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Deutsches Arzteblatt International Sep 2022
Topics: Humans; Exophthalmos
PubMed: 36507730
DOI: 10.3238/arztebl.m2022.0128 -
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 -
Frontiers in Endocrinology 2020Graves' Orbitopathy (GO) is an autoimmune orbital disorder usually presenting as a sequala of autoimmune thyroid disease. The presence of GO is associated with increased... (Review)
Review
Graves' Orbitopathy (GO) is an autoimmune orbital disorder usually presenting as a sequala of autoimmune thyroid disease. The presence of GO is associated with increased psychological burden and, in severe cases may cause blindness. While most patients with GO present with bilateral disease, asymmetric or unilateral GO may affect a significant proportion of patients diagnosed with GO. Older age, male sex, active and severe disease correlate with asymmetric disease. However, the exact mechanisms causing asymmetry remain elusive. Herein, we review the literature on asymmetric GO and highlight its differences compared with bilateral GO.
Topics: Age Factors; Animals; Graves Disease; Graves Ophthalmopathy; Humans; Sex Factors
PubMed: 33391188
DOI: 10.3389/fendo.2020.611845 -
Ugeskrift For Laeger May 2023
Topics: Humans; Meningioma; Exophthalmos; Meningeal Neoplasms
PubMed: 37170741
DOI: No ID Found -
CMAJ : Canadian Medical Association... Apr 2019
Topics: Amphotericin B; Antifungal Agents; Blindness; Brain Diseases; Debridement; Exophthalmos; Eye Diseases; Fatal Outcome; Female; Humans; Magnetic Resonance Imaging; Maxillary Sinusitis; Middle Aged; Mucormycosis; Optic Neuritis
PubMed: 31015350
DOI: 10.1503/cmaj.181210 -
BMJ Case Reports Dec 2019
Topics: Adult; Conservative Treatment; Exophthalmos; Humans; Magnetic Resonance Imaging; Male; Orbital Diseases; Varicose Veins
PubMed: 31818898
DOI: 10.1136/bcr-2019-232887 -
Journal of Neuro-ophthalmology : the... Sep 2016We describe 2 unique cases of visual symptoms occurring during mastication in patients with lateral orbital wall defects. A 57-year-old man reported intermittent double...
We describe 2 unique cases of visual symptoms occurring during mastication in patients with lateral orbital wall defects. A 57-year-old man reported intermittent double vision and oscillopsia after a right fronto-temporal-orbito-zygomatic craniotomy with osteotomy of the lesser wing of the sphenoid for a complex invasive pituitary adenoma. Proptosis of the right globe was present only during mastication. Computed tomography (CT) revealed a bony defect in the right lateral orbital wall. A 48-year-old man presented with transient diplopia and scotoma in the right eye elicited by chewing. CT and magnetic resonance imaging demonstrated a bilobed lesion connecting the temporal fossa to the orbit through a defect in the right lateral orbital wall. The regional neuroanatomy and pathophysiology as pertaining to these cases are discussed.
Topics: Craniotomy; Diplopia; Exophthalmos; Humans; Magnetic Resonance Imaging; Male; Mastication; Middle Aged; Orbit; Postoperative Complications; Sphenoid Bone; Tomography, X-Ray Computed
PubMed: 26919071
DOI: 10.1097/WNO.0000000000000354 -
PloS One 2022This study aimed at evaluating the orbital anatomy of patients concerning the relevance of orbital anatomy in the etiology of EO (endocrine orbitopathy) and exophthalmos...
PURPOSE
This study aimed at evaluating the orbital anatomy of patients concerning the relevance of orbital anatomy in the etiology of EO (endocrine orbitopathy) and exophthalmos utilizing a novel approach regarding three-dimensional measurements. Furthermore, sexual dimorphism in orbital anatomy was analyzed.
METHODS
Orbital anatomy of 123 Caucasian patients (52 with EO, 71 without EO) was examined using computed tomographic data and FAT software for 3-D cephalometry. Using 56 anatomical landmarks, 20 angles and 155 distances were measured. MEDAS software was used for performing connected and unconnected t-tests and Spearman´s rank correlation test to evaluate interrelations and differences.
RESULTS
Orbital anatomy was highly symmetrical with a mean side difference of 0.3 mm for distances and 0.6° for angles. There was a small albeit statistically significant difference in 13 out of 155 distances in women and 1 in men concerning patients with and without EO. Two out of 12 angles showed a statistically significant difference between female patients with and without EO. Regarding sex, statistically significant differences occurred in 39 distances, orbit volume, orbit surface, and 2 angles. On average, measurements were larger in men. Concerning globe position within the orbit, larger distances to the orbital apex correlated with larger orbital dimensions whereas the sagittal position of the orbital rim defined Hertel values.
CONCLUSION
In this study, little difference in orbital anatomy between patients with and without EO was found. Concerning sex, orbital anatomy differed significantly with men presenting larger orbital dimensions. Regarding clinically measured exophthalmos, orbital aperture anatomy is an important factor which has to be considered in distinguishing between true exophthalmos with a larger distance between globe and orbital apex and pseudoexophthalmos were only the orbital rim is retruded. Thus, orbital anatomy may influence therapy regarding timing and surgical procedures as it affects exophthalmos.
Topics: Cephalometry; Exophthalmos; Female; Graves Ophthalmopathy; Humans; Male; Orbit; Retrospective Studies
PubMed: 35275980
DOI: 10.1371/journal.pone.0265324 -
Ophthalmic Plastic and Reconstructive... Dec 2023Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves disease. Patients may be severely affected with eyelid retraction, exophthalmos,... (Review)
Review
PURPOSE
Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves disease. Patients may be severely affected with eyelid retraction, exophthalmos, diplopia, pain, and threatened vision. Autoantibodies against thyroid-stimulating hormone receptor and insulin-like growth factor 1 receptor have shown associations with pathophysiological and clinical traits. Autoantibodies against thyroid-stimulating hormone receptor is in current clinical use as biomarker, but not with unambiguous diagnostic performance. A biomarker with high diagnostic accuracy and/or prognostic capability would be of immense value in diagnosing TED, especially in subclinical cases or when TED precedes the thyroid dysfunction. This article is a literature review on molecular biomarkers of TED.
METHODS
A literature search was performed using PubMed and Embase. Studies on molecular biomarkers in blood, tear fluid, and urine were included in the review.
RESULTS
Forty-six papers were included, of which 30, 14, and 2 studies on biomarkers in blood, tears, and urine, respectively. Fourteen of the papers evaluated the diagnostic performance of various biomarkers, 12 in blood and 2 in tears. Most studies evaluated single biomarkers, but 3 tested a panel of several markers. Except for autoantibodies against thyroid-stimulating hormone receptor, the reported diagnostic performances for the biomarkers were not confirmed in independent cohorts. In 32 studies, no or insufficient performance data were given, but the findings indicated involvement of various biologic mechanisms in TED including inflammation, oxidative stress, fibrosis, lipid metabolism, and ocular surface microflora.
CONCLUSIONS
Currently, serum autoantibodies against thyroid-stimulating hormone receptor is the only molecular biomarker with clinical utility in patients with TED. Several potential biomarkers have been investigated, and particularly panels of multiple biomarkers in tears are promising. To improve patient care, biomarkers in TED should be studied further.
Topics: Humans; Graves Ophthalmopathy; Biomarkers; Graves Disease; Autoantibodies; Thyrotropin
PubMed: 38054982
DOI: 10.1097/IOP.0000000000002466 -
BMJ Case Reports Mar 2022A postpartum woman presented with sudden-onset left eyelid swelling and severe pain. Clinical examination revealed left exophthalmos and ophthalmoplegia with marked...
A postpartum woman presented with sudden-onset left eyelid swelling and severe pain. Clinical examination revealed left exophthalmos and ophthalmoplegia with marked resistance to retropulsion of the left globe. The patient was not able to perceive light in the affected left eye and a relative afferent pupillary defect was present. CT orbits showed an enhancing lesion in the left retrobulbar space, suggestive of a lateral rectus haemorrhage. An emergency left lateral canthotomy and inferior cantholysis was performed. A day later, an MRI showed expansion of the left lateral rectus with significant mass effect on the globe. As the visual acuity remained reduced at counting fingers and there was a persistent relative afferent pupillary defect (RAPD), an exploratory orbitotomy and haematoma evacuation was performed. Three days postoperatively, the visual acuity had returned to 6/6. Eye movements normalised within 2 weeks and follow-up imaging revealed near complete resolution of the haematoma.
Topics: Exophthalmos; Female; Humans; Oculomotor Muscles; Orbit; Postpartum Period; Retrobulbar Hemorrhage
PubMed: 35241450
DOI: 10.1136/bcr-2021-248133