Pathogenetic mechanisms in thyroid-associated ophthalmopathy.
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Autoimmunity↗
Biomedical subjects
P Perros
Publications and source records attributed to P Perros.
Antibodies to orbital tissues in thyroid-associated ophthalmopathy.
Thyroid-associated ophthalmopathy is thought to be an autoimmune disease affecting the orbit. The precise pathogenetic mechanisms are not known, but extraocular muscle and/or orbital fibroblasts are the likely targets of the autoimmune attack. Sera from 41 normal controls, 79 patients with thyroid-associated ophthalmopathy and 72 patients with other autoimmune diseases were examined for antibodies to cultured orbital fibroblasts and extraocular muscle by enzyme-linked immunosorbent assay. Orbital fibroblast antibody levels varied widely in all subject groups studied, and failed to distinguish patients with thyroid-associated ophthalmopathy from patients with other autoimmune diseases or controls. Eye-muscle binding antibody levels were higher amongst patients with ophthalmopathy compared to normal controls and patients with Graves' hyperthyroidism without clinical evidence of ophthalmopathy. Furthermore, eye-muscle binding antibody levels were found to be particularly high in patients with ophthalmopathy and concurrent dermopathy, and in patients with ophthalmic (euthyroid) Graves' disease.
Adult↗
Biological activity of autoantibodies from patients with thyroid-associated ophthalmopathy: in vitro effects on porcine extraocular myoblasts.
To determine whether antibodies to orbital tissue have a pathogenic role in thyroid-associated ophthalmopathy, the in vitro effects of IgG from patients with thyroid-associated ophthalmopathy on porcine extraocular myoblast growth were studied. Growth of primary extraocular myoblast cultures and extraocular myoblast clones was stimulated by patients' IgG, as measured by [3H]thymidine uptake and bromodeoxyuridine incorporation. Myoblasts responded in a dose-related fashion to increasing concentrations of patients' IgG, and the response was reversed by anti-human IgG. The growth stimulating effect of patients' IgG was relatively specific to extraocular myoblasts, compared to skeletal myoblasts. Individual IgG samples from 36 patients with ophthalmopathy gave rise to higher growth responses of cloned extraocular myoblasts, than either 31 normal controls (p < 0.005), or IgG from 10 patients with Graves' disease without evidence of ophthalmopathy (p < 0.001). Myoblast growth-stimulating antibody did not correlate with thyroid autoantibody levels (thyrotrophin receptor antibody or thyroid microsomal antibody levels), but correlated significantly with binding to extraocular muscle membranes (r = 0.524, p < 0.001). Eye-muscle stimulating antibodies were demonstrable in sera of patients with thyroid-associated ophthalmopathy, and may be responsible for the enlargement of eye muscle in this disease.
Animals↗
Autoantibodies to eye muscle and orbital fibroblasts in the pathogenesis of thyroid-associated ophthalmopathy.
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Autoantibodies↗
Measurement of cell proliferation by enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody to bromodeoxyuridine.
An ELISA was developed and optimized to measure cell proliferation using a monoclonal antibody to bromodeoxyuridine (BrdUrd). Incorporation of BrdUrd into myoblast monolayers, measured as the optical density at 492 nm, increased in response to fetal calf serum, IGF-I and EGF, the ELISA data correlated closely with data obtained by BrdUrd immunocytochemistry (r = 0.984), cell counting (r = 0.972) and tritiated thymidine uptake by liquid scintillation counting (r = 0.990). The BrdUrd ELISA is a useful alternative to measurement of tritiated thymidine uptake by scintillation counting, and has the added advantages of dispensing with the use of radioactivity and of being less labour intensive.
Animals↗
Azathioprine in the treatment of thyroid-associated ophthalmopathy.
Azathioprine is used in the treatment of thyroid-associated ophthalmopathy, but its effectiveness has not been evaluated. In the present study 20 patients with moderately severe ophthalmopathy were recruited; 10 patients received azathioprine and the other 10 matched patients served as controls. During the treatment period (lasting 1 year) and 1 year later, no changes were detected in exophthalmometer readings, visual acuity or measurement of palpebral aperture. Differential intraocular pressure fell with time in both groups. Azathioprine treatment did not significantly influence these parameters, although it did induce significant decrease in thyroid microsomal antibodies and in thyroid-stimulating hormone binding inhibiting immunoglobulin index. The study demonstrates that thyroid-associated ophthalmopathy of moderate severity, often improves with time without treatment. Azathioprine is not an effective treatment for patients with moderately severe thyroid-associated ophthalmopathy. The study emphasises the necessity for an adequately matched control population in the evaluation of therapy.
Azathioprine↗
The pathogenesis of thyroid-associated ophthalmopathy.
TAO is an autoimmune disease the pathogenesis of which is unclear. Autoimmunity against orbital antigens has been demonstrated, although the precise immunological mechanisms responsible are unidentified. Cytokines probably play an important mediating role. Activation of orbital fibroblasts appears to be essential in bringing about interstitial oedema and enlargement of EOM. The challenge for the future lies in clarifying the role of cytokines, identifying the autoantigen and elucidating the immunological mechanisms underlying the disease.
Autoantigens↗
Psoas abscess due to retroperitoneal tuberculous lymphadenopathy.
A case of psoas abscess occurring during treatment of tuberculous lymphadenopathy is described. There was no evidence of a bony origin for this abscess. It appears likely that it arose from involved glands on the posterior abdominal wall.
Abscess↗
Differentiation of autoimmune ophthalmopathy from Graves' hyperthyroidism by analysis of genetic markers.
Graves' hyperthyroidism and dysthyroid eye disease are closely related autoimmune conditions. Whether the eye disease is an integral part of Graves' disease or a separate entity is controversial. To investigate this we have examined the genetic associations of ophthalmopathy and hyperthyroidism, and compared their phenotype and gene frequencies with a control normal population. HLA-A, B, and DR antigens were typed in 67 patients with dysthyroid eye disease (GO), 60 hyperthyroid patients without significant eye disease (HT) and 500 normal subjects. Patients were also typed for a variety of other genetic markers: blood group systems (10), serum proteins (6) and red cell enzyme systems (10). Increased frequency of B8 and DR3 in Graves' disease was confirmed; B17 occurred less frequently and appears to be protective. HLA antigen frequencies for GO did not differ from HT. The MNS blood group showed a significant association with Graves' disease, the HT patients having a deficit of the s gene compared with controls. The most interesting finding was an increased frequency of blood group P in GO patients compared with either HT or controls. Significant differences were not seen with any of the other HLA antigens, blood groups, protein or enzyme markers considered individually. Multivariate analysis applied first to the HLA and then to the non-HLA systems indicated clear separation of the two patient groups. Although Graves' eye disease shares the same HLA associations as hyperthyroidism, it differs in the increased frequency of P blood group, suggesting that additional genetic factors may determine which patients with Graves' disease develop ophthalmopathy.
Autoimmune Diseases↗
Evaluation of serum markers of neuronal damage following severe hypoglycaemia in adults with insulin-treated diabetes mellitus.
BACKGROUND: Neurone-specific enolase (NSE) and protein S-100 (S-100) may be used as markers of acute neuronal damage in humans with neurological disorders. METHOD: To evaluate their use following a single episode of severe hypoglycaemia (defined as an episode requiring external assistance to aid recovery), serum concentrations of NSE and S-100 were measured following hypoglycaemia which had not caused persistent neurological impairment in 16 patients with insulin-treated diabetes (the 'hypo' subjects), and in three diabetic patients who died following severe hypoglycaemia. The serum proteins were also measured in 10 subjects with insulin-treated diabetes who had not experienced an episode of severe hypoglycaemia within the preceding year (the 'control' subjects). RESULTS: No differences in serum concentrations of NSE and S-100 were observed between the 'control' and the 'hypo' subjects at either 36 hours or seven days after the episode of severe hypoglycaemia (p>0.05). However, in two of the three subjects who died following hypoglycaemia, serum concentrations of the markers were markedly elevated. CONCLUSIONS: Any neuronal injury occurring during severe hypoglycaemia that is not associated with persistent neurological deficit is insufficient to provoke elevation of these serum markers. However, the measurement of serum concentrations of NSE and S-100 may have a prognostic role in evaluating clinical outcome following severe hypoglycaemia which is associated with neurological damage.
Adult↗
Elevated serum growth hormone in a patient with Type 1 diabetes: a diagnostic dilemma.
The biochemical confirmation of acromegaly is rarely difficult and is based on an elevated fasting serum growth hormone (GH) concentration, which fails to suppress in response to an oral glucose load. Impaired glucose tolerance and Type 2 diabetes are common in patients with acromegaly, however the development of acromegaly in a patient with pre-existing Type 1 diabetes has not been well documented. Poorly controlled Type 1 diabetes in non-acromegalic patients is associated with dysregulation of the hypothalamic-GH/insulin-like growth factor-1 (IGF-1) axis, leading to elevation of serum GH concentrations. Therefore the diagnosis of acromegaly in a Type 1 diabetic patient may be fraught with practical difficulties in performing and interpreting the results of an oral glucose tolerance test (OGTT) and other biochemical investigations. When, in addition, the clinical and radiological features of acromegaly are equivocal, the clinician is faced with a formidable diagnostic challenge. In this paper we report such a case, review the pathophysiology of hypersomatotrophinaemia in poorly controlled Type 1 diabetes, and recommend a diagnostic algorithm for the investigation of acromegaly in patients with diabetes.
Acromegaly↗