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Thyroid : Official Journal of the... Dec 2022Thyroid eye disease (TED) remains challenging for clinicians to evaluate and manage. Novel therapies have recently emerged, and their specific roles are still being...
Thyroid eye disease (TED) remains challenging for clinicians to evaluate and manage. Novel therapies have recently emerged, and their specific roles are still being determined. Most patients with TED develop eye manifestations while being treated for hyperthyroidism and under the care of endocrinologists. Endocrinologists, therefore, have a key role in diagnosis, initial management, and selection of patients who require referral to specialist care. Given that the need for guidance to endocrinologists charged with meeting the needs of patients with TED transcends national borders, and to maximize an international exchange of knowledge and practices, the American Thyroid Association and European Thyroid Association joined forces to produce this consensus statement.
Topics: Humans; Consensus; Graves Ophthalmopathy; Hyperthyroidism; United States; Europe
PubMed: 36480280
DOI: 10.1089/thy.2022.0251 -
Revue Medicale de Liege May 2022A thyroiditis is an inflammatory disease of the thyroid whether autoimmune, infectious or drug-induced. Autoimmune thyroid diseases (including Hashimoto's thyroiditis...
A thyroiditis is an inflammatory disease of the thyroid whether autoimmune, infectious or drug-induced. Autoimmune thyroid diseases (including Hashimoto's thyroiditis and Graves' disease) are the most frequent of all autoimmune pathologies. The clinical presentation and history are often revealing of the pathology and its etiology. Complementary examinations allow to confirm the diagnosis and to follow the evolution of the disease. Sometimes the disease could have a mixed presentation associating two different causes (like a mixed autoimmunity for Graves and Hashimoto diseases). In these cases, the treatment options are not always straightforward and may need to be adapted with the clinical evolution.
Topics: Graves Disease; Hashimoto Disease; Humans; Thyroiditis
PubMed: 35657195
DOI: No ID Found -
The Journal of Clinical Endocrinology... Nov 2023Inhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Inhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye disease (TED).
OBJECTIVE
We report the first clinical studies of an FcRn inhibitor, batoclimab, in TED.
DESIGN
Proof-of-concept (POC) and randomized, double-blind placebo-controlled trials.
SETTING
Multicenter.
PARTICIPANTS
Patients with moderate-to-severe, active TED.
INTERVENTION
In the POC trial, patients received weekly subcutaneous injections of batoclimab 680 mg for 2 weeks, followed by 340 mg for 4 weeks. In the double-blind trial, patients were randomized 2:2:1:2 to weekly batoclimab (680 mg, 340 mg, 255 mg) or placebo for 12 weeks.
MAIN OUTCOME
Change from baseline in serum anti-TSH-R-Ab and total IgG (POC); 12-week proptosis response (randomized trial).
RESULTS
The randomized trial was terminated because of an unanticipated increase in serum cholesterol; therefore, data from 65 of the planned 77 patients were analyzed. Both trials showed marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels (P < .001) with batoclimab. In the randomized trial, there was no statistically significant difference with batoclimab vs placebo in proptosis response at 12 weeks, although significant differences were observed at several earlier timepoints. In addition, orbital muscle volume decreased (P < .03) at 12 weeks, whereas quality of life (appearance subscale) improved (P < .03) at 19 weeks in the 680-mg group. Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation.
CONCLUSIONS
These results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED.
Topics: Infant, Newborn; Humans; Graves Ophthalmopathy; Quality of Life; Antibodies, Monoclonal; Exophthalmos; Immunoglobulin G; Double-Blind Method; Treatment Outcome
PubMed: 37390454
DOI: 10.1210/clinem/dgad381 -
Best Practice & Research. Clinical... Mar 2023The chemokine receptor CXCR3 and its chemokines CXCL9, CXCL10, and CXCL11 are involved in the pathogenesis of autoimmune diseases. Th1 lymphocytes are recruited by Th1... (Review)
Review
The chemokine receptor CXCR3 and its chemokines CXCL9, CXCL10, and CXCL11 are involved in the pathogenesis of autoimmune diseases. Th1 lymphocytes are recruited by Th1 chemokines, secreted by damaged cells. In inflamed tissues, the attracted Th1 lymphocytes induce the IFN-gamma and TNF-alpha release, that stimulates the secretion of Th1 chemokines, initiating and reiterating an amplification feedback loop. Autoimmune thyroid disorders (AITD) are the most recurrent autoimmune diseases, including Graves' disease (GD) and autoimmune thyroiditis, clinically defined by thyrotoxicosis and hypothyroidism, respectively. Graves' ophthalmopathy is one of GD extrathyroidal manifestations, occurring in ~30-50% of GD patients. In the early phase of AITD, the Th1 immune response is prevalent, and a following switch to a Th2 immune response has been shown in the late, inactive, phase. The reviewed data underline the importance of chemokines in thyroid autoimmunity and suggest CXCR3-receptor and its chemokines as potential targets of novel drugs for these disorders.
Topics: Humans; Autoimmunity; Chemokine CXCL10; Autoimmune Diseases; Graves Disease; Graves Ophthalmopathy; Hashimoto Disease
PubMed: 36907786
DOI: 10.1016/j.beem.2023.101773 -
Deutsches Arzteblatt International Sep 2022
Topics: Humans; Exophthalmos
PubMed: 36507730
DOI: 10.3238/arztebl.m2022.0128 -
CMAJ : Canadian Medical Association... Jan 2022
Topics: Delayed Diagnosis; Female; Graves Disease; Humans; Postpartum Period
PubMed: 35039394
DOI: 10.1503/cmaj.212115 -
Missouri Medicine 2022Thyroid eye disease, although rare, is the most common inflammatory orbital disorder and is associated with autoimmune thyroid dysfunction. It is a progressive disorder...
Thyroid eye disease, although rare, is the most common inflammatory orbital disorder and is associated with autoimmune thyroid dysfunction. It is a progressive disorder with symptoms and signs that may cause significant facial disfigurement, visual disability, but rarely blindness. We will review the diagnostic criteria, immunologic basis, clinical course, and medical and surgical treatments for thyroid eye disease. Recent developments in the use of biologic agents to treat this disorder appear to be changing its progression curve and offer the first specific and preventative therapeutic options.
Topics: Biological Factors; Blindness; Graves Ophthalmopathy; Humans
PubMed: 36118816
DOI: No ID Found -
Clinical Endocrinology Jun 2022In Graves' disease (GD), autoantibodies to the thyroid stimulating hormone receptor (TSHR) cause hyperthyroidism. The condition is often associated with eye signs...
TSH receptor specific monoclonal autoantibody K1-70 targeting of the TSH receptor in subjects with Graves' disease and Graves' orbitopathy-Results from a phase I clinical trial.
OBJECTIVES
In Graves' disease (GD), autoantibodies to the thyroid stimulating hormone receptor (TSHR) cause hyperthyroidism. The condition is often associated with eye signs including proptosis, oedema, and diplopia (collectively termed Graves' orbitopathy [GO]). The safety profile of K1-70 (a human monoclonal TSHR specific autoantibody, which blocks ligand binding and stimulation of the receptor) in patients with GD was evaluated in a phase I clinical trial.
PATIENTS AND STUDY DESIGN
Eighteen GD patients stable on antithyroid drug medication received a single intramuscular (IM) or intravenous (IV) dose of K1-70 during an open label phase I ascending dose, safety, tolerability, pharmacokinetic and pharmacodynamic (PD) study. Immunogenic effects of K1-70 were also determined.
RESULTS
K1-70 was well-tolerated in all subjects at all doses and no significant immunogenic response was observed. There were no deaths or serious adverse events. Increased systemic exposure to K1-70 was observed following a change to IV dosing, indicating this was the correct dosage route. Expected PD effects occurred after a single IM dose of 25 mg or single IV dose of 50 mg or 150 mg with fT3, fT4, and TSH levels progressing into hypothyroid ranges. There were also clinically significant improvements in symptoms of both GD (reduced tremor, improved sleep, improved mental focus, reduced toilet urgency) and GO (reduced exophthalmos measurements, reduced photosensitivity).
CONCLUSIONS
K1-70 was safe, well tolerated and produced the expected PD effects with no immunogenic responses. It shows considerable promise as a new drug to block the actions of thyroid stimulators on the TSHR.
Topics: Antithyroid Agents; Autoantibodies; Graves Disease; Graves Ophthalmopathy; Humans; Receptors, Thyrotropin
PubMed: 35088429
DOI: 10.1111/cen.14681 -
Ugeskrift For Laeger May 2023
Topics: Humans; Meningioma; Exophthalmos; Meningeal Neoplasms
PubMed: 37170741
DOI: No ID Found -
The Journal of the American Osteopathic... Jun 2020
Topics: Graves Ophthalmopathy; Humans
PubMed: 32451543
DOI: 10.7556/jaoa.2020.068