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The Journal of Clinical Endocrinology... Dec 2020Invited update on the management of systemic autoimmune Graves disease (GD) and associated Graves orbitopathy (GO). (Review)
Review
CONTEXT
Invited update on the management of systemic autoimmune Graves disease (GD) and associated Graves orbitopathy (GO).
EVIDENCE ACQUISITION
Guidelines, pertinent original articles, systemic reviews, and meta-analyses.
EVIDENCE SYNTHESIS
Thyrotropin receptor antibodies (TSH-R-Abs), foremost the stimulatory TSH-R-Abs, are a specific biomarker for GD. Their measurement assists in the differential diagnosis of hyperthyroidism and offers accurate and rapid diagnosis of GD. Thyroid ultrasound is a sensitive imaging tool for GD. Worldwide, thionamides are the favored treatment (12-18 months) of newly diagnosed GD, with methimazole (MMI) as the preferred drug. Patients with persistently high TSH-R-Abs and/or persistent hyperthyroidism at 18 months, or with a relapse after completing a course of MMI, can opt for a definitive therapy with radioactive iodine (RAI) or total thyroidectomy (TX). Continued long-term, low-dose MMI administration is a valuable and safe alternative. Patient choice, both at initial presentation of GD and at recurrence, should be emphasized. Propylthiouracil is preferred to MMI during the first trimester of pregnancy. TX is best performed by a high-volume thyroid surgeon. RAI should be avoided in GD patients with active GO, especially in smokers. Recently, a promising therapy with an anti-insulin-like growth factor-1 monoclonal antibody for patients with active/severe GO was approved by the Food and Drug Administration. COVID-19 infection is a risk factor for poorly controlled hyperthyroidism, which contributes to the infection-related mortality risk. If GO is not severe, systemic steroid treatment should be postponed during COVID-19 while local treatment and preventive measures are offered.
CONCLUSIONS
A clear trend towards serological diagnosis and medical treatment of GD has emerged.
Topics: Antithyroid Agents; Biomarkers; Diagnosis, Differential; Disease Management; Female; Graves Disease; Graves Ophthalmopathy; Humans; Hyperthyroidism; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Pregnancy; Pregnancy Complications; Receptors, Thyrotropin; Thyroid Gland; Thyroidectomy; Ultrasonography
PubMed: 32929476
DOI: 10.1210/clinem/dgaa646 -
The Journal of Clinical Endocrinology... Mar 2021Both hyperthyroidism and hypothyroidism can have adverse effects in pregnancy. The most common causes of thyrotoxicosis in pregnancy are gestational transient... (Review)
Review
Both hyperthyroidism and hypothyroidism can have adverse effects in pregnancy. The most common causes of thyrotoxicosis in pregnancy are gestational transient thyrotoxicosis and Graves' disease. It is important to distinguish between these entities as treatment options differ. Women of reproductive age who are diagnosed with Graves' disease should be counseled regarding the impact of treatment options on a potential pregnancy. Although the absolute risk is small, antithyroid medications can have teratogenic effects. Propylthiouracil appears to have less severe teratogenicity compared to methimazole and is therefore favored during the first trimester if a medication is needed. Women should be advised to delay pregnancy for at least 6 months following radioactive iodine to minimize potential adverse effects from radiation and ensure normal thyroid hormone levels prior to conception. As thyroid hormone is critical for normal fetal development, hypothyroidism is associated with adverse obstetric and child neurodevelopmental outcomes. Women with overt hypothyroidism should be treated with levothyroxine (LT4) to a thyrotropin (thyroid-stimulating hormone; TSH) goal of <2.5 mIU/L. There is mounting evidence for associations of maternal hypothyroxinemia and subclinical hypothyroidism with pregnancy loss, preterm labor, and lower scores on child cognitive assessment. Although there is minimal risk of LT4 treatment to keep TSH within the pregnancy-specific reference range, treatment of mild maternal thyroid hypofunction remains controversial, given the lack of clinical trials showing improved outcomes with LT4 treatment.
Topics: Adult; Embryo Loss; Female; Graves Disease; Humans; Infant, Newborn; Maternal Serum Screening Tests; Monitoring, Physiologic; Pregnancy; Pregnancy Complications; Prenatal Care; Tachycardia; Thyroid Diseases; Thyroid Function Tests; Thyrotoxicosis; Weight Loss
PubMed: 33349844
DOI: 10.1210/clinem/dgaa945 -
AIMS Genetics 2019The aims of this review were to understand the roles of bitter taste genes in humans. Some of the peoples have the capacity to taste some chemical substance such as... (Review)
Review
The aims of this review were to understand the roles of bitter taste genes in humans. Some of the peoples have the capacity to taste some chemical substance such as phenylthiocarbamide (PTC) while others cant not based on the dietary hazards and food preferences. There are two alleles responsible to express these phenotypes which are homozygous recessive. In human TAS2R38 genes located on the chromosome number 7 and consist of different nucleotide polymorphism that related to detection of the phenotype of different chemical compounds such as 6-n-propylthiouracil (PROP) and phenylthiocarbamide bitterness and this Gene is the member of the TAS2R genes which are eleven pseudogenes and twenty that has roles in many biological processes. There are many factors that affect the bitter taste such as food, age, sex, and different diseases. The mechanism of food bitter taste and genotype of TAS2R38 until know not well understood due to that the proof of relation between bitter taste sensitivity and food is harmful. there are many different diseases can impact the influence of taste such as neoplasm and lifestyle such as consumption of alcohol along with the use of medication, head trauma, upper tract infections. On the other hand, A relation between TAS2R38 genotype and meal preferences has been observed among children, however, no associations have been mentioned among older adults. Some previous research proved some vital points that show an association between type 1 of diabetes and phenylthiocarbamide (PTC) but other studies cannot demonstrate that. However, of other disease such as obesity is controversial but other studies reported to the relationship between them.
PubMed: 31922012
DOI: 10.3934/genet.2019.4.88 -
Trends in Endocrinology and Metabolism:... Aug 2019The microbiota has been identified as an important factor in health and in a variety of diseases. An altered microbiota composition increases the prevalence of... (Review)
Review
The microbiota has been identified as an important factor in health and in a variety of diseases. An altered microbiota composition increases the prevalence of Hashimoto's thyroiditis (HT) and Graves' disease (GD). Microbes influence thyroid hormone levels by regulating iodine uptake, degradation, and enterohepatic cycling. In addition, there is a pronounced influence of minerals on interactions between host and microbiota, particularly selenium, iron, and zinc. In manifest thyroid disorders, the microbiota may affect L-thyroxine uptake and influence the action of propylthiouracil (PTU). Although it is relatively well documented that thyroid disorders are linked to the composition of the microbiota, the role of specific genera and the potential use of therapies targeting the microbiota are less clear.
Topics: Animals; Graves Disease; Hashimoto Disease; Humans; Microbiota; Probiotics; Thyroid Gland; Thyroid Hormones
PubMed: 31257166
DOI: 10.1016/j.tem.2019.05.008 -
European Thyroid Journal Jan 2022Hyperthyroidism caused by Graves' disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults - antithyroid drugs (ATD),...
Hyperthyroidism caused by Graves' disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults - antithyroid drugs (ATD), radioactive iodine (RAI) or thyroid surgery, but the risks and benefits of each modality are different. The European Thyroid Association guideline provides new recommendations for the management of pediatric GD with and without orbitopathy. Clinicians should be alert that GD may present with behavioral changes or declining academic performance in children. Measurement of serum TSH receptor antibodies is recommended for all pediatric patients with hyperthyroidism. Management recommendations include the first-line use of a prolonged course of methimazole/carbimazole ATD treatment (3 years or more), a preference for dose titration instead of block and replace ATD, and to avoid propylthiouracil use. Where definitive treatment is required either total thyroidectomy or RAI is recommended, aiming for complete thyroid ablation with a personalized RAI activity. We recommend avoiding RAI in children under 10 years of age but favor surgery in patients with large goiter. Pediatric endocrinologists should be involved in all cases.
PubMed: 34981748
DOI: 10.1530/ETJ-21-0073 -
JAMA Network Open Apr 2023Thyroid storm is the most severe form of thyrotoxicosis, with high mortality, and is treated with propylthiouracil and methimazole. Some guidelines recommend...
IMPORTANCE
Thyroid storm is the most severe form of thyrotoxicosis, with high mortality, and is treated with propylthiouracil and methimazole. Some guidelines recommend propylthiouracil over methimazole, although the difference in outcomes associated with each treatment is unclear.
OBJECTIVE
To compare outcomes associated with use of propylthiouracil vs methimazole for the treatment of thyroid storm.
DESIGN, SETTING, AND PARTICIPANTS
This comparative effectiveness study comprised a large, multicenter, US-based cohort from the Premier Healthcare Database between January 1, 2016, and December 31, 2020. It included 1383 adult patients admitted to intensive or intermediate care units with a diagnosis of thyroid storm per International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and treated with either propylthiouracil or methimazole. Analyses were conducted from July 2022 to February 2023.
EXPOSURE
Patients received either propylthiouracil or methimazole for treatment of thyroid storm. Exposure was assigned based on the initial thionamide administered.
MAIN OUTCOMES AND MEASURES
The primary outcome was the adjusted risk difference of in-hospital death or discharge to hospice between patients treated with propylthiouracil and those treated with methimazole, assessed by targeted maximum likelihood estimation.
RESULTS
A total of 1383 patients (656 [47.4%] treated with propylthiouracil; mean [SD] age, 45 [16] years; 473 women [72.1%]; and 727 [52.6%] treated with methimazole; mean [SD] age, 45 [16] years; 520 women [71.5%]) were included in the study. The standardized mean difference for age was 0.056, and the standardized mean difference for sex was 0.013. The primary composite outcome occurred in 7.4% of of patients (102 of 1383; 95% CI, 6.0%-8.8%). A total of 8.5% (56 of 656; 95% CI, 6.4%-10.7%) of patients who initiated propylthiouracil and 6.3% (46 of 727; 95% CI, 4.6%-8.1%) who initiated methimazole died in the hospital (adjusted risk difference, 0.6% [95% CI, -1.8% to 3.0%]; P = .64). There were no significant differences in duration of organ support, total hospitalization costs, or rates of adverse events between the 2 treatment groups.
CONCLUSION AND RELEVANCE
In this comparative effectiveness study of a multicenter cohort of adult patients with thyroid storm, no significant differences were found in mortality or adverse events in patients who were treated with propylthiouracil or methimazole. Thus, current guidelines recommending propylthiouracil over methimazole for treatment of thyroid storm may merit reevaluation.
Topics: Adult; Humans; Female; Middle Aged; Methimazole; Propylthiouracil; Thyroid Crisis; Antithyroid Agents; Critical Illness; Hospital Mortality
PubMed: 37067797
DOI: 10.1001/jamanetworkopen.2023.8655 -
Iranian Journal of Pharmaceutical... 2019The thionamide drugs, carbimazole and its metabolite methimazole (MMI), and propylthiouracil (PTU) have extensively been used in the management of various forms of... (Review)
Review
The thionamide drugs, carbimazole and its metabolite methimazole (MMI), and propylthiouracil (PTU) have extensively been used in the management of various forms of hyperthyroidism over the past eight decades. This review aims to summarize different aspects of these outstanding medications. Thionamides have shown their own acceptable efficacy and even safety profiles in treatment of hyperthyroidism, especially GD in both children and adults and also during pregnancy and lactation. Of the antithyroid drugs (ATDs) available, MMI is the preferred choice in most situations taking into account its better efficacy and less adverse effects accompanied by once-daily dose prescription because of a long half-life and similar cost. Considering the more severe teratogenic effects of MMI, PTU would be the selected ATD for treatment of hyperthyroidism during pre-pregnancy months and the first 16 weeks of gestation. Recent studies have confirmed the efficacy and safety of long-term MMI therapy with low maintenance doses for GD and toxic multinodular goiter. Despite the long-term history of ATD use, there is still ongoing debate regarding their pharmacology and diverse mechanisms of action, viz. their immunomodulatory effects, and mechanisms and susceptibility factors to their adverse reactions.
PubMed: 32802086
DOI: 10.22037/ijpr.2020.112892.14005