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Scientific Reports Nov 2023Although antithyroid drug (ATD)-induced agranulocytosis is a significant concern, its risks associated with long-term use and re-administration are not fully elucidated....
Although antithyroid drug (ATD)-induced agranulocytosis is a significant concern, its risks associated with long-term use and re-administration are not fully elucidated. Therefore, we performed this study to determine the incidence of ATD-induced leukopenia and G-CSF administration using administrative claims database. Retrospective cohort study. This study was performed using the DeSC Japanese administrative claims database. A total of 12,491 patients with newly diagnosed Graves' disease (GD) who received methimazole or propylthiouracil between April 2014, and February 2021 among 3.44 million patients in the database were included in the study. We measured the six-year incidence of leukopenia and granulocyte colony-stimulating factor (G-CSF) administration. The incidence of leukopenia and G-CSF administration was 1.34% (168 patients) and 0.30% (38 patients), respectively. Leukopenia had a dose-dependent and biphasic incidence. The incidence of leukopenia and G-CSF administration was 37.2 (0.7%) and 8.0 (0.2%) per 1000 person-years during the first 72 days of ATD initiation, whereas it was 3.1 and 0.7 per 1000 person-years during the subsequent 6 years, respectively. The incidence of both outcomes was comparable between first administration and re-administration of ATD. The incidence of ATD-induced leukopenia and G-CSF administration was high in the first 72 days, with a reduced risk for at least 6 years thereafter. The incidence was similar between first administration and re-administration. ATD, a standard therapy, is often administered for a long period; therefore, our findings can guide the treatment of GD.
Topics: Humans; Antithyroid Agents; Cohort Studies; Retrospective Studies; Graves Disease; Neutropenia; Granulocyte Colony-Stimulating Factor; Thrombocytopenia
PubMed: 37935745
DOI: 10.1038/s41598-023-46307-5 -
Internal Medicine (Tokyo, Japan) Jun 2024A 49-year-old Japanese woman was admitted to our hospital with weight loss of 15 kg, nephrotic-range proteinuria (4.5 g/g.Cre), and hematuria over a 6-month period. She...
A 49-year-old Japanese woman was admitted to our hospital with weight loss of 15 kg, nephrotic-range proteinuria (4.5 g/g.Cre), and hematuria over a 6-month period. She had received two doses of the coronavirus disease 2019 (COVID-19) vaccine one year before the onset of the disease, after which the estimated glomerular filtration rate increased. Laboratory tests and other tests led to a diagnosis of hyperthyroidism, and a kidney biopsy showed thrombotic microangiopathy-like glomerular microangiopathy comprising mainly glomerular endothelial cell damage. Thiamazole (30 mg) was started for the hyperthyroidism. Three months later, the thyroid function normalized, and two months later, the proteinuria and hematuria disappeared, suggesting that COVID-19 vaccination and these events were related.
Topics: Humans; Female; Middle Aged; Hyperthyroidism; Thrombotic Microangiopathies; Methimazole; Kidney Glomerulus; COVID-19; Antithyroid Agents; COVID-19 Vaccines; Hematuria; Kidney Diseases
PubMed: 37926548
DOI: 10.2169/internalmedicine.2436-23 -
JCEM Case Reports Jul 2023Thyroid storm is a life-threatening endocrine emergency that warrants early clinical recognition and aggressive intervention. We present a 64-year-old female with no...
Thyroid storm is a life-threatening endocrine emergency that warrants early clinical recognition and aggressive intervention. We present a 64-year-old female with no known history of thyroid disease, who presented to her primary care physician with dyspnea on exertion and was found to have an anterior mediastinal mass. She had elective thymectomy. Pathology confirmed thymic lymphoepithelial carcinoma. Postoperatively, she developed altered mental status, fever, and atrial fibrillation with marked elevation of thyroid hormones, consistent with thyroid storm. She decompensated rapidly and was treated aggressively with standard therapies for thyroid storm, including beta-blockers, methimazole, cholestyramine, steroids, and iodine, with poor response. The patient eventually underwent 4 sessions of therapeutic plasma exchange (TPE) with marked improvement in her symptoms. This case reports a possible association between thymic lymphoepithelial carcinoma and Graves disease and highlights the utility of TPE in cases of severe thyroid storm that are refractory to traditional treatments. We learn from this case that evaluating thyroid function tests in patients with thymic or mediastinal masses before surgery might be helpful. TPE should be considered in patients with thyroid storm refractory to traditional therapies.
PubMed: 37909005
DOI: 10.1210/jcemcr/luad053 -
JCEM Case Reports Sep 2023We present 2 cases referred for evaluation of Graves disease (GD) associated with an incidental mediastinal mass. Chest computed tomography (CT) scans showed a 1.2 ×...
We present 2 cases referred for evaluation of Graves disease (GD) associated with an incidental mediastinal mass. Chest computed tomography (CT) scans showed a 1.2 × 2.4 × 4.3 cm and a 5.7 × 2.6 × 7 cm thymic enlargement, respectively, consistent with thymic hyperplasia (TH) in the 2 patients. Patient 1 had been assessed by thoracic surgery for the mediastinal mass, and thymectomy had been performed to exclude thymoma, with an anatomopathological diagnosis consistent with thymic hyperplasia. Patient 2 was treated with methimazole. CT scan was repeated after he maintained a euthyroid state, which revealed total regression of the mass. There is a well-documented association between these 2 entities, but it is often underdiagnosed and unrecognized in routine clinal practice. The benign evolution, as evidenced by regression of thymic hyperplasia after resolution of the hyperthyroidism, is characteristic. These cases highlight the importance of recognizing the association of GD and TH and warrant a conservative approach, preventing unnecessary thymic evaluation and surgery.
PubMed: 37908219
DOI: 10.1210/jcemcr/luad083 -
Journal of Clinical Medicine Oct 2023Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism.
BACKGROUND
Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism.
METHODOLOGY
Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves' disease ( = 21), amiodarone-induced thyrotoxicosis ( = 7), and hyperfunctioning multinodular goiter ( = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil.
RESULTS
The median (IQR) time to development of agranulocytosis was 6.0 (4.0-11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves' disease), and two patients died of septic shock secondary to AIA.
CONCLUSIONS
AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously.
PubMed: 37892693
DOI: 10.3390/jcm12206556 -
ACS Bio & Med Chem Au Oct 2023Sulfur mustard (SM), designated by the military as HD, is a highly toxic and dangerous vesicant that has been utilized as a chemical warfare agent since World War I....
Sulfur mustard (SM), designated by the military as HD, is a highly toxic and dangerous vesicant that has been utilized as a chemical warfare agent since World War I. Despite SM's extensive history, an effective antidote does not exist. The effects of SM are predominantly based on its ability to alkylate important biomolecules. Also, with the potential for a fraction of SM to remain unreacted up to days after initial contact, a window of opportunity exists for direct neutralization of unreacted SM over the days following exposure. In this study, we evaluated the structure-activity relationship of multiple nucleophilic molecules to neutralize the toxic effects of 2-chloroethyl ethyl sulfide (CEES), a monofunctional analogue of SM, on human keratinocyte (HaCaT) cells. Cell viability, relative loss of extracellular matrix adhesions, and apoptosis caused by CEES were measured via MTT, cell-matrix adhesion (CMA), and apoptosis protein marker assays, respectively. A set of five two-carbon compounds with various functional groups served as a preliminary group of first-generation neutralizing agents to survey the correlation between mitigation of CEES's toxic effects and functional group nucleophilicity. Apart from thioacids, which produced additive toxicity, we generally observed the trend of increasing protection from cytotoxicity with increasing nucleophilicity. We extended this treatment strategy to second-generation agents which contained advantageous structural features identified from the first-generation molecules. Our results show that methimazole (MIZ), a currently FDA-approved drug used to treat hyperthyroidism, effectively reduced cytotoxicity, increased CMA, and decreased apoptosis resulting from CEES toxicity. MIZ selectively reacts with CEES to produce 2-(2-(ethylthio)ethylthio)-1-methyl-1-imidazole (EEMI) in media and cell lysate treatments resulting in the reduction of toxicity. Based on these results, future development of MIZ as an SM therapeutic may provide a viable approach to reduce both the immediate and long-term toxicity of SM and may also help mitigate slower developing SM toxicity due to residual intact SM.
PubMed: 37876493
DOI: 10.1021/acsbiomedchemau.2c00087 -
BMC Endocrine Disorders Oct 2023This study aimed to evaluate the association between the initial dose of MMI and the clinical course, as well as adverse effects on young people with GD.
OBJECTIVE
This study aimed to evaluate the association between the initial dose of MMI and the clinical course, as well as adverse effects on young people with GD.
METHODS
One hundred and sixty-one children and adolescents with newly diagnosed GD were enrolled for this study and categorized into four groups based on initial serum-free T3 and T4 levels and daily MMI doses: Group A (mild, 0.3-0.5 mg/kg/day, n = 78), Group B (moderate, 0.6-0.8 mg/kg/day, n = 37), Group C (severe, 0.6-0.8 mg/kg/day, n = 24), and Group D (severe, 0.8-1.0 mg/kg/day, n = 22). The thyroid function, blood cell analysis and liver function were examined before treatment and at 4, 8 and 12 weeks after treatment. Outcome of long-term follow-up were also observed.
RESULTS
After 12 weeks of treatment, 91.0% of the patients in group A and 90.9% of the patients in group D recovered to normalization of FT3, which was slightly higher than the other two groups; 70.8% of the patients in group C recovered to normalization of FT4, which was slightly lower than that in the other three groups. The incidence of minor adverse effects was 12.8% in group A, 13.5% in group B, 16.7% in group C and 40.9% in group D (P < 0.01). Remission was achieved in 38 patients (23.6%).
CONCLUSIONS
Lower doses of MMI (0.3-0.5 mg/kg/day) are suitable for mild GD, and higher doses of MMI (0.6-0.8 mg/kg/day) are advisable for moderate or severe GD. Much higher doses of MMI (0.8-1.0 mg/kg/day) are harmful for initial use in children and adolescents with GD patients.
Topics: Humans; Adolescent; Child; Methimazole; Antithyroid Agents; Outpatients; Thyroxine; Graves Disease
PubMed: 37872592
DOI: 10.1186/s12902-023-01484-2 -
International Journal of Molecular... Oct 2023Pancreatic alterations such as inflammation and insulin resistance accompany hypothyroidism. Molecular iodine (I) exerts antioxidant and differentiation actions in...
Pancreatic alterations such as inflammation and insulin resistance accompany hypothyroidism. Molecular iodine (I) exerts antioxidant and differentiation actions in several tissues, and the pancreas is an iodine-uptake tissue. We analyzed the effect of two oral I doses on pancreatic disorders in a model of hypothyroidism for 30 days. Adult female rabbits were divided into the following groups: control, moderate oral dose of I (0.2 mg/kg, M-I), high oral dose of I (2.0 mg/kg, H-I), oral dose of methimazole (MMI; 10 mg/kg), MMI + M-I, and MMI + H-I. Moderate or high I supplementation did not modify circulating metabolites or pancreatic morphology. The MMI group showed reductions of circulating thyroxine (T4) and triiodothyronine (T3), moderate glucose increments, and significant increases in cholesterol and low-density lipoproteins. Acinar fibrosis, high insulin content, lipoperoxidation, and overexpression of GLUT4 were observed in the pancreas of this group. M-I supplementation normalized the T4 and cholesterol, but T3 remained low. Pancreatic alterations were prevented, and nuclear factor erythroid-2-related factor-2 (Nrf2), antioxidant enzymes, and peroxisome proliferator-activated receptor gamma (PPARG) maintained their basal values. In MMI + H-I hypothyroidism was avoided, but pancreatic alterations and low PPARG expression remained. In conclusion, M-I supplementation reestablishes thyronine synthesis and diminishes pancreatic alterations, possibly related to Nrf2 and PPARG activation.
Topics: Animals; Rabbits; Female; Antioxidants; NF-E2-Related Factor 2; PPAR gamma; Hypothyroidism; Triiodothyronine; Thyroxine; Iodine; Cholesterol
PubMed: 37834351
DOI: 10.3390/ijms241914903 -
Food Science & Nutrition Oct 2023The seeds of (L.) Webb ex Prantl contain goitrogenic glucosinolates, such as gluconapin (3-butenyl glucosinolate). Because of the important role of iodine in the...
The seeds of (L.) Webb ex Prantl contain goitrogenic glucosinolates, such as gluconapin (3-butenyl glucosinolate). Because of the important role of iodine in the synthesis of thyroid hormones and the inhibitory activity of on iodine uptake by the thyroid gland, this study aimed to determine the effects of syrup on clinical and biochemical variables of thyrotoxicosis in hyperthyroid patients. In this randomized, double-blind trial, 10 newly diagnosed hyperthyroid female patients were randomly assigned to treatment with (1) methimazole (MMI) plus capsules (350 mg/d) or (2) MMI plus placebo capsules. The primary outcomes were clinical and biochemical manifestations of hyperthyroidism after 60 days. Serum levels of FT3 and FT4 significantly decreased (5.9 ± 2.5 vs. 9.4 ± 5.9 and 29.1 ± 3.1 vs. 31.77 ± 3.7, respectively) and the serum thyroid-stimulating hormone (TSH) concentration significantly increased in the group contrasted to the placebo group (4.7 ± 0.1 vs. 0.05 ± 0.02). Significant improvement in the thyrotoxicosis clinical symptoms was reported in the group contrasted to the placebo group ( < .05). can suppress plasma levels of FT3 and FT4 and may be useful as adjunctive therapy for hyperthyroidism.
PubMed: 37823162
DOI: 10.1002/fsn3.3522 -
The Journal of Clinical Endocrinology... Jan 2024In 2005, a nationwide program of iodine prophylaxis on a voluntary basis was implemented in Italy by law. However, recent data on iodine status are lacking.
CONTEXT
In 2005, a nationwide program of iodine prophylaxis on a voluntary basis was implemented in Italy by law. However, recent data on iodine status are lacking.
OBJECTIVE
The aim of this study was to evaluate efficiency, effectiveness, and possible adverse effects (increased occurrence of thyroid autoimmunity and hyperthyroidism) of the Italian iodine prophylaxis program.
METHODS
From 2015 to 2019, a nationwide survey was performed. The use of iodized salt was evaluated in a sample of 164 593 adults and in 998 school canteens. A sample of 4233 schoolchildren (aged 11-13 years) was recruited to assess urinary iodine concentration, prevalence of goiter, and thyroid hypoechogenicity on ultrasound, with the latter being an indirect indicator of thyroid autoimmunity. Neonatal TSH values of 197 677 infants screened in regions representative of Northern, Central, and Southern Italy were analyzed to investigate the percentage of TSH values >5.0 mIU/L. Data on methimazole prescriptions were analyzed as indirect indicators of new cases of hyperthyroidism.
RESULTS
The prevalence of the use of iodized salt was 71.5% in adult population and 78% in school canteens. A median urinary iodine concentration of 124 μg/L, a prevalence of goiter of 2.2%, and a prevalence of thyroid hypoechogenicity of 5.7% were observed in schoolchildren. The percentage of neonatal TSH values >5.0 mIU/L resulted still higher (5.1%) than the World Health Organization threshold of 3.0%, whereas the prescriptions of methimazole showed a reduction of 13.5%.
CONCLUSION
Fifteen years of iodine prophylaxis have led to iodine sufficiency in Italy, although there still is concern about iodine nutritional status during pregnancy.
Topics: Adult; Female; Infant; Pregnancy; Infant, Newborn; Humans; Child; Methimazole; Goiter; Sodium Chloride, Dietary; Iodine; Hyperthyroidism; Italy; Prevalence; Thyrotropin
PubMed: 37820735
DOI: 10.1210/clinem/dgad593