Evolving Approaches in Managing Radioactive Iodine-Refractory Differentiated Thyroid Cancer

ObjectiveTo discuss the approach to care of patients with advanced differentiated thyroid cancer (DTC), in particular those with radioactive iodine (RAI)-refractory disease, and the transition to systemic treatment.MethodsA PubMed search was conducted using the search terms “radioactive iodine-refractory, differentiated thyroid cancer and treatment” restricted to a 2000-2012 timeframe, English language, and humans. Relevant articles were identified from the bibliographies of selected references. Four patient cases are presented to illustrate the clinical course of RAI-refractory DTC.ResultsThe current standard of care for early stage DTC could include surgery, RAI in some cases, and thyroid hormone suppression. For advanced RAI-refractory DTC, clinical practice guidelines established by the National Comprehensive Cancer Network and the American Thyroid Association recommend, as one option, the use of systemic therapy, including kinase inhibitors. Numerous trials are underway to evaluate the clinical benefit of these targeted therapies.ConclusionPreliminary results are encouraging with respect to the clinical benefit of targeted systemic therapies. However, at present there is no consensus on the criteria that define RAI-refractory disease and the optimal timing for transition to systemic therapy. There remains a need to establish common criteria to enhance patient care and enable better comparison across clinical studies. (Endocr Pract. 2014;20:263-275)     

Male Sex,African American Race or Ethnicity,and Triiodothyronine Levels at Diagnosis Predict Weight Gain After Antithyroid Medication and Radioiodine Therapy for Hyperthyroidism

ObjectiveTo determine whether racial or ethnic differences affect weight gain after treatment of hyperthyroidism and to reassess established risk factors such as sex, age, and cause of hyperthyroidism.MethodsWe conducted a retrospective review of medical records of 111 patients treated with radioiodine (RAI) for hyperthyroidism, with or without preceding antithyroid medication, during 2002 to 2005. We ascertained age, sex, race or ethnicity, insurance status, compliance with visits, serum triiodothyronine (T₃) level at diagnosis, and cause of hyperthyroidism. Weights and serum thyroidstimulating hormone levels were obtained at diagnosis, at time of RAI therapy, and at 0 to 4 months, 4 to 8 months, 8 to 12 months, and 24 months after RAI treatment.ResultsThere was a significant weight increase after treatment of hyperthyroidism. Levels of T₃ at initial diagnosis of hyperthyroidism, male sex, and black or Hispanic ethnicity were found to be independent predictors of weight gain after RAI treatment. We found a significant interaction between race or ethnicity and sex in multivariate models. There was no difference in thyroid function across racial or ethnic groups or the sexes. Age, cause of hyperthyroidism, posttreatment thyroid-stimulating hormone level, compliance, and insurance status were not found to be significant predictors of weight gain.ConclusionThe T₃ level at the time of diagnosis of hyperthyroidism is a strong predictor of weight gain after treatment of hyperthyroidism. Black race or ethnicity and male sex are also risk factors for weight gain. (Endocr Pract. 2010;16:609-616)     

Increased Risk of Radioiodine Treatment Failure Associated with Graves Disease Refractory to Methimazole

Objective: Iodine 131 (I-131) radioactive iodine (RAI) therapy has been the preferred treatment for Graves disease in the United States; however, trends show a shift toward antithyroid drug (ATD) therapy as first-line therapy. Consequently, this would favor RAI as second-line therapy, presumably for ATD refractory disease. Outcomes of RAI treatment after first-line ATD therapy are unclear. The purpose of this study was to investigate treatment failure rates and potential risk factors for treatment failure, including ATD use prior to RAI treatment.Methods: A retrospective case control study of Graves disease patients (n = 200) after I-131 RAI therapy was conducted. Treatment failure was defined as recurrence or persistence of hyperthyroidism in the follow-up time after therapy (mean 2.3 years). Multivariable regression models were used to evaluate potential risk factors associated with treatment failure.Results: RAI treatment failure rate was 16.5%. A majority of patients (70.5%) used ATD prior to RAI therapy, predominantly methimazole (MMI) (91.9%), and approximately two-thirds of patients used MMI for >3 months prior to RAI therapy. Use of ATD prior to RAI therapy (P = .003) and higher 6-hour I-123 thyroid uptake prior to I-131 RAI therapy (P<.001) were associated with treatment failure. MMI use >3 months was also associated with treatment failure (P = .002).Conclusion: More patients may be presenting for RAI therapy after failing first-line ATD therapy. MMI use >3 months was associated with RAI treatment failure. Further studies are needed to investigate the association between long-term first-line ATD use and RAI treatment failure.     

Autonomously Functioning Thyroid Nodules In Patients &#x003c;21 Years Of Age: The Rhode Island Hospital Experience From 2003&#x00C2;&#x20AC;&#x201C;2013

Objective: This study evaluates the clinical characteristics, workup, treatment, and outcomes of pediatric patients diagnosed with an autonomously functioning thyroid nodule (AFTN) in a large cohort of patients presenting for evaluation of a thyroid nodule. There are few prior studies on AFTN in pediatrics, with limited data on treatment and outcomes. Rates of malignancy in AFTN are perceived as low, but prior studies have varying reports.Methods: This is a retrospective chart review of patients less than 21 years of age at Rhode Island Hospital over an 11-year period (2003&#x00E2;&#x20AC;&#x201C;2013). We reviewed 354 charts, which yielded 242 patients with a diagnosis of thyroid nodule and 17 patients with AFTN.Results: The prevalence of AFTN in patients presenting with thyroid nodules was 7%. Mean age of patients was 15.8 years at diagnosis, and mean nodule size was 3.3 cm. There was female predominance. Thyroid-stimulating hormone levels were suppressed at diagnosis in 87% of patients. Six patients were treated with surgery, 5 patients with radioactive iodine therapy (RAI), 2 patients with medication, and 1 patient was observed without treatment. Three patients treated with RAI required subsequent treatment for hypothyroidism or continued hyperthyroidism. One patient had papillary thyroid carcinoma based on final surgical pathology.Conclusion: Our study found a higher prevalence of AFTN compared to the reported prevalence in adults. We concur with the new guidelines on management of thyroid nodules in recommending surgery for treatment of AFTN, based on the variability of outcomes after treatment with RAI.Abbreviations:AFTN = autonomously functioning thyroid noduleanti-TG = thyroglobulin antibodiesanti-TPO = thyroid peroxidase antibodiesFNA = fine-needle aspirationICD-9 = International Classification of Diseases, Ninth RevisionPTC = papillary thyroid carcinomaRAI = radioactive iodineT₃ = triiodothyronineT₄ = thyroxineTSH = thyroid-stimulating hormoneTSI = thyroid-stimulating immunoglobulin     

Recombinant Human Thyroid-Stimulating Hormone To Stimulate 131-1 Uptake For Remnant Ablation And Adjuvant Therapy

ObjectiveTo review the current literature with regard to the use of recombinant human thyroid stimulating hormone (rhTSH) as an adjunct to radioactive iodine (RAI) remnant ablation and adjuvant therapy.MethodsLiterature review of clinical studies examining rhTSH and/or thyroid hormone withdrawal preparations for RAI remnant ablation. The primary endpoints evaluated were (1) effectiveness at ablating the thyroid bed as demonstrated by the lack of significant uptake in the thyroid bed on follow-up diagnostic imaging and (2) effectiveness in facilitating the adjuvant therapy function of RAI ablation as manifested by follow-up thyroid stimulating hormone (TSH)-stimulated serum thyroglobulin levels and clinical outcomes (recurrence rates, likelihood of having no evidence of disease at final follow-up).ResultsRAI remnant ablation can be successfully achieved using either traditional thyroid hormone withdrawal or recombinant human TSH preparation. While initial studies included primarily thyroid cancer patients at low risk of recurrence, more recent studies suggest that rhTSH can also be effectively used as preparation for RAI ablation in patients with an intermediate or high risk of recurrence. Furthermore, while early studies focused primarily on the endpoint of thyroid bed remnant ablation, more recent retrospective studies suggest that final clinical outcomes (recurrence rates, likelihood of achieving no evidence of disease status at final follow-up) over 5-10 years of follow-up are very similar with either method of preparation.ConclusionrhTSH is an effective alternative to thyroid hormone withdrawal in preparation for RAI remnant ablation in patients without evidence of distant metastases who are at low, intermediate, or high risk of recurrence.     

Effect of Post-Surgical Rai Therapy on Parathyroid Function in Patients with Differentiated Thyroid Cancer

Objective: Radiotherapy with radioactive iodine (RAI) has become a common treatment for postsurgical differentiated thyroid carcinoma (DTC). The objective of this study was to determine the effect of RAI therapy following surgery on the function of the parathyroid glands in DTC patients.Methods: A total of 81 DTC patients who received RAI therapy after surgery were enrolled in the study. The size of the residual thyroid was detected by technetium-99m (^99mTc)-pertechnetate thyroid scan (^99mTc thyroid scan) before RAI therapy. The iodine uptake ability of residual thyroid was evaluated by iodine-131 (¹³¹I) whole-body scan (WBS). All patients were treated with an activity of 3.7 GBq (100 mCi) ¹³¹I. Parathyroid hormone (PTH), serum calcium, phosphorus, and magnesium were evaluated at 1 day before treatment, and at 1 month and 3 months after treatment.Results: The results show that there was no statistically significant difference in blood PTH level observed (P>.05) between 3 time points (pre-treatment, 1 month post-treatment and 3 months post-treatment). The serum calcium and phosphorus did not change significantly (P>.05), but serum magnesium level was elevated after treatment (P<.05). There were no significant differences between PTH changes and sex, age, scores of ^99mTc thyroid scan, scores of ¹³¹I WBS, Tumor (T) stage, and Node (N) stage.Conclusion: RAI therapy following surgery did not significantly affect parathyroid function in DTC patients.Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid carcinoma; FT3 = free triiodothyronine; FT4 = free thyroxine; 131I = iodine-131; PTH = parathyroid hormone; RAI = radioiodine; 99mTc = Technetium-99m; TG = thyroglobulin; TNM = Tumor Node Metastasis; TSH = thyroid-stimulating hormone; WBS = whole-body scan     

Timing of Radioactive Iodine Therapy does not Impact Overall Survival in High-Risk Papillary Thyroid Carcinoma

Objective: Postthyroidectomy radioiodine (RAI) therapy is indicated for papillary thyroid carcinoma (PTC) with high-risk features. There is variability in the timing of RAI therapy with no consensus. We analyzed the impact of the timing of initial RAI therapy on overall survival (OS) in PTC.Methods: The National Cancer Data Base (NCDB) was queried from 2003 to 2006 for patients with PTC undergoing near/subtotal or total thyroidectomy and RAI therapy. High-risk patients had tumors >4 cm in size, lymph node involvement, or grossly positive margins. Early RAI was ≤3 months, whereas delayed was between 3 and 12 months after thyroidectomy. Kaplan-Meier (KM) and Cox survival analyses were performed after adjusting for patient and tumor-related variables. A propensity-matched set of high-risk patients after eliminating bias in RAI timing was also analyzed.Results: There were 9,706 patients in the high-risk group. The median survival was 74.7 months. KM analysis showed a survival benefit for early RAI in high-risk patients (P = .025). However, this difference disappeared (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.98–1.62, P = .07) on adjusted Cox multivariable analysis. Timing of RAI therapy failed to affect OS in propensity-matched high-risk patients (HR 1.09, 95% CI 0.75–1.58, P = .662).Conclusion: The timing of postthyroidectomy initial RAI therapy does not affect OS in patients with high-risk PTC.Abbreviations:CI = confidence intervalCLNM = cervical lymph node metastasisFVPTC = follicular variant papillary thyroid carcinomaHR = hazard ratioKM = Kaplan-MeierNCDB = National Cancer Data BaseOS = overall survivalPTC = papillary thyroid carcinomaRAI = radioactive iodine     

Clinical Aspects of Hyperthyroidism,Hypothyroidism, and Thyroid Screening in Pregnancy

ObjectiveTo evaluate the peer-reviewed literature on hypothyroidism, hyperthyroidism, and thyroid autoimmunity in pregnancy.MethodsWe review published studies on thyroid autoimmunity and dysfunction in pregnancy, the impact of thyroid disease on pregnancy, and discuss implications for screening.ResultsOvert hyperthyroidism and hypothyroidism are responsible for adverse obstetric and neonatal events. Several studies of association suggest that either subclinical hypothyroidism or thyroid autoimmunity increase the risk of complications. One randomized controlled trial showed that pregnant women with subclinical hypothyroidism benefit from treatment in terms of obstetric and neonatal complications, whereas another study demonstrated no benefit in the intelligence quotient of babies born to women with subclinical hypothyroidism. Thyroid autoimmunity has been associated with increased rate of pregnancy loss, recurrent miscarriage, and preterm delivery.ConclusionCurrent guidelines agree that overt hyperthyroidism and hypothyroidism need to be promptly treated and that as potential benefits outweigh potential harm, subclinical hypothyroidism also requires substitutive treatment. The chance that women with thyroid autoimmunity may benefit from levothyroxine treatment to improve obstetric outcome is intriguing, but adequately powered randomized controlled trials are needed. The issue of universal thyroid screening at the beginning of pregnancy is still a matter of debate, and aggressive case-finding is supported. (Endocr Pract. 2014;20:597-607)     

Role of Vitamin D in the Onset,Progression, and Severity of Multiple Sclerosis

ObjectiveTo review and assess the role of vitamin D in the onset, progression, and relapse of multiple sclerosis (MS), based on evidence acquired from the analysis of preclinical, observational, and interventional studies.MethodsAll English language literature in MEDLINE (January 1969 through April 2012) was searched for observational and interventional studies on the dosage effect of vitamin D on the onset, progression, and relapse rate of MS. The medical subject heading (MeSH) terms used in the search included Vitamin D and Multiple Sclerosis. Additional publications and abstracts were identified from review articles and from the references cited in the previously found articles. In addition to the experimental studies, only those human studies that specified the population size, doses of vitamin D used, and the resulting effect on MS were considered.ResultsVitamin D deficiency is very common among MS patients. Multiple preclinical studies have shown that vitamin D is a potent regulator of inflammation in MS. Most observational studies support an association between high vitamin D levels and a reduced risk of developing MS. However, conflicting results have been reported by observational studies on the correlation between vitamin D and MS severity and by interventional studies using vitamin D as a therapeutic agent for MS.ConclusionVitamin D deficiency in MS patients should be avoided. In addition, the risk of developing MS might be reduced by maintaining optimal vitamin D levels in the healthy population. Larger randomized interventional trials are needed to clarify the therapeutic effect of vitamin D in MS. (Endocr Pract. 2013;19:129-136)     

Complete Blood Counts are Frequently Abnormal 1 Year after Dosimetry-Guided Radioactive Iodine Therapy for Metastatic Thyroid Cancer

ObjectiveRadioactive iodine (RAI) has been associated with hematologic abnormalities. Previous research has shown that even a single dose of RAI can cause changes in the peripheral complete blood count (CBC). It is unclear if the use of dosimetry guidance would prevent the effects of high doses of RAI on bone marrow suppression.MethodsCBC at baseline was compared to a CBC obtained 1 year after the last RAI treatment in 50 thyroid cancer patients that received ≥ 250 mCi RAI during the course of their disease. Cumulative dose, number of treatments, patients’ age, and the use of external beam radiation therapy (EBRT) were considered in the analysis.ResultsWe observed a small but statistically significant decrease in hemoglobin (Hb), hematocrit (Hct), and platelet (Plt) counts at 1 year in 50 patients who had received ≥ 250 mCi RAI. We did not find a significant change in white blood cell count (WBC). Approximately 60% of patients who developed anemia had concomitant WBC and Plt abnormalities. RAI dose, number of treatments, and age at diagnosis did not confer a higher risk of bone marrow suppression.ConclusionHigh cumulative activities of RAI administered under dosimetric guidance are associated with a small but statistically significant decreases in Hb, Hct, and Plt counts. The clinical implications of these changes, if any, are unclear. The benefits obtained with high doses of RAI, when indicated, are likely to outweigh the minimal hematologic risks observed in the present study. (Endocr Pract. 2014;20:213-220)     

Persistent Neonatal Thyrotoxicosis in a Neonate Secondary to a Rare Thyroid-Stimulating Hormone Receptor Activating Mutation:

ObjectiveTo report the case of a neonate presenting with nonautoimmune thyrotoxicosis and failure to thrive in whom an activating TSHR mutation was suspected.MethodsWe describe the clinical and laboratory findings in a neonate who presented with nonautoimmune thyrotoxicosis and failure to thrive, including results of DNA analysis of TSHR, which encodes the thyroid-stimulating hormone receptor (TSHR). Relevant literature is also reviewed.ResultsThe proband was born spontaneously at 35 weeks’ gestation, and his early neonatal period was remarkable for meconium aspiration, pneumothorax, hepatomegaly with associated elevated transaminases, and direct hyperbilirubinemia. On days 9 and 11 of life, thyroid function studies revealed hyperthyroidism, which remained persistent on day 26 of life. On day 44 of life, the infant was admitted to the hospital. The mother reported he had an increased activity level, disturbed sleep, jitteriness, and exaggerated startle response. Weight was at the third percentile. After additional workup, Lugol’s iodine solution, propanolol, and propylthiouracil were prescribed, which led to improvement in thyroid function. No TSHR antibodies were detected in the mother’s or patient’s sera. Analysis of the patient’s DNA revealed a heterozygous T-to-C substitution at amino acid 568 in exon 10 (Ile568Thr), which predicts an isoleucine to threonine conversion in the second extracellular loop of TSHR. The mutation was not identified in the parents’ DNA.ConclusionsA mutation causing constitutive activation of TSHR was confirmed in this patient, a finding that has implications for genetic counseling and consideration of total thyroidectomy or long-term thionamide therapy followed by radioiodide ablation as treatment options. Although rare, TSHR mutations should be considered in an infant presenting with thyrotoxicosis in absence of demonstrable TSHR antibodies in serum. (Endocr Pract. 2008;14:479-483)     

Comparison of Radioiodine Utilization in Adolescent and Young Adult and Older Thyroid Cancer Patients

ObjectiveDifferentiated thyroid cancer (DTC) is 1 of the most common cancers in adolescents and young adults (AYA, ages 15-39). Although most AYAs with DTC are considered low risk compared to older patients, there are no specific postoperative radioiodine (RAI) treatment recommendations despite the potential adverse effects specific to this age group, namely secondary malignancies and fertility difficulties. This study compares factors influencing RAI utilization in AYA and older patients.MethodsA total of 5,687 primary DTC patients were identified from the SEER (Surveillance, Epidemiology, and End Results) database between January 1, 2004 and January 31, 2009. The 2009 American Thyroid Association (ATA) guidelines were used to classify patients as low (LR) or intermediate/high risk (IHR) based on tumor characteristics. Multivariate logistic regression analysis was performed.ResultsOverall, 56.9% of AYA (n = 1,963) patients received postoperative RAI compared to 52.2% of older (n = 3,724) patients (odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.09-1.35, P = .001). For AYA patients, having a total thyroidectomy (TTx) (OR: 3.53, 95% CI: 2.7-4.61, P < .001) predicted RAI in a multivariate model whereas LR status (OR: 0.52, 95% CI: 0.43-0.63, P < .001) and northeast residence (OR: 0.39, 95% CI: 0.29-0.52, P < .001) decreased the probability. All 3 factors similarly affected older patients in addition to an increased likelihood after lymph node (LN) dissection. Additionally, after selecting for TTx (n = 1,077), no factor influenced the use of RAI for AYA patients, whereas LR (OR: 0.30, 95% CI: 0.21-0.43, P < .001) and northeast residence (OR: 0.39, 95% CI: 0.19-0.79, P = .008) were associated with decreased RAI use in older patients.ConclusionDespite their excellent prognosis, AYA thyroid cancer patients are more likely to receive postoperative RAI compared to older patients. Increased awareness of the unique survivorship implications for AYA patients will be an important aspect to address going forward. (Endocr Pract. 2014;20:405-411)     

Thyrotoxicosis due to Ectopic Lateral Thyroid Tissue Presenting 5 Years After Total Thyroidectomy

ObjectiveTo describe a patient who, 5 years after total thyroidectomy to treat Graves disease, presented with thyrotoxicosis due to nonmalignant lateral ectopic thyroid tissue.MethodWe describe the laboratory, imaging, and physical findings of the study patient and review the relevant literature.ResultsA 32-year-old white woman with a history of Graves disease presented with recurrent hyperthyroidism 5 years after total thyroidectomy. A radioactive iodine scan was performed, which revealed elevated uptake (40%) and positive imaging in the left mid-neck. Ultrasonography examination of the neck confirmed the absence of any thyroid tissue within the thyroid bed, but documented 2 nodular, hypoechoic left upper-neck masses with punctuate hyperlucency. Contrast-enhanced computed tomography was performed to precisely localize the nodules, which were excised surgically via selective neck dissection. Histopathologic examination revealed chronic lymphocytic inflammatory infiltrate with focal thyroid hyperplasia and papillary infoldings and no evidence of malignancy.ConclusionsTo our knowledge, this represents the first report of ectopic benign thyroid tissue as the sole cause of hyperthyroid symptoms, and this entity should be considered in patients who have undergone thyroidectomy and have persistent hyperthyroidism. (Endocr Pract. 2011;17:70-73)     

Potential Use of Recombinant Human Thyrotropin in the Treatment of Distant Metastases in Patients with Differentiated Thyroid Cancer

ObjectiveIn order to effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum TSH levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The goal of this review is to present current data on the relative efficacy and side effects profile of rhTSH-aided versus THW-aided RAI therapy for the treatment of patients with distant metastases of DTC.MethodsWe have searched the PubMed database for articles including the keywords "rhTSH", "thyroid cancer", and "distant metastases" published between January 1, 1996 and January 7, 2012. As references, we used clinical case series, case reports, review articles, and practical guidelines.ResultsExogenous stimulation of TSH is associated with better quality of life because it obviates signs and symptoms of hypothyroidism resulting from endogenous TSH stimulation. The rate of neurological complications after rhTSH and THW-aided RAI therapy for brain and spine metastases is similar. The rate of leukopenia, thrombocytopenia, xerostomia, and pulmonary fibrosis is similar after preparation for RAI treatment with rhTSH and THW. There is currently a controversy regarding RAI uptake in metastatic lesions after preparation with rhTSH versus THW, with some studies suggesting equal and some superior uptake after preparation with THW. Analysis of available retrospective studies comparing survival rates, progression free survival, and biochemical and structural response to a dosimetrically-determined dose of RAI shows similar efficacy after preparation for therapy with rhTSH and THW.ConclusionThe rhTSH stimulation is not presently approved by the FDA as a method of preparation for adjunctive therapy with RAI in patients with metastatic DTC. Data on rhTSH compassionate use suggest that rhTSH stimulation is as equally effective as THW as a method of preparation for dosimetry-based RAI treatment in patients with RAI-avid metastatic DTC. (Endocr Pract. 2013;19:139-148)     

Side Effects of PTU and MMI in the Treatment of Hyperthyroidism: A Systematic Review and Meta-Analysis

Objective: The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating hyperthyroidism.Methods: Qualitative analysis was performed for studies identified in a literature search up to April 20, 2019, and 30 studies were selected for meta-analysis. The study designs included case-control, randomized controlled, and retrospective cohort. Patients were in four age groups: childhood, gestating mothers, older adults, and other ages, and all were receiving PTU or MMI/CMZ. Adverse reactions to MMI/CMZ and PTU were evaluated and compared.Results: Odds of liver function injury were higher in the PTU group than in the MMI/CMZ group (odds ratio &lsqb;OR], 2.40; 95% confidence interval &lsqb;CI], 1.16 to 4.96; P = .02). Odds of elevated transaminase were much higher in the PTU group than in the MMI/CMZ group (OR, 3.96; 95% CI, 2.49 to 6.28; P<.00001). No significant between-group differences were found in odds of elevated bilirubin, agranulocytosis, rash, or urticaria; incidence of other adverse events; or in children. Odds of birth defects during the first trimester of pregnancy were higher in the MMI/CMZ group than in the PTU group (OR, 1.29; 95% CI, 1.09 to 1.53; P = .003).Conclusion: The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children. In treating pregnancy-related hyperthyroidism, PTU should be used in the first trimester and MMI reserved for use in late pregnancy.Abbreviations: ALT = alanine aminotransferase; ATD = antithyroid drug; CI = confidence interval; CMZ = carbimazole; GD = Graves disease; MMI = methimazole; MTU = methylthiouracil; NOS = Newcastle-Ottawa Scale; OR = odds ratio; PTU = propylthiouracil; RAI = radioactive iodine     

Time to Normalization and Sustainable Normal Serum Thyrotropin Concentrations in Patients with Hyperthyroidism: Comparison of Methimazole and Radioactive Iodine Treatments

ObjectiveThe aim of this study was to compare the “time to euthyroidism” and “time spent in euthyroidism” following methimazole (MMI) and radioactive iodine (RAI) treatments.MethodsThree hundred fifty-eight patients with hyperthyroidism, 178 who underwent long-term MMI treatment and 180 patients who underwent RAI treatment, were analyzed. The time to normalization of increased serum values of free thyroxine and triiodothyronine and suppressed serum thyroid-stimulating hormone (TSH) values as well as the percentage of time that the thyroid hormone levels remained within normal ranges during a mean follow-up time of 12 years were compared.ResultsThe mean time to euthyroidism was 4.59 ± 2.63 months (range, 2-16 months) in the MMI group and 15.39 ± 12.11 months (range, 2-61 months) in the RAI group (P < .001). During follow-up, the percentage of time spent in euthyroidism was 94.5% ± 7.3% and 82.5% + 11.0% in the MMI and RAI groups, respectively (P < .001). Serum TSH values above and below the normal range were observed in 5.3% and 0.2% of patients, respectively, in the MMI group and 9.8% and 7.7% of patients, respectively, in the RAI group (P < .001). The time to euthyroidism and the percentage of time spent in euthyroidism in 40 RAI-treated patients with euthyroidism were similar to those in the MMI group and significantly shorter than those in the RAI-treated hypothyroid and relapsed subgroups. In patients who continued MMI therapy for >10 years, the percentage of time spent in euthyroidism was >99%.ConclusionIn our cohort of selected patients, MMI therapy was accompanied by faster achievement of the euthyroid state and more sustained normal serum TSH levels during long-term follow-up compared with RAI therapy.     

The Iodine Status and Prevalence of Thyroid Disorders Among Women of Childbearing Age in China: National Cross-sectional Study

ObjectiveMandatory universal salt iodization in China was implemented 20 years ago. However, the current iodine status and prevalence of thyroid disorders among childbearing-age women are unknown.MethodsA nationally representative cross-sectional study with 26 166 enrolled participants aged 18 to 49 years from all 31 provincial regions of mainland China was performed. The participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. The serum concentrations of thyroid hormones and thyroid antibodies and the urinary iodine concentration (UIC) were measured.ResultsThe median UIC was 178.7 μg/L, indicative of adequate iodine status. pHowever, 19.04% and 19.87% of the participants were classified as having iodine deficiency and excessive iodine, respectively. The weighted prevalence of thyroid disorders was as follows: 1.08% had overt hyperthyroidism, 0.58% had subclinical hyperthyroidism, 0.76% had Graves disease, 1.28% had overt hypothyroidism, 14.28% had subclinical hypothyroidism, 13.53% were positive for thyroid peroxidase antibodies, and 14.55% were positive for thyroglobulin antibodies. Excessive iodine and overweight were associated with higher odds of subclinical hypothyroidism. A family history of thyroid disorders and an age between 40 and 49 years were significantly associated with higher odds of positivity for thyroid peroxidase antibodies and thyroglobulin antibodies.ConclusionIodine deficiency, excessive iodine, subclinical hypothyroidism, and positivity for thyroid autoantibodies remain prevalent among women of childbearing age in China. Women of childbearing age who are relatively older, are overweight, or have a family history of thyroid disorders are encouraged to undergo active screening of their UIC and thyroid function when planning a pregnancy.     

Unfavorable Responses to Radioiodine Therapy in N1b Papillary Thyroid Cancer: A Propensity Score Matching Study

Objective: Regional nodal metastases carry prognostic significance in papillary thyroid cancer (PTC). However, whether different locational nodal metastases correlate with different therapeutic responses remains controversial. We innovatively applied the response to therapy restratification system to evaluate the dynamic disease status after surgery and radioactive iodine (RAI) therapy in PTC patients with different locational nodal metastases.Methods: A total of 585 nondistant-metastatic PTC patients who underwent total thyroidectomy and RAI therapy were retrospectively enrolled. Patients with nodal metastases were categorized into N1a and N1b groups. Propensity score matching was used to balance the bias between the 2 groups. Therapeutic responses were dynamically evaluated, and responses to RAI therapy were classified into excellent (ER), indeterminate (IDR), biochemical incomplete (BIR) and structural incomplete response (SIR).Results: N1b group patients showed a significantly higher pre-ablation stimulated thyroglobulin (Ps-Tg) level than N1a group patients (7.4 ng/mL versus 3.2ng/mL, P<.001). After RAI therapy, N1b group patients took a longer time to achieve ER (9.86 months versus 3.29 months, P<.001) and exhibited a higher proportion of non-ER (IDR, BIR, and SIR) (39.15% versus 17.46%, P<.001) compared to N1a group patients. In logistic regression, N1b and Ps-Tg ≥10 ng/mL were confirmed to be independent factors predicting non-ER (odds ratio: 2.591, and 9.196, respectively). In Cox regression, patients with N1b disease and Ps-Tg ≥10 ng/mL showed significantly lower hazards for achieving ER (hazard ratio: 0.564, and 0.223, respectively).Conclusion: N1b PTC patients showed inferior responses to surgery and RAI therapy compared to N1a patients. N1b was confirmed to be an independent factor predicting unfavorable responses to RAI therapy.Abbreviations: AJCC = American Joint Committee on Cancer; ATA = American Thyroid Association; BIR = biochemical incomplete response; BRAF^V600E = proto-oncogene B-Raf V600E mutation; CI = confidence interval; CT = computed tomography; DNA = deoxyribonucleic acid; DTC = differentiated thyroid cancer; ER = excellent response; ETE = extrathyroidal extension; HR = hazard ratio; IDR = indeterminate response; LNM = lymph node metastasis; N1a = central cervical LNM; N1b = lateral cervical LNM; OR = odds ratio; PSM = propensity score matching; Ps-Tg = pre-ablation stimulated thyroglobulin; PTC = papillary thyroid cancer; RAI = radioactive iodine; SIR = structural incomplete response; Tg = thyroglobulin; TgAb = thyroglobulin antibody; TSH = thyroid-stimulating hormone