A longitudinal study of medial temporal lobe volumes in Graves' disease

Background Neuropsychiatric symptoms are common features of Graves' disease (GD), in hyperthyroidism and after treatment. The mechanism behind these symptoms is unknown, but reduced hippocampal volumes have been observed in association with increased thyroid hormone levels. Methods Sixty-two women with newly diagnosed GD underwent assessment including magnetic resonance (MR) imaging in hyperthyroidism and 48 of them were followed up after a mean of 16.4 ± 4.2 SD months of treatment. Matched thyroid-healthy controls were also assessed twice at a 15-month interval. MR images were automatically segmented using multi-atlas propagation with enhanced registration. Regional medial temporal lobe (MTL) volumes for amygdalae and hippocampi were compared with clinical data and data from symptom questionnaires and neuropsychological tests. Results Patients had smaller MTL regions than controls at inclusion. At follow-up, all four MTL regions had increased volumes and only the volume of the left amygdala remained reduced compared to controls. There were significant correlations between the level of TSH receptor antibodies (TRAb) and MTL volumes at inclusion and also between the longitudinal difference in the levels of fT3 and TRAb and the difference in MTL volumes. There were no significant correlations between symptom or test scores and any of the four MTL volumes. Conclusion Dynamic alterations in the amygdalae and hippocampi in GD reflect a previously unknown level of brain involvement both in the hyperthyroid state of the condition and after treatment. The clinical significance, as well as the mechanisms behind these novel findings, warrant further study of neurological consequences of GD.

Caracterización de recién nacidos hijos de madres portadoras de enfermedad de Graves

El hipertiroidismo neonatal es una enfermedad que puede asociarse a mortalidad y secuelas. No existe a la fecha, una serie clínica de casos que permita conocer la realidad local de esta condición.Objetivo: Caracterizar desde el punto de vista clínico y de laboratorio a recién nacidos (RN) hijos de madres con Enfermedad de Graves (EG).Sujetos y Método: Estudio prospectivo de RN hijos de madres con antecedente de EG, en dos hospitales públicos de Santiago, por un período de 5 años. Se analizaron variables clínicas y de laboratorio de los binomios madre-hijo. Se analizaron los anticuerpos antireceptor de hormona tiroestimulante (por su acrónimo en inglés: TSH receptor antibodies, TRAbs). Se buscaron asociaciones entre estas variables y el desarrollo de hipertiroidismo neonatal.Resultados: Se incluyeron 76 binomios madre-hijo (0,2% del total de partos). Cinco neonatos (6,6%) presentaron hipertiroidismo bioquímico, y 3 de ellos desarrollaron enfermedad clínica y requirieron tratamiento. Los 5 RN que desarrollaron hipertiroidismo tenían madres con TRAbs positivos o indeterminados. Ningún hijo de madre con TRAbs negativo desarrolló la enfermedad. Sólo un 65% de las madres y un 72% de los RN pudieron tener determinación de TRAbs. Hubo una correlación significativa entre los títulos de TRAbs maternos (p < 0,03), TRAbs neonatales (p < 0,008) y la TSH neonatal tomada entre los días 2-6 (p < 0,006), con el desarrollo posterior de hipertiroidismo. Todos los casos de hipertiroidismo neonatal fueron transitorios. No hubo mortalidad en nuestra casuística.Conclusiones: En esta primera serie nacional de casos de hijos de madres con EG. Los TRAbs maternos, neonatales y la TSH entre los días 2-6 de vida fueron predictores de hipertiroidismo neonatal.

Hyperthyroidism in Children

Hyperthyroidism is the state of excessive synthesis and release of the thyroid hormones by thyrocytes. Graves’ disease is the most common cause of hyperthyroidism in children. The condition may occur at any age but the prevalence increases with age. According to the classical paradigm, coexistence of genetic susceptibility, environment triggers and immunological dysfunction are responsible for its development. Diagnosis of Graves’ disease is based on presence of characteristic clinical symptoms, TSH receptor antibodies and excess of thyroid hormones. The management in pediatric population involves mainly pharmacotherapy (thyrostatics, β-adrenolitics), in resistant cases radical radioiodine I131 therapy or surgical treatment is necessary.

How to Stop a Thyroid Storm When the Liver Is Bad: A Case Report and Literature Review

Introduction: Patients with thyroid storm and resistance or contraindications to conventional medications may receive plasmapheresis until they have the definitive therapy. Case Presentation: A 42 years old lady with no past medical history was brought by the EMS with palpitations, shortness of breath, vomiting, and profuse diarrhea. She was found to have an atrial flutter with low blood pressure, received synchronized cardioversion, but unfortunately, she developed ventricular tachycardia, tonic-clonic seizure and went to pulseless electrical activity (PEA). Upon examination, the patient was intubated, heart rate of 200 beats/min, blood pressure of 80/60 on vasopressors. She had exophthalmos and icteric eyes. Neck examination revealed palpable goiter. There was bibasal fine cracked and mild lower limb edema. Laboratory showed FT4 39 (11.6-21.9 pmol/L), FT3 5 (3.7- 6.4 pmol/L), and TSH &lt;0.01 (0.3-4.2 mIU/L). Burch- Wartofsky’s score was 55/140. Her presentation was suggestive of Graves’ disease with thyroid storm. Further labs showed high liver enzymes, high INR, ammonia as well as high creatinine. She was started on IV hydrocortisone and cholestyramine. Thionamides were contraindicated due to liver impairment. Extracorporeal membrane oxygenation (ECMO) was initiated for cardiopulmonary support and continued for 6 days. TSH receptor antibodies result was pending, thus a thyroid uptake scan was done while the patient connected to ECMO to confirm the diagnosis. Thyroid scan showed increased uptake suggestive of grave’s disease despite iodine contrast received for CT scan chest two days back. After 5 sessions of plasmapheresis, FT3 2.8, and FT4 30, Lugol’s iodine started and she underwent total thyroidectomy. She was successfully extubated and thyroxine replacement was started after normalization of thyroid hormones Discussion: The raised liver enzymes (shock liver) were a barrier to thioamides. With the contraindication to antithyroid medications, plasmapheresis was a rapid and safe option before thyroidectomy. The mechanism of plasmapheresis is to eliminate thyroid hormones, TSH-receptor antibodies, and cytokines. The current guidelines lack clear indications, the timing of initiation, and patient selection for plasmapheresis. Conclusion: Plasmapheresis should be considered as a stabilising measure, especially when patients cannot tolerate conventional medications. Plasmapheresis leads to rapid decline in thyroid hormone levels, providing a window to treat definitively with thyroidectomy.

Manifestation of Marine Lenhart Syndrome after failed Radioactive Iodine therapy

Marine Lenhart Syndrome (MLS) is caused by a coexistence of active thyroid nodules and Graves’ disease1. Here, we present a case of hyperthyroidism characterized by the presence of stimulating TSH receptor antibodies, unsuccessful radioactive iodine ablation, ultimately requiring Methimazole followed by thyroidectomy. We review the current literature.

The Efficiency of Pulse Therapy with Glucocorticoids in Inflammatory Orbital Disorders: Case Report

Orbital pseudotumor represents a benign inflammatory disorder of the orbit, with unspecified etiology, whose clinical presentation can mimic the ocular pathology of Basedow disease, namely Graves’ ophthalmopathy, the two of them representing two of the most common orbital conditions. Imagistic methods and laboratory analyses can establish the diagnosis through orbital MRI images specific for the orbital pseudotumor, especially by dosage of the TSH receptor antibodies (TRAb) which will have increased values in Basedow disease with ocular damage. In both situations, the treatment is represented as a first therapeutic line by administration of corticotherapy in high dosage orally or intravenously, with favorably evolution, which is also observable in the case of our patient who was diagnosed with orbital pseudotumor based on MRI images, with associated thyroid dysfunction with negative TRAb, in which the pulse therapy with Solumedrol has determined the improvement of ocular symptoms and signs.

SAT-415 Clinical Performance of Thyroid-Stimulating Immunoglobulin for Graves′ Disease Diagnosis

INTRODUCTION The diagnosis of Graves′disease (GD) is likely when patient presents hyperthyroidism, symmetrical goiter and orbitopathy and further evaluation is unnecessary. Nevertheless patient with nodular thyroid or in the absence of clinical orbitopathy, measurement of TSH receptor antibodies (TRAb) is recommended to distinguish GD from toxic multinodular goiter, toxic adenoma and other etiologies. Radioiodine uptake (RAIU) also helps to diagnosis when TRAb is unavailable. Third generation TRAb assays measure all types of TSH receptor antibodies: stimulating, blocking and neutral with an excellent sensitivity and specificity for GD diagnosis. Recently, an automated bioassay for the thyroid stimulating immunoglobulin (TSI) was introduced to improve GD diagnosis. OBJECTIVE To analyze clinical performance of TSI and compare with TRAb assay for GD diagnosis. MATERIAL AND METHODS Serum samples of 117 patients with thyrotoxicosis due to GD, toxic multinodular goiter and toxic adenoma were runned simultaneously in two analytical system commercially available. TRAb was analyzed by Elecsys Anti-TSHR assay (Roche Diagnostics, Germany) in a Cobase411 analyzer (Roche Diagnostics, Germany) and results, according to the manufacturer interval reference, were negative if &lt; 1.75 IU/L (analytical range: 0.3 to 40 IU/L). TSI was measured by Immulite TSI assay (Siemens Healthcare, UK) in Immulite XPi 2000 and results, according to the manufacturer interval reference, were negative if &lt; 0.55 IU/L (analytical range: 0.1 to 40 IU/L). Clinical diagnoses of thyrotoxicosis were determined according to ATA guideline (2016). Statistical analyses were performed using SPSS and MedCalc softwares. Comparison were evaluated by regression equations and were considered significant when p values were &lt; .05. RESULTS From 2017 to 2019 a total of 312 serum samples from 117 patients (96 females) were evaluated with mean age 49.5 ±15.8 years-old (18 to 90 yrs). We excluded 26 results above the analytical measurement range of both assays. A high degree correlation was observed with a slope of 0.647 and an intercept -.094 IU/L. Spearman correlation coefficient was 0.858 (p &lt; 0.0001, 95% CI 0.825 to 0.886). TSI assay had higher sensibility and negative predictive value compared to TRAb (95.6% vs 88.5% and 83.6% vs 54.8%, respectively) but lower specificity and positive predictive value (90.3% vs 100% and 97.5% vs 100%, respectively). The results of TSI assay showed good agreement with those of the TRAb assay (k=0.74). A total of 31 samples were discordant, favoring to TSI assay in all but one case of GD according to clinical diagnosis (TRAb positive and TSI negative). CONCLUSION TSI assay showed an excellent performance for GD diagnosis with a better sensibility than TRAb assay.

OR18-03 Functional TSH Receptor Antibodies Are a Biomarker for Graves’ Disease - a Prospective Trial

Objective We aimed to evaluate the clinical utility and predictive value of stimulatory (TSAb) and blocking (TBAb) TSH receptor antibodies in the management of Graves’ disease (GD). Methods Hundred well-defined, consecutive, unselected, untreated hyperthyroid patients with GD were enrolled in a prospective two-year trial. Methimazole (MMI) was administered for 24 weeks according to baseline serum concentrations of free T3/free T4. Starting dose was 5–30 mg/day. Through a titration regimen, this dose was respectively tapered or increased at each subsequent study visit as the patient became euthyroid or remained hyperthyroid. Goals of therapy were to maintain normal fT4 and TSH levels. MMI therapy was stopped at week 24. The main outcome measure was clinical response versus non-response to a 24-week MMI treatment defined as biochemical euthyroidism versus persistent hyperthyroidism at week 24 and/or relapse at weeks 36, 48, and 96. TSAb was reported as percentage of specimen-to-reference ratio (cut-off SRR% &lt;140). Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off &gt;40% inhibition). Results Forty-four patients responded to MMI of whom 43% had Graves’ orbitopathy (GO) while 56 were non-responders (66% with GO, p&lt;0.01). At baseline, undiluted serum TSAb but not thyroid binding inhibiting immunoglobulins (TBII) differentiated between thyroidal GD only versus GD+GO (p&lt;0.001). Further, at baseline responders demonstrated marked differences in diluted TSAb titers compared with non-responders (p&lt;0.001). All patients with a TSAb dilution titer above three did not respond to MMI treatment. In contrast, TBII dilution titers did not differentiate between responders and non-responders to MMI and serum samples became TBII negative already at low dilutions. During treatment, serum TSAb levels decreased markedly in responders (p&lt;0.001) but increased in non-responders (p&lt;0.01). In contrast, TBII strongly decreased in non-responders (p=0.002). All non-responders at week 24 and/or those who relapsed during the 72-week follow-up were TSAb positive at week 24. A shift from TSAb to TBAb was noted in eight patients during treatment and/or follow-up and led to remission. Conclusions Serum TSAb levels are a biomarker for and mirror severity of GD. Their increase during MMI treatment is a marker for on-going disease activity. TSAb dilution analysis had additional predictive value.

SAT-410 Long Term Evaluation of TSH Receptor Antibodies and Thyroid Stimulating Immunoglobulin After Radioiodine Therapy for Thyrotoxicosis

Background Radioioactive iodine therapy (RAI) is an excellent choice to treat thyrotoxicosis, particularly Graves′ disease (GD) patients. After RAI therapy, it is well known that TSH receptor antibodies (TRAb) rise in GD patients and autoimmunity can eventually surge in patients with toxic multinodular or uninodular goiter (TNG). Recently, biological assay distinguishes stimulating TRAb, called thyroid stimulating immunoglobulin (TSI) bringing a new perspective on follow-up, as TSI is involved in Graves′ pathogenesis of persistent thyrotoxicosis and ophthalmopathy after RAI therapy. Objective Analyze TRAb and TSI levels after 6 and 12 months of RAI therapy for thyrotoxicosis. Patients and Methods Patients were evaluated prospectively immediately before and 6 to 12 months after RAI therapy for thyrotoxicosis. Thyroid hormones were all measured using immunoassays (Roche Diagnostics Ltd). TRAb was analyzed by Elecsys Anti-TSHR assay (Roche Diagnostics, Germany) and was considered negative if &lt; 1.75 IU/L (analytical range: 0.3 to 40 IU/L). TSI was measured by Immulite TSI assay (Siemens Healthcare, UK) and was considered negative if &lt; 0.55 IU/L (analytical range: 0.1 to 40 IU/L). Clinical data and comparison of assays were analyzed by SPSS and MedCalc softwares. Results From 2017 to 2019, 54 patients (44 females) were prospectively evaluated after 6 months of RAI therapy, mostly because of GD (40 patients). A high degree correlation was observed between TRAb and TSI (Spearman correlation coefficient =0.875; p &lt; 0.0001, 95% CI 0.784 to 0.929). After 6 months, among patients with GD, 5/40 patients had negative TRAb levels and 2/40 had negative TSI levels, whereas all TNG patients had both negative TRAb and TSI levels. In GD group, 4 patients showed subclinical hyperthyroidism and relapse occurred in 1 case. All patients with TNG showed euthyroidism status with or without thyroid medications. One year after RAI therapy, we evaluated 32 patients (23 GD) and 4/23 of GD had negative TRAb levels and only 1/23 had negative TSI level. All patients with TNG had negative TRAb and TSI levels after one year fo treatment. Subclinical hyperthyroidism was diagnosed in 5 patients with GD but none with TNG. Along follow-up, 4 patients with clinical diagnosis of GD with TRAb negative before RAI therapy became positive after RAI therapy and 3 patients became TSI positive. Conclusions Long term after RAI therapy for thyrotoxicosis treatment, TRAb and TSI are still positive in most GD patients and few cases can even turned to positive levels. Nevertheless, in TNG patients, RAI therapy is safe as TRAb and TSI maintained at negative concentrations and thyrotoxicosis is properly resolved.