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Kenneth D. Burman - One of the best experts on this subject based on the ideXlab platform.
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The relationship of 123I breast uptake on Thyroid scan to Thyroid Stimulating Immunoglobulin in hyperThyroid patients: A pilot study
The Journal of Nuclear Medicine, 2011Co-Authors: Gauri Khorjekar, Douglas Van Nostrand, Pejman Kharazi, Meg Imig, Bridgette Skelton, Kenneth D. BurmanAbstract:1296 Objectives Radioiodine (RAI) uptake in breast tissue has been observed on RAI whole body scan in patients (pts) with differentiated Thyroid cancer. Although this breast uptake has been reported in pts who has been lactating, breast uptake in pts with hyperThyroidism has not been reported or studied to our knowledge. The objective of this pilot study was to evaluate the relationship of Thyroid Stimulating Immunoglobulin levels with breast uptake on 123I scans in pts with hyperThyroidism. Methods A prospective study was conducted on female pts who were (1) diagnosed with hyperThyroidism based upon signs, symptoms and had abnormal Thyroid function tests compatible with hyperThyroidism and (2) referred for an 123I scan of the Thyroid. After informed consent, anterior and lateral images of the breasts were obtained shortly after imaging of the Thyroid bed. Thyroid Stimulating Immunoglobulin level was drawn at the time of imaging. Scans were evaluated by two reviewers (dvn/gk) for 123I uptake in the breast. Intensity was graded as 0 = background activity (bkg), 1+ = mildly >bkg, 2+ = moderately >bkg, and 3+ = >bkg. The relationship of 123I uptake in the breast was compared with the Thyroid Stimulating Immunoglobulin levels. This was an IRB-approved study. Results Thirteen pts met the criteria above, but none of the pts had 123I breast uptake. Elevated Thyroid Stimulating Immunoglobulin was observed in 6/13 (46%) of pts with a range of 2.42-4.6 (nl index Conclusions Based on this pilot study, increase 123I uptake in the breasts was not observed with either hyperThyroidism or elevated Thyroid Stimulating Immunoglobulin levels
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Immunogenicity of a unique region of the human thyrotropin receptor
Journal of Endocrinological Investigation, 1993Co-Authors: E. V. Nagy, H. B. Burch, Y. G. Lukes, F. E. Carr, S. Kosugi, L. D. Kohn, Kenneth D. BurmanAbstract:Clarifying the role of the TSH receptor protein in the autoimmune process may be the key to understanding the development of Graves’ disease. In the present study we used a 16 amino acid peptide of the human TSH receptor (hTSHR) to immunize rabbits. A comparable, but theoretically less immunogenic, peptide was injected into other rabbits. The antibody response against these and other peptides, as well as against solubilized human Thyroid membrane (TM) and guinea pig fat cell membrane (GPF) proteins, was tested using ELISA and Western blots. The GPF and TM binding pattern of rabbits’ sera was compared to that of Graves’ patients’ sera. We have identified an area of antigenic cross-reactivity between GPF and TM; a 63 kD protein was present in both GPF and TM, and this protein uniformly bound IgG-s of the rabbits’ postimmunization sera and one of eight Graves’ patient’s serum. We have shown that i) a theoretically immunogenic 16 amino acid peptide was indeed highly immunogenic in rabbits, ii) antibodies binding to GPF and TM were detected after immunization, and iii) the peak of Thyroid Stimulating Immunoglobulin activity of sera was followed by a transient elevation of serum triiodothyronine levels. Further studies investigating the immunogenic epitopes of the hTSHR as well as characterizing the 63 kD protein are indicated.
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Adjunctive cholestyramine therapy for thyrotoxicosis
Clinical endocrinology, 1993Co-Authors: Barbara Solomon, Leonard Wartofsky, Kenneth D. BurmanAbstract:Summary OBJECTIVE Initial therapy of thyrotoxicosis usually includes beta-blockade for symptom relief and thionamides to block new Thyroid hormone synthesis. In view of the increased enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) in thyrotoxicosis, we proposed that cholestyramine, an anion exchange resin which binds iodothyronines, when used adjunctively with thionamides and a beta-blocker, would lower serum iodothyronine levels faster than would standard therapy alone. DESIGN A double blind placebo-controlled cross-over design was used with patients randomly assigned to either the treatment or control groups. They received their initial treatment for two weeks (Phase 1) followed by a one-week washout period, and then crossed to the opposite treatment for two weeks (Phase 2). Standard therapy included atenolol 50 mg daily, individualized dosages of methimazole and either 4 g of cholestyramine or 4 g of placebo powder four times per day. PATlENTS Fifteen patients with thyrotoxicosis (14 Graves' disease, 1 toxic adenoma) participated in this study. MEASUREMENTS Total and free thyroxine and triiodothyronine, as well as Thyroid-Stimulating Immunoglobulin and thyrotrophin-binding inhibitory Immunoglobulin, were measured weekly. RESULTS Seven patients received cholestyramine and eight patients received placebo during Phase 1. A more rapid decline in all Thyroid hormone levels was seen in the cholestyramine-treated group (F= 4–7, P >0.01) than in the placebo group (F= 2–3.1, P= 0 05). In Phase 2, the eight patients who received cholestyramine showed an additional decline in free thyroxine from weeks one to two, but the overall rate of decline in hormone levels was not different between the groups. Immunoglobulin levels remained unaffected regardless of group, treatment, or time. CONCLUSIONS We conclude that cholestyramine is a safe and effective adjunctive agent in the treatment of thyrotoxicosis and that its greatest efficacy may be during the first few weeks of treatment.
Bernard Champion - One of the best experts on this subject based on the ideXlab platform.
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Thyroid Stimulating Immunoglobulins as measured in a reporter bioassay are not detected in patients with hashimoto s Thyroiditis and ophthalmopathy or isolated upper eyelid retraction
Clinical Ophthalmology, 2014Co-Authors: Jack R Wall, Hooshang Lahooti, Ilhem El Kochairi, Simon D Lytton, Bernard ChampionAbstract:Although ophthalmopathy is mainly associated with Graves' hyperThyroidism, milder eye changes are also found in about 25% of patients with Hashimoto's Thyroiditis (HT). The recent finding of negative thyrotropin receptor (TSHR) antibodies, as measured in the Thyretain™ Thyroid-Stimulating Immunoglobulin (TSI) reporter bioassay, in patients with euThyroid Graves' disease raises the possibility that TSHR antibodies are not the cause of ophthalmopathy in all situations. Here, we have tested serum from patients with HT with and without ophthalmopathy or isolated upper eyelid retraction (UER) for TSHR antibodies, using the TSI reporter bioassay and collagen XIII as a marker of autoimmunity against the orbital fibroblast. Study groups were 23 patients with HT with ophthalmopathy, isolated UER, or both eye features and 17 patients without eye signs. Thyretain™ TSI results were expressed as a percentage of the sample-to-reference ratio, with a positive test being taken as a sample-to-reference ratio of more than 140%. Serum collagen XIII antibodies were measured in standard enzyme-linked immunosorbent assay. TSI tests were positive in 22% of patients with HT with no eye signs but in no patient with eye signs. In contrast, TSI tests were positive in 94% of patients with Graves' ophthalmopathy. Tests were negative in all normal subjects tested. Collagen XIII antibodies were detected in 83% of patients with ophthalmopathy, UER, or both eye features, but in only 30% of patients with no eye signs. Our findings suggest that TSHR antibodies do not play a major role in the pathogenesis of ophthalmopathy or isolated UER in patients with HT. Moreover, the role of TSHR antibodies in the development of ophthalmopathy in patients with Graves' disease remains to be proven. In contrast, collagen XIII antibodies appear to be a good marker of eye disease in patients with HT.
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Eye findings and immunological markers in probands and their euThyroid relatives from a single family with multiple cases of Thyroid autoimmunity
Thyroid Research, 2012Co-Authors: Melissa Ardley, Thomas Mccorquodale, Hooshang Lahooti, Bernard Champion, Jack R WallAbstract:Background Ophthalmopathy is a common manifestation of Graves’ disease (GD) occurring in up to 50% of patients. Mild eye signs are also common in patients with Hashimoto’s Thyroiditis. Whilst a genetic predisposition to GD has been demonstrated this is not the case for the ophthalmopathy which often runs a separate course. Objective We determined the prevalences of eye and eyelid signs and positive Thyroid and orbital antibody tests in first and second degree relatives from a single family with multiple cases of Graves’ disease, ophthalmopathy and Hashimoto’s Thyroiditis. Design The study cohort comprised 16 subjects from the same family, 4 probands namely, 3 with GD and one with Hashimoto’s Thyroiditis and hypoThyroidism and 12 of their euThyroid first or second degree relatives. We measured antibodies against calsequestrin (CASQ1) and collagen XIII in an enzyme-linked-immunosorbent assays and TSH-Receptor (TSH-R) antibodies as i) TSH-R binding inhibiting Immunoglobulin (TBII) and ii) Thyroid Stimulating Immunoglobulin (TSI). Eye signs were classified and quantified using the clinical activity score (CAS), NOSPECS classes, Nunery types 1 and 2 and the margin-reflex-distance (MRD) as a measure of upper eyelid retraction (UER). Main outcomes Whilst significant ophthalmopathy was uncommon in the relatives, mild eye signs, in particular UER, were demonstrated in about a third of them. The presence of eye signs was moderately, but not significantly, associated with the detection of CASQ1 and collagen XIII antibodies, but not TSH-R antibodies. Conclusion Our study demonstrates a significant prevalence of positive orbital antibody tests and ophthalmopathy in probands with Thyroid autoimmunity and their euThyroid relatives, favouring a role of genetic factors in the development of ophthalmopathy in patients with Thyroid autoimmunity.
Jack R Wall - One of the best experts on this subject based on the ideXlab platform.
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Thyroid Stimulating Immunoglobulins as measured in a reporter bioassay are not detected in patients with hashimoto s Thyroiditis and ophthalmopathy or isolated upper eyelid retraction
Clinical Ophthalmology, 2014Co-Authors: Jack R Wall, Hooshang Lahooti, Ilhem El Kochairi, Simon D Lytton, Bernard ChampionAbstract:Although ophthalmopathy is mainly associated with Graves' hyperThyroidism, milder eye changes are also found in about 25% of patients with Hashimoto's Thyroiditis (HT). The recent finding of negative thyrotropin receptor (TSHR) antibodies, as measured in the Thyretain™ Thyroid-Stimulating Immunoglobulin (TSI) reporter bioassay, in patients with euThyroid Graves' disease raises the possibility that TSHR antibodies are not the cause of ophthalmopathy in all situations. Here, we have tested serum from patients with HT with and without ophthalmopathy or isolated upper eyelid retraction (UER) for TSHR antibodies, using the TSI reporter bioassay and collagen XIII as a marker of autoimmunity against the orbital fibroblast. Study groups were 23 patients with HT with ophthalmopathy, isolated UER, or both eye features and 17 patients without eye signs. Thyretain™ TSI results were expressed as a percentage of the sample-to-reference ratio, with a positive test being taken as a sample-to-reference ratio of more than 140%. Serum collagen XIII antibodies were measured in standard enzyme-linked immunosorbent assay. TSI tests were positive in 22% of patients with HT with no eye signs but in no patient with eye signs. In contrast, TSI tests were positive in 94% of patients with Graves' ophthalmopathy. Tests were negative in all normal subjects tested. Collagen XIII antibodies were detected in 83% of patients with ophthalmopathy, UER, or both eye features, but in only 30% of patients with no eye signs. Our findings suggest that TSHR antibodies do not play a major role in the pathogenesis of ophthalmopathy or isolated UER in patients with HT. Moreover, the role of TSHR antibodies in the development of ophthalmopathy in patients with Graves' disease remains to be proven. In contrast, collagen XIII antibodies appear to be a good marker of eye disease in patients with HT.
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Eye findings and immunological markers in probands and their euThyroid relatives from a single family with multiple cases of Thyroid autoimmunity
Thyroid Research, 2012Co-Authors: Melissa Ardley, Thomas Mccorquodale, Hooshang Lahooti, Bernard Champion, Jack R WallAbstract:Background Ophthalmopathy is a common manifestation of Graves’ disease (GD) occurring in up to 50% of patients. Mild eye signs are also common in patients with Hashimoto’s Thyroiditis. Whilst a genetic predisposition to GD has been demonstrated this is not the case for the ophthalmopathy which often runs a separate course. Objective We determined the prevalences of eye and eyelid signs and positive Thyroid and orbital antibody tests in first and second degree relatives from a single family with multiple cases of Graves’ disease, ophthalmopathy and Hashimoto’s Thyroiditis. Design The study cohort comprised 16 subjects from the same family, 4 probands namely, 3 with GD and one with Hashimoto’s Thyroiditis and hypoThyroidism and 12 of their euThyroid first or second degree relatives. We measured antibodies against calsequestrin (CASQ1) and collagen XIII in an enzyme-linked-immunosorbent assays and TSH-Receptor (TSH-R) antibodies as i) TSH-R binding inhibiting Immunoglobulin (TBII) and ii) Thyroid Stimulating Immunoglobulin (TSI). Eye signs were classified and quantified using the clinical activity score (CAS), NOSPECS classes, Nunery types 1 and 2 and the margin-reflex-distance (MRD) as a measure of upper eyelid retraction (UER). Main outcomes Whilst significant ophthalmopathy was uncommon in the relatives, mild eye signs, in particular UER, were demonstrated in about a third of them. The presence of eye signs was moderately, but not significantly, associated with the detection of CASQ1 and collagen XIII antibodies, but not TSH-R antibodies. Conclusion Our study demonstrates a significant prevalence of positive orbital antibody tests and ophthalmopathy in probands with Thyroid autoimmunity and their euThyroid relatives, favouring a role of genetic factors in the development of ophthalmopathy in patients with Thyroid autoimmunity.
Kyung In Woo - One of the best experts on this subject based on the ideXlab platform.
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course of upper eyelid retraction in Thyroid eye disease
British Journal of Ophthalmology, 2020Co-Authors: Dong Cheol Lee, Yoon Duck Kim, Stephanie Ming Young, Kyung In WooAbstract:Aims To evaluate the natural course of upper eyelid retraction (UER) in patients with Thyroid eye disease (TED) and factors affecting its course. Methods Retrospective non-interventional cohort study in a single tertiary institution from March 2006 to March 2015 on patients with TED with (1) unilateral or bilateral UER within 6 months from initial presentation, and (2) no prior interventions nor surgical treatment for their UER. Main outcomes and measures were mean margin reflex distance 1 (MRD1) and factors associated with UER improvement. Results There were a total of 61 patients and 81 eyes (41 unilateral and 20 bilateral UER). Mean age was 42.3±15.1 years. Mean MRD1 decreased from 6.1 mm at presentation to 4.8 mm at 12 months, and 4.4 mm at 24 months. The proportion of eyes with normalisation of lid height increased from 0% at presentation to 22.2% at 6 months, 37.0% at 12 months and 49.4% at 24 months. Mean time to normalisation of MRD1 was 18.0±12.4 months. A positive family history of TED was found to be associated with a 6.2 times lower likelihood of normalisation. Change in exophthalmometry, clinical activity score and Thyroid-Stimulating Immunoglobulin were significantly correlated to change in MRD1 (p Conclusion An improved knowledge of the natural history of UER in TED will allow us to better decide and evaluate the optimal management for such patients.
Hooshang Lahooti - One of the best experts on this subject based on the ideXlab platform.
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Thyroid Stimulating Immunoglobulins as measured in a reporter bioassay are not detected in patients with hashimoto s Thyroiditis and ophthalmopathy or isolated upper eyelid retraction
Clinical Ophthalmology, 2014Co-Authors: Jack R Wall, Hooshang Lahooti, Ilhem El Kochairi, Simon D Lytton, Bernard ChampionAbstract:Although ophthalmopathy is mainly associated with Graves' hyperThyroidism, milder eye changes are also found in about 25% of patients with Hashimoto's Thyroiditis (HT). The recent finding of negative thyrotropin receptor (TSHR) antibodies, as measured in the Thyretain™ Thyroid-Stimulating Immunoglobulin (TSI) reporter bioassay, in patients with euThyroid Graves' disease raises the possibility that TSHR antibodies are not the cause of ophthalmopathy in all situations. Here, we have tested serum from patients with HT with and without ophthalmopathy or isolated upper eyelid retraction (UER) for TSHR antibodies, using the TSI reporter bioassay and collagen XIII as a marker of autoimmunity against the orbital fibroblast. Study groups were 23 patients with HT with ophthalmopathy, isolated UER, or both eye features and 17 patients without eye signs. Thyretain™ TSI results were expressed as a percentage of the sample-to-reference ratio, with a positive test being taken as a sample-to-reference ratio of more than 140%. Serum collagen XIII antibodies were measured in standard enzyme-linked immunosorbent assay. TSI tests were positive in 22% of patients with HT with no eye signs but in no patient with eye signs. In contrast, TSI tests were positive in 94% of patients with Graves' ophthalmopathy. Tests were negative in all normal subjects tested. Collagen XIII antibodies were detected in 83% of patients with ophthalmopathy, UER, or both eye features, but in only 30% of patients with no eye signs. Our findings suggest that TSHR antibodies do not play a major role in the pathogenesis of ophthalmopathy or isolated UER in patients with HT. Moreover, the role of TSHR antibodies in the development of ophthalmopathy in patients with Graves' disease remains to be proven. In contrast, collagen XIII antibodies appear to be a good marker of eye disease in patients with HT.
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Eye findings and immunological markers in probands and their euThyroid relatives from a single family with multiple cases of Thyroid autoimmunity
Thyroid Research, 2012Co-Authors: Melissa Ardley, Thomas Mccorquodale, Hooshang Lahooti, Bernard Champion, Jack R WallAbstract:Background Ophthalmopathy is a common manifestation of Graves’ disease (GD) occurring in up to 50% of patients. Mild eye signs are also common in patients with Hashimoto’s Thyroiditis. Whilst a genetic predisposition to GD has been demonstrated this is not the case for the ophthalmopathy which often runs a separate course. Objective We determined the prevalences of eye and eyelid signs and positive Thyroid and orbital antibody tests in first and second degree relatives from a single family with multiple cases of Graves’ disease, ophthalmopathy and Hashimoto’s Thyroiditis. Design The study cohort comprised 16 subjects from the same family, 4 probands namely, 3 with GD and one with Hashimoto’s Thyroiditis and hypoThyroidism and 12 of their euThyroid first or second degree relatives. We measured antibodies against calsequestrin (CASQ1) and collagen XIII in an enzyme-linked-immunosorbent assays and TSH-Receptor (TSH-R) antibodies as i) TSH-R binding inhibiting Immunoglobulin (TBII) and ii) Thyroid Stimulating Immunoglobulin (TSI). Eye signs were classified and quantified using the clinical activity score (CAS), NOSPECS classes, Nunery types 1 and 2 and the margin-reflex-distance (MRD) as a measure of upper eyelid retraction (UER). Main outcomes Whilst significant ophthalmopathy was uncommon in the relatives, mild eye signs, in particular UER, were demonstrated in about a third of them. The presence of eye signs was moderately, but not significantly, associated with the detection of CASQ1 and collagen XIII antibodies, but not TSH-R antibodies. Conclusion Our study demonstrates a significant prevalence of positive orbital antibody tests and ophthalmopathy in probands with Thyroid autoimmunity and their euThyroid relatives, favouring a role of genetic factors in the development of ophthalmopathy in patients with Thyroid autoimmunity.