anti-TSH Receptor Antibodies Research Articles

Characteristics of patients with Graves’ disease who developed drug resistance and required surgery

Although antithyroid drugs (ATDs) are the first-line treatment for patients with Graves' disease (GD) in Japan and other countries, some patients do not achieve remission due to drug resistance, leading to surgery. Even if ATD doses are increased, they often have uncontrolled thyroid function and enlarged goiters, necessitating high-risk emergency surgical treatment. In this study, we aimed to identify the characteristics of patients resistant to ATDs who underwent thyroidectomy and those who achieved remission. We retrospectively analyzed 45 patients with GD who underwent thyroidectomy and 73 patients who achieved remission with ATDs at Shinshu University Hospital between April 1, 2015 and September 30, 2023. In patients who underwent surgery, the drug-resistant patients (DR group; n = 15) had longer disease durations (8.0 vs. 3.0 years, respectively; p = 0.013), higher free triiodothyronine (FT3) / free thyroxine (FT4) ratios (5.54 vs. 3.52, respectively; p = 0.005), higher anti-TSH receptor antibody (TRAb) levels (39.16 vs. 13.31 IU/L, respectively; p = 0.002), and larger thyroid glands (251.00 vs. 54.80 g, respectively; p < 0.001) than non-drug-resistant patients (NDR group; n = 30). Compared with patients who achieved remission with ATDs (Remission group; n = 73), the DR group had higher FT3/FT4 ratios (5.54 vs. 2.99, respectively; p < 0.001) and higher TRAb levels (39.16 vs. 5.9 IU/L, respectively; p < 0.001). Notably, most of the patients in the DR group had a combination of these factors. This suggests that in patients with large thyroid, high FT3/FT4 ratios, and high TRAb levels, early consideration of definitive-curative treatment such as surgery or RI therapy may be warranted instead of continuing prolonged ineffective ATDs treatment.

Assessing a Novel Thyroid-Stimulating Antibody Bioassay as a Predictor of Radioactive Iodine Therapy Efficacy in Graves' Disease.

No studies have reported the use of the Biosensor TSAb assay (TSAb (Bio)) for predicting the therapeutic efficacy of radioactive iodine therapy (RAIT) for Graves' disease (GD). Therefore, we evaluated the usefulness of this novel thyroid-stimulating antibody (TSAb) bioassay kit, which uses a cyclic adenosine monophosphate (cAMP) biosensor, in predicting the therapeutic efficacy of RAIT in 20 patients with GD. We defined the RAIT outcome using two criteria: (i) thyroid weight reduction to <8 g and (ii) thyroid weight reductionto >80% at 12 months post-RAIT. For criteria (i) and (ii), regression analysis was performed for thyroid-stimulating hormone (TSH) receptor autoantibody (TRAb), TSAb (Bio), TSAb (Bio)/TRAb, I-131 absorbed dose/TSAb (Bio), and I-131 absorbed dose/(TSAb (Bio)/TRAb). After evaluating the significance of each factor, receiver operating characteristic (ROC) analysis was also performed. Among the five aforementioned anti-TSH receptor antibody parameters, only I-131 absorbed dose/(TSAb (Bio)/TRAb) showed statistical significance in the multivariate analysis (p = 0.004 and p = 0.021 for each criterion). Although I-131 absorbed dose/(TSAb (Bio)/TRAb) correlated significantly with the thyroid weight (r = -0.54, p = 0.015), it did not correlate with thyroid weight reduction rates at 12 months post-RAIT. ROC analysis also demonstrated a good predictive value (area under the curve of approximately 0.8 with a cut-off value of 3.9) for I-131 absorbed dose/(TSAb (Bio)/TRAb) in predicting thyroid weight at 12 months post-RAIT. TSAb (Bio) is a useful predictor of RAIT efficacy when evaluated as I-131 absorbed dose/(TSAb (Bio)/TRAb). This index was defined by dividing a factor that positively affects RAIT outcomes (I-131 absorbed dose) by a factor negatively affecting it (i.e., (TSAb (Bio)/TRAb)). The therapeutic efficacy of RAIT can be expected with an I-131 absorbed dose/(TSAb (Bio)/TRAb) value of ≥3.9. Adjusting the I-131 dosage based on this index may lead to more effective treatment outcomes.

Thyroid orbitopathy associated with primary hypothyroidism and anti-TSH receptor antibodies; clues from a functional TSH receptor bioassay

Thyroid orbitopathy associated with primary hypothyroidism and anti-TSH receptor antibodies; clues from a functional TSH receptor bioassay

Hyperthyroïdie : diagnostic et suivi

AbstractHyperthyroidism is defined by thyroid hormones hyperproduction leading to clinical signs of thyrotoxicosis. It mainly results from thyroid primary hyperfunction due to either hyperstimulation by activating anti-TSH receptor antibodies (TRAK) in Graves’ disease, or to hyperfunction of one or more lesions of the thyroid parenchyma in nodular pathology. Positive diagnosis relies on clinical examination, scintigraphy, and biology. Biological investigations are based on a decreased serum TSH. A TSH between 0.1 -0.4 mIU/L will be checked at six weeks. To any TSH below 0.1 mIU/L or any TSH confirmed between 0.1 - 0.4 mIU/L, the addition of fT4 assay allows the distinction between proven hyperthyroidism (fT4 increased), and sub-clinical hyperthyroidism (normal fT4) a situation in which fT3 assay can be helpful to establish T3 hyperthyroidism The etiological diagnosis is essentially based on the TRAK measurement, whose positivity establishes Graves’ disease diagnosis, palpation and thyroid scintigraphy. Hyperthyroidism can be treated medically starting with synthetic antithyroid drugs (ATS), then with iratherapy or surgery, depending on the etiology. ATS efficiency will be biologically assessed following fT4 every 3-6 weeks, then monitoring TSH every 2-4 months after fT4 normalization. Treatment with ATS requires a specific biological follow up (hCG, WBC, ASAT, ALAT) to detect any complication.

Evaluation of Anti-Thyroperoxidase (A-TPO) and Anti-Thyroglobulin (A-Tg) Antibodies in Women with Previous Hashimoto's Thyroiditis during and after Pregnancy.

Background/Objective: Autoimmune thyroid diseases (AITD) affect 2 to 5% of the general population. This study aimed to determine changes in activity of A-Tg and A-TPO antibodies before, during, and after pregnancy in women with previous AITD. Methods: This was a single-center study with a retrospective review of the medical records of 30 female patients aged 25-41 years who came to our endocrinology service in the city of Santo André, state of São Paulo, Brazil, to investigate thyroid diseases. The following data were reviewed: total triiodothyronine (totalT3), total thyroxine (totalT4), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and anti-TSH receptor antibodies (anti-TSH receptor or anti-thyrotropin receptor antibodies (TRAb), anti-thyroid peroxidase (A-TPO), and anti-thyroglobulin (A-Tg)). These data were reviewed for 30 patients before and during the three trimesters of pregnancy and during the three months after pregnancy. Results: During gestation, we observed a progressive decrease in the blood values of A-TPO and A-Tg, which reached their lowest values in the third trimester of pregnancy, but after birth, they returned to values statistically equivalent to those before pregnancy. Analyzing the three trimesters and the post-pregnancy period, A-TPO increased 192% between the first trimester and postpartum (p = 0.009); it increased 627% between the second trimester and postpartum (p < 0.001); and it increased >1000% between the third trimester and postpartum (p < 0.001). There was no significant difference in the A-TPO values between the pre- and post-gestational periods (p = 1.00), between the first and second trimesters (p = 0.080), or between the second and third trimesters (p = 0.247). Conclusions: According to the results presented here, we observed changes in the activities of A-Tg and A-TPO antibodies during and after pregnancy in women with previous AITD. In women who intend to become pregnant, are pregnant, or have given birth within three months, it is essential to monitor A-TPO, A-Tg, and thyroid function as well as serum thyroid hormones and TSH to identify thyroid dysfunction in a timely manner and adjust the treatment strategy to avoid the deleterious effects of hypothyroidism on both mother and baby during and after pregnancy.

Graves' Disease in Hypopituitarism Due to Pituitary Apoplexy.

Central hypothyroidism and autoimmune hyperthyroidism are contrasting pathologies requiring careful hormone monitoring for restoring euthyroidism. Their coexistence is rare and challenging for clinicians [1, 2]. We have, herein, presented the case of a 41-year-old female patient with an unremarkable clinical history except for chronic autoimmune thyroiditis in euthyroidism. At the 21st week of gestation, she experienced a spontaneous abortion. The patient underwent an assessment of the uterine cavity, which was complicated by bleeding and hypotensive shock. In the postoperative course, the patient presented worsening headache, and after an MRI, the diagnosis of pituitary apoplexy due to an ischemic-hemorrhagic base was made. Laboratory tests showed anterior panhypopituitarism. Multiaxial replacement therapy was initiated with hydrocortisone, levothyroxine (LT4), and subsequently estrogen-progestin and GH. After two years of good recovery with stable LT4 dosage, the patient experienced palpitations and fine tremors; blood tests showed hyperthyroidism with suppressed Thyroid-stimulating Hormone (TSH) levels and elevated free thyroid fractions and anti-TSH receptor antibodies. Diagnosis of Graves' disease was made, and therapy with methimazole was initiated. During antithyroid therapy, TSH remained persistently suppressed, consistent with the underlying central hypothyroidism. This condition required close follow-up, with monitoring based solely on free thyroid hormone levels. After six months of antithyroid therapy, disease remission was achieved, with negative antibodies and mild hypothyroxinemia. Therefore, methimazole was discontinued and replacement therapy gradually resumed until optimal hormone levels were reached. This case is unique demonstrating autoimmune hyperthyroidism to coexist with central hypothyroidism, rendering TSH a misleading disease progression indicator. Consequently, managing Graves' disease has become more complex and challenging.

Association of Graves' disease and Moyamoya syndrome in a Caucasian woman from Western Europe: vascular effects of anti-TSH receptor antibodies?

Moyamoya syndrome (MMS) refers to a rare cerebrovascular disorder characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches, leading to an increased risk of stroke. While prevalent in Asia, this condition is considerably less common in Western countries, including Europe. The association between MMS and Graves' disease (GD) has been well documented, primarily in Asian and American populations, notably Latin Americans. In this report, we report the first case of GD with MMS in a Caucasian woman from Western Europe. The precise mechanisms underpinning the correlation between these two conditions remain poorly elucidated but are hypothesized to involve hemodynamic alterations, the toxic effects of anti-thyroid-stimulating hormone receptor antibodies, or a shared genetic predisposition. Our clinical case underscores the significance of thyroid disease screening in suspected MMS cases, as the management of thyroid dysfunction may suffice to improve neurological symptoms. The association between Graves' disease (GD) and Moyamoya syndrome (MMS) can manifest in a Caucasian European patient. Screening for thyroid disease is essential when MMS is suspected, as treating GD might effectively alleviate neurological symptoms. The mechanisms linking GD and MMS remain incompletely understood but may involve hemodynamic shifts, the toxic effect of anti-TSH receptor antibodies, or shared genetic factors.

Implications of thyroid-related autoantibodies in patients with Sjögren's syndrome without overt thyroid diseases.

We investigated the prevalence of anti-thyroid autoantibodies and thyroid dysfunction, and their association with clinical and laboratory features in Korean patients with primary Sjögren's syndrome (pSS) without overt thyroid illnesses. We consequently included 196 pSS patients (190 women) and cross-sectionally collected clinical and laboratory data including the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and Patient Reported Index (ESSPRI). The fatigue-dominant group was defined as those in the highest quartile of the fraction of fatigue, calculated as the ESSPRI fatigue score divided by the total ESSPRI score. Thyroid stimulating hormone (TSH), free T4 (fT4), anti-thyroglobulin (TG), anti-thyroid peroxidase (TPO), and anti-TSH receptor antibody (TRAb) were measured. Of 196 patients, 31 (15.8%) were positive for anti-TG, 28 (14.3%) for anti-TPO, and 28 (14.3%) for TRAb. Subclinical hypothyroidism (S-Hypo) was identified in 23 (11.7%) patients. Anti-TG had no correlations with thyroidal function or pSS-related features. Meanwhile, anti-TPO was significantly associated with TSH levels or anti-centromere antibody. TRAb-positive patients exhibited significantly higher ESSDAI and clinical ESSDAI scores. Moreover, the most influential independent predictor for TRAb was lymphopenia (odds ratio [OR] = 5.541), which has been known as a prognostic factor. Additionally, significant bidirectional associations were found between the fatigue-dominant group (OR = 3.482) and anti-TPO-positive S-Hypo (OR = 7.586) in multivariate regression analyses. Latent thyroid autoimmunity, particularly TRAb and anti-TPO, may be associated with clinical and laboratory manifestations of pSS, such as disease activity or fatigue, even without overt thyroid dysfunction.

Atypical Clinical Courses of Graves&apos; Disease Confound Differential Diagnosis of Hyperthyroidism

This study examined the appropriateness of the current paradigm for differential diagnosis of painless thyroiditis and Graves' disease (GD) in patients with thyrotoxicosis. We retrospectively evaluated the clinical course of 343 consecutive patients with hyperthyroidism diagnosed by Tc-99m pertechnetate thyroid uptake (TcTU) testing at our hospital from January 2011 to December 2017. Of the 263 patients with normal or high TcTU levels (≥1.0%), 255 (97%) had unequivocal GD and 5 had spontaneous remission GD or atypical GD. Of the 10 patients with low TcTU levels (<1.0% and ≥0.5%), 7 had GD, while others had subclinical GD, spontaneous remission GD with later relapse, and painless thyroiditis. Of those with very low TcTU levels (<0.5%), most had thyroiditis (painless thyroiditis, 33/67 [49%]; subacute thyroiditis, 29/67 [43%]), and some were positive for anti-TSH receptor antibodies. Given that atypical GD may confound the diagnosis of thyrotoxicosis, it is essential to follow the patient as a tentative diagnosis, whatever the diagnosis. This is the first report clearly demonstrating that so far there is no gold standard for the diagnosis of GD. It is therefore urgent to establish a consensus on the definition of GD so that the specificity and sensitivity of future diagnostic tests can be determined.

P-65 A case of relapse of Graves ophthalmopathy due to an ophthalmic herpes zoster infection in a thyroidectomized patient with multiple comorbidities

Abstract Introduction Graves ophthalmopathy usually occurs in patients with hyperthyroidism or a history of Graves disease, but it can appear in euthyroid patients or patients with chronic thyroiditis also. It is a possible cause of sight-threatening eye disease. Its incidence is 16 for women and 3 cases for men, per 100 000 population but more severe in men, and it's higher among smokers. In mild forms, treatment can be local, but in severe cases and recurrences, systemic glucocorticoids are compulsory, with or without immunosuppressive drugs, surgery or radiotherapy. in recurrences. Clinical Case We present the case of a 76-year-old male, former smoker, diagnosed with Graves disease in 2017. He was treated with anti-thyroid treatment and in 2018 he was thyroidectomized. He also developed a progressive Graves ophthalmopathy from April to July 2017 with a reduced visual acuity for both eyes, conjunctival erythema, palpebral edema and erythema. He received methyl-prednisolone (MP) pulse therapy 6×125 mg weekly with favorable outcome. In 2019, he underwent a recession of internal rectus and inferior rectus for both eyes to correct a divergent strabism and his eye-sight improved. He presents now for an aggravation of the ophthalmopathy after an episode of a herpes zoster infection affecting the ophthalmic branch of the trigeminal nerve. He also suffers from heart failure NYHA III, permanent atrial fibrillation, large aortic stenosis, asymptomatic hyperuricemia, secondary pulmonary hypertension and chronic kidney disease stage IIIb. His medical history revealed hypercholesterolemia, hyperuricemia, heart failure, insufficient status of vitamin D3 and confirmed the chronic kidney disease stage IIIb; normal thyroid function but with high anti TSH receptor antibodies (TRAb=18.37 U/L). Given the age and the comorbidities but also the high activity of the Graves disease and the orbital CT that revealinged a great hypertrophy of the ocular muscles, our ophthalmologist suggested methyl-prednisolone pulse therapy in a standard regimen, but our cardiologist contradicted it because of the heart conditions. As the patient's left eye sight was only 2% and for the right one 20%, we decided to adapt the doses of the pulse therapy and closely monitor the patient. The first dose was 125mg MP, after that 7 doses of 250mg MP weekly was followed by 3 doses of 125mg MP weekly. After a total of 2250 mg MP at a 3 months follow-up, the patients’ eyesight improved to 60% on the left eye and 75% on the right eye and a lower level of TRAb=5.59 UI/L. Conclusion Even in patients with comorbidities where corticosteroid therapy may be detrimental, there is a possibility to adapt the doses in a safe way and with a continuous clinical monitoring so that the patients’ eyesight can be saved, therefore increasing the quality of life.

Exacerbation of Thyroid Eye Disease and Dysthyroid Optic Neuropathy During Pregnancy: A Case Report

A 37-year-old, never-smoker, pregnant woman diagnosed with Graves' disease who had stable thyroid eye disease (TED) before pregnancy presented with aggravated proptosis and eyelid swelling at 13 weeks of pregnancy. Despite the administration of local triamcinolone and 3 cycles of corticosteroid pulse therapy from 25 to 28 weeks, the patient's visual acuity decline necessitated postpartum orbital decompression surgery. Although TSH receptor antibody (TRAb) levels decreased during the mid- to late term of pregnancy, the TED worsened. This finding suggests that factors other than anti-TSH receptor antibodies may have a significant effect on disease severity.

IgG4 serum levels in Graves' orbitopathy.

IgG4-related disease (IgG4-RD) can involve many organs, including thyroid and orbital tissues. A link between IgG4, Graves' disease (GD) and Graves' orbitopathy (GO) has been proposed, but results are conflicting. Here we investigated the possible association between IgG4 and GO. Retrospective investigation in 297 patients with Graves' disease (GD), 152 with GO. prevalence of IgG4 ≥ 135mg/dL (cut-off for IgG4-RD). (1) serum IgG4 concentrations; (2) IgG4/IgG ratio; (3) prevalence of IgG4/IgG ratio ≥ 8.0%; (4) relationship between IgG4 and eye features; (5) relationship between IgG4 and anti-TSH receptor antibodies (TRAbs). Because GO patients had lower FT3 concentrations, we evaluated the main objectives in the second and third FT3 quartiles subpopulation, in which there were no relevant differences between patients with (n = 81) or without GO (n = 67) for baseline parameters. Within this population, the prevalence of IgG4 levels ≥ 135mg/dL did not differ between patients without and with GO (17.9% vs 17.3%). No difference was observed concerning IgG4 concentrations, prevalence of IgG4/IgG ≥ 8.0%, and IgG4/IgG ratio. There was no relationship between IgG4 and eye features and no correlation between IgG4 levels and TRAb was found. Our results suggest that, within GD, there is no relationship between serum IgG4 and GO.

Type 2 amiodarone-induced thyrotoxicosis: prevalence, time and predictors of development

Amiodarone takes a leading position in arrhythmological practice in the prevention and relief of various cardiac arrhythmias. Type 2 amiodarone-induced thyrotoxicosis is a frequent side effect of the drug. It is the most complex type of thyroid dysfunction both in terms of the severity of clinical manifestations, and in terms of understanding the mechanisms of pathogenesis, possibility of differential diagnosis and providing effective treatment. Due to the increasing life expectancy of the population, corresponding increase in the frequency of cardiac arrhythmias, the problem does not lose its relevance. Identification of predictors, assessment and prediction of the individual risk of developing this thyroid pathology is a necessity in daily clinical practice for making a reasonable decision when prescribing the drug, determining the algorithm for further dynamic monitoring of the patient. To evaluate the structure of amiodarone-induced thyroid dysfunction, prevalence, time and predictors of development type 2 amiodarone-induced thyrotoxicosis in a prospective cohort study.MATERIALS AND METHODS: The study involved 124 patients without thyroid dysfunction who received amiodarone therapy for the first time. Evaluation of the functional state of the thyroid gland was performed initially, after prescribing the drug for the first 3 months 1 time per month, in the future - every 3 months. The follow-up period averaged 12-24 months. The end of the observation occurred with the development of amiodaron-induced thyroid dysfunction or patient's refusal to further participate in the study. For the differential diagnosis of the type of amiodarone-induced thyrotoxicosis, the level of anti-TSH receptor antibodies and thyroid scintigraphy with technetium pertechnetate were determined. The type and frequency of thyroid dysfunction, time and predictors of development type 2 amiodarone-induced thyrotoxicosis were evaluated. The structure of amiodarone-induced thyroid dysfunction was represented by hypothyroidism in 19,3% (n=24), type 1 thyrotoxicosis in 1,6% (n=2), type 2 thyrotoxicosis in 23,4% (n=29). The median time of its development was 92,0 [69,0;116,0] weeks; the average period of common survival - 150,2±12,6 weeks (95% CI: 125,5-175,0), median - 144±21,7 weeks (95% CI: 101,4-186,6). The main predictors of type 2 amiodarone-induced thyrotoxicosis were: age (OR=0,931; 95% CI: 0,895-0,968; p&lt;0.001), BMI (OR=0,859; 95% CI: 0,762-0,967; p=0,012), time from the start of amiodarone therapy (OR=1,023; 95% CI: 1,008-1,038; p=0,003). Age ≤60 years was associated with increased risk of the dysfunction by 2.4 times (OR=2,352; 95% CI: 1,053-5,253; p=0,037), BMI≤26,6 kg/m2 - 2,3 times (OR=2,301; 95% CI: 1,025-5,165; p=0,043).CONCLUSION: The results allow to personalized estimate the risk of type 2 amiodarone-induced thyrotoxicosis and determine the patient's management tactic.

FRI547 Orbital Surgery In Moderate-To-Severe Graves´Ophthalmopathy: Institutional Experience

Abstract Disclosure: L. Delfino: None. Z. Anabela: None. V. Ilera: None. V. García Roel: None. A. Reyes: None. A.T. Gauna: None. Management of moderate-to-severe Graves´ophtalmopathy (GO) depends mainly on the degree of soft tissue inflammation. While immunosuppressive therapy is indicated in the active phase, orbital surgery (OS) is reserved for sequelae disease. Indication of OS during active phase is sight-threatening GO not responding to steroids. Although not a common practice, OS during active disease has been performed in our institution as a second line therapy. We aim to describe our experience in patients that underwent OS for active and inactive GO. Methods: retrospective study. Activity and severity were defined according to 2021 EUGOGO guidelines. Response to OS was classified as: adequate (improvement of GO), partial (stabilization without progression) and poor (progression of GO). Results: 32 patients underwent OS, 59.4% were women, median age 47 years (25-67), 48.4% smokers. Management of hyperthyroidism comprised antithyroid drugs in 19 cases (59.3%), radioiodine in 11 (34.4%) and thyroidectomy in 2. At the time of surgery 27 patients (84.4%) were euthyroid, 4 (12.5%) subclinical hyperthyroid and 1 (3.1%) hypothyroid. GO was inactive in 18 (56.3%) of cases and active in 14 (43.7%). All patients with active GO and 6 patients with inactive GO had been treated with weekly intravenous steroids as proposed by Kahaly or with 1 g methylprednisolone/d for 3 days. Indications for OS were rehabilitation for aesthetic/functional sequelae in 53.1%, dysthyroid optic neuropathy in 15.6%, poor response to steroids in 15.6% and others (optic nerve elongation, exposure keratopathy, ocular subluxation) in 15.6% of cases. At the time of OS 16 patients received concomitant steroids, 10 with active and 6 with inactive GO but positive anti-TSH receptor antibodies (TRAb) and risk factors. Response to treatment was considered adequate in 81.3%, stable in 12.5% and poor in 6.3% (one active and one inactive GO). Before OS TRAb were positive in 90.6% of patients. After surgery TRAb decreased in 64.3%, remained stable in 10.7% and were negative in 25% of cases. No patient with negative TRAb before OS presented positive levels after procedure. The percentage of patients with negative TRAb was significantly higher post-surgery [90.6% vs 65.6%, X2 (1) =5, p=0.025]. Evolution of TRAb was not related with concomitant use of steroids for OS. Conclusions: in our experience, response to OS was satisfactory in more than 90% of cases. In patients with active GO and inadequate response to previous intravenous steroids treatment, OS achieved favorable results in more than 80%. TRAb levels decreased or became negative in most cases, with no increments after surgery. We consider that OS can be an appropriate second-line treatment option in cases of unfavorable response to steroids and inaccessibility to other treatment modalities, and that positivity of TRAb should not be a condition to preclude OS. Presentation: Friday, June 16, 2023

Description of thyroid disorders the year before conception: a population-based study.

This study aimed to monitoring the prevalence of previously identified thyroid disorders and hypothyroidism monitoring before pregnancy. A retrospective cross-sectional study of women whose pregnancies occurred between 2014 and 2016 was conducted, including 120,763 pregnancies in Catalonia (Spain). The presence of thyroid disorders in women was based on disease diagnostic codes and/or prescription of levothyroxine or antithyroid drugs. To evaluate the thyroid disorder diagnosis and monitoring, thyrotropin (TSH), free T4 (FT4), antiperoxidase antibody (TPOAb), and anti-TSH receptor antibody (TRAb) records were gathered and categorised according to the reference values of each laboratory. The prevalence of recorded thyroid disorders before the last menstrual period was 5.09% for hypothyroidism and 0.64% for hyperthyroidism,showing a significant increase with age. A thyroid monitoring test was not performed in the year before the last menstrual period in approximately 40% of women with a known thyroid disorder. Amongst the women with hypothyroidism who underwent a TSH test, 31.75% showed an above-normal result. Amongst women previously unknown to have thyroid disorders, 3.12% had elevated TSH levels and 0.73% had low TSH levels. A high percentage of Catalan women with a known thyroid disorder were not properly monitored during the year before pregnancy. Amongst those monitored, more than one-third had TSH values outside the reference range. Therefore, it is important to evaluate women with thyroid disorders during pre-pregnancy visits.

Renal function changes in patients with subclinical hyperthyroidism: a novel postulated mechanism

BackgroundSubclinical hyperthyroidism (SCH) is found to be associated with renal dysfunction. Hyperthyroidism is a well-known cause of secondary systolic hypertension. However, the effect of SCH on the kidney and its vasculature is still unknown.AimTo assess the presence of renal function changes and renal vasodysfunction in SCH patients and their relation to hypertension.MethodsThe study included 321 patients with SCH and 80 healthy matched controls. Laboratory investigations included thyroid function tests, anti-TSH receptor antibody (TRAb), creatinine, estimated glomerular filtration rate (eGFR), serum osmolarity (S. Osmol), urine osmolarity (U. Osmol), Fractional Excretion of Sodium (FeNa), Fractional Excretion of Potassium (FeK), copeptin (CPP), and aldosterone/renin ratio (ARR). Ultrasound for the thyroid gland, echocardiography, total peripheral resistance (TPR), flow-mediated dilatation (FMD), and Renal Arterial distensibility (RAD) was also done.ResultsSerum creatinine was significantly lower while eGFR was significantly higher in SCH patients compared to euthyroid subjects (mean 0.59 ± 0.11 mg/dl Vs mean 0.8 ± 0.1 mg/dl, p = 0.001 and mean 128.28 ± 14.69 ml/min/1.73m2 Vs mean 100.49 ± 14.9 ml/min/1.73m2, p = 0.013, respectively). The TPR and FMD showed a significant decrease in SCH group compared to controls (mean 975.85 ± 159.33 mmHg.min/L Vs mean 1120.24 ± 135.15 mmHg.min/L, p = 0.045 and mean 7.03 ± 4.02% Vs mean 13.48 ± 4.57%, p = 0.003, respectively). RAD was significantly higher in hypertensive SCH patients compared to normotensive SCH patients (mean 17.82 ± 2.46 mmHg Vs mean 11.98 ± 3.21 mmHg, p = 0.001).ConclusionSCH patients showed vascular resistance reduction. Alterations in thyroid hormones and blood pressure could be the driving mechanisms for the change in renal functions in patients with SCH.

Use of Plasmapheresis in the Treatment of Thyrotoxicosis Secondary to Graves' Disease at the National Medical Center 20 de Noviembre ISSSTE: Case Report

Thyrotoxicosis refers to the clinical syndrome secondary to excess of circulating thyroid hormones, thyroid storm is an extreme manifestation of thyrotoxicosis, and which can reach 10-30% mortality with treatment depending on the series. This rare but serious complication occurs mainly in patients with Graves' disease (GD) who account for 60% to 80% of cases of hyperthyroidism. Both plasmapheresis/therapeutic plasma exchange (TPE) and emergency surgery have been used to treat thyroid storm in patients who respond poorly to first-line therapeutic measures. We present the case report of three patients with severe disease (GD) managed at the National Medical Center 20 de Noviembre ISSSTE using TPE as a bridge treatment to thyroidectomy, of which the indication for two patients was intolerance to antithyroid drugs and one with intolerance to antithyroid drugs in addition to impending thyroid storm. Between 4-5 sessions of TPE were performed in which there was a decrease in T4L and anti-TSH receptor antibodies (TSH-R-Ab), in addition to significant clinical improvement, which allowed us to perform thyroidectomy safely. Therefore, we consider that TPE is a fast, safe, and effective bridge treatment to surgery, which should be considered in patients with no response or intolerance to thionamide treatment, in centers where TPE and immediate surgery are available.

Abstract #1406804: Study of Thyroid Parenchymal Vascularity Pattern and its Predictors in Untreated Graves’ Disease

Increased thyroid gland vascularity is an important diagnostic finding in case of Graves’ disease. However, the relation of thyroid gland vascularity with thyroid hormones or autoantibody levels with is less clear. Few studies have reported correlation of gland vascularity and thyroid hormones whereas few have found no such association. We aimed to study different patterns of thyroid parenchymal vascularity and its determinants in untreated Graves’ disease patients. A total of 71 treatment naïve Graves’ disease patients were included in the study. Detailed clinical, hormonal and radiological evaluations were done and data were recorded. The thyroid parenchymal vascularity was divided into three patterns (Grade 1, Grade 2 and Grade 3) based on increasing vascularity pattern with Grade 1 being least to Grade 3 being highest as described previously in literature. Comparison and correlation analysis were done using appropriate statistical tools. Our cohort consisted of 52 females and 19 males with a mean age of 34.4±9.4 years. Among all patients, 14.08% patients had Grade1 vascularity pattern (Group A), 47.89% had Grade 2 vascularity pattern (Group B) and rest 38.03% had Grade 3 vascularity pattern (Group C) respectively. No difference was noted with regards to thyroid hormone levels (FT3, FT4 or TSH) or thyroid autoantibody levels (anti-TSH receptor antibodies) between the three subgroups (p–non-significant). Thyroid volumes were significantly higher in patients with higher vascularity pattern with Group C having highest (median volume-23.9 cc) and Group A having lowest (median volume-11.3cc) respectively (p<0.01). Among our Graves’ disease patients, majority had Grade 2 thyroid parenchymal vascularity pattern. No significant difference was noted between the three groups with regards to thyroid hormone levels or anti TSH receptor antibody titres. Thyroid gland volumes were significantly higher in patients having higher gland vascularity pattern.

Subacute Hyperthyroidism Induced by Treatment with Lithium Salts

Lithium treatment is usually indicated in bipolar disorder. It is associated with hypothyroidism and very rarely with hyperthyroidism. We report here the results of the exploration of a case of thyrotoxicosis occurring during treatment with lithium salts. This was a 16-year-old patient with ongoing lithium treatment for two and a half years who presented with a thyrotoxicosis syndrome without a context of iodine overload or an episode of anterior cervical pain that could suggest subacute thyroiditis or orthopathic sign. The assessment of the exploration of this patient reveals biological hyperthyroidism without anti-TSH receptor antibodies, a normal ultrasound, and white scintigraphy which makes it possible to evoke the diagnosis of subacute thyroiditis (absence of the context of iodine overload). Note the interest in a thyroid assessment before and during treatment with lithium salts. Moreover, scintigraphy occupies a place of choice in the exploration of hyperthyroidism, particularly in the context of normal thyroid ultrasound imaging.

Graves' orbitopathy post-SARS-CoV-2 vaccines: report on six patients.

Autoimmune and inflammatory thyroid diseases (Graves' disease, subacute thyroiditis, chronic autoimmune thyroiditis) have been reported following SARS-CoV-2 vaccines but Graves' orbitopathy (GO) post-COVID-19 vaccination is uncommon. We describe six new patients seen in Endocrinology Departments with Outpatient Clinics for GO following SARS-CoV-2 vaccines in France. After COVID-19 vaccination, GO was observed in six patients (three men, three women, mean age 53 ± 6years) with a personal past history of Graves' disease (5/6) or orbitopathy (4/6). New-onset (n = 2) or recurrence (n = 4) of GO was observed following mRNA vaccines after the first (3/6) or second (3/6) dose, with the mean time from vaccination to GO at 23.8 ± 10.4days. In one patient, thyrotoxicosis was confirmed by increased free T4 and low TSH concentrations while others had normal TSH levels, during chronic levothyroxine treatment in three patients. Four patients had significant anti-TSH receptor antibodies levels. According to the severity and activity of GO, the patients were treated using selenium (n = 2), intravenous glucocorticoids (n = 2), teprotumumab (n = 1), tocilizumab (n = 2) and orbital decompression (n = 1) with a significant improvement in GO signs and symptoms observed by most patients. In this study, we report the main data from six new patients with GO following SARS-CoV-2 vaccines. Clinicians need to be aware of the risk of new-onset or recurrent GO in predisposed patients with autoimmune thyroid diseases after COVID-19 vaccination. This study should not raise any concerns regarding SARS-CoV-2 vaccination since the risk of COVID-19 undoubtedly outweighs the incidence of uncommon GO after SARS-CoV-2 vaccination.