Hyperthyroid Graves Research Articles

The Effect of Anti Thyroid Medications on the Therapeutic outcome of I-131 in Hyperthyroid Patients with Graves ' disease

Objective: to detect the effect of antithyroid drugs (ATD) on the therapeutic outcome of I-131 in hyperthyroid Graves' patients. Methods: Retrospective study was done on 200 patients with Graves' disease treated with fixed dose of radioactive iodine (RAI) (12mCi). The patients were classified into three groups: Group I (n = 70) were treated by ATDs for more than 6 months and stopped it 5 days; group II (n = 70) were treated by ATDs for more than 6 months but stopped it only for two days or less, and group III (n = 60) had never been treated with ATD before RAI treatment (control group). Results: There was a statistical significant difference in the cure rate between group I and group II (P < 0.001), group II and group III (P < 0.001), but no significant difference between group I and group III (P = 0.453) three months after RAI therapy. There was a statistical significant difference in the cure rate observed between group I and the group II (P =0.002), group II and group III (P < 0.001), but no significant difference between group I and group III (P =0.060) 6 months after RAI therapy. There was a statistical significant difference between the three groups 3 (P < 0.001), and 6 months (P < 0.001), after RAI therapy.Conclusion: Administration of ATDs more than 6 month without discontinuation decreased response of RAI treatment in 3 and 6 months' follow-up. Discontinuation of ATDs for 5 days before RAI treatment is recommended.

A study of serum IgG4 levels in the clinical metamorphosis of autoimmune thyroid disease

BackgroundMeasurement of serum IgG4 had been suggested to distinguish the unique subtypes of autoimmune thyroid disease (AITD) which demonstrated patterns of fluctuating between hyperthyroidism and hypothyroidism. However, the clinical utility of serum IgG4 measurement is inconclusive due to few studies having addressed these unusual patients compared with the specificity of serum IgG4 in healthy patients. AimTo investigate whether elevated serum IgG4 levels could be used as a marker to identify fluctuating AITD patients. Materials and Methods20 AITD patients who evolved from hyperthyroid Graves’ disease to spontaneous hypothyroidism or vice versa were compared with 40 healthy subjects, 40 patients with hyperthyroid Graves’ disease (GD) and 40 patients with subclinical or overt hypothyroid Hashimoto’s thyroiditis (HT). Serum levels of total IgG and IgG4 were measured and the proportion of elevated serum IgG4 levels (defined by serum IgG4 levels≥135mg/dL) was compared with control patients. ResultsA series of 20 Thai patients with clinical evolution of AITD was analyzed with a median follow-up at 92months (range 3–380months). Elevated serum IgG4 levels were not found in fluctuating AITD patients but were found in 5% of the control GD patients, 2.5% of the control HT, and 2.5% of healthy subjects which were not statistically significant between each group. ConclusionOur results contrasted with those of previous studies from Japan which reported elevated serum IgG4 as a marker to identify subset of AITD patients. At present, the clinical utility of serum IgG4 measurements in AITD is inconclusive and requires further investigation.

Observation of the curative effect of Jianpi pill in the treatment of leucocytopenia induced by anti-thyroid drug

Objective To evaluate the clinical efficacy of Jianpi pill in the treatment of leucocytopenia induced by anti-thyroid drug. Methods According to the digital table, 195 Graves hyperthyroidism patients with leucocytopenia induced by anti-thyroid drug were randomly divided into the observation group(100 cases) and the control group(95 cases). The observation group was given Jianpi pill treatment, while the control group adopted the combination therapy of batilol tablets, leucogen tablets, vitamin B4 tablets.The facial color, whether or not limb weakness, whether or not palpitations after strenuous exercise in the two groups were observed.The number of white blood cells and the number of neutrophils in the two groups were observed.3 months later, the curative effect of the two groups was determined according to the degree of cure. Results The total effective rates of the control group and the observation group were 52.63% and 85.00% respectively, the difference was statistically significant between the two groups(χ2=23.96, P 0.05). The incidence rates of dry mouth, hyperactive bowel sounds and liver damage, constipation and diarrhea in the control group were 4.21%, 2.10% and 1.05% respectively, and the incidence rates of dry mouth, hyperactive bowel sounds and liver damage in the observation group were 3.00% and 1.00% respectively, there was no significant difference in adverse reactions between the two groups(P>0.05). Conclusion The curative effect of Jianpi pill in the treatment of Graves hyperthyroidism patients with leucocytopenia induced by anti-thyroid drug is sure, and it is superior to the combination therapy of batilol tablets, leucogen tablets, vitamin B4 tablets. Key words: Jianpi pill; Hyperthyroidism; Leucocytopenia

The “GREAT” Score Predicts the Outcome of Antithyroid Drug Therapy of Graves’ Disease

Clinical ThyroidologyVol. 29, No. 3 SummariesThe “GREAT” Score Predicts the Outcome of Antithyroid Drug Therapy of Graves’ DiseaseJacques OrgiazziJacques OrgiazziSearch for more papers by this authorPublished Online:1 Mar 2017https://doi.org/10.1089/ct.2017;29.110-113AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited byWhich Factors Predict the Outcome of Ablative Radioactive Iodine Treatment of Hyperthyroid Graves' Disease? Jacques Orgiazzi14 November 2018 | Clinical Thyroidology, Vol. 30, No. 11 Volume 29Issue 3Mar 2017 InformationCopyright 2017 American Thyroid Association, Inc.To cite this article:Jacques Orgiazzi.The “GREAT” Score Predicts the Outcome of Antithyroid Drug Therapy of Graves’ Disease.Clinical Thyroidology.Mar 2017.110-113.http://doi.org/10.1089/ct.2017;29.110-113Published in Volume: 29 Issue 3: March 1, 2017PDF download

Cerebral Venous Thrombosis Associated With Graves Hyperthyroidism

ABSTRACT Objective: We report a case of cerebral venous thrombosis (CVT) associated with Graves hyperthyroidism in order to increase awareness of this association in the literature. CVT entails significant morbidity and mortality, and awareness of its risk factors may assist both with expediting its diagnosis and completing an appropriate workup. Methods: A 62-year-old female with a 3-week history of symptoms of hyperthyroidism secondary to Graves disease, and a 2-week history of treatment with methimazole, presented with sudden onset of severe headache, right-sided weakness, and generalized seizure. Results: A computed tomography scan of her head identified extensive CVT, located within the superior sagittal sinus and extending into the right transverse sinus. She remained biochemically hyperthyroid at the time of her presentation (thyroid-stimulating hormone = 0.10 mIU/L; free thyroxine = 32.8 pmol/L; free triiodothyronine = 10.0 pmol/L). A thrombotic workup revealed normal antithrombin, protein C, and ...

Pregnancy and Autoimmune Thyroid Disease: Alternating Between Hypothyroidism and Hyperthyroidism And The Role of Thyrotropin-Receptor Antibodies

ABSTRACT Objective: To report the case of a female patient with hypothyroidism who spontaneously developed Graves hyperthyroidism during pregnancy and then reverted back to hypothyroidism in a subsequent pregnancy. Methods: The pertinent clinical features, laboratory data, and clinical course of the case are reported, along with a brief literature review. Results: A 30-year-old female with hypothyroidism diagnosed at age 20 years unexpectedly required decreased levothyroxine dosing during her second pregnancy. She was taking levothyroxine 12.5 μg daily when she became pregnant a third time. In the first trimester, levothyroxine was discontinued, and she presented in the third trimester with clinical and biochemical hyperthyroidism and a diffusely enlarged goiter. Propylthiouracil (PTU) was initiated. Thyroid-stimulating hormone–receptor antibodies (TRAbs) were positive. After delivery, her baby developed transient neonatal Graves disease. She was continued on a stable dose of PTU for 10 months postpartum ...

Can we predict relapse in Graves' disease? Results from a systematic review and meta-analysis.

Identification of pretreatment risk factors predicting relapse in patients with hyperthyroidism of Graves' disease after stopping anti-thyroid drugs (ATD) is decisive to guide therapeutic options. We performed a systematic search and meta-analysis to study predictors for relapse after stopping ATD in patients with Graves' disease. Based on a pre-specified protocol, we searched PubMed, EMBASE and Cochrane in July 2015 for case-control, controlled and randomized-controlled trials reporting risk factors for relapse after stopping ATD. The primary endpoint was relapse of disease until follow-up. PRISMA and SIGN statements were used for reviewing the data and assessing the quality of included trials. We included 54 trials with a total of 7595 participants. Most trials were small with moderate-to-high risk for bias. Ten trials were assessed only qualitatively (2227 patients), genomic data were reported in 13 trials (2178 patients) and 31 trials (4346 patients) were assessed quantitatively. In total, there were 3696 relapses in 7595 patients (48.7%). By using random-effects meta-analysis, orbitopathy, smoking, thyroid volume measured by sonography, goiter size, fT4, tT3, TRAb and TBII were significantly associated with relapse, whereas male vs female sex, age and initial tT4 level did not show significant associations. This analysis found several risk factors to predict relapse in Graves' disease, which can be combined in a risk score. Prospective studies should evaluate the prognostic accuracy of such a score to guide treatment decisions.

Update in graves’ orbitopathy

SummaryThyroid eye disease or Graves’ orbitopathy (GO) is an autoimmune condition most common in people with hyperthyroid Graves’ disease (GD). GD is caused by thyroid stimulating antibodies which bind the thyrotropin receptor (TSHR). The TSHR is probably also implicated in GO since it is expressed in orbital fat, particularly during adipogenesis. GO is the result of tissue remodelling, mainly overproduction of extra‐cellular matrix and excess adipogenesis, which together produce proptosis. In vitro models have increased understanding of the signalling cascades regulating these processes and identified possible novel treatments. However progress in identifying the triggers of the autoimmune response is lacking but a possible role for the microbiome has been proposed. Hopefully recent developments, including a TSHR induced model of GO in mice, will help to address these issues.

The Natural History of Subclinical Hyperthyroidism in Graves' Disease: The Rule of Thirds.

There is little information regarding the natural history of subclinical hyperthyroidism (SH) due to Graves' disease (GD). A prospective analysis was conducted of patients with SH due to GD between 2007 and 2013 with at least 12 months of follow-up. SH was diagnosed if serum thyrotropin (TSH) was below the laboratory reference range (0.4-4.0 mIU/L) and when thyroid hormones were normal. GD was confirmed by either a raised TSH receptor antibody (TRAb) level or uniform uptake on Technetium scan. Forty-four patients (89% female, 16% current smokers, and 5% with active Graves' orbitopathy) were diagnosed with SH due to GD. Over the follow-up period (median 32 months), approximately one third (34%) of the cohort progressed to overt hyperthyroidism, one third (34%) normalized their thyroid function, slightly less than one third (30%) remained in the SH state, while one person became hypothyroid. Multivariate regression analysis showed that older age and positive antithyroid peroxidase (TPO) antibody status had a positive association with risk of progression to overt hyperthyroidism, with hazard ratios of 1.06 ([confidence interval (CI) 1.02-1.10], p < 0.01) per year and 10.15 ([CI 1.83-56.23], p < 0.01), respectively, independent of other risk factors including, smoking, TRAb levels at diagnosis, and sex. A third each of patients with SH due to GD progress, normalize, or remain in the SH state. Older people and those with positive anti-TPO antibodies have a higher risk of progression of the disease. These novel data need to be verified and confirmed in larger cohorts and over longer periods of follow-up.

Risk Factors for Graves' Orbitopathy; the Australian Thyroid-Associated Orbitopathy Research (ATOR) Study.

Previous association studies suggest the development of Graves' orbitopathy (GO) is variably influenced by environmental risk factors. To determine the risk factors and predict odds for developing GO in Graves' hyperthyroidism (GH). Case-control study. Multi-centre Australian Thyroid-associated Orbitopathy Research group consisting of tertiary endocrinology and ophthalmology outpatients and related private practices. A total of 1042 participants with GH were designated as cases if they had GO (n = 604) and controls if they did not have GO (n = 438). Primary outcome was GO risk factors and secondary outcome was dysthyroid optic neuropathy (DON) with the effects of risk factors measured by odds ratio (OR) using multiple logistic regression, adjusted for known risk factors and exploratory variables. The odds of GO increased by 17% for each decade increase in the age of onset of GH (OR 1.17, confidence interval (CI): 1.06-1.29; P = .002) and by 7% for each year increase in the duration of GH (OR 1.07, CI: 1.05-1.10; P < .001). Smoking increased the odds for GO by 2.22 for current smoker and 2.07 for exsmoker (P < .001), compared with never smoking. The odds of GO are 86% less in Graves' patients using antithyroid medication than those not (OR 0.14, CI: 0.06-0.34; P < .001). Predictors for DON were older age, oculomotility restriction, strabismus, reduced palpebral aperture, and active GO. This study identified increase age of onset, duration of GH, and smoking as risk factors for GO. Usage of antithyroid medication was negatively related to GO. Older patients with restricted ocular motility, strabismus, and active GO are at higher risk of DON and may benefit from early medical intervention.

Anti-eye Muscle IgG and IgM Antibodies are Associated with Eye Muscle Type 2 Deiodinase Activities in Hyperthyroid Graves Ophthalmopathy

Objective: Antibodies to eye muscle tissue are demonstrated in hyperthyroid Graves’ disease but their pathognomonic roles have not been clarified yet. We suggest that type 2 deiodinase (DIO2) enzyme can be a target between orbital and thyroid diseases in hyperthyroid Graves’ ophthalmopathy. In this study, the relationship between anti-eye muscle membrane (EyeM) and cytosol (EyeC) IgG, IgA and IgM antibodies and eye muscle DIO2 activity was investigated in hyperthyroid Graves’ disease. Methods: Thirty-two patients with hyperthyroid Graves’ disease (20 had ophthalmopathy), mean age 36 ± 13 years, 27 females and 5 males formed the patient group. Thyroid hormone levels were measured with chemiluminescence immunoassay, antithyroid antibody and anti-eye muscle antibody levels with enzyme-linked immunosorbent assay, but TSH receptor antibodies with radioimmunoassay. Eye muscle DIO2 activity was measured using 125I-T4. Results: EyeM and EyeC IgG antibodies were associated with increased eye muscle DIO2 activity compared to those who were negative for these antibodies (2.79 ± 2.53 vs 17.88 ± 20.06 pmol/mg/min, P<0.015 for EyeM-IgG and 6.88 ± 9.62 vs 26.76 ± 23.86 pmol/mg/min, P<0.008 for EyeC-IgG). The difference in EyeC-IgM antibodies was significant between patients with and without ophthalmopathy (10.1 ± 4.73 vs 3.46 ± 3.18 pmol/mg/min, P<0.023). The presence of EyeM-IgM antibodies was associated with lower eye muscle DIO2 activities with significantly decreased eye muscle thicknesses (8.51 ± 15.38 vs 2.6 ± 0.1 pmol/mg/min and 4.71 ± 1.23 vs 3.9 ± 0.14 mm, P<0.04). Conclusion: Anti-eye muscle antibodies were associated with increased or decreased eye muscle DIO2 activities affecting eye muscle thicknesses in hyperthyroid Graves’ ophthalmopathy. DIO2 enzyme can be a new target between orbital and thyroid diseases in hyperthyroid Graves’ ophthalmopathy.

A 33-Year-Old Man with Gynaecomastia and Galactorrhea as the First Symptoms of Graves Hyperthyroidism

Graves' hyperthyroidism has a various number of well-recognized manifestations. Galactorrhea is a rare manifestation in this disease. We describe a 33-year-old man who presented with the symptoms of hyperthyroidism, gynaecomastia, and galactorrhea for 2 months. Physical examination revealed goitre, gynaecomastia, and galactorrhea, bilaterally. Laboratory investigations demonstrated high free thyroxine with suppressed thyroid-stimulating hormone level together with elevated anti-TSH receptor; therefore, the diagnosis of Graves' disease was confirmed. Other investigations to elucidate the etiology of galactorrhea were normal, so the galactorrhea was hypothesized to be caused by Graves' disease. The gynaecomastia and galactorrhea resolved with the successful treatment of hyperthyroidism. Although the galactorrhea is extremely rare in thyrotoxicosis male patients, to the best of our knowledge, this is the third case which reported gynaecomastia and galactorrhea in male patient who presented with thyrotoxicosis.

The characteristics of osteoporotic patients in Graves' disease patients newly diagnosed after menopause: a prospective observational study.

Overt hyperthyroidism is associated with reduced bone density. The extent of restoration of reduced bone density caused by hyperthyroidism in postmenopausal Graves' disease (GD) patients has not fully been investigated. We examined 85 newly diagnosed postmenopausal GD patients, and we measured their serum thyroid hormone levels as well as their bone turnover marker levels and the bone mineral density (BMD) of their lumbar spine (LS), both femoral necks (FN), and left distal radius (DR). We prospectively observed the patients for changes in BMD and bone turnover marker levels during a 24-month period after euthyroidism had been established by ATD treatment. The median age of the subjects was 57 years old (range: 50 to 79). 46 (54.1%) patients had osteoporosis. 42 of the 46 osteoporosis patients had low BMD in the DR. The patients with osteoporosis were significantly older, had a significantly lower BMI, and had significantly higher bone turnover marker levels compared to the normal BMD patients. The best predictor of the BMD in the DR was BMD in the FN (β = 0.40, p < 0.0001). A total of 42 patients were followed up for 24 months after attainment of euthyroidism, and 19 of them were osteoporosis at the first visit. The BMD of the 19 osteoporotic patients had increased by 4.9% in the LS, 11.9% in the FN, and 9.3% in the DR at 24 months. After maintaining a euthyroid state for 24 months by means of ATD treatment, 26% of the osteoporotic patients had recovered from osteoporosis.

Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease.

BackgroundHyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse.MethodsThis retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal.ResultsTwenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%.ConclusionTSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

Clinical Relevance of Environmental Factors in the Pathogenesis of Autoimmune Thyroid Disease.

Genetic factors contribute for about 70% to 80% and environmental factors for about 20% to 30% to the pathogenesis of autoimmune thyroid disease (AITD). Relatives of AITD patients carry a risk to contract AITD themselves. The 5-year risk can be quantified by the so-called Thyroid Events Amsterdam-score, based on serum thyroid-stimulating hormone, thyroid peroxidase (TPO)-antibodies and family history. Subjects at risk may ask what they can do to prevent development of AITD. This review summarizes what is known about modulation of exposure to environmental factors in terms of AITD prevention. To stop smoking decreases the risk on Graves disease but increases the risk on Hashimoto disease. Moderate alcohol intake provides some protection against both Graves and Hashimoto disease. Low selenium intake is associated with a higher prevalence of thyroid autoimmunity, but evidence that selenium supplementation may lower TPO antibodies and prevent subclinical hypothyroidism remains inconclusive. Low serum vitamin D levels are associated with a higher prevalence of TPO antibodies, but intervention studies with extra vitamin D have not been done yet. Stress may provoke Graves hyperthyroidism but not Hashimoto thyroiditis. Estrogen use have been linked to a lower prevalence of Graves disease. The postpartum period is associated with an increased risk of AITD. Taking together, preventive interventions to diminish the risk of AITD are few, not always feasible, and probably of limited efficacy.

Thyroid surgery for Graves' disease and Graves' ophthalmopathy.

Graves' disease is an autoimmune disease caused by the production of auto-antibodies against the thyroid-stimulating hormone receptor, which stimulates follicular cell production of thyroid hormone. It is the commonest cause of hyperthyroidism and may cause considerable morbidity with increased risk of cardiovascular and respiratory adverse events. Five per cent of people with Graves' disease develop moderate to severe Graves' ophthalmopathy. Thyroid surgery for Graves' disease commonly falls into one of three categories: 1) total thyroidectomy, which aims to achieve complete macroscopic removal of thyroid tissue; 2) bilateral subtotal thyroidectomy, in which bilateral thyroid remnants are left; and 3) unilateral total and contralateral subtotal thyroidectomy, or the Dunhill procedure. Recent American Thyroid Association guidelines on treatment of Graves' hyperthyroidism emphasised the role of surgery as one of the first-line treatments. Total thyroidectomy removes target tissue for the thyroid-stimulating hormone receptor antibody. It controls hyperthyroidism at the cost of lifelong thyroxine replacement. Subtotal thyroidectomy leaves a thyroid remnant and may be less likely to lead to complications, however a higher rate of recurrent hyperthyroidism is expected and revision surgery would be challenging. The choice of the thyroidectomy technique is currently largely a matter of surgeon preference, and a systematic review of the evidence base is required to determine which option offers the best outcomes for patients. To assess the optimal surgical technique for Graves' disease and Graves' ophthalmopathy. We searched the Cochrane Library, MEDLINE and PubMed, EMBASE, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The date of the last search was June 2015 for all databases. We did not apply any language restrictions. Only randomised controlled trials (RCTs) involving participants with a diagnosis of Graves' disease based on clinical features and biochemical findings of hyperthyroidism were eligible for inclusion. Trials had to directly compare at least two surgical techniques of thyroidectomy. There was no age limit to study inclusion. Two review authors independently extracted and cross-checked the data for analysis, evaluation of risk of bias and establishment of 'Summary of findings' tables using the GRADE instrument. The senior review authors reviewed the data and reconciled disagreements. We included five RCTs with a total of 886 participants; 172 were randomised to total thyroidectomy, 383 were randomised to bilateral subtotal thyroidectomy, 309 were randomised to the Dunhill procedure and 22 were randomised to either bilateral subtotal thyroidectomy or the Dunhill procedure. Follow-up ranged between six months and six years. One trial had three comparison arms. All five trials were conducted in university hospitals or tertiary referral centres for thyroid disease. All thyroidectomies were performed by experienced surgeons. The overall quality of the evidence ranged from low to moderate. In all trials, blinding procedures were insufficiently described. Outcome assessment for objective outcomes was blinded in one trial. Surgeons were not blinded in any of the trials. One trial blinded participants. Attrition bias was a substantial problem in one trial, with 35% losses to follow-up. In one trial the analysis was not carried out on an intention-to-treat basis.Total thyroidectomy was more effective than subtotal thyroidectomy techniques (both bilateral subtotal thyroidectomy and the Dunhill procedure) at preventing recurrent hyperthyroidism in 0/150 versus 11/200 participants (OR 0.14 (95% CI 0.04 to 0.46); P = 0.001; 2 trials; moderate quality evidence). Total thyroidectomy was also more effective than bilateral subtotal thyroidectomy at preventing recurrent hyperthyroidism in 0/150 versus 10/150 participants (odds ratio (OR) 0.13 (95% confidence interval (CI) 0.04 to 0.44); P = 0.001; 2 trials; moderate quality evidence). Compared to bilateral subtotal thyroidectomy, the Dunhill procedure was more likely to prevent recurrent hyperthyroidism in 20/283 versus 8/309 participants (OR 2.73 (95% CI 1.28 to 5.85); P = 0.01; 3 trials; low quality evidence). Total thyroidectomy compared with subtotal thyroidectomy conferred a greater risk of permanent hypocalcaemia/hypoparathyroidism in 8/172 versus 3/221 participants (OR 4.79 (95% CI 1.36 to 16.83); P = 0.01; 3 trials; low quality evidence). Effects of the various surgical techniques on permanent recurrent laryngeal nerve palsy and regression of Graves' ophthalmopathy were neutral. One death was reported in one study in year three of follow-up. No study investigated health-related quality of life or socioeconomic effects. Total thyroidectomy is more effective than subtotal thyroidectomy (both bilateral subtotal thyroidectomy and the Dunhill procedure) at preventing recurrent hyperthyroidism in Graves' disease. The type of surgery performed does not affect regression of Graves' ophthalmopathy. There was some evidence that total thyroidectomy compared with subtotal thyroidectomy conferred a greater risk of permanent hypocalcaemia/hypoparathyroidism, which however, was not seen in comparison with bilateral subtotal thyroidectomy. Permanent recurrent laryngeal nerve palsy did not seem to be affected by type of thyroidectomy. Health-related quality of life as a patient-important outcome measure should form a core determinant of any future trial on the effects of thyroid surgery for Graves' disease.

Novel single-nucleotide polymorphisms in the calsequestrin-1 gene are associated with Graves' ophthalmopathy and Hashimoto's thyroiditis.

BackgroundThe eye disorder associated with Graves’ disease, called Graves’ ophthalmopathy (GO), greatly reduces the quality of life in affected patients. Expression of the calsequestrin (CASQ1) protein in thyroid tissue may be the trigger for the development of eye muscle damage in patients with GO. We determined the prevalence of rs74123279, rs3747673, and rs2275703 single-nucleotide polymorphism (SNPs) in patients with autoimmune thyroid disorders, GO, Graves’ hyperthyroidism (GH), or Hashimoto’s thyroiditis (HT) and control subjects with no personal or family history of autoimmune thyroid disorders. Furthermore, we measured the concentration of the CASQ1 protein in normal and Graves’ thyroid tissue, correlating levels with parameters of the eye signs, CASQ1 antibody levels, and the CASQ1 gene polymorphism rs74123279 and rs2275703.MethodsHigh-quality genomic DNA was isolated from fresh blood samples, assayed for identification of rs74123279, rs3747673, and rs2275703 SNPs in CASQ1 gene by MassARRAY SNP analysis using iPLEX technology of SEQUENOM.ResultsDNA samples from 300 patients and 106 control subjects (100 males, 306 females) with GO (n=74), GH (n=130), HT (n=96) and control subjects (n=106) were genotyped for the SNPs rs74123279, rs3747673 (n=405), and rs2275703 (n=407). The SNP rs74123279, rs3747673, and rs2275703 were identified as 1) common homozygous or wild type, 2) heterozygote, and 3) rare homozygous. Minor allele frequency for rs74123279, rs3747763, and rs2275703 were 21%, 40%, and 44%, respectively. Multiple comparisons of genotype frequency for rs74123279, rs3747763, and rs2275703 in the GO, GH, HT, and control groups showed P=0.06, 0.641, and 0.189, respectively. These results were substantiated by multiple comparison of alleles frequency for rs74123279, rs3838216, rs3747763, and rs2275703 in the GO, GH, HT, and control groups showed, P=0.36, 0.008, 0.66, and 0.05, respectively. Pairwise analysis of alleles frequency distribution in patients with GO showed significant probability for rs2275703, P=0.008.ConclusionBased on their evolutionary conservation and their significant prevalence, we suggest that CASQ1 gene SNPs rs74123279, rs3838216, and rs2275703 may be considered as genetic markers for GO.

Mechanisms of Action of TSHR Autoantibodies

The availability of human monoclonal antibodies (MAbs) to the TSHR has enabled major advances in our understanding of how TSHR autoantibodies interact with the receptor. These advances include determination of the crystal structures of the TSHR LRD in complex with a stimulating autoantibody (M22) and with a blocking type autoantibody (K1-70). The high affinity of MAbs for the TSHR makes them particularly suitable for use as ligands in assays for patient serum TSHR autoantibodies. Also, M22 and K1-70 are effective at low concentrations in vivo as TSHR agonists and antagonists respectively. K1-70 has important potential in the treatment of the hyperthyroidism of Graves' disease and Graves' ophthalmopathy. Small molecule TSHR antagonists described to date do not appear to have the potency and/or specificity shown by K1-70. New models of the TSHR ECD in complex with various ligands have been built. These models suggest that initial binding of TSH to the TSHR causes a conformational change in the hormone. This opens a positively charged pocket in receptor-bound TSH which attracts the negatively charged sulphated tyrosine 385 on the hinge region of the receptor. The ensuing movement of the receptor's hinge region may then cause activation. Similar activation mechanisms seem to take place in the case of FSH and the FSHR and LH and the LHR. However, stimulating TSHR autoantibodies do not appear to activate the TSHR in the same way as TSH.

Insulin resistance and low folate levels are associated with hyperthyroidism in Graves' disease

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Smoking associated with TSH receptor antibody and serum IL17A elevation in hyperthyroid Graves' disease

Smoking associated with TSH receptor antibody and serum IL17A elevation in hyperthyroid Graves' disease