Risk of recurrence at the time of withdrawal of short- or long-term methimazole therapy in patients with Graves' hyperthyroidism: a randomized trial and a risk-scoring model.

PURPOSE: In Graves' disease, administration of low-dose methimazole for more than 60 months induces higher remission rates compared with the conventional duration of 12-18 months. However, the risk of recurrence and its predictors beyond 48 months of drug withdrawal are not known. The aims of this study were to determine the risk of recurrence during 84 months after withdrawal of short- or long-term methimazole therapy and a risk stratification for recurrence of hyperthyroidism. METHODS: A total of 258 patients were treated with methimazole for a median of 18 months and randomized to discontinuation of the drug(conventional short-term group; n = 128) or continuation of the treatment up to 60-120 months(long-term group; n = 130). Patients were followed for 84 months after methimazole withdrawal. Cox proportional hazards modeling was performed to identify factors associated with relapse and develop a risk-scoring model at the time of discontinuing the treatment. RESULTS: Hyperthyroidism recurred in 67 of 120(56%) of conventionally-treated patients versus 20 of 118(17%) of those who received long-term methimazole treatment, p < 0.001. Age, sex, goiter grade, triiodothyronine, thyrotropin, and thyrotropin receptor antibodies were significant predictors of recurrence in both "conventional" and "long-term" groups but free thyroxine just in the "long-term" group. The risk-scoring model had a good discrimination power (optimism corrected c-index = 0.78,95%CI = 0.73-0.82) with a range of 0-14 and sensitivity of 86% and specificity of 62% at the risk-score of eight. CONCLUSION: A relapse-free state was achieved in 83% of patients with Graves' hyperthyroidism 84 months after cessation of long-term methimazole treatment which could be predicted by some significant predictors in a simple risk-scoring system.

Antibody-mediated Rejection of Kidney Allografts Following COVID-19: A Report of Two Cases.

Increased risk of graft rejection could be the consequence of COVID-19 in kidney transplant recipients (KTRs). We report two cases of kidney transplant (KT) with stable graft function who experienced antibody-mediated rejection (ABMR) following recovery from COVID-19. It seems that reduced immunosuppression during the acute illness, is the main explanation for post-COVID-19 ABMR. However, the inflammatory state associated with COVID-19, as well as direct cytopathic effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can predispose the kidney allograft to rejection. There is no definite guideline for the modification of immunosuppressives during COVID-19 in kidney transplant recipients. However, re-institution of full-dose immunosuppressives soon after recovery from COVID-19 and frequent outpatient follow-up visits are recommended.  DOI: 10.52547/ijkd.7176.

Parity and Incidence of Thyroid Autoimmunity: A Population-Based Tehran Thyroid Study.

Introduction: Autoimmune thyroid disease is the most common autoimmune disorder. Evidence regarding causes of the high prevalence and incidence of thyroid autoimmunity in women, and especially women of reproductive age, is still inconclusive and previous studies have suggested genetic, environmental, and existential factors to play a role in its pathogenesis. In this study, we aimed to investigate the effect of parity and other reproductive factors on the incidence of thyroid autoimmunity within the framework of the Tehran Thyroid Study (TTS). Materials and Methods: This study was conducted within the framework of the TTS and 1999 nonpregnant euthyroid thyroid peroxidase antibody (TPOAb) negative women were followed up for an average of 8.3 years. A pooled logistic regression model was used to assess the association (odds ratio) between time-dependent covariates parity, menopause, and abortion, and incidence of TPOAb positivity. Results: The total incidence rate of TPOAb positivity was 8.65 [7.35-10.18] per 1000 person-years. We found no significant association between changes in the number of parity and risk of developing TPOAb using multiple pooled logistic models both as crude effect and after adjustment for age, body mass index, and smoking. Similarly, there was no association between changes of parity, menopause, and abortion status, and incidence of TPOAb positivity. Conclusions: Parity does not seem to have an independent role in triggering thyroid autoimmunity, but vast immunological and physiological changes during pregnancy may act as a precipitating factor in the context of other genetic and environmental modifiers.

Increased Remission Rates After Long-Term Methimazole Therapy in Patients with Graves' Disease: Results of a Randomized Clinical Trial.

Background: Studies differ regarding whether, compared with courses of conventional duration, longer-term antithyroid drug treatment increases frequency of remission in patients with Graves' hyperthyroidism. We prospectively conducted a randomized, parallel-group study comparing relapse rates in patients receiving longer-term versus conventional-length methimazole therapy. We also sought variables associated with relapse following the latter. Methods: We enrolled 302 consecutive patients with untreated first episodes of Graves' hyperthyroidism. After 18-24 months of methimazole, 258 patients (85.4%) were randomized to an additional 36-102-month courses ("long-term group": n = 130; scheduled total time on methimazole: 60-120 months) or discontinuation of methimazole ("conventional group": n = 128). Patients were followed 48 months postmethimazole cessation. We performed Cox proportional hazards modeling to identify factors associated with relapse after conventional courses. Results: Methimazole was given for 95 ± 22 months in long-term patients and 19 ± 3 months in the conventional group. Fourteen patients experienced cutaneous reactions and 2 liver enzyme elevations during the first 18 months of treatment; no further methimazole-related reactions were observed despite therapy for up to another 118 months. Hyperthyroidism recurred within 48 months postmethimazole withdrawal in 15% (18/119) of long-term patients versus 53% (65/123) of conventional group patients. In the conventional group, older age, higher triiodothyronine or thyrotropin receptor antibody concentrations, lower thyrotropin concentration, or possession of the rs1879877 CD28 polymorphism or the DQB1-05 HLA polymorphism were independently associated with relapse. Conclusion: Administration of low-dose methimazole for a total of 60-120 months safely and effectively treats Graves' hyperthyroidism, with much higher remission rates than those attained by using conventional 18-24-month courses.

Long-term Methimazole Therapy in Juvenile Graves' Disease: A Randomized Trial.

BACKGROUND AND OBJECTIVES: Recent studies show that long-term (LT) antithyroid drugs reduce relapse of hyperthyroidism in patients with Graves' disease. Our objective was to evaluate the effectiveness and safety of LT methimazole treatment and to compare remission rates in Graves' disease patients after LT and short-term (ST) therapy. METHODS: In this randomized, parallel group trial, 66 consecutive patients with untreated juvenile Graves' hyperthyroidism were enrolled. After a median 22 months of methimazole treatment, 56 patients were randomly assigned to either continue low-dose methimazole treatment (n = 24, LT group) or to discontinue treatment (n = 24, ST group). Twenty-four patients in LT group completed 96 to 120 months of methimazole treatment. Patients in both groups were managed for 48 months after discontinuation of treatment. RESULTS: Except for 3 cases of cutaneous reactions, no other adverse events were observed throughout 120 months of methimazole therapy. Serum free thyroxine, triiodothyronine, thyrotropin, and thyrotropin receptor antibody remained normal, and the required daily dosage of methimazole was gradually decreased from 5.17 ± 1.05 mg at 22 months to 3.5 ± 1.3 mg between 96 and 120 months of treatment (P < .001). Hyperthyroidism was cured in 92% and 88% of LT patients and in 46% and 33% of ST patients, 1 and 4 years after methimazole withdrawal, respectively. CONCLUSIONS: LT methimazole treatment of 96 to 120 months is safe and effective for treatment of juvenile Graves' disease. The four-year cure rate of hyperthyroidism with LT methimazole treatment is almost 3 times more than that of ST methimazole treatment.

Treatment of Toxic Multinodular Goiter: Comparison of Radioiodine and Long-Term Methimazole Treatment.

Background: This study aimed to compare the effectiveness and safety of long-term methimazole (MMI) and radioiodine (RAI) in the treatment of toxic multinodular goiter (TMNG). Methods: In this randomized, parallel-group trial, 130 consecutive and untreated patients with TMNG, aged <60 years, were enrolled and randomized to either long-term MMI or RAI treatment. Both groups of patients were followed for 60-100 months, with median durations of 72 and 84 months in the MMI and RAI groups, respectively. Results: In the MMI and RAI groups, 12 and 11 patients, respectively, were excluded because of side effects, choosing other modes of treatment and not returning for follow-up; 53 and 54 patients, respectively, completed the study for 60-100 months. In the MMI group, two patients (3.8%) experienced subclinical hypothyroidism, and 51 (96.2%) remained euthyroid until the end of study. The dosage of MMI to maintain euthyroidism was 6.3 ± 2.0, 4.5 ± 0.9, and 4.1 ± 1.0 mg daily during the first, third, and fifth years of continuous MMI treatment. One patient had elevated liver enzymes, and three developed skin reactions during the first three months, but no adverse effects from MMI occurred from 4 to 100 months of therapy. In the RAI group, 22 (41%) became hypothyroid, 12 (22%) had persistence or recurrence of hyperthyroidism, and 20 (37%) became euthyroid after 16.7 ± 2.7 mCi 131I. Conclusion: Long-term, low-dose MMI treatment for 60-100 months is a safe and effective method for treatment of TMNG, and is not inferior to RAI treatment.

Tehran Thyroid Study (TTS).

CONTEXT: This review summarizes key findings of the Tehran thyroid study (TTS), a large scale community-based study with approximately a two decade follow-up, about the incidence, prevalence, and natural course of thyroid disorders as well as associations between thyroid diseases and metabolic syndrome (MetS), dysglycemia, and cardiovascular disease (CVD). EVIDENCE ACQUISITION: PubMed, Scopus, and Web of Science databases, and the library of Research Institute for Endocrine Sciences were used to search for TTS articles. Articles were subdivided based on the fields of prevalence, incidence and natural course, and associations of thyroid function with the incident hypertension (HTN), MetS and CVDs. RESULTS: The 2.5th and 97.5th percentiles of serum thyrotropin (TSH) were 0.32 and 5.06 mU/L, respectively. Estimated reference intervals (2.5th and 97.5th percentiles) for thyroid peroxidase antibody (TPOAb) levels were 1.5 - 32.8 and 2.1 - 35 IU/mL in men and women, respectively. Euthyroid persistency was 93.24% during 6 years. There was a negative association between free thyroxine (FT4) levels and insulin resistance. Decreasing FT4 values over time would predict MetS in euthyroid and subclinical hypothyroid subjects (TSH < 10 mU/L). The incidence of thyroid disorders in patients with diabetes, pre-diabetes and healthy controls was 14, 18, and 21 per 1000 person-years, respectively, indicating significantly lower incidence in individuals with diabetes compared to healthy controls. Serum FT4 within the reference range was positively associated with all blood pressure (BP) measures in the total population and in men; however, serum TSH was positively associated with only systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure of men. No associations were found between various states of thyroid function and prevalence and incidence of CVD. CONCLUSIONS: A well designed cohort study aimed to investigate the gap in knowledge regarding thyroid disorders can generate many hypotheses to be examined in randomized controlled trials.

Review of Rationale, Design, and Initial Findings: Tehran Lipid and Glucose Study.

In the late 1990s the non-communicable diseases were becoming increasingly more prevalent and a significant proportion of evidence in this regard had originated from industrialized "Western" countries. This had led to a landscape where most national and local health decisions regarding non-communicable diseases (NCDs) were informed by data generated elsewhere. Iran, as a large country in the Middle East was no exception and was going through significant population growth and urban development at the time. An initiative by the Iranian National Scientific Research Council funded an idea that was aimed at delineating the local epidemiology of NCDs and their risk factors in a manner that was unprecedented. The result was Tehran Lipid and Glucose Study (TLGS), the first and longest running cohort of its sort in Iran. Initial data out of TLGS reported the characteristics of 15005 people aged over 3 years in a representative population of Tehranians. Additionally, distribution and prevalence of cardiovascular risk factors among the study population were characterized. This population was selected through a multistage stratified cluster random sampling technique from the population of district 13 in Tehran. In addition, TLGS gave rise to a great deal of important and highly effective initial findings on national cut-off points for various variables, information about nutrition, hypertension, dyslipoproteinemia, and metabolic syndrome. TLGS also generated information about metabolic health indicators among children and adolescents. Here we present a brief overview of rationale, design, and initial findings of TLGS.

Contributions and Implications of the Tehran Lipid and Glucose Study.

Tehran Lipid and Glucose Study (TLGS), an epidemiological study of non-communicable disease with 20 years follow up in a developing country in nutrition transition is a unique study in 15000 family based individuals, 3 - 75 years of age in a part of large city of Tehran. The success rate of recruitment for 20 years, intervention for lifestyle change, and thyroid, reproduction and cardiometabolic genetic studies derived from TLGS have paved suitable path towards precision medicine. In this review, baseline findings and changes of risk factors for the development of NCD including body weight, nutrition, physical activity, blood pressure, tobacco smoking, serum glucose and serum lipids as well as metabolic syndrome, chronic kidney disease, quality of life and biochemical findings in TLGS cohort have been summarized. The results of community based intervention for lifestyle change caused decreases in the prevalence of metabolic syndrome and the incidence of diabetes. It is concluded that TLGS has served as a model for other cohort studies in Iran and the region; it has helped to mobilize scientists in developing countries; it has established locally needed definitions of NCD variables; has served as a model for cohort studies in developing countries in nutrition transition with all socioeconomic constraints and has helped manpower education and development of local CVD risk scores for implementation of NCD management.