Serum Metabolomic Patterns in Patients with Autoimmune Thyroid Disease

Objective: Autoimmune thyroid disease, including Graves disease (GD) and Hashimoto thyroiditis (HT), is one of the most common endocrine diseases. GD and HT are the main etiologies for hyperthyroidism and hypothyroidism, respectively. This study aimed to provide a metabolomic analysis of GD patients with hyperthyroidism and HT patients with hypothyroidism.Methods: This study investigated serum metabolomics in 43 GD patients with hyperthyroidism, 45 HT patients with hypothyroidism, and 52 age- and sex-matched healthy controls. The metabolomic data were analyzed by performing multivariate statistical analysis.Results: The 186 metabolites including amino acids, bile acids, free fatty acids, and lipids were identified in all participants. Multivariate models indicated systematic differences in the hyperthyroidism, hypothyroidism, and control groups. Compared to healthy controls, the 22 metabolites in the hyperthyroidism group and the 17 metabolites in the hypothyroidism group were significantly changed. Pathway analysis showed that hyperthyroidism had a significant impact on arginine and proline metabolism and aminoacyl-transfer ribonucleic acid biosynthesis, while hypothyroidism had a significant impact on alanine, aspartate, and glutamate metabolism.Conclusion: The serum metabolomic pattern changes in patients with autoimmune thyroid dysfunction.Abbreviations: BMI = body mass index; CA = cholic acid; CDCA = chenodeoxycholic acid; DCA = deoxycholic acid; FBG = fasting plasma glucose; FINS = fasting plasma insulin; FT3 = free triiodothyronine; FT4 = free thyroxine; GD = Graves disease; GDCA = glycodeoxycholic acid; HDL-C = high-density lipoprotein cholesterol; HOMA-IR = homeostasis model assessment of insulin resistance; HT = Hashimoto thyroiditis; LDL-C = low-density lipoprotein cholesterol; PC = phosphatidylcholine; PCA = principal component analysis; PLS-DA = partial least squares discriminant analysis; SM = sphingomyelin; TBA = total bile acid; TC = total cholesterol; TG = triglyceride; TSH = thyrotropin; VIP = variable influences on projection     

A Novel Monoclonal Antibody Degrades the Thyrotropin Receptor Autoantibodies in Graves' Disease

ObjectiveAutoantibodies against the thyrotropin receptor (TSH-R-Ab) are key mediators for the pathogenesis of Graves' disease (GD). TSH-R-Ab degradation was evaluated using several immunoassays within an exploratory, controlled trial in patients with GD receiving a monoclonal antibody (mAb) targeting the neonatal crystallizable fragment receptor (FcRn).MethodsSerial measurements of TSH-R-Ab serum levels were performed using 3 different binding and cell-based assays in patients with GD either on medication or on placebo.ResultsIn contrast to the placebo group, in which no changes were observed, a 12-week mAb therapy led to an early and significant decrease (>60%) in the serum TSH-R-Ab levels in patients with thyroidal and extrathyroidal GD, as unanimously shown in all 3 assays. These marked changes were noted already at week 7 post baseline (P <.0001 for the binding immunoassay and for the luciferase (readout) bioassay). The 3 TSH-R-Ab binding and bioassays were highly correlated in the samples of both study groups (binding immunoassay vs luciferase bioassay, r =.91, P <.001, binding vs cyclic adenosine monophosphate (cAMP) bioassay, r = 0.86, P <.001, and luciferase vs cAMP bioassay, r = 0.71, P =.006). The serological results correlated with the course of the extrathyroidal clinical parameters of GD, that is, clinical activity score and proptosis.ConclusionTargeting the FcRn markedly reduces the disease-specific TSH-R-Ab in patients with GD. The novel and rapid TSH-R-Ab bioassay improves diagnosis and management of patients with GD.     

Age related changes of soluble Fas, Fas ligand and Bcl-2 in autoimmune thyroid diseases

INTRODUCTION: Apoptosis plays a pivotal role in the regulation of immune mechanisms in the pathogenesis of autoimmune thyroid diseases (AITD). The prevalence of AITD increases with age. Purpose to compare soluble Fas, FasL and Bcl-2 in Graves disease (GD) and Hashimoto thyroiditis (HT) in relation to the age of the studied patients. MATERIAL AND METHODS: 3 groups of subjects: 1/25 patients with GD in euthyreosis on methimazol 2/27 patients with ChH in euthyreosis on levothyroxine. 3/12 healthy volunteers age and sex-matched to group 1-2. The serum levels of Fas, FasL and Bcl-2 were determined by the ELISA kit. RESULTS: We found positive correlations between sFas and age in GD patients (r = 0.35; p < 0.05). In GD patients we found a negative correlation between sFasL and age in all studied patients with AITD (r = -0.34; p < 0.01). We also found a negative correlation between sBcl-2 and age in HT patients (r = -0.42; p < 0.05). CONCLUSIONS: Fas/FasL and Bcl-2 signaling pathways seem to be age-related and may explain, at least in part, milder course of Graves disease in elderly patients and increased prevalence of Hashimoto disease in this group of subjects.     

Positive Thyrotropin Receptor Antibodies in Patients with Transient Thyrotoxicosis

Objective: Thyrotropin (TSH) receptor antibody (TRAb) testing is considered accurate for the diagnosis of Graves disease (GD) and has been identified rarely in thyrotoxic patients without GD. We describe 4 patients with transient thyrotoxicosis and positive TRAb to highlight this clinical possibility.Methods: Patient demographics, symptoms, laboratory findings, and time to resolution of thyrotoxicosis are summarized. TRAb testing was performed by either a third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) competitive-binding assay or a thyroid-stimulating immunoglobulin (TSI) bioassay from either Mayo Clinic Laboratory or Quest Diagnostics.Results: Four patients with transient thyrotoxicosis and positive TRAb testing were identified. Of these, three were female, and the median age was 44 years (range, 25 to 49 years). Median symptom duration at evaluation was 6.5 weeks (range, 3 to 12 weeks). No patient had any clinical manifestations unique to GD or exposure to biotin, thyroid hormone, supplements, iodine, or relevant medications. The TSH was <0.1 mIU/L in all patients. Three patients had a positive TSI, which was elevated less than twice the upper limit of the reference range in all cases, and 1 patient had a strongly positive TBII. None of the patients were treated with thionamides or radioactive iodine. Spontaneous resolution occurred in all patients at a median of 5.5 weeks (range, 2 to 14.4 weeks).Conclusion: These cases demonstrate that TSI or TBII may be present in thyrotoxic patients with transient thyrotoxicosis. For clinically stable patients presenting without pathognomonic evidence of GD, mildly elevated TRAb results may require cautious interpretation, and alterative diagnostic testing or close monitoring should be considered.Abbreviations: cAMP = cyclic adenosine monophosphate; FT4 = free thyroxine; GD = Graves disease; TBII = thyrotropin-binding inhibitory immunoglobulin (also known as TBI); TRAb = thyrotropin receptor antibody; TSH = thyrotropin; TSHR = thyrotropin receptor; TSI = thyroid-stimulating immunoglobulin; TT3 = total triiodothyronine; TT4 = total thyroxine     

Management of Thyrotoxicosis: Preconception,Pregnancy, and the Postpartum Period

Objective: To review the diagnosis and management of thyrotoxicosis in women who are preconception, pregnant, and in the postpartum period.Methods: Literature review of English-language papers published between 1980 and 2018.Results: Overt thyrotoxicosis occurs in 0.2% of pregnancies and subclinical thyrotoxicosis in 2.5%. Hyperthyroidism in women of childbearing age most frequently is caused by Graves disease (GD). Gestational thyrotoxicosis, transient human chorionic gonadotropin (hCG)-mediated hyperthyroidism, may develop in the first trimester. In the first year following delivery, postpartum thyroiditis, which frequently includes a thyrotoxic phase, occurs in 5% of women. Hyperthyroidism from nodular autonomy is uncommon in women of childbearing age. It is essential to understand the underlying etiology for thyrotoxicosis in order to recommend appropriate treatment. Gestational thyrotoxicosis requires supportive care, without antithyroid drug therapy. GD may be treated with antithyroid drugs, radioactive iodine, or thyroidectomy. Pregnancy, plans for pregnancy, and lactation have important implications for the choice of GD treatment. When thyrotoxicosis presents following delivery, postpartum thyroiditis must be differentiated from GD.Conclusion: The diagnosis and management of thyrotoxicosis in the peripregnancy period present specific challenges. In making management decisions, it is essential to weigh the risks and benefits of treatments not just for the mother but also for the fetus and for breastfed infants. A team approach to management is critical, with close collaboration among endocrinologists, maternal-fetal medicine specialists, and neonatologists.Abbreviations: GD = Graves disease; hCG = human chorionic gonadotropin; MMI = methimazole; PPT = postpartum thyroiditis; PTU = propylthiouracil; T3 = triiodothyronine; T4 = thyroxine; TBG = thyroxine-binding globulin; TRAb = TSH receptor antibody; TSH = thyroid-stimulating hormone     

Short-Term Versus 6-Week Prednisone In The Treatment Of Subacute Thyroiditis: A Randomized Controlled Trial

Objective: Moderate-to-severe subacute thyroiditis is clinically managed with 6 to 8 weeks of glucocorticoid therapy. However, no studies have evaluated short-term prednisone treatment for subacute thyroiditis.Methods: This 24-week, prospective, single-blind, randomized controlled study enrolled patients (aged 18 to 70 years) with subacute thyroiditis who were hospitalized between August, 2013, and December, 2014. Patients with moderate-to-severe symptoms were randomly assigned to receive either 30 mg/day prednisone for 1 week, followed by 1 week of nonsteroidal anti-inflammatory drugs, or the conventional 6-week prednisone therapy. The primary endpoint was intergroup differences in treatment efficacy at the end of the treatment course. Secondary endpoints included between-group differences in post-withdrawal adverse effect parameters and thyroid function at weeks 6, 12, and 24.Results: We screened 96 patients, randomized 52 participants, and 50 participants completed the study. Efficacy and recurrence rates were not significantly different at withdrawal in both groups (P = .65). At treatment discontinuation, parathyroid hormone (28.8 versus 38.9 pg/mL; P = .011) and systolic blood pressure (113.9 versus 122.4 mm Hg; P = .023) were significantly lower in the experimental group than in the control group. There were no significant intergroup differences in other secondary endpoints at withdrawal and in thyroid function at weeks 6, 12, and 24.Conclusion: Fewer side effects of glucocorticoids and similar efficacy and recurrence rates were observed with short-term prednisone compared with the 6-week treatment for subacute thyroiditis. Short-term prednisone, with a better safety profile, may be an alternative strategy for ameliorating moderate-to-severe symptoms of subacute thyroiditis.Abbreviations: BPPG = breakfast postprandial plasma glucose; CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; FPG = fasting plasma glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; GA = glycated albumin; NSAIDs = nonsteroidal anti-inflammatory drugs; OC = osteocalcin; PINP = type I procollagen amino-terminal peptide; PTH = parathyroid hormone; RCT = randomized controlled trial; SAT = subacute thyroiditis; SBP = systolic blood pressure; TC = total cholesterol; TSH = thyroid-stimulating hormone; TBG = thyroid-binding globulin; TG = triglyceride; TGAb = antithyroglobulin antibody; TPOAb = antithyroid peroxidase antibody; TRAb = antithyroid-stimulating hormone receptor antibody     

Role of Thyroid Doppler in Differential Diagnosis of Thyrotoxicosis

ObjectiveTo evaluate the role of thyroid blood flow assessment by color-flow Doppler ultrasonography in the differential diagnosis of thyrotoxicosis.MethodsConsecutive patients with thyrotoxicosis presenting to our center between June 2007 and March 2008 were included in the study. Clinical data were collected, and thyroid function tests including measurements of thyrotropin, total thyroxine, and total triiodothyronine were performed. Thyroid glands of all patients were evaluated with color-flow Doppler ultrasonography for size, vascularity, and peak systolic velocity of the inferior thyroid artery. Technetium Tc 99m pertechnetate scan was done when the diagnosis was not clear on the basis of clinical findings. Patients were divided into 2 groups for analysis: patients with destructive thyrotoxicosis and patients with Graves disease. Paired t tests and Fisher exact tests were used for statistical analysis.ResultsA total of 65 patients participated in the study; 31 had destructive thyrotoxicosis and 34 had Graves disease. Thyroid blood flow, as assessed by peak systolic velocity of the inferior thyroid artery, was significantly higher in patients with Graves disease than in patients with destructive thyroiditis (57.6 ± 13.1 cm/s vs 22.4 ± 5.4 cm/s; P < .05). All patients with destructive thyroiditis had low peak systolic velocity of the inferior thyroid artery, and 32 of 34 patients with Graves disease had high peak systolic velocity. Color-flow Doppler ultrasonography parameters correlated significantly with pertechnetate scan results, demonstrating a comparable sensitivity of 96% and specificity of 95%.ConclusionsDifferentiating Graves thyrotoxicosis from destructive thyrotoxicosis is essential for proper selection of therapy. Assessment of thyroid blood flow by color-flow Doppler ultrasonography is useful in this differentiation. (Endocr Pract. 2009;15:6-9)     

A Stepwise Approach to the Evaluation and Treatment of Subclinicalhyperthyroidism

ObjectivesTo review a stepwise approach to the evaluation and treatment of subclinical hyperthyroidism.MethodsEnglish-language articles regarding clinical management of subclinical hyperthyroidism published between 2007 and 2012 were reviewed.ResultsSubclinical hyperthyroidism is encountered on a daily basis in clinical practice. When evaluating patients with a suppressed serum thyrotropin value, it is important to exclude other potential etiologies such as overt triiodothyronine toxicosis, drug effect, nonthyroidal illness, and central hypothyroidism. In younger patients with mild thyrotropin suppression, it is acceptable to perform testing again in 3 to 6 months to assess for persistence before performing further diagnostic testing. In older patients or patients with thyrotropin values less than 0.1 mIU/L, diagnostic testing should proceed without delay. Persistence of thyrotropin suppression is more typical of nodular thyroid autonomy, whereas thyroiditis and mild Graves disease frequently resolve spontaneously. The clinical consequences of subclinical hyperthyroidism, such as atrial dysrhythmia, accelerated bone loss, increased fracture rate, and higher rates of cardiovascular mortality, are dependent on age and severity. The decision to treat subclinical hyperthyroidism is directly tied to an assessment of the potential for clinical consequences in untreated disease. Definitive therapy is generally selected for patients with nodular autonomous function, whereas antithyroid drug therapy is more appropriate for mild, persistent Graves disease.ConclusionThe presented stepwise approach to the care of patients presenting with an isolated suppression of serum thyrotropin focuses on the differential diagnosis, a prediction of the likelihood of persistence, an assessment of potential risks posed to the patient, and, finally, a personalized choice of therapy. (Endocr Pract. 2012;18: 772-780)     

Association between IL-18 gene polymorphisms and Hashimoto thyroiditis

Molecular Biology Reports - Hashimoto’s thyroiditis (HT), which is also called lymphocytic thyroiditis, is the most frequent autoimmune thyroid disease (AITD), in which T helper-1 lymphocytes...     

Clock gene PERIOD3 polymorphism is associated with susceptibility to Graves’ disease but not to Hashimoto’s thyroiditis

ABSTRACT

Circadian disruption has been linked with immune-related morbidities including autoimmune diseases. PERIOD3 (PER3) clock gene is a key player in the mammalian circadian system. This study evaluated the possible association of PER3 rs2797685 (G/A) polymorphism and susceptibility of autoimmune thyroid diseases (AITD) and assessed if this SNP contributes to disease characteristics and serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The PER3 rs2797685 (G/A) polymorphism was assessed in 125 patients with AITD [Graves’ disease (GD), 69; Hashimoto’s thyroiditis (HT), 56] and 115 unrelated healthy controls. Subjects carrying at least one variant allele of PER3 rs2797685 (GA+AA) had increased risk for GD (OR 1.9, 95% CI 1–3.61, p= .05). There were no differences in the frequencies of genotypes and alleles of the PER3 rs2797685 polymorphism between HT patients and control subjects. No association was observed between genotypes of the studied SNP and any of the disease characteristics in GD and HT patients. The GA+AA genotype of PER3 rs2797685 was associated with lower levels of IL-6 in patients with Graves’ disease. There were no differences between genotypes of the studied SNP regarding TNF-α levels in GD, HT or control groups. In conclusion, this study provides the first evidence for a genetic association between GD and the PER3 gene, highlighting the possible relevance of polymorphisms in clock genes in the etiopathogenesis of AITD. However, functional studies to identify the underlying molecular mechanisms of this association are needed to translate these findings to clinical applications.     

Lymphocytic Thyroiditis is Associated with Increased Number of Benign Cervical Nodes and Fewer Central Neck Compartment Metastatic Lymph Nodes in Patients with Differentiated Thyroid Cancer

Objective: Whether or not autoimmune thyroid disease influences the progression of differentiated thyroid cancer (DTC) remains controversial. Findings of previous studies are influenced by lead time bias and/or procedure bias selection. These biases can be reduced by studying a single-institution patient population that underwent a similar extent of surgical resection.Methods: From a cohort of 660 patients with DTC who underwent thyroidectomy, we retrospectively studied 357 patients who underwent total thyroidectomy and central compartment node dissection (CCND) for DTC between 2003 and 2013.Results: Forty-one percent (140/345) of study patients had lymphocytic thyroiditis (LT), and 30% (91/301) had serum positive for thyroglobulin antibody (TgAb). LT was reported in 78% of the TgAb-positive cases. Sixty percent (213/357) of cases had metastatic thyroid carcinoma in 1 or more neck lymph nodes (55% [198/357] central compartment, and 22% [77/356] lateral compartment). Patients with LT had fewer metastatic cervical lymph nodes than those with no LT (2.7 ± 4.7 vs 3.5 ± 4.8, respectively, P = .0285). Patients with positive TgAb and thyroiditis had a larger number of benign cervical lymph nodes removed than those with negative TgAb or no LT. No significant difference was observed in age, tumor size, multifocality, extrathyroidal extension, vascular invasion, or frequency of cervical lymph node metastasis between TgAb-negative and -positive cases or between cases with and without LT.Conclusion: Lymphocytic thyroiditis is associated with fewer central neck compartment metastatic lymph nodes and a larger number of excised reactive benign cervical lymph nodes. Whether this association indicates a protective role of thyroid autoimmunity in lymph node spreading remains unclear.Abbreviations:CCND = central compartment node dissectionDTC = differentiated thyroid cancerHT = Hashimoto thyroiditisLT = lymphocytic thyroiditisTgAb = thyroglobulin antibodyTPO = thyroid peroxidase     

A Comparative Study of Real-Time and Static Ultrasonography Diagnoses for the Incidental Detection of Diffuse Thyroid Disease

Objective: The aim of this study was to compare the diagnostic accuracy of real-time and static ultrasonography (US) for the incidental detection of diffuse thyroid disease (DTD).Methods: In 118 consecutive patients, a single radiologist performed real-time US before thyroidectomy. For static US, the same radiologist retrospectively investigated the sonographic findings on a picture-archiving and communication system after 3 months. The diagnostic categories of both real-time and static US diagnoses were determined based on the number of abnormal findings, and the diagnostic indices were calculated by a receiver operating characteristic (ROC) curve analysis using the histopathologic results as the reference standard.Results: Histopathologic results included normal thyroid (n = 77), Hashimoto thyroiditis (n = 11), non-Hashimoto lymphocytic thyroiditis (n = 29), and diffuse hyperplasia (n = 1). Normal thyroid and DTD showed significant differences in echogenicity, echotexture, glandular margin, and vascularity on both real-time and static US. There was a positive correlation between US categories and histopathologic results in both real-time and static US. The highest diagnostic indices were obtained when the cutoff criteria of real-time and static US diagnoses were chosen as indeterminate and suspicious for DTD, respectively. The ROC curve analysis showed that real-time US was superior to static US in diagnostic accuracy.Conclusion: Both real-time and static US may be helpful for the detection of incidental DTD, but real-time US is superior to static US for detecting incidental DTD.Abbreviations: DTD = diffuse thyroid disease ROC = receiver operating characteristic US = ultrasonography     

Significant Attenuation of Stimulated Cortisol In Early Graves Disease Without Adrenal Autoimmunity

ObjectiveTo investigate cortisol responses to adreno corticotropic hormone during thyrotoxic (G1) and euthyroid (G2) phases in patients with Graves disease (GD) who were without adrenal autoimmunity.MethodsFifteen patients with GD, who were thyrotropin receptor antibody positive and 21-hydroxylase antibody negative, were recruited to this prospective pilot study. A modified short Synacthen test (SST) was per formed, in which cortisol was measured every 30 minutes for 2 hours during G1 and G2.ResultsThe median times to SST were 3 weeks (G1) and 27 weeks (G2) after diagnosis of GD. Integrated stimulated cortisol levels were significantly lower at G1 in comparison with G2: mean ± standard error of the mean for area under the curve was 78,091.6 ± 4,462.1 nmol/L (G1) versus 89,055 ± 4,434 nmol/L at 120 minutes (G2), P = .017; and for delta area under the curve was 36,309.9 ± 3,526 nmol/L (G1) versus 44,041.7 ± 2,147 nmol/L at 120 minutes (G2), P = .039. Mean cortisol levels were significantly lower for G1 versus G2 at 60, 90, and 120 minutes of the SST (P = .001 to .013). The cortisol level was abnormal in 2 patients (13%) at 30 minutes during G1 but in none during G2. There was no correlation of inte grated cortisol with free thyroxine or thyrotropin receptor antibody. There was no significant difference in median adrenocorticotropic hormone level (17 versus 20.4 ng/mL at G1 and G2, respectively; P = .14).ConclusionSignificant attenuation of stimulated cortisol occurs in the early thyrotoxic phase in comparison with the euthyroid phase in patients with GD without adrenal autoimmunity. Clinicians treating patients with GD should have a low threshold for investigating symptoms suggestive of hypoadrenalism at times of “stress.” (Endocr Pract. 2012;18:924-930)     

Biologic activity of anti-thyrotropin anti-idiotypic antibody

We raised an antihuman thyrotropin anti-idiotypic antibody and showed that it was active at the thyrotropin receptor. Thus this antibody inhibited ¹²⁵I b-TSH binding to thyroid plasma membranes, stimulated adenylate cyclase activity through a guanyl nucleotide-dependent mechanism, increased radioiodide entry rate into isolated porcine thyroid follicular cells, and induced such cultured cells to organize into follicles. All these parameters are typical of thyrotropin action. This work raises the possibility that thyroid stimulating antibodies that cause the hyperthyroidism of Graves disease may be, at least in some patients, anti-thyrotropin anti-idiotypic antibodies. It also offers a novel method whereby antireceptor antibodies used in the isolation and characterization of the receptor may be raised from ligands.     

American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: Postoperative Hypoparathyroidism - Definitions and Management

Abbreviations: BID = bis in die DSPTC = diffuse sclerosing papillary thyroid cancer FNA = fine-needle aspiration HT = Hashimoto thyroiditis iPTH = intact parathyroid hormone 25OHD = 25-hydroxy vitamin D PTH = parathyroid hormone TPO = thyroid peroxidase US = ultrasonography     

Identification of a correlation between Helicobacter pylori infection and Graves' disease

Background: viral and bacterial antigens have been suspected to be able to mimic the antigenic profile of the thyroid cell membrane and to play an important role in the onset of the autoimmune diseases, such as Graves’ disease and Hashimoto thyroiditis. The Helicobacter pylori infection is worldwide diffused and is present in the developed countries up to 50% of the population. The presence of the cytotoxin‐associated gene A antigens identifies the most virulent strains of the bacterium. Previous studies have demonstrated the possible correlation between the Helicobacter pylori and Hashimoto’s thyroiditis but these results are controversial. Aims: We studied the prevalence rate of this bacterium in the Graves’ disease and two selected subgroups such as the hyperthyroid patients, at the first time of diagnosis, and the euthyroid methimazole‐treated patients. Materials and Methods: We analyzed Helicobacter pylori in fresh stool samples with an enzyme immunoassay method and the presence of cytotoxin‐associated gene A antigens with a serological test. Results: Our results show that a significative increased rate of prevalence is present in Graves' patients, when the disease is ongoing, with an overall prevalence of the strains expressing the cytotoxin‐associated gene A antigens compared to the control group. Conclusions: The association between the Helicobacter pylori and Graves’ disease suggests a possible role of this bacterium in the onset and/or the maintenance of the disease.     

Hashimoto Thyroiditis not Associated with Vitamin D Deficiency

Objective: Vitamin D deficiency is associated with several autoimmune diseases. This study assessed whether vitamin D deficiency is associated with Hashimoto thyroiditis (HT).Methods: Two groups of patients were selected for which serum 25-hydroxyvitamin D (25(OH)D) levels had been measured: (1) a study group of patients diagnosed with HT as indicated by thyroid antibodies, and (2) a healthy control group. Each group was separated by sex and then controlled for age and body mass index (BMI). Groups' mean 25(OH)D levels were compared by analysis of variance (ANOVA), and percent frequencies of vitamin D sufficiency, insufficiency, and deficiency were compared with a Z-test. The correlations between 25(OH)D levels and thyroid antibodies and thyroid-stimulating hormone (TSH) levels were also tested.Results: The mean 25(OH)D levels for the HT and control groups were significantly different in females (30.75 vs. 27.56 ng/mL, respectively) but not in males (14.24 vs. 13.26 ng/mL). HT females had a higher rate of vitamin D sufficiency (51.7% vs. 31.1%) and a lower rate of insufficiency (48.3% vs. 68.9%) relative to control females. No such differences were found in the male groups. None of the females were vitamin D deficient, but almost all males were. A significant (P = .016) positive correlation (r_s = 0.436) between 25(OH)D and TPOAb was observed in males.Conclusion: HT is not associated with higher rates of vitamin D deficiency relative to a control group.Abbreviations:BMI = body mass indexHT = Hashimoto thyroiditis25(OH)D = 25-hydroxyvitamin DTgAb = thyroglobulin antibodyTSH = thyroid-stimulating hormoneTPOAb = thyroid-peroxidase antibodyVDR = Vitamin D receptor     

Use of Methotrexate to Treat Isolated Graves Ophthalmopathy Developing Years After Thyroidectomy and Iodine 131 Treatment of Papillary Thyroid Cancer

ObjectiveTo describe a case of Graves ophthalmopathy developing years after subtotal thyroidectomy and radioactive iodine treatment of papillary thyroid cancer.MethodsWe present a case report including clinical and laboratory data. Current relevant literature is reviewed and summarized with regard to Graves ophthalmopathy.ResultsIn 2001, a 51-year-old woman presented with an asymptomatic thyroid nodule. Fine-needle aspiration biopsy results showed Hürthle cells, and the patient had a subtotal thyroidectomy in 2002. Stage 2 follicular variant of papillary thyroid carcinoma was diagnosed. She received radioactive iodine (I 131) therapy (94.8 mCi and 147.2 mCi) in 2003. Thyrotropin was suppressed with levothyroxine. The patient remained asymptomatic and had undetectable thyroglobulin antibodies. In 2007, her eyes became irritated (ie, erythematous, pruritic, watery). Thyroperoxidase and thyroglobulin antibodies were undetectable, but thyrotropin receptor antibody was elevated to 44% (reference range, < 16%). On physical examination, moderate periorbital edema and conjunctival injection were present; orbital magnetic resonance imaging was normal. Computed tomography of her orbits showed symmetric bilateral exophthalmos and prominence of orbital fat. Other ophthalmologic etiologies were ruled out by 2 independent ophthalmologists. She had minimal improvement with oral and intravenous steroids. Subsequent treatment with methotrexate resulted in marked symptomatic improvement and lowered the thyrotropin receptor antibody level to 24%.ConclusionsIsolated Graves ophthalmopathy in a patient after treatment of thyroid cancer and radioactive iodine ablation has not been previously reported. Methotrexate therapy may be a useful therapeutic approach in this setting. (Endocr Pract. 2008;14:422-425)     

Disease Presentation and Remission Rate in Graves Disease Treated With Antithyroid Drugs: is Gender Really A Factor?

Objective: Male gender is considered an adverse prognostic factor for remission of Graves disease treatment with antithyroid drugs (ATDs), although published data are conflicting. This often results in early consideration of radioiodine treatment and surgery for men. Our objective was to compare disease presentation and outcome in men versus women treated with ATDs.Methods: Retrospective study of 235 patients (64 men, 171 women) with Graves disease who were evaluated for features at presentation and outcome at the end of follow-up between 2010 and 2015.Results: Disease presentation was similar in men and women for age at diagnosis (41.4 ± 14 years vs. 40 ± 15 years), duration of follow-up (6.6 ± 7 years vs. 7.7 ± 6 years), rates of comorbid autoimmune diseases, and rate of Graves ophthalmopathy. Smoking was more prevalent in males (31% vs. 15%; P = .009). Free thyroxine and triiodothyronine levels were comparable. ATDs were first-line treatment in all males and in 168 of 171 females, for a median duration of 24 and 20 months, respectively (P = .55). Remission rates were 47% in men and 58% in women (P = .14). Males had fewer adverse events (9% vs. 18%) and treatment discontinuation (5% vs. 16%). Disease recurrence was comparable (14% vs. 20%; P = .32), as was requirement for second-line treatment, either radioiodine therapy or thyroidectomy.Conclusion: Graves disease presentation is similar in men and women. Men treated with ATDs have high remission rates and similar recurrence rates compared to women, with fewer adverse events and less discontinuation of treatment. ATDs are an attractive first-line treatment for both genders.Abbreviations: ATA = American Thyroid Association; ATD = antithyroid drug; GO = Graves ophthalmopathy; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone