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Petros Perros and Pat Kendall-Taylor

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.

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Petros Perros, David R. Weightman, Alex L. Crombie and Pat Kendall-Taylor

Abstract

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.

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Pat Kendall-Taylor, Peter J Jönsson, Roger Abs, Eva Marie Erfurth, Maria Koltowska-Häggström, David Anthony Price and Johan Verhelst

Background: Craniopharyngioma is a parasellar tumour that, although benign, tends to behave aggressively. It can occur at any age but most commonly presents in childhood or adolescence.

Objectives: To investigate the frequency and severity of problems associated with craniopharyngioma, using the large international database (KIMS) for adult patients with GH deficiency (GHD), and to assess the differences between the adult onset (AO, aged 18 or above) disease and adults with childhood onset (CO) craniopharyngioma.

Design: Inclusion criteria were: an established diagnosis of craniopharyngioma, severe GHD and no recent GH treatment. These criteria were fulfilled by 393 (184 female, 209 male) patients; 241 had AO (mean age 28.7±8.7 years) and 152 had CO disease (age 42.0±12.3 years). Disease history, clinical features and anthropometric data were recorded at the time of enrolment in the database, and body composition, serum IGF-I, serum lipids and quality of life (QoL) were assessed.

Results: Peak age at onset of craniopharyngioma was 15–20 years. Ninety percent of patients had been treated surgically. CO patients were shorter than AO patients and had much lower IGF-I standard deviation scores (SDS). The majority had hypopituitarism and over 60% had diabetes insipidus. Body mass index (BMI) was higher in AO males (30.2±5.5) than in CO males (28.5±7.5); waist circumference was also greater. Obesity was more common in AO patients (51.8% vs 39.1%). Body composition did not differ between groups. Cholesterol and triglycerides were higher in AO than in CO patients, but high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol did not differ. Quality of life, assessed by Quality of Life-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA) and the Nottingham Health Profile, was markedly reduced in all groups with no significant differences between them; the QoL-AGHDA score correlated with age at onset of both craniopharyngioma and GHD, and also with BMI in AO patients.

Conclusions: These data emphasise the generally poor state of health of patients treated for craniopharyngioma, with respect to endocrine and metabolic function, and also the markedly reduced quality of life. In addition to GHD, most patients have evidence of hypothalamic damage with associated obesity, diabetes insipidus and hypopituitarism. Adults with CO craniopharyngioma were shorter, had lower IGF-I, lower BMI, less obesity and slightly lower blood lipid levels than patients with AO craniopharyngioma.

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Luigi Bartalena, Lelio Baldeschi, Alison Dickinson, Anja Eckstein, Pat Kendall-Taylor, Claudio Marcocci, Maarten Mourits, Petros Perros, Kostas Boboridis, Antonella Boschi, Nicola Currò, Chantal Daumerie, George J Kahaly, Gerasimos E Krassas, Carol M Lane, John H Lazarus, Michele Marinò, Marco Nardi, Christopher Neoh, Jacques Orgiazzi, Simon Pearce, Aldo Pinchera, Susanne Pitz, Mario Salvi, Paolo Sivelli, Matthias Stahl, Georg von Arx and Wilmar M Wiersinga