared with the Con group. Besides, the Res group had notably lower FT3, FT4, ALT and AST and statistically higher TSH after treatment compared with the baseline (before treatment) and the Con group. Higher SF-36 scores were also determined in the Res group. Finally, the results of Logistic regression analysis revealed that AST was an independent risk factor for ineffective treatment. CONCLUSIONS: Prop plus MMI is effective in the treatment of HT, which can effectively improve the HR, thyroid hormone levels, hepatic function, and quality of life of patients, with a lower incidence of ARs.

Anemia aplásica inducida por metimazol: presentación de caso / Methimazole Induced Aplastic Anemia: Case Report / Anemia aplástica induzida por metimazol: relato de caso

Introducción: los medicamentos antitiroideos son una de las alternativas terapéuticas en el tratamiento de la enfermedad de Graves. Sin embargo, pueden generar efectos adversos severos poco frecuentes en el plano hematológico, como la anemia aplásica, la cual se ha asociado con altas dosis de estos medicamentos, aunque con reversión de esta afección ante el retiro del medicamento. Descripción del caso: mujer de 38 años con antecedente de enfermedad de Graves en tratamiento con metimazol, quien consultó por síntomas como epistaxis anterior de difícil control, petequias, astenia e hiporexia. Se documentó pancitopenia en el hemo-grama, con posterior hallazgo en biopsia de médula ósea de aplasia medular, sin respuesta ante el retiro del metimazol y soporte transfusional. Posteriormente, la paciente falleció. Conclusión: la presentación de aplasia medular asociada con metimazol es poco común y se relaciona con altas dosis de este medicamento. En la mayoría de casos, el retiro de este agente genera recuperación clínica y celular. No obstante, en algu-nos pacientes persiste el compromiso hematológico que va desde importantes repercusiones clínicas hasta desenlaces fatales. Por lo tanto, el presente caso busca hace hincapié en la importancia de vigilar este efecto adverso ante el inicio de esta medicación

Introduction: Antithyroid drugs are one of the therapeutic alternatives in the treatment of Graves' dis-ease. However, it can generate severe but infrequent adverse effects at the hematological level, such as aplastic anemia, which has been associated with high doses of these drugs, although with reversal of this hematological condition when the drug is withdrawn. Case description: A 38-year-old woman with a his-tory of Graves' disease treated with methimazole, who consult for symptoms such as anterior epistaxis, petechiae, asthenia, and hyporexia. Pancytopenia is documented in the blood count, with a subsequent finding of bone marrow aplasia in bone marrow biopsy, without response to withdrawal of Methimazole and transfusion support. The patient subsequently died. Conclusion: The methimazole-associated bone marrow aplasia is uncommon and it ́s associated with high doses of methimazole, in most cases with-drawal of methimazole leads to clinical and cellular recovery. However, in some patients hematological involvement persists with significant clinical repercussions up to fatal outcomes. Therefore, this case seeks to highlight the importance of monitoring for this adverse effect before starting this medication

Introdução: as drogas antitireoidianas são uma das alternativas terapêuticas no tratamento da doença de Graves. No entanto, pode causar efeitos adversos graves, mas infrequentes, no nível hematológico, como a anemia aplástica, que tem sido associada a altas doses desses medicamentos, embora com rever-são desse quadro hematológico quando a droga é retirada. Descrição do caso: mulher de 38 anos com história de doença de Graves tratada com metimazol, que consultou por sintomas como epistaxe ante-rior de difícil controle, petéquias, astenia e hiporexia. A pancitopenia é documentada no hemograma, com achado posterior de aplasia da medula óssea na biópsia da medula óssea, sem resposta à retirada do metimazol e suporte transfusional. O doente faleceu posteriormente. Conclusão: a apresentação de aplasia da medula óssea associada ao metimazol é pouco frequente em associação com doses elevadas de metimazol. Na maioria dos casos, a retirada do metimazol conduz à recuperação clínica e celular. No entanto, nalguns doentes, o envolvimento hematológico persiste com repercussões clínicas significati-vas, podendo mesmo ocorrer desfechos fatais. Assim, o presente caso pretende realçar a importância da monitorização deste efeito adverso antes de iniciar esta medicação

Protective role of the ginsenoside Rg1 against methimazole-induced gestational hypothyroidism on reflexive behaviors, conditioned fear and cortical antioxidant levels in mice offspring.

Ginsenoside Rg1(Rg1), a monomer of a tetracyclic triterpenoid derivative, possesses diverse medicinal properties attributed to its unique chemical structure and may have beneficial effects on fetal development. This study aimed to investigate the protective effects of prenatal exposure to Rg1 against Methimazole-induced gestational hypothyroidism on reflexive behaviors, conditioned fear, and cortical antioxidant levels in mouse offspring.40 female virgin mice and 12 male NMRI mice were assigned to four groups: group 1 served as the control, group 2 received Methimazole(MMI) at a concentration of 0.02% in their drinking water, group 3 received Rg1(150 mg/kg), and group 4 received both MMI and Rg1.Groups of 2-4 were administered the substances from days 1-9 of gestation. After delivery, pups were selected, and reflexive motor behaviors and conditioned fear were assessed. Additionally, levels of brain tissue catalase(CAT), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione peroxidase(GPx) levels were measured. Furthermore, postpartum immobility time in the forced swimming test (FST), tail suspension test (TST), and the number of squares crossed in the open field test (OFT)were determined. The results demonstrated that maternal exposure to Rg1 improved ambulation score, hind-limb suspension score, grip strength, front-limb suspension, hind-limb foot angle, negative geotaxis, surface righting, and conditioned fear in hypothyroidism-induced offspring(P<0.05). Rg1 decreased immobility time in the FST, and TST, and increased the number of squares crossed in the OFT in postpartum hypothyroidism-induced mice(P<0.05). Moreover, Rg1 reduced brain tissue MDA levels and increased brain tissue CAT, SOD, and GPx levels in mice and their offspring(P<0.05). These findings indicate that Rg1 mitigated postpartum depression in mice and improved reflexive motor behaviors in their pups.

Impact of methimazole-induced hypothyroidism on postnatal swine.

Thyroid hormones regulate metabolic rate, nutrient utilization, growth, and development. Swine are susceptible to thyroid suppression in response to disease or environmental conditions, but the physiological impact of such disruption has not been established. The objective of this study was to evaluate the impact of hypothyroidism induced with the antithyroid medication methimazole (MMI). 10 mg/kg MMI significantly decreased circulating triiodothyronine (T3) for the duration of treatment but had only a transient effect on circulating thyroxine (T4). Thyroid tissue weight was significantly increased by more than 3.5-fold in response to MMI treatment. Histologically, the eosinophilic colloid was largely absent from the thyroid follicle which displayed a disorganized columnar epithelium consistent with goiter. MMI induced hypothyroidism has no effect on growth rate over 28 days. Hepatic expression of genes associated with thyroid metabolism (DIO1, DIO2, and DIO3), lipid utilization (CD36, FASN, and ACACA), apoptosis (TP53, PERP, SIVA1, and SFN) and proliferation (CDK1, CDK2, CDK4, and CDKN1A) were unaffected by treatment. Collectively these results demonstrate that MMI induces mild systemic hypothyroidism and pronounced goiter, indicating a strong homeostatic central regulation within the hypothalamic pituitary thyroid axis. This combined with limited peripheral effects, indicates resilience to hypothyroidism in modern swine.

A Novel Enhanced-Fluorescent Probe Based on DHLA-Stabilized Red-Emitting Copper Nanoclusters for Methimazole Detection Via Aggregation-Induced Emission Effect.

Herein, an aqueous phase synthesis approach was presented for the fabrication of copper nanoclusters (Cu NCs) with aggregation-induced emission (AIE) property, utilizing lipoic acid and NaBH4 as ligands and reducing agent, respectively. The as-synthesized Cu NCs exhibit an average size of 3.0 ± 0.2 nm and demonstrate strong solid-state fluorescence upon excitation with UV light. However, when dissolved in water, no observable fluorescent emission is detected in the aqueous solution of Cu NCs. Remarkably, the addition of Methimazole induced a significant red fluorescence from the aqueous solution of Cu NCs. This unexpected phenomenon can be ascribed to the aggregation of negatively charged Cu NCs caused by electrostatic interaction with positively charged imidazole groups in Methimazole, resulting in enhanced fluorescence through AIE mechanism. Therefore, there exists an excellent linear correlation between the fluorescent intensities of Cu NCs aqueous solution and the concentration of Methimazole within a range of 0.1-1.5 mM with a low limit of detection of 82.2 µM. Importantly, the designed enhanced-fluorescent nanoprobe based on Cu NCs exhibits satisfactory performance in assaying commercially available Methimazole tablets, demonstrating its exceptional sensitivity, reliability, and accuracy.

A Case of Diffuse Thyroid Lipomatosis With Amyloid Deposits Presenting With Thyrotoxicosis.

Diffuse thyroid lipomatosis (DTL) is a rare entity of unknown etiology that can be associated with amyloidosis and rarely, thyrotoxicosis. Here, we present a case of DTL with amyloid deposits and concurrent thyrotoxicosis. A 64-year-old South-Asian woman with a several-year history of an enlarging goiter, unintentional weight loss, and work-up 10 months prior suggestive of thyroiditis presented with a viral syndrome in setting of several weeks of progressive fatigue. Her examination was notable for resting sinus tachycardia and massive painless goiter. Initial work-up revealed nephrotic range proteinuria with hypoalbuminemia, which progressed to end-stage-renal disease, elevated inflammatory markers, and elevated free thyroxine (FT4) with a suppressed thyrotropin. Hemodialysis was initiated. Further testing revealed a negative antithyroid antibody panel, an enlarged fatty thyroid per thyroid ultrasound and neck computed tomography, and normal 24-hour uptake on radioactive iodine uptake scan. Both renal and thyroid core biopsies showed amyloid deposits, with the latter confirming benign adipose tissue with entrapped thyroid follicles. Given her rising FT4 levels and persistent tachycardia, methimazole and atenolol were initiated. FT4 levels nearly normalized after uptitration of methimazole and dosing after dialysis. Although the etiopathogenesis and natural history of DTL remain unclear, we discuss the possible mechanisms of thyrotoxicosis in our patient.

Methimazole-induced urticaria in hyperthyroid patients: A safe re-administration protocol.

PURPOSE: The safety profile of methimazole (MMI) seems to be better than propylthiouracil in the management of hyperthyroidism. It is therefore advisable to use IMM as the first choice in Graves' patients. It is important to keep this drug in patients regardless of minor side effects. We report a case series of MMI-induced urticaria and provide a stepwise protocol for the safe re-administration of MMI. METHODS: It was a retrospective case series including all patients having manifested urticaria following MMI intake for hyperthyroidism; notified to the Pharmacovigilance Unit of the Clinical Pharmacology Department (March 2013-January 2022). RESULTS: We have included 11 patients (SR: 0.22). The median time interval between the start of MMI and the onset of urticaria averaged 14.5 days. The median daily dose of MMI was 40mg. MMI was interrupted in all patients. Urticaria has progressively resolved after drug interruption and antihistamine intake. Reintroduction of MMI was performed in 10/11 patients as follows: one quarter of the daily dose on the first day, half of the daily dose on the 4th day, the three quarters of the daily dose on the 7th day, to reach the scheduled total dose on the 10th day. Cetirizine was added at the time of reintroduction and withdrawn 2 weeks later. All the patients were successfully controlled. CONCLUSION: Given the importance of this drug in the management of hyperthyroidism, MMI should not be withdrawn in cases of urticaria. After the resolution of urticaria, a gradual reintroduction of MMI should be attempted with concomitant antihistamine therapy.

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

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

Radioactive Iodine Therapy of Graves' Disease in Patients Pretreated With Methimazole Without Radioiodine Uptake for Dose Estimation.

OBJECTIVE: To assess response predictors to radioactive iodine (RAI) therapy without using thyroid uptake for dose estimate in patients pretreated with methimazole. METHODS: Retrospective analysis was performed of patients with Graves' disease treated with RAI doses determined without using uptake studies. RESULTS: In 242 patients (median age, 41.9 years; 66.1% female), initial mean free thyroxine (FT4) level was 4.7 ng/dL with an estimated thyroid size of 49.15 g. Prior to RAI therapy, average methimazole dose was 22.7 mg/day. Mean RAI dose was 737.0 ±199.4 MBq (19.9 ± 5.4 mCi). Two hundred eight patients (85.9%) responded to RAI therapy; 185 (88.9%) became hypothyroid and 23 (11.1%) became euthyroid. The majority (90.4%) responded within 6 months of therapy with a quicker response (13.9 ± 8.3 vs 17.5 ± 13.5 weeks) for those treated with doses per gram of ≥14.8 MBq (0.4 mCi). Thirty-four nonresponders had a higher initial FT4 level and larger thyroid size with a lower RAI dose per gram of thyroid tissue. In multivariate analysis, the independent response predictor to therapy was dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) (hazard ratio, 3.18; 95% CI, 1.1-9.7). Doses per gram of 14.8 to 18.1 MBq (0.4-0.5 mCi) achieved maximal response rate without added advantage of higher doses. Thyroid size prior to RAI therapy, FT4 levels at diagnosis, and age were inversely related to response. CONCLUSION: RAI therapy for Graves' disease without uptake studies for dose estimates is an effective treatment method. In patients pretreated with methimazole, an RAI dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) showed high response rate. Prospective studies are needed to confirm the viability of this simplified and cost-effective approach.