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Guideline Consensus statement of the European group on Graves' orbitopathy (EUGOGO) on management of Graves' orbitopathy. 2008
Bartalena L, Baldeschi L, Dickinson AJ, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits MP, Perros P, Boboridis K, Boschi A, Currò N, Daumerie C, Kahaly GJ, Krassas G, Lane CM, Lazarus JH, Marinò M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM. · Department of Clinical Medicine, University of Insubria, Varese, Italy. · Thyroid. · Pubmed #18341379 No free full text.
This publication has no abstract.
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Editorial Introduction to the updated guidelines on the management of thyroid cancer. 2007
Perros P, Anonymous00066. · No affiliation provided · Clin Med. · Pubmed #17882843 No free full text.
This publication has no abstract.
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Editorial Optimizing the management of differentiated thyroid cancer. 2000
Mallick UK, Lucraft H, Proud G, Perros P, Fenwick J, Kendall-Taylor P, Johnson S, Lennard T, Ball S, James RA, Douglas F, Weightman DR. · No affiliation provided · Clin Oncol (R Coll Radiol). · Pubmed #11202089 No free full text.
This publication has no abstract.
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Review Thyroid-associated orbitopathy: who and how to treat. 2009
Dickinson J, Perros P. · Department of Ophthalmology, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK. · Endocrinol Metab Clin North Am. · Pubmed #19328417 No free full text.
Abstract: Thyroid-associated orbitopathy is the most frequent and troublesome nonthyroidal complication of Graves' disease. It is mandatory to determine whether sight-threatening orbitopathy is present, as this requires prompt and aggressive treatment. Therapies for non-sight-threatening disease range from supportive measures only to medical therapies for active eye disease and surgical rehabilitation for burnt-out disease. Intravenous steroids and orbital radiotherapy are the mainstays of medical therapy. Rehabilitative surgery is frequently a staged process that may involve sequentially: orbital decompression, strabismus surgery, and eyelid procedures. Smoking cessation is recommended at all disease stages. Treatment within a multidisciplinary team consisting of both endocrinologists and ophthalmologists may lead to optimal patient outcomes.
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Review Psychological implications of Graves' orbitopathy. free! 2007
Coulter I, Frewin S, Krassas GE, Perros P. · Endocrine Unit, Level 6, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, UK. · Eur J Endocrinol. · Pubmed #17656589 links to free full text
Abstract: Patients with thyroid eye disease, Graves' orbitopathy (GO), often appear distressed and it is likely that features of the condition such as disturbances in visual function, orbital discomfort and alterations in facial appearance can impart significant psychological morbidity upon the patient, which in turn can be detrimental to their quality of life. When considering the psychological impact of GO, two elements of the disease are important. The disfiguring changes to the eyes and face can have a direct effect upon psychological health, while physical aspects of the disease such as altered visual acuity, diplopia, orbital pain and lacrimation may influence psychological function as a secondary phenomenon, due to interference with daily living. Evidence appears to confirm the anecdotal impression of many clinicians dealing with GO patients that the prevalence of psychological morbidity in this patient group is high. A 'biopsychosocial' approach to care that addresses biological and psychosocial functioning as major determinants of health is an appropriate strategy when treating patients with GO.
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Review Prevention of thyroid associated-ophthalmopathy in children and adults: current views and management of preventable risk factors. 2007
Krassas GE, Perros P. · Department of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, Thessaloniki, Greece. · Pediatr Endocrinol Rev. · Pubmed #17551483 No free full text.
Abstract: Primary, secondary and tertiary prevention are defined according to the timing of the preventive intervention in the natural history of a disease. Secondary prevention in Graves' ophthalmopathy (GO) is challenging in the absence of reliable specific serum markers for subclinical GO that would allow an early diagnosis.Some risk factors for occurrence or progression of GO have been identified. Cigarette smoking, thyroid dysfunction and radioactive iodine (RAI) are known preventable risk factors. The list is probably much longer, and future research should be aimed at identifying more. Smoking cessation, restoration of euthyroidism by antithyroid drugs or L-thyroxine, glucocorticoid coverage after RAI or deferring RAI until the eye disease is inactive, may prevent progression of GO. Passive smoking seems to exacerbate autoimmune thyroid disease (AITD) in general, and may have a deleterious effect on childhood GO in particular, therefore avoidance of passive smoking is likely to be beneficial.
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Review Clinical assessment of patients with Graves' orbitopathy: the European Group on Graves' Orbitopathy recommendations to generalists, specialists and clinical researchers. free! 2006
Anonymous00251, Wiersinga WM, Perros P, Kahaly GJ, Mourits MP, Baldeschi L, Boboridis K, Boschi A, Dickinson AJ, Kendall-Taylor P, Krassas GE, Lane CM, Lazarus JH, Marcocci C, Marino M, Nardi M, Neoh C, Orgiazzi J, Pinchera A, Pitz S, Prummel MF, Sartini MS, Stahl M, von Arx G. · Department of Endocrinology, Academic Medical Centre, Amsterdam, The Netherlands. · Eur J Endocrinol. · Pubmed #16914591 links to free full text
This publication has no abstract.
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Review Thyrotoxicosis and pregnancy. free! 2005
Perros P. · Endocrine Unit, Freeman Hospital, Newcastle upon Tyne, United Kingdom. · PLoS Med. · Pubmed #16363909 links to free full text
This publication has no abstract.
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Review rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma: a comprehensive review. free! 2005
Luster M, Lippi F, Jarzab B, Perros P, Lassmann M, Reiners C, Pacini F. · Department of Nuclear Medicine, University of Würzburg, Josef-Schneider-Str.2,97080 Würzburg, Germany. · Endocr Relat Cancer. · Pubmed #15788638 links to free full text
Abstract: Traditionally, withdrawal of thyroid hormone has been used to attain the increase in serum TSH concentrations that are believed to optimize the trapping and retention of radioiodine for diagnostic procedures, thyroid remnant ablation and treatment of patients with differentiated thyroid cancer (DTC). However, withdrawal frequently causes clinical hypothyroidism, with resultant cognitive impairment, emotional dysfunction, physical discomfort, health risks in patients who are elderly, frail or have concomitant illness, and impaired quality of life and ability to work. Recombinant human TSH (rhTSH) was developed to provide TSH stimulation without withdrawal of thyroid hormone and the associated morbidity. rhTSH has been approved as an adjunct for diagnostic procedures in patients with DTC, but is currently an experimental aid in thyroid remnant ablation and the treatment of thyroid tumours. In the period 1997-2004, nearly 30 medical centres worldwide have reported on almost 400 patients with DTC who were given rhTSH in preparation for radioiodine ablation of thyroid remnants or treatment of local tumours of metastatic disease. We have analysed and summarized the findings reported in this literature. Ablation aided by the standard course of rhTSH, two consecutive daily injections of 0.9 mg, had success rates better than 84% in 90 patients given radioiodine activities in excess of 4000 MBq. However, when 1110 MBq was administered, success rates were 81.2% in 16 patients given the standard course of rhTSH and 4-day withdrawal of thyroid hormone around the time of radioiodine administration in one study, but 54% in 70 patients in another study. rhTSH-aided treatment of persistent or recurrent local or metastatic cancer, or both, with from one to six courses of radioiodine 1000-19055 MBq, achieved 2% complete remission, 36% partial response and 27% disease stabilization rates, for a 65% clinical benefit rate, in 115 primarily elderly, late-stage patients for whom responses were reported. Twelve of these patients died as a result of progressive disease or were discharged from hospital into hospice care. Generally, rhTSH was very well tolerated. However, in a minority of patients with central nervous system, spinal or bone metastases, or bulky thyroid remnant or neck lesions with or without poor pulmonary reserve, administration of rhTSH, like thyroid hormone withdrawal, was found to stimulate expansion of the tumour, with ensuing compression of key anatomical structures and neurological, respiratory or other clinical complications. The rapid onset, response to glucocorticoids and radiological findings of peritumoural oedema or, less commonly, haemorrhage in the published cases, strongly suggest that the tumour expansion was the result of swelling rather than growth. As in the case of thyroid hormone withdrawal, special attention and glucocorticoid premedication are thus warranted when rhTSH is given to patients known or suspected to have the above characteristics. Dosimetric data suggest that whole-body and whole-blood radioiodine clearance may be faster in euthyroid patients after administration of rhTSH. In theory, the faster clearance could allow, or demand, increased radioiodine activities when rhTSH is used, but clinical data to date suggest that this may be unnecessary. The faster clearance also might result in safety or convenience benefits with the use of rhTSH, such as decreased exposure of extrathyroid areas to radiation, and shorter hospital stays. In conclusion, in preliminary results from open-label studies, both rhTSH-aided tumour ablation and treatment have been well tolerated and have shown efficacy in substantial proportions of patients. rhTSH-aided ablation merits further study. rhTSH-aided treatment may be preferred in patients who are at greater risk of hypothyroid complications from withdrawal of thyroid hormone or are unable to produce sufficient endogenous TSH, and warrants additional investigation in younger patients at earlier stages of thyroid cancer.
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Review Glucocorticoids in the medical management of Graves' ophthalmopathy. 2003
Hart RH, Perros P. · Department of Ophthalmology, Newcastle Hospitals NHS Trust, Newcastle upon Tyne, UK. · Minerva Endocrinol. · Pubmed #14605604 No free full text.
Abstract: Graves' ophthalmopathy (GO) is a challenging disease that poses therapeutic dilemmas for endocrinologists and ophthalmologists. Progress in medical therapy has been slow. Numerous new treatments have been reported to have a beneficial effect. However, current evidence indicates that glucocorticoids (GC) represent the only class of drug therapy which either in isolation or combined with other therapies has an unequivocal role in the routine clinical management of patients with GO. Recent advances include better definition of factors predictive of response to treatment and the formulation of specific GC regimens that combine high efficacy with a low risk of unwanted side-effects.
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Review Thyroid disease and male reproductive function. 2003
Krassas GE, Perros P. · Department of Endocrinology and Metabolism, Panagia General Hospital, Thessaloniki, Greece. · J Endocrinol Invest. · Pubmed #12841547 No free full text.
Abstract: Despite the high prevalence of thyroid diseases in the general population, male reproductive function in patients with thyroid disease has been the subject of only a few studies. Hyperthyroidism appears to cause sperm abnormalities (mainly reduction in motility), which reverse after restoration of euthyroidism. Radioiodine therapy for hyperthyroidism or thyroid cancer may cause transient reductions in sperm count and motility, but there appears to be little risk of permanent effects provided that the cumulative dose is less than 14 MBq. The effects of hypothyroidism on male reproduction appear to be more subtle than those of hyperthyroidism and reversible. Severe, prolonged hypothyroidism in childhood may be associated with permanent abnormalities in gonadal function.
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Review Medical treatment for thyroid-associated ophthalmopathy. 2002
Perros P, Kendall-Taylor P. · Department of Endocrinology, University of Newcastle upon Tyne, United Kingdom. · Thyroid. · Pubmed #11952047 No free full text.
Abstract: The medical management of thyroid-associated ophthalmopathy has been, and remains a clinical challenge. Several drugs have been used. Systemic steroids seem to be beneficial in patients with active disease. The evidence for the remaining drugs reported to be potentially useful, is unconvincing.
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Review Controversies in the clinical evaluation of active thyroid-associated orbitopathy: use of a detailed protocol with comparative photographs for objective assessment. 2001
Dickinson AJ, Perros P. · Department of Ophthalmology, Newcastle Hospitals NHS Trust, Newcastle upon Tyne, UK. · Clin Endocrinol (Oxf). · Pubmed #11589671 No free full text.
Abstract: Despite many learned publications over recent decades, the assessment of active thyroid-associated orbitopathy (TAO) remains difficult and controversial. There are no biochemical, immunological or imaging investigations which can identify active disease reliably, and clinical assessment is still of paramount importance. We therefore review the strengths and weaknesses of all methods of clinical assessment. A new atlas for clinical assessment of soft tissue signs has been developed, and its reproducibility assessed. It details a suggested protocol that could help standardize descriptions of TAO and allow more objective assessment of its activity and severity. This is relevant to general endocrinologists, who have a crucial role in the identification of patients who require ophthalmological assessment. Certain aspects are more relevant to ophthalmologists and endocrinologists who have a special clinical and research interest in TAO. Unless a reproducible system of assessment is devised and widely adopted, it will remain difficult to interpret research meaningfully, particularly if results appear to contradict.
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Review Recombinant human thyroid-stimulating hormone (rhTSH) in the radioablation of well-differentiated thyroid cancer: preliminary therapeutic experience. 1999
Perros P. · Freeman Hospital, Newcastle upon Tyne, United Kingdom. · J Endocrinol Invest. · Pubmed #10727003 No free full text.
Abstract: Iodine-131 (I-131) ablation of thyroid remnant and/or persistent, recurrent or metastatic tumour is part of the initial and subsequent management of well-differentiated thyroid carcinoma. Key to optimizing the safety and efficacy of radioablation is maximizing the selective uptake of radioiodine by normal or neoplastic thyroid tissue. This is achieved by ensuring adequate serum concentrations of thyroid-stimulating hormone (TSH). Exogenous TSH administration obviates the thyroid hormone suppression therapy withdrawal that is necessary for endogenous TSH elevation. It also avoids the marked morbidity, discomfort, and impairment in professional and educational pursuits and quality of life that often result from such withdrawal. Multicentre clinical studies have documented the safety and efficacy of recombinant human TSH (rhTSH) in promoting radioiodine uptake in the diagnostic scanning of well-differentiated thyroid cancer. Study of the use of rhTSH to facilitate radioablation of remnant and malignant thyroid tissue is at an earlier stage, with formal clinical investigation underway. Since April 1995, however, rhTSH has been employed as a radioablative adjunct in over 100 patients in the manufacturer's Compassionate Use Program. Twelve of these cases, reported or reviewed in the present paper, provide preliminary evidence that rhTSH is safe and effective in the radioablation setting. More data are needed to confirm these observations and to provide guidelines for optimal radioiodine dosing, and should be furnished by ongoing clinical investigation. rhTSH is the only acceptable treatment option in a subgroup of patients with well-differentiated thyroid cancer, including those with hypopituitarism, ischaemic heart disease, a history of "myxoedema madness," debilitation due to very advanced disease or inability to produce TSH due to continued production of thyroxine by thyroid remnant or metastatic tumour. Therapeutic use of rhTSH may be considered in an increasing number of other cases.
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Clinical Conference A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active graves' ophthalmopathy. free! 2005
Perros P, Kendall-Taylor P, Neoh C, Frewin S, Dickinson J. · Endocrine Unit, Freeman Hospital, Freeman Road, Newcastle upon Tyne NE7 7DN, United Kingdom. · J Clin Endocrinol Metab. · Pubmed #15985483 links to free full text
Abstract: CONTEXT: Radioiodine is an effective and safe treatment for hyperthyroidism but has been implicated as a risk factor for deterioration or new presentation of Graves' ophthalmopathy (GO). Prophylactic glucocorticoids appear to prevent this effect. OBJECTIVE: The objective of this study was to document the course of GO after radioiodine therapy. DESIGN: This was a prospective observational study. Patients were assessed at baseline and 2, 4, 6, and 12 months after radioiodine therapy. SETTING: The study was conducted at a tertiary referral center. PATIENTS: Seventy-two GO patients with minimally active eye disease participated in the study. Intervention: A fixed dose of radioiodine was administered. T(4) was commenced 2 wk later to prevent hypothyroidism. MAIN OUTCOME MEASURES: Change in activity and severity of GO were analyzed. RESULTS: Exophthalmometer readings, the width of the palpebral aperture, diplopia scores, and the clinical activity score improved significantly. By clinically significant criteria, the eye disease improved in four patients (transiently in three of the four cases), most likely attributable to the natural course of the disease. No patient's eyes deteriorated. CONCLUSIONS: Radioiodine is not associated with deterioration of GO in patients with minimally active eye disease when postradioiodine hypothyroidism is prevented.
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Clinical Conference Double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR) in thyroid-associated ophthalmopathy. free! 2004
Dickinson AJ, Vaidya B, Miller M, Coulthard A, Perros P, Baister E, Andrews CD, Hesse L, Heverhagen JT, Heufelder AE, Kendall-Taylor P. · Department of Ophthalmology, Royal Victoria Infirmary, Newcastle on Tyne NE1 4LP, United Kingdom. · J Clin Endocrinol Metab. · Pubmed #15579735 links to free full text
Abstract: Several uncontrolled studies suggest octreotide is beneficial in thyroid-associated ophthalmopathy (TAO); however, the natural tendency of TAO to improve mandates randomized, controlled trials. We report results of a double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR). Fifty euthyroid patients (11 males, 39 females; age 22-74 yr, median 50 yr) with active TAO [clinical activity score (CAS) > or =3, NOSPECS (no signs or symptoms; only signs, no symptoms; signs only; proptosis; eye muscle involvement; corneal involvement; sight visual acuity reduction) 2a-5a] of median duration 0.9 yr received either 30 mg LAR or placebo every 4 wk for 16 wk; both groups then received 30 mg LAR for wk 16-32 and were followed up without treatment for a further 24 wk. Objective assessments included all individual parameters of TAO, CAS, and derived scores for soft tissue inflammation (STI) and ophthalmopathy index (OI). During wk 0-16 there was significant reduction in STI, subjective diplopia, and CAS in LAR-treated patients; STI and CAS were also reduced with placebo. The OI reduced by -1.12 in LAR (P = 0.0017) vs. -0.23 in placebo (P = 0.33), giving a barely significant treatment effect by Wilcoxon (P = 0.043), but analysis of covariance failed to confirm this (P = 0.16). During wk 16-32 there was no significant change in OI in either group. The overall results (wk 0-32) showed reduction in STI and CAS in both groups. In this double-blind, placebo-controlled trial, no significant therapeutic effect of octreotide LAR was seen in patients with moderately severe TAO. The improvements in both treated and placebo groups emphasize that the results of open studies must be viewed with caution.
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Article Thyroid eye disease. 2009
Perros P, Neoh C, Dickinson J. · Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP. · BMJ. · Pubmed #19270020 No free full text.
This publication has no abstract.
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Article Medical image. Acute pretibial myxoedema following thyroidectomy for Graves' disease. 2008
Syed AA, Jones NA, Perros P. · Salford Royal NHS Foundation Trust, Salford M6 8HD, United Kingdom. · N Z Med J. · Pubmed #18841193 No free full text.
This publication has no abstract.
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Article Mortality from thyroid cancer in patients with hyperthyroidism: the Theagenion Cancer Hospital experience. 2008
Pazaitou-Panayiotou K, Perros P, Boudina M, Siardos G, Drimonitis A, Patakiouta F, Vainas I. · Department of Endocrinology-Endocrine Oncology, Theagenion Cancer Hospital, 2, Alexandrou Simeonidi Street, 54007 Thessaloniki, Greece. · Eur J Endocrinol. · Pubmed #18819945 No free full text.
Abstract: 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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Article Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO. free! 2008
Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits M, Perros P, Boboridis K, Boschi A, Currò N, Daumerie C, Kahaly GJ, Krassas GE, Lane CM, Lazarus JH, Marinò M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM, Anonymous00022. · Department of Clinical Medicine, University of Insubria, 21100 Varese, Italy. · Eur J Endocrinol. · Pubmed #18299459 links to free full text
This publication has no abstract.
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Article Erectile dysfunction in patients with hyper- and hypothyroidism: how common and should we treat? free! 2008
Krassas GE, Tziomalos K, Papadopoulou F, Pontikides N, Perros P. · Department of Endocrinology, Diabetes, and Metabolism, Panagia General Hospital, North Plastira 22, North Krini, 55132 Thessaloniki, Greece. · J Clin Endocrinol Metab. · Pubmed #18270255 links to free full text
Abstract: CONTEXT: Erectile dysfunction (ED) is associated with numerous diseases and aging. OBJECTIVE: The objective of the study was to investigate the impact of hyper- and hypothyroidism on male sexual health by using the Sexual Health Inventory for Males (SHIM). DESIGN: Seventy-one men, 27 hyper- and 44 hypothyroid and a similar number of controls were included in the study. A validated SHIM 5-item questionnaire was administered to all participants. Patients were asked to respond before and a year after initiation of treatment for thyroid dysfunction. A score between 25 and 22 is considered normal, between 21 and 11 diagnostic of mild to moderately severe ED, and 10 or less diagnostic of severe ED. RESULTS: Fifty-six men with thyroid dysfunction (78.9%; 19 hyperthyroid and 37 hypothyroid) had a SHIM score of 21 or less, compared with 24 controls (33.8%) (P < 0.0001). Twenty-one patients with ED (37.5%) had SHIM scores 10 or less, indicative of severe ED, compared with six controls (25%) (P < 0.01). ED was more prevalent in patients with hyperthyroidism and hypothyroidism, compared with controls (P < 0.001 and P < 0.0001, respectively). Positive correlation was found between SHIM scores and serum free T(4) (r = 0.413, P = 0.005) and negative for TSH (r = -0.669, P < 0.001). After treatment a significant increase of SHIM scores was noted in both hyperthyroid (P < 0.0001) and hypothyroid (P < 0.0001) patients. CONCLUSIONS: ED is extremely common in males with dysthyroidism. Treatment of the latter restores erectile function. Screening for thyroid dysfunction in men presenting with ED is recommended, whereas specific treatment for ED should be postponed in such patients for at least 6 months after achieving euthyroidism because the latter might be responsible for ED.
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Article Detection of Hurthle cell carcinoma using sestamibi. 2008
Chamnanrabiabkij E, Welch A, Jayapaul MK, Perros P. · Department of Endocrinology, Freeman Hospital, Newcastle upon Tyne, United Kingdom. · Thyroid. · Pubmed #18044993 No free full text.
This publication has no abstract.
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Article A patient with asymmetric parotid uptake on a diagnostic iodine-131 scan during thyroid cancer follow-up. 2007
Frew J, Mallick U, Perros P. · Oncology, NCCT, Newcastle upon Tyne, United Kingdom. · Thyroid. · Pubmed #17725441 No free full text.
This publication has no abstract.
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Article Genomic polymorphism at the interferon-induced helicase (IFIH1) locus contributes to Graves' disease susceptibility. free! 2007
Sutherland A, Davies J, Owen CJ, Vaikkakara S, Walker C, Cheetham TD, James RA, Perros P, Donaldson PT, Cordell HJ, Quinton R, Pearce SH. · Institute of Human Genetics, Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom. · J Clin Endocrinol Metab. · Pubmed #17535987 links to free full text
Abstract: CONTEXT: A recent large-scale analysis of nonsynonymous coding polymorphisms showed strong evidence that an alanine to threonine amino acid change at codon 946 of the interferon-induced helicase (IFIH1) gene (SNP ID rs1990760) was associated with type 1 diabetes. Previous investigations have also demonstrated that an intronic polymorphism (termed PD1.3; SNP ID rs11568821) in the programmed cell death (PDCD1) gene was associated with systemic lupus erythematosus and rheumatoid arthritis. OBJECTIVE: We sought to replicate these genetic associations in Graves' disease and autoimmune Addison's disease patient cohorts. PATIENTS AND METHODS: A total of 602 Graves' disease subjects, 214 Addison's disease subjects, and 446 healthy controls were genotyped for the IFIH1 and PDCD1 single-nucleotide polymorphisms using mass spectrometer analysis of primer extension products (Sequenom). RESULTS: The alanine-carrying allele at the IFIH1 codon 946 polymorphism was present in 796 of 1204 (66%) Graves' disease patient alleles compared with 508 of 892 (57%) control subject alleles [odds ratio 1.47 (5-95% confidence interval, 1.23-1.76); P = 1.9 x 10(-5)]. In contrast, there was no association of alleles at this marker in autoimmune Addison's disease. Neither was there evidence for association in either patient cohort at the PD1.3 polymorphism. CONCLUSIONS: We confirm a significant contribution of the Ala946Thr IFIH1 polymorphism to organ-specific autoimmune diseases, extending the range of conditions associated with this variant to include Graves' disease. This polymorphism may also contribute to several other autoimmune disorders.
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Article Clinical features of dysthyroid optic neuropathy: a European Group on Graves' Orbitopathy (EUGOGO) survey. 2007
McKeag D, Lane C, Lazarus JH, Baldeschi L, Boboridis K, Dickinson AJ, Hullo AI, Kahaly G, Krassas G, Marcocci C, Marinò M, Mourits MP, Nardi M, Neoh C, Orgiazzi J, Perros P, Pinchera A, Pitz S, Prummel MF, Sartini MS, Wiersinga WM, Anonymous00103. · Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff CF 4 4XN, UK. · Br J Ophthalmol. · Pubmed #17035276 No free full text.
Abstract: BACKGROUND: This study was performed to determine clinical features of dysthyroid optic neuropathy (DON) across Europe. METHODS: Forty seven patients with DON presented to seven European centres during one year. Local protocols for thyroid status, ophthalmic examination and further investigation were used. Each eye was classified as having definite, equivocal, or no DON. RESULTS: Graves' hyperthyroidism occurred in the majority; 20% had received radioiodine. Of 94 eyes, 55 had definite and 17 equivocal DON. Median Clinical Activity Score was 4/7 but 25% scored 3 or less, indicating severe inflammation was not essential. Best corrected visual acuity was 6/9 (Snellen) or worse in 75% of DON eyes. Colour vision was reduced in 33 eyes, of which all but one had DON. Half of the DON eyes had normal optic disc appearance. In DON eyes proptosis was > 21 mm (significant) in 66% and visual fields abnormal in 71%. Orbital imaging showed apical muscle crowding in 88% of DON patients. Optic nerve stretch and fat prolapse were infrequently reported. CONCLUSION: Patients with DON may not have severe proptosis and orbital inflammation. Optic disc swelling, impaired colour vision and radiological evidence of apical optic nerve compression are the most useful clinical features in this series.
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