Pre-Ablation Thyroglobulin and Thyroglobulin to Thyroid-Stimulating Hormone Ratio may be Associated with Pulmonary Metastases in Children with Differentiated Thyroid Cancer

Objective: Pediatric differentiated thyroid cancer (DTC) frequently presents with extensive disease. We studied the value of pre-ablation thyroglobulin (Tg) and Tg normalized to thyroid-stimulating hormone (TSH) levels in predicting distant metastases in pediatric patients with DTC.Methods: This is a retrospective cohort study of patients <21 years old who underwent thyroidectomy followed by ¹³¹I ablation for DTC at 3 university hospitals over 20 years. Tg levels and the Tg/TSH ratio following surgery but prior to ¹³¹I ablation were assessed. The presence of distant metastatic disease was determined from the postablation whole-body scan.Results: We studied 44 patients with a mean age of 15.2 years (range 7 to 21 years) and mean tumor size of 2.8 cm. Eight patients had distant metastases and had a higher mean pre-ablation Tg value compared to patients without distant metastases (1,037 μg/L versus 93.5 μg/L, P<.01). The pre-ablation Tg/TSH ratio was also associated with the presence of distant metastases: 12.5 ± 18.8 μg/mU in patients with distant metastases versus 0.7 ± 1.8 μg/mU in patients without (P<.01). A nomogram to predict distant metastases yielded areas under the receiver operating characteristic curve of 0.85 for Tg and 0.83 for Tg/TSH ratio.Conclusion: After initial thyroidectomy, elevated preablation Tg and Tg/TSH ratio are associated with distant metastatic disease in pediatric DTC. This may inform the decision to ablate with ¹³¹I, as well as the dosage.Abbreviations:ATA = American Thyroid AssociationCI = confidence intervalDTC = differentiated thyroid cancerOR = odds ratioROC = receiver operating characteristicTg = thyroglobulin     

Factors Influencing the Successful Maintenance of Euthyroidism after Lobectomy in Patients with Papillary Thyroid Microcarcinoma: A Single-Center Study

Objective: This study aimed to evaluate factors influencing the successful maintenance of postoperative euthyroidism in patients who did not undergo immediate thyroid hormone replacement after lobectomy for papillary thyroid microcarcinoma (PTMC).Methods: From September 2015 to June 2017, 186 patients underwent lobectomy for PTMC in our hospital. Patients taking medications for hypothyroidism and hyperthyroidism before and after lobectomy were excluded. Multiple parameters, including sex, age, pre-operative free thyroxine (T4), thyroid-stimulating hormone (TSH), thyroglobulin (TG), and thyroid autoantibody levels, body mass index (BMI), postoperative histopathology of the thyroid gland, remnant thyroid gland volume, and session number of levothyroxine discontinuation were retrospectively evaluated. These factors were compared between groups based on the maintenance of postoperative euthyroidism.Results: In 88 of the 175 patients (50.3%), postoperative euthyroidism was successfully maintained without thyroid hormone replacement during the first year after lobectomy. There were significant differences in sex (P = .003), pre-operative TSH levels (P = .002), and histopathology of the thyroid gland (P = .035) between the groups showing maintenance success and failure. The group showing successful maintenance had a higher percentage of male patients, lower levels of pre-operative TSH, and normal parenchymal histology of the thyroid gland. However, there were no significant between-group differences in age, pre-operative free T4, TG, and thyroid autoantibody levels, BMI, remnant thyroid gland volume, and session number of levothyroxine discontinuation.Conclusion: Patient sex, pre-operative TSH levels, and histopathology of the thyroid gland may influence the maintenance of postoperative euthyroidism after lobectomy.Abbreviations: BMI = body mass index; PTMC = papillary thyroid microcarcinoma; RR = reference range; T4 = thyroxine; TFT = thyroid function test; TG = thyroglobulin; TSH = thyroid-stimulating hormone     

Is it Worth Suppressing Tsh in low- and Intermediate-Risk Papillary Thyroid Cancer Patients Before the First Disease Assessment?

Objective: Guidelines recommend thyroid-stimulating hormone (TSH) suppression before the first response to treatment assessment in papillary thyroid cancer (PTC) patients. The aim of this study was to assess the rate of structural disease (SD) in low- and intermediate-risk PTC patients according to TSH levels measured 1 year after primary treatment.Methods: A consecutive, prospective series of low- and intermediate-risk PTC patients with 3-years follow-up was collected. TSH, thyroglobulin (Tg), antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) 1 and 3 years after primary treatment were analyzed. Recurrence risk and disease status at 1 year were defined according to the American Thyroid Association (ATA) guidelines and as the presence or absence of SD after 3 years. Patients were grouped according to TSH level at 1 year: group 1, TSH <0.1 μUI/mL; group 2, TSH 0.1 to 0.5 μUI/mL; group 3, 0.5 to 2 μUI/mL; and group 4 >2 μUI/mL.Results: This study included 263 patients (70.9% female, median age 47.2 years) of whom the risk of recurrence was low in 170 (65%), intermediate-low in 63 (24%), and intermediate-high in 30 (11%). The response to initial treatment at 1 year was excellent in 149 (57%), biochemical incomplete in 18 (7%), indeterminate in 84 (32%), and structural incomplete in 12 (4%). Group 1 consisted of 53 (20%) patients, group 2 of 85 (32%), group 3 of 61 (23%), and group 4 of 64 (24%). The rate of SD at 1 and 3 years from primary treatment was not significantly different between TSH groups.Conclusion: TSH suppression before the first response to treatment assessment does not appear to influence the rate of SD evaluated 1 and 3 years after primary treatment.Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; LT4 = levothyroxine; PTC = papillary thyroid cancer; SD = structural disease; Tg = thyroglobulin; TgAb = antithyroglobulin antibodies; TSH = thyroid-stimulating hormone; US = ultrasonography     

Lack of a Threshold Size for Autonomously Functioning Thyroid Nodules that Excludes Hyperthyroidism

Objective: To correlate the size of autonomously functioning thyroid nodules (AFTNs) with thyroid function tests.Methods: A retrospective analysis was performed of data from patients with a diagnosis of a single AFTN who were seen in a university-based endocrinology clinic between January 1, 2003, and December 31, 2015. Patients with a nuclear thyroid scan confirming the presence of an AFTN without significant cystic degeneration were included in the study.Results: The volume of the AFTN and the corresponding thyroid function tests were compared in 32 patients who met inclusion criteria. There was no correlation between the volume of the AFTN and thyroid-stimulating hormone (TSH) levels (r² = 0.044). There was also no volume threshold below which an AFTN was always associated with a TSH within the reference range.Conclusion: The results agree with the findings of other recent studies comparing the volume of AFTNs with TSH levels, suggesting that smaller nodules can still demonstrate subclinical and overt hyperthyroidism and that a normal TSH level does not preclude the presence of an AFTN.Abbreviations: AFTN = autonomously functioning thyroid nodule; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Unknown and Already Known Thyroid Abnormalities in Primary Hyperparathyroidism

Objective: Primary hyperparathyroidism (PHPT) and thyroid diseases are highly prevalent in the general population, but the putative link between the 2 conditions remains unclear.Methods: A monocentric consecutive series of 434 patients with PHPT was retrospectively evaluated by lab and ultrasonography to look for thyroid abnormalities. Patients were classified in 3 groups: without thyroid abnormalities (group 1, n = 171), with thyroid diseases not previously known (group 2a, n = 69), and thyroid diseases previously known (group 2b, n = 194).Results: In terms of thyroid disease, no significant difference was found between groups 2a and 2b, except for the significantly larger number of patients with toxic nodular goiter in group 2b. PHPT was more frequently symptomatic in group 2a than in group 2b, despite no differences in serum calcium, creatinine, parathyroid hormone (PTH), or 25-hydroxyvitamin D (25OHD) levels.Conclusion: A total of 60% of PHPT patients had a thyroid disease that was unknown prior to PHPT diagnosis in almost one-third of cases. The newly diagnosed and previously known thyroid diseases were similar, both mostly affecting postmenopausal females.Abbreviations: Ab = antibody; aPHPT = asymptomatic PHPT; 25OHD = 25-hydroxyvitamin D; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; Tg = thyroglobulin; TPO = thyroperoxidase; TSH = thyroid-stimulating hormone; US = ultrasound     

Serum Thyrotropin in Graves’ Disease: A More Reliable Index of Circulating Thyroid-Stimulating Immunoglobulin Level than Thyroid Function?

ObjectiveTo assess the relationship between serum thyrotropin (thyroid-stimulating hormone or TSH) on one hand and thyroid-stimulating immunoglobulin (TSI), free thyroxine (T₄), and triiodothyronine (T₃) levels on the other in Graves’ disease, inasmuch as TSH may be suppressed in the presence of TSI because TSI may bind to the TSH receptor on the thyroid gland membrane and thus eliminate the need for circulating TSH for stimulating the thyroid gland.MethodsWe determined serum TSI levels in 37 women and 13 men with Graves’ disease, stratified into 4 groups on the basis of serum TSH levels irrespective of serum free T₄ and T₃ levels. Our reference ranges were 0.72 to 1.74 ng/dL for free T₄, 80 to 200 ng/dL for T₃, and to 4.0 μU/mL for TSH.ResultsMean serum TSI concentrations were highest (215% ± 28%) in patients with undetectable TSH levels (< 0.03 μU/mL) and lowest (103% ± 9%) in those with supernormal TSH concentrations (> 4.0 μU/mL). TSI levels were intermediate in the other study groups: 157% ± 16% in patients with subnormal though detectable TSH levels (0.03 to 0.39 μU/mL) and 125% ± 12% in those with normal TSH levels (0.4 to 4.0 μU/mL). Moreover, a progressive decline in TSI levels with increasing serum TSH concentrations was noted, along with a significant negative correlation (r = -0.45; P < 0.01) between serum TSI and TSH concentrations. Finally, relationships between free T₄ and T₃ levels on one hand and TSI or TSH levels on the other were not significant, with a considerable variability in free T₄ and T₃ levels being noted in individual study groups.ConclusionSerum TSH is frequently suppressed after treatment with antithyroid drugs or radioiodine (¹³¹I), irrespective of clinical thyroid function as expressed by increased, normal, or decreased free T₄ and T₃ concentrations. In an individual patient with Graves’ disease, the serum TSH level may be more reflective of the circulating TSI concentration than is thyroid gland function as expressed by free T₄ and T₃ concentrations and therefore may be as reliable a predictor of remission as TSI. (Endocr Pract. 2007;13:615-619)     

Thyroid And Aging

Objective: Review physiologic thyroid function changes with aging and emphasize careful interpretation of tests in the aging population.Methods: Literature review.Results: Using age-specific thyroid-stimulating hormone (TSH) reference ranges should minimize or avoid the unnecessary diagnosis of thyroid disease in elderly patients. Subclinical thyroid dysfunction and abnormal TSH with normal thyroid levels may improve with time, so careful monitoring of thyroid function is recommended. Overt thyroid disease should always be treated.Conclusion: Clinical judgement is always warranted to decide how and when to treat subclinical thyroid disease in the elderly.Abbreviations: FT4 = free thyroxine; rT3 = reverse triiodothyronine; T3 = triiodothyronine; T4 = thyroxine; TFT = thyroid function test; TSH = thyroid-stimulating hormone     

Thyroid Function and Metabolic Syndrome: A Cross-Sectional Study in Obese and Overweight Patients

Objective: Metabolic syndrome (MetS) is associated with increased risks of developing cardiovascular disease and type 2 diabetes. Thyroid dysfunction is also a known cardiovascular risk factor. In obese patients, serum thyroid-stimulating hormone (TSH) levels tend to be higher than in lean controls. The objective of this study was to assess potential associations between serum TSH levels and MetS as well as individual components of MetS.Methods: This was a cross-sectional observational study of obese and overweight patients seen for initial evaluation at the Boston Medical Center weight-management clinic between February 1, 2013 and February 1, 2014. Demographic, anthropometric, and laboratory data including serum TSH, insulin, glucose, hemoglobin A_1c, and lipid levels were obtained from electronic medical records. Associations between serum TSH levels and presence of MetS and its components were assessed.Results: A total of 3,447 patients, 75.6% female and 38% African American, without known thyroid dysfunction, were included. Mean ± SD age was 46.74 ± 15.11 years, and mean ± SD body mass index was 36.06 ± 9.89 kg/m². Among 1,005 patients without missing data, the prevalence of MetS was 71.84%. In patients with MetS, the median serum TSH was 1.41 μIU/mL, compared with 1.36 μIU/mL in patients without MetS (P = .45). In multivariate models, there was no significant association between serum TSH levels and the presence of MetS, adjusting for age, sex, race, education, socioeconomic status, and smoking. There were also no significant associations between serum TSH and individual components of the MetS.Conclusion: Serum TSH level does not appear to be a potentially modifiable risk factor for MetS in obese and overweight individuals.Abbreviations: BMI = body mass index FT₄ = free thyroxine HDL-C = high-density-lipoprotein cholesterol HbA_1c = hemoglobin A_1c MetS = metabolic syndrome SE = standard error TSH = thyroid-stimulating hormone     

Thyroid Hormone Signaling In Vivo Requires a Balance between Coactivators and Corepressors

Resistance to thyroid hormone (RTH), a human syndrome, is characterized by high thyroid hormone (TH) and thyroid-stimulating hormone (TSH) levels. Mice with mutations in the thyroid hormone receptor beta (TRβ) gene that cannot bind steroid receptor coactivator 1 (SRC-1) and Src-1^−/− mice both have phenotypes similar to that of RTH. Conversely, mice expressing a mutant nuclear corepressor 1 (Ncor1) allele that cannot interact with TRβ, termed NCoRΔID, have low TH levels and normal TSH. We hypothesized that Src-1^−/− mice have RTH due to unopposed corepressor action. To test this, we crossed NCoRΔID and Src-1^−/− mice to create mice deficient for coregulator action in all cell types. Remarkably, NCoR^ΔID/ΔID Src-1^−/− mice have normal TH and TSH levels and are triiodothryonine (T₃) sensitive at the level of the pituitary. Although absence of SRC-1 prevented T₃ activation of key hepatic gene targets, NCoR^ΔID/ΔID Src-1^−/− mice reacquired hepatic T₃ sensitivity. Using in vivo chromatin immunoprecipitation assays (ChIP) for the related coactivator SRC-2, we found enhanced SRC-2 recruitment to TR-binding regions of genes in NCoR^ΔID/ΔID Src-1^−/− mice, suggesting that SRC-2 is responsible for T₃ sensitivity in the absence of NCoR1 and SRC-1. Thus, T₃ targets require a critical balance between NCoR1 and SRC-1. Furthermore, replacement of NCoR1 with NCoRΔID corrects RTH in Src-1^−/− mice through increased SRC-2 recruitment to T₃ target genes.     

Study Of The Prevalence Of Autoimmune Thyroid Disease In Women With Breast Cancer

Objective: The aim of this study was to analyze the prevalence of thyroid disorders in patients with a positive biopsy for breast cancer prior to specific antitumor treatment.Methods: The frequency and pattern of thyroid disorders were evaluated in 112 patients with breast cancer (G1) and 125 control patients (G2) by analyzing serum thyroid-stimulating hormone (TSH), anti–thyroid peroxidase antibodies, and anti-thyroglobulin antibodies. In addition, the expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2) was assessed in the breast biopsies by immunohistochemistry.Results: The frequency of thyroid disorders, such as changes in TSH levels and/or the presence of thyroid antibodies, was not different between the 2 groups examined (30.4% in G1 versus 28.0% in G2) (P = .69). However, a family history of thyroid disease was more frequent in patients with breast cancer (50.5% in G1 versus 28.2% in G2) (P = .001). Regarding the clinical stage of breast cancer, there was no difference between women with autoimmune thyroiditis and those without thyroid dysfunction (P = .316). Similarly, there were no differences in hormone receptor (estrogen or progesterone) and HER2 expression between patients who tested positive and those who tested negative for anti-thyroid antibodies (P = .052 and P = .549, respectively).Conclusion: The data obtained in this study did not reveal a higher frequency of autoimmune thyroid disease in patients with breast cancer compared to controls. A family history of thyroid disease was more common in those with breast cancer.Abbreviations:anti-Tg = anti-thyroglobulinanti-TPO = anti–thyroid peroxidaseBIRADS = Breast Imaging-Reporting and Data SystemER = estrogen receptorFT₄ = free thyroxineG1 = study groupG2 = final control groupHER2 = human epidermal growth factor receptor 2PR = progesterone receptorTSH = thyroid-stimulating hormone     

Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice

The molecular chaperone receptor-associated protein (RAP) is required for biosynthesis of megalin, an endocytic receptor for follicular thyroglobulin (Tg), the thyroid hormone precursor. RAP also binds to Tg itself, suggesting that it may affect Tg trafficking in various manners. To elucidate RAP function, we have studied the thyroid phenotype in RAP-knockout (RAP-KO) mice and found a reduction of Tg aggregates into thyroid follicles. Serum Tg levels were significantly increased compared with those of wild-type (WT) mice, suggesting a directional alteration of Tg secretion. In spite of these abnormalities, hormone secretion was maintained as indicated by normal serum thyroxine levels. Because Tg in thyroid extracts from RAP-KO mice contained thyroxine residues as in WT mice, we concluded that in RAP-KO mice, follicular Tg, although reduced, was nevertheless sufficient to provide normal hormone secretion. Serum TSH was increased in RAP-KO mice, and although no thyroid enlargement was observed, some histological features resembling early goiter were present. Megalin was decreased in RAP-KO mice, but this did not affect thyroid function, probably because of the concomitant reduction of follicular Tg. In conclusion, RAP is required for the establishment of Tg reservoirs, but its absence does not affect hormone secretion. low-density lipoprotein; knockout mice     

The Correlation Between Metabolic Disorders And Tpoab/Tgab: A Cross-Sectional Population-Based Study

Objective: Studies have shown that metabolic abnormalities influence the immune system. Because the prevalence of metabolic and autoimmune thyroid diseases has increased synchronously, the correlation between them was worth exploring. The study objective was to investigate the relationship between metabolic disorders and thyroid auto-antibodies in euthyroid subjects.Methods: Data were obtained from the Thyroid Diseases and Diabetes Mellitus project survey of 55,891 subjects from 31 provinces in China. The body mass index (BMI), waist circumference (WC), blood pressure, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), thyroid-stimulating hormone (TSH), urinary iodine concentration, blood glucose, lipid profile, and uric acid levels were evaluated. Free thyroxine and free triiodothyronine levels were measured in patients with abnormal serum TSH levels.Results: In males, the BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), and 2-hour post-glucose oral glucose tolerance test results of the TPOAb-/TgAb-positive group were significantly higher than those of the TPOAb-/TgAb-negative group. In females, the BMI, WC, SBP, DBP, total cholesterol, and low-density-lipoprotein cholesterol (LDL-C) in the TPOAb-/TgAb-positive group were significantly increased compared to the TPOAb-/TgAb-negative group. Multivariate analysis showed that in males, the odds ratio (OR) of positive TgAbs in the abdominal obesity group was 1.175 (95% confidence interval [CI], 1.016 to 1.359; P = .03), and the OR of positive TPOAbs in the hyperuricemia group was 1.195 (95% CI, 1.041 to 1.372; P = .011). In females, the OR of positive TgAbs was 1.19 (95% CI, 1.068 to 1.326; P = .002) in the high LDL-C group.Conclusion: Obesity, high LDL-C, and hyperuricemia were positively correlated with the prevalence of positive thyroid autoantibodies in euthyroid subjects in a gender-dependent manner. This cross-sectional survey showed that metabolic disorders are associated with increased positive thyroid autoantibody levels in euthyroid subjects in a gender-dependent manner.Abbreviations: AIT = autoimmune thyroiditis; BMI = body mass index; CI = confidence interval; DBP = diastolic blood pressure; FPG = fasting plasma glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; HbA1c = glycated hemoglobin; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; OGTT2hPG = oral glucose tolerance test 2-hours post-glucose; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyroid-stimulating hormone; UA = uric acid; WC = waist circumference     

No Longterm Severe Thyroid Dysfunction Seen In Patients With Preexisting Reduced Serum Tt3 Concentrations After A Single Large Dose Of Iodinated Contrast

Objective: After an intravenous bolus injection of 100 mL of iodinated contrast agent (370 mgI/mL), the amount of iodine atoms entering the blood is tens of thousands of times the daily dose of iodine recommended by the World Health Organization. However, the effect of iodinated contrast in patients with nonthyroidal illness, manifested as reduced serum total triiodothyronine (TT3) concentrations, is unclear. We studied the effect of iodinated contrast on thyroid function and auto-antibodies in patients with reduced TT3 after diagnosis and treatment of coronary heart disease.Methods: This was a prospective cohort study. One hundred and fifty-four stable angina pectoris patients with reduced TT3 and normal thyroid-stimulating hormone (TSH), free thyroxine (FT4), and reverse triiodothyronine (rT3) were enrolled from January, 2017, to June, 2018. All subjects had no history of thyroid dysfunction and had no recent infections, tumors, trauma, or other critical illnesses. Fourty-one patients underwent coronary angiography and 113 patients underwent coronary intervention.Results: There were 6 patients (3.9%) with hypothyroidism and 30 patients (19.5%) developed subclinical hypothyroidism (SCHypo) on the first day after surgery. There were 6 patients (3.9%) with hypothyroidism, 6 patients (3.9%) with SCHypo, and 18 patients (11.7%) with subclinical hyperthyroidism (SCHyper) at the first month postsurgery. There were 23 patients (14.9%) with SCHyper and 6 patients (3.9%) with SCHypo at the sixth month after surgery. No patient with longterm severe thyroid dysfunction occurred during follow-up. The levels of free triiodothyronine, FT4, TT3, total thyroxine, and TSH showed statistically significant changes at 1 day, and 1, 3, and 6 months postoperative (P<.005). The level of rT3 showed no statistically significant change at 1, 3, and 6 months postoperative (P>.05). The levels of thyroglobulin antibody and thyroid peroxidase antibody decreased at 6 months postoperative (P<.001).Conclusion: The risk of subclinical thyroid dysfunction and transient hypothyroidism occurred with a single large dose of iodinated contrast in the diagnosis and treatment of coronary heart disease, but no longterm severe thyroid dysfunction occurred. Patients with preoperative thyroid antibody elevation were more likely to have subclinical thyroid dysfunction after surgery.Abbreviations: FT3 = free triiodothyronine; FT4 = free thyroxine; PCI = percutaneous coronary intervention; rT3 = reverse triiodothyronine; SCHyper = subclinical hyperthyroidism; SCHypo = subclinical hypothyroidism; TGAB = thyroglobulin antibody; TPOAB = thyroid peroxidase antibody; TT3 = total triiodothyronine; TT4 = total thyroxine; TSH = thyroid-stimulating hormone; WHO = World Health Organization     

Baseline TSH Level is Associated with Risk of Anti–PD-1–Induced Thyroid Dysfunction

Objective: To characterize anti–programmed cell death 1 (PD-1)–induced thyroid immune-related adverse events (irAEs) in metastatic melanoma patients treated at our institution and to identify risk factors associated with their development.Methods: We reviewed the files of 154 patients with metastatic melanoma treated with PD-1 inhibitors at a single institution from November 1, 2011, to February 28, 2017. The association of thyroid irAEs within 120 days posttreatment initiation with age, gender, melanoma characteristics, treatment protocol, and baseline thyroid-stimulating hormone (TSH) was examined.Results: Overall, 42.4% developed thyroid dysfunction following treatment, including 20.2% (20/99) subclinical thyroid dysfunction, 13.1% (13/99) overt hypothyroidism, and 9.1% (9/99) overt hyperthyroidism. Of those that developed overt hyperthyroidism, 8 progressed to overt hypothyroidism, consistent with thyroiditis. Age, gender, melanoma characteristics, or treatment protocol did not modify the risk of developing thyroid irAEs. Higher baseline TSH was observed in patients who developed overt hypothyroidism versus hyperthyroidism versus those who remained euthyroid (P = .05). A pretreatment TSH >2.19 mIU/mL was associated with an increased risk of overt thyroid dysfunction (odds ratio, 3.46; 95% confidence interval, 1.2 to 9.8).Conclusion: Thyroid dysfunction following treatment with PD-1 inhibitors is common, and patients with a higher baseline TSH appear to be at increased risk. Such patients may benefit from closer monitoring of their thyroid function following initiation of anti PD-1 agents.Abbreviations: CTLA-4 = cytotoxic T-lymphocyte antigen 4; FT3 = free triiodothyronine; FT4 = free thyroxine; irAE = immune-related adverse event; PD-1 = programmed cell death 1; TFT = thyroid function test; TPO = thyroid peroxidase; TSH = thyroid-stimulating hormone     

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     

Practical Barriers to Implementation of Thyroid Cancer Guidelines in the Asia-Pacific Region

Objective: Numerous published guidelines have described the optimal management of thyroid cancer. However, these rely on the clinical availability of diagnostic and therapeutic modalities. We hypothesized that the availability of medical resources and economic circumstances vary in Asia-Pacific countries, making it difficult to implement guideline recommendations into clinical practice.Methods: We surveyed participants at the 2009 and 2013 Congresses of the Association of Southeast Asian Nations Federation of Endocrine Societies by distributing questionnaires to attendees at registration.Results: Responses were obtained from 268 respondents in 2009 and 163 respondents in 2013. Similar to the high prevalence of low-risk thyroid cancer observed in the Surveillance, Epidemiology, and End Results database, across the Asia-Pacific countries surveyed in 2009 and 2013, 50 to 100% of the respondents from the Philippines, Malaysia, Singapore, China, Taiwan, Thailand, Hong Kong, Korea, and Sri Lanka reported that more than 50% of the patients had low-risk thyroid cancer on follow-up. Importantly, there was much variation with regards to the perceived availability of investigation and treatment modalities.Conclusion: We found a wide variation in clinicians' perception of availability of diagnostic and therapeutic modalities in the face of a rise in thyroid cancer incidence and thyroid cancer management guidelines that emphasized their importance. The lack of availability of management tools and treatments will prove to be a major barrier to the implementation of thyroid cancer management guidelines in Southeast Asia, and likely in other parts of the world as well.Abbreviations: AFES = ASEAN Federation of Endocrine Societies ASEAN = Association of Southeast Asian Nations ATA = American Thyroid Association FNA = fine-needle aspiration PET = positron emission tomography RAI = radioactive iodine Tg = thyroglobulin TSH = thyroid-stimulating hormone     

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     

Thyroid-stimulating Hormone Levels Are Inversely Associated With Serum Total Bile Acid Levels: a Cross-Sectional Study

Objective: Bile acids (BAs) synthesized from cholesterol play a critical role in eliminating excess cholesterol to maintain cholesterol homeostasis. BAs are also signaling molecules that are involved in the regulation of lipid, glucose, and energy metabolism. Thyroid-stimulating hormone (TSH) has been found to decrease liver BA synthesis via a sterol regulatory element-binding protein 2/hepatocyte nuclear factor 4 alpha/cholesterol 7α-hydroxylase (SREBP-2/HNF-4α/CYP7A1) pathway in vivo and in vitro. However, the relationship between serum TSH and total BA levels in humans is still unclear.Methods: This was a single-center cross-sectional study of 339 subclinical hypothyroidism (SCH) patients and an equal number of controls matched by age and sex from 11,000 subjects.Results: Serum total BA levels significantly decreased (3.11 ± 2.05 vs. 5.87 ± 2.39, P<.01), while total cholesterol (TC) levels increased (5.02 ± 0.65 vs. 4.88 ± 0.63, P<.01) in subclinical hypothyroidism (SCH) patients compared to control subjects. Serum TSH and BA levels were significantly and negatively correlated in subclinical hypothyroid patients who were also hypercholesterolemic (r_s = -0.189, P = .004). Each 1 μIU/mL increase in TSH level was associated with a decrease in log-transformed values of total BAs (logTBAs) by 0.182 after controlling for confounding factors relevant to BA metabolism. The relationship between TSH and serum total BAs was more significant in subjects younger than 65 years.Conclusion: Our results suggested that TSH is correlated with the total BA level in SCH patients independent of thyroid hormone, which suggests a potential physiological role of TSH and the importance of maintaining normal range TSH in SCH patients.Abbreviations:BA = bile acidCYP7A1 = cholesterol 7α-hydroxylaseFBG = fasting blood glucoseHDL-C = highdensity lipoprotein cholesterolLDL-C = low-density lipoprotein cholesterollogTBAs = log-transformed values of total BAsSCH = subclinical hypothyroidismTC = total cholesterolTG = triglycerideTH = thyroid hormoneTSH = thyroid-stimulating hormone     

Gender Influences the Clinical Presentation and Long-Term Outcome of Graves Disease

Objective: The outcome of antithyroid drug (ATD) treatment for Graves disease (GD) is difficult to predict. In this study, we investigated whether male gender, besides other factors usually associated with a poor outcome of ATD treatment, may affect disease presentation and predict the response to medical treatment in subjects with GD.Methods: We studied 294 patients with a first diagnosis of GD. In all patients, ATD treatment was started. Clinical features, thyroid volume, and eye involvement were recorded at baseline. Serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and TSH-receptor antibodies (TRAb) were measured at baseline and during the follow-up. Treatment outcome (FT4, FT3, and TSH serum levels and further treatments for GD after ATD withdrawal) was evaluated.Results: When compared to women, men showed a significantly larger thyroid volume and a higher family positivity for autoimmune diseases. During ATD, the mean serum levels of TSH, FT4, FT3, and TRAb did not differ between groups. Within 1 year after ATD discontinuation, relapse of hyperthyroidism was significantly more frequent in men than in women. Within the 5-year follow-up period, the prevalence of men suffering a late relapse was higher compared with that of women. The outcome at the end of the 5-year follow-up period was significantly associated with gender and TRAb levels at disease onset.Conclusion: Male patients with GD have a poorer prognosis when submitted to medical treatment with ATDs. A larger goiter at presentation and a stronger genetic autoimmune background might explain this gender difference in patients with GD.Abbreviations:ATD = antithyroid drugFT3 = free triiodothyronineFT4 = free thyroxineGD = Graves diseaseGO = Graves orbitopathyRAI = radioiodineTRAb = thyroid-stimulating hormone-receptor antibodyTSH = thyroid-stimulating hormone     

Immunoglobulin Preparations Can Mislead Clinical Decision-Making in Follow-Up of Differentiated Thyroid Cancer

Objective: Intravenous and subcutaneous immunoglobulins are commonly used for immune substitution or as immune modulators in a variety of inflammatory and autoimmune disorders. Exogenous thyroid-specific thyroglobulin (Tg) antibodies present in the donor plasma may interfere with the interpretation of measurements of Tg autoantibodies (Tg-Abs) in the recipient’s plasma and potentially trigger an immune response in the recipient’s immune cells. Levels of antibodies causing bioassay interferences or those leading to clinically relevant changes in patient outcomes are not known. Tg is used as a biomarker in the long-term surveillance of patients with differentiated thyroid cancer (DTC) following total thyroidectomy and radioactive iodine ablation. However, the presence of Tg-Abs in the circulation interferes with Tg measurements. Assessment of levels of Tg-Abs is thus recommended as a part of standard follow-up of DTC together with Tg testing.Methods: To understand the potential mechanisms and pathophysiologic significance of possible interferences associated with administration immunoglobulin preparations and Tg measurement, we overview the current knowledge on interactions between Tg autoimmunity and immunoglobulin preparations and illustrate diagnostic challenges and perspectives for follow-up of patients with DTC treated with exogenous immunoglobulins.Results: In patients with DTC treated with immunoglobulin preparations, monitoring of thyroid cancer using Tg and Tg-Abs is challenging due to possible analytical interferences through passive transfer of exogenous antibodies from immunoglobulin preparations.Conclusion: Analytical interferences must be suspected when a discrepancy exists between clinical examination and diagnostic tests. Collaboration between endocrinologists, biologists, and pharmacologists is fundamental to avoid misdiagnosis and unnecessary medical or radiologic procedures.Abbreviations: CT = computed tomography; DTC = differentiated thyroid cancer; FNAB = fine-needle aspiration biopsy; HAb = heterophile antibody; IMA = immunometric assay; IVIg = intravenous immunoglobulin; RAI = radioactive iodine; RIA = radioimmunoassay; SCIg = subcutaneous immunoglobulin; Tg = thyroglobulin; Tg-Ab = thyroglobulin autoantibody; Tg-MS = thyroglobulin mass spectrometry; TPO-Ab = thyroid peroxidase autoantibody; TSHR-Ab = thyrotropin receptor autoantibody