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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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Stephanie Estcourt, Janis Hickey, Petros Perros, Colin Dayan and Bijay Vaidya

Background

A recent consensus statement from the European Group on Graves' Orbitopathy recommends referring all patients with thyroid eye disease (TED), except the mildest cases, to a specialist multidisciplinary clinic.

Objective

To study the patients' experiences of accessing services for the treatment of TED in the UK.

Methods

A postal questionnaire survey of 395 members of two patients support organisations for TED in the UK, the TED Charitable Trust and the British Thyroid Foundation.

Results

The response rate was 67%. The majority of responders were females (91%) and aged above 45 (74%). There were delays in the diagnosis and referral. In 26% of responders, the time lapsed from the first symptoms to the diagnosis of TED for over 12 months. There was a wide variation in the type of clinic and healthcare professionals involved in the treatment of TED. Only 25% of the responders attended a specialist TED clinic. Out of these, 33% waited over 6 months from the first consultation with a doctor to being seen at a specialist TED clinic. Only 56% of responders were satisfied with the treatment they received for TED. More responders who had attended a specialist TED clinic were satisfied with the treatment than those who had not attended a specialist clinic (67 vs 52%, P<0.05).

Conclusion

Only a minority of patients with TED are treated at a specialist TED clinic in the UK. Those patients who are treated at a specialist TED clinic are more likely to be satisfied with the treatment.

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Salman Razvi, Bijay Vaidya, Petros Perros and Simon H S Pearce

Block-replace and titration antithyroid drug regimens both give similar rates of medium- to long-term remission of hyperthyroid Graves’ disease. Recent meta-analysis, however, has suggested that titration regimens may be preferable owing to a higher rate of adverse events seen in the block-replace arms of published comparative studies. This article critically re-evaluates the evidence upon which these meta-analyses were based. We suggest that there is little objective evidence that is pertinent to current clinical practice to separate block-replace from titration antithyroid drug regimens and that both remain satisfactory approaches to the medical management of hyperthyroid Graves’ disease.

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Kalliopi Pazaitou-Panayiotou, Petros Perros, Maria Boudina, George Siardos, Apostolos Drimonitis, Frideriki Patakiouta and Iraklis Vainas

Background

Thyroid carcinoma has been reported in patients operated for different types of hyperthyroidism and the probability of a hot nodule being malignant seems to be low. The aim of the present study was to explore the relationship between thyroid cancer, hyperthyroidism and outcome in a large cohort of patients who presented to a tertiary cancer centre in Northern Greece.

Patients

Among 720 patients treated for thyroid cancer, 60 had a concomitant diagnosis of hyperthyroidism due to Graves' disease (n=14), solitary autonomous adenoma (n=17), or multinodular goiter (n=29). Adverse prognostic factors were common in patients with a previous history of hyperthyroidism at the time of diagnosis of thyroid cancer, including cases where the cancer was discovered coincidentally after thyroid surgery for hyperthyroidism and cases where tumor size was more than 10 mm.

Results

In 10 out of 17 patients with hyperthyroidism due to solitary autonomous adenomas, the tumor was located within the hot nodule and two of these patients developed local and distant metastases and died from the disease 4 and 15 years after thyroidectomy.

Conclusion

Clinicians managing patients with hyperthyroidism need to be aware of the possible increased risk of thyroid cancer in this patient group.

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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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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

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Wilmar Wiersinga, Miloš Žarković, Luigi Bartalena, Simone Donati, Petros Perros, Onyebuchi Okosieme, Daniel Morris, Nicole Fichter, Jurg Lareida, Georg von Arx, Chantal Daumerie, Maria-Christina Burlacu, George Kahaly, Susanne Pitz, Biljana Beleslin, Jasmina Ćirić, Goksun Ayvaz, Onur Konuk, Füsun Balos̜ Törüner, Mario Salvi, Danila Covelli, Nicola Curro, Laszlo Hegedüs, Thomas Brix and EUGOGO (European Group on Graves’ Orbitopathy)

Objective

To construct a predictive score for the development or progression of Graves’ orbitopathy (GO) in Graves’ hyperthyroidism (GH).

Design

Prospective observational study in patients with newly diagnosed GH, treated with antithyroid drugs (ATD) for 18 months at ten participating centers from EUGOGO in 8 European countries.

Methods

348 patients were included with untreated GH but without obvious GO. Mixed effects logistic regression was used to determine the best predictors. A predictive score (called PREDIGO) was constructed.

Results

GO occurred in 15% (mild in 13% and moderate to severe in 2%), predominantly at 6–12 months after start of ATD. Independent baseline determinants for the development of GO were clinical activity score (assigned 5 points if score > 0), TSH-binding inhibitory immunoglobulins (2 points if TBII 2–10 U/L, 5 points if TBII > 10 U/L), duration of hyperthyroid symptoms (1 point if 1–4 months, 3 points if >4 months) and smoking (2 points if current smoker). Based on the odds ratio of each of these four determinants, a quantitative predictive score (called PREDIGO) was constructed ranging from 0 to 15 with higher scores denoting higher risk; positive and negative predictive values were 0.28 (95% CI 0.20–0.37) and 0.91 (95% CI 0.87–0.94) respectively.

Conclusions

In patients without GO at diagnosis, 15% will develop GO (13% mild, 2% moderate to severe) during subsequent treatment with ATD for 18 months. A predictive score called PREDIGO composed of four baseline determinants was better in predicting those patients who will not develop obvious GO than who will.