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

2021 ◽  
Author(s):  
Mats Holmberg ◽  
Helge Malmgren ◽  
Rolf A Heckemann ◽  
Birgitta Johansson ◽  
Niklas Klasson ◽  
...  
Keyword(s):  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Neuropsychiatric Symptoms ◽  
Graves Disease ◽  
Mr Images ◽  
Brain Involvement ◽  
The Difference ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

Abstract 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.

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

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
George Jean Kahaly ◽  
Tanja Diana ◽  
Michael Kanitz ◽  
Paul D Olivo
Keyword(s):  
Predictive Value ◽  
Prospective Trial ◽  
Tsh Receptor ◽  
Luciferase Expression ◽  
Graves Disease ◽  
Free T4 ◽  
Baseline Serum ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

Abstract 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% <140). Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off >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<0.01). At baseline, undiluted serum TSAb but not thyroid binding inhibiting immunoglobulins (TBII) differentiated between thyroidal GD only versus GD+GO (p<0.001). Further, at baseline responders demonstrated marked differences in diluted TSAb titers compared with non-responders (p<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<0.001) but increased in non-responders (p<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.

Normal magnetic resonance imaging and medial temporal lobe epilepsy: the clinical syndrome of paradoxical temporal lobe epilepsy

2005 ◽  
Vol 102 (5) ◽  
pp. 902-909 ◽  
Author(s):  
Aaron A. Cohen-Gadol ◽  
Christopher C. Bradley ◽  
Anne Williamson ◽  
Jung H. Kim ◽  
Michael Westerveld ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Mr Images ◽  
Content Type ◽  
Medial Temporal Lobe Epilepsy ◽  
Fine Print

Object. The syndrome of medial temporal lobe epilepsy (MTLE) may occur in patients in whom magnetic resonance (MR) images demonstrate normal findings. In these patients, there is no evidence of hippocampal sclerosis on neuroimaging, and histopathological examination of the resected hippocampus does not reveal significant neuron loss. In this paper the authors describe the distinct clinical features of this MTLE subtype, referred to as paradoxical temporal lobe epilepsy (PTLE). Methods. The authors selected 12 consecutive patients with preoperative findings consistent with MTLE in whom MR imaging did not demonstrate any hippocampal abnormality. Onset of hippocampal seizure was confirmed by long-term intracranial monitoring. There were six female and six male patients with a mean age of 32 ± 11 years (mean ± standard deviation [SD]) at presentation. These patients' seizure histories, available hippocampal volumetric measurements, and hippocampal cell densities in different subfields were reviewed. Sharp electrode recordings from dentate granule cells that had been maintained in hippocampal slices provided a measure of excitation and inhibition in the tissue. We compared these data with those of a cohort of 50 randomly selected patients who underwent anteromedial temporal resection for medial temporal sclerosis (MTS) during the same time period (1987–1999). The durations of follow up (means ± SDs) for the PTLE and MTS groups were 51 ± 59 months and 88 ± 44 months, respectively. A history of febrile seizure was present less frequently in the PTLE group (8%) than in the MTS group (34%). Other risk factors for epilepsy such as trauma, meningoencephalitis, or perinatal injuries were present more frequently in the PTLE group (50%) than in the MTS cohort (36%). In patients in the PTLE group the first seizure occurred later in life (mean age at seizure onset 14 years in the PTLE group compared with 9 years in the MTS group, p = 0.09). Ten patients (83%) in the PTLE cohort and 23 patients (46%) in the MTLE cohort had secondary generalization of their seizures. Among patients with PTLE, volumetric measurements (five patients) and randomized blinded visual inspection (seven patients) of the bilateral hippocampi revealed no atrophy and no increased T2 signal change on preoperative MR images. All patients with PTLE underwent anteromedial temporal resection (amygdalohippocampectomy, in five patients on the left side and in seven on the right side). Electrophysiological studies of hippocampal slices demonstrated that dentate granule cells from patients with PTLE were significantly less excitable than those from patients with MTS. The mean pyramidal cell loss in the CA1 subfield in patients in the PTLE group was 20% (range 0–59%) and that in patients in the MTS group was 75% (range 41–90%) (p < 0.001). Maximal neuron loss (mean loss 38%) occurred in the CA4 region in six patients with PTLE (end folium sclerosis). At the last follow-up examination, six patients (50%) in the PTLE group were seizure free compared with 38 patients (76%) in the MTS group. Conclusions. Clinical PTLE is a distinct syndrome with clinical features and surgical outcomes different from those of MTS.

Anti-TSH receptor antibodies in Graves' disease modulate the kinetic behaviour of autologous thyroid TSH receptors. Evidence of the IgG-induced cross-linkage of autologous TSH receptors

1984 ◽  
Vol 105 (3) ◽  
pp. 330-340 ◽  
Author(s):  
Tjerk W. A. de Bruin ◽  
Daan van der Heide ◽  
Maria C. Krol
Keyword(s):  
Binding Sites ◽  
Plasma Membranes ◽  
Tsh Receptor ◽  
Human Thyroid ◽  
Graves Disease ◽  
Kinetic Behaviour ◽  
High Affinity ◽  
Cross Linkage ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

Abstract. The effect of the anti-TSH receptor antibodies present in the sera of 8 patients with Graves' disease on the affinity constant (Ka) and the number (R) of TSH receptors in autologous human thyroid plasma membranes was investigated. Kinetic analysis of [125I]bTSH binding to human thyroid plasma membranes in the presence of autologous Graves' and normal gammaglobulins was carried out by means of a computer fitting programme. Analysis of the TSH-TSH receptor interaction in the presence of TSH alone yielded curvilinear Scatchard plots, indicating the existence of two independent classes of binding sites (high affinity Ka: 8.5 ± 4.8 × 108 m−1; low affinity Ka: 5.3 ± 2.7 × 106 m−1). Similarly the Scatchard plot for this interaction in the presence of normal gammaglobulins is also curvilinear. Linear Scatchard plots, indicating the existence of only one class of high affinity TSH binding sites (Ka: 3.5 ± 1.8 × 108 m−1), were obtained for both autologous gammaglobulins and pure IgG from 8 patients with Graves' disease. The number of high affinity TSH binding sites in the presence of Graves' gammaglobulins had increased on the average by a factor 3.76 ± 0.74 (sd) with respect to the number found in the presence of normal gammaglobulins. This marked change in the kinetic behaviour of the TSH binding sites provided evidence that there is a direct interaction between anti-TSH receptor antibodies and autologous TSH receptors. Divalency of Graves' IgG or linkage of Fab fragments by anti-Fab antiserum proved to be necessary to produce this specific change in the kinetic behaviour of TSH binding sites. Graves' IgG monovalent Fab and Fc fragments had no effect. We suggest that the mechanism by which anti-TSH receptor antibodies in Graves' disease mimick the biological action of TSH is the IgG-induced cross-linkage of TSH receptors.

scholarly journals High Titers of Thyrotropin Receptor Antibodies Are Associated With Orbitopathy in Patients With Graves Disease

2019 ◽  
Vol 104 (7) ◽  
pp. 2561-2568 ◽  
Author(s):  
George J Kahaly ◽  
Christian Wüster ◽  
Paul D Olivo ◽  
Tanja Diana
Keyword(s):  
De Novo ◽  
Graves Disease ◽  
Serum Dilution ◽  
Tertiary Referral Center ◽  
Thyrotropin Receptor Antibodies ◽  
High Dilutions ◽  
Graves Orbitopathy ◽  
Serial Serum ◽  
Receptor Antibodies

Abstract Context Serum TSH receptor autoantibody (TSH-R-Ab) is a biomarker of Graves disease (GD). Studies have shown that the levels of this TSH-R-Ab have clinical significance. Objective To differentiate between thyroidal GD only and Graves orbitopathy (GD + GO). Design Controlled, follow-up study. Setting Academic tertiary referral center for GD + GO. Subjects Sixty patients with GD, GD + GO, and controls. Intervention Serial serum dilution analyses with six automated, ELISA, and cell-based assays for TSH-R-Ab. Main Outcome Measure Differentiation among GD phenotypes. Results All undiluted samples of hyperthyroid-untreated GD patients were positive with the six assays but became negative at dilution 1:9 in four of six assays. In contrast, all undiluted samples of hyperthyroid-untreated GD + GO patients remained positive up to dilution 1:81, P &lt; 0.001. At high dilutions 1:243, 1:729, 1:2187, and 1:6561, the rate of stimulating TSH-R-Ab positivity in the bioassay for GD + GO patients was 75%, 35%, 5%, and 0%, respectively (all P &lt; 0.001). The five ELISA and/or automated assays confirmed this marked difference of anti-TSH-R-Ab detection between GD-only and GD + GO. In comparison, the baseline-undiluted samples of GD vs GD + GO showed an overlap in the ranges of TSH-R-Ab levels. Subsequent to 12-month methimazole treatment, samples from euthyroid GD + GO patients were still TSH-R-Ab positive at the high dilution of 1:243. In contrast, all GD samples were negative already at dilution 1:3. A GD patient with TSH-R-Ab positivity at dilution 1:729 developed de novo GO. Conclusions TSH-R-Ab titers, as determined by dilution analysis, significantly differentiate between GD and GD + GO.

scholarly journals Structural brain changes in hyperthyroid Graves’ disease: protocol for an ongoing longitudinal, case-controlled study in Göteborg, Sweden—the CogThy project

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e031168
Author(s):  
Mats Olof Holmberg ◽  
Helge Malmgren ◽  
Peter Berglund ◽  
Lina Bunketorp-Käll ◽  
Rolf A Heckemann ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Near Infrared ◽  
Well Being ◽  
Secondary Outcome ◽  
Controlled Study ◽  
Ethical Review ◽  
Graves Disease ◽  
Functional Near Infrared Spectroscopy

IntroductionCognitive impairment and reduced well-being are common manifestations of Graves’ disease (GD). These symptoms are not only prevalent during the active phase of the disease but also often prevail for a long time after hyperthyroidism is considered cured. The pathogenic mechanisms involved in these brain-derived symptoms are currently unknown. The overall aim of the CogThy study is to identify the mechanism behind cognitive impairment to be able to recognise GD patients at risk.Methods and analysisThe study is a longitudinal, single-centre, case-controlled study conducted in Göteborg, Sweden on premenopausal women with newly diagnosed GD. The subjects are examined: at referral, at inclusion and then every 3.25 months until 15 months. Examinations include: laboratory measurements; eye evaluation; neuropsychiatric and neuropsychological testing; structural MRI of the whole brain, orbits and medial temporal lobe structures; functional near-infrared spectroscopy of the cerebral prefrontal cortex and self-assessed quality of life questionnaires. The primary outcome measure is the change in medial temporal lobe structure volume. Secondary outcome measures include neuropsychological, neuropsychiatric, hormonal and autoantibody variables. The study opened for inclusion in September 2012 and close for inclusion in October 2019. It will provide novel information on the effect of GD on medial temporal lobe structures and cerebral cortex functionality as well as whether these changes are associated with cognitive and affective impairment, hormonal levels and/or autoantibody levels. It should lead to a broader understanding of the underlying pathogenesis and future treatment perspectives.Ethics and disseminationThe study has been reviewed and approved by the Regional Ethical Review Board in Göteborg, Sweden. The results will be actively disseminated through peer-reviewed journals, national and international conference presentations and among patient organisations after an appropriate embargo time.Trial registration number44321 at the public project database for research and development in Västra Götaland County, Sweden (https://www.researchweb.org/is/vgr/project/44321).

scholarly journals Graves disease with negative TSH receptor antibodies: a presentation of 5 cases

2020 ◽  
Vol 93 (6) ◽  
pp. 417-419
Author(s):  
Aina Scatti Regàs ◽  
Ricard Pujol Borrell ◽  
Roser Ferrer Costa ◽  
Elsa Puerto Carranza ◽  
María Clemente León
Keyword(s):  
Tsh Receptor ◽  
Graves Disease ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

scholarly journals Stress-induced hashitoxicosis: case report and relative HLA serotype and genotype

2019 ◽  
Vol 65 (6) ◽  
pp. 830-833 ◽  
Author(s):  
Roberto Vita ◽  
Valeria Cernaro ◽  
Salvatore Benvenga
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Stressful Life Events ◽  
Normal Values ◽  
White Cell Count ◽  
Hashimoto's Thyroiditis ◽  
Stressful Event ◽  
Graves Disease ◽  
Thyroid Function Tests ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

SUMMARY OBJECTIVE Even though stress has been long known as a provocative factor for Graves’ disease, its relationship with Hashimoto's thyroiditis is more controversial. Studies on this topic are scanty. This paper aims to report a case of stress-induced Hashitoxicosis. RESULTS Here we report a case of Hashitoxicosis induced by a psychological stressful event in a 28-year-old woman with Hashimoto's thyroiditis. She had remained stably euthyroid for 12 years. She was first observed in April 2016, while euthyroid. She came back after 11 months because of fatigue and palpitations, in the absence of neck pain. Thyroid function tests revealed moderate thyrotoxicosis (undetectable TSH; FT4 36.94 pmol/L, normal values 9.0-24.46; FT3 13.50 pmol/L, normal values 3.07-6.14) with negative TSH-receptor antibodies. In the previous three months, she had experienced a psychological stressful event. Inflammatory markers were negative, and the white cell count was normal. Thyroid ultrasound revealed a modest increase in vascularization. Transient subclinical hypothyroidism ensued after seven weeks and spontaneously recovered. On the last visit, the patient was still on euthyroidism. (TSH 1.01 mU/L; FT4 9.22 pmol/L; FT3 3.98 pmol/L). We also performed HLA serotyping and genotyping. CONCLUSION This case demonstrates that, similarly to Graves’ disease, Hashitoxicosis can also be triggered by stressful life events.

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