Thyroid Diseases: Dickinson AJ

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.

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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.

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.

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.

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.

Anonymous00698, Perros P, Baldeschi L, Boboridis K, Dickinson AJ, Hullo A, Kahaly GJ, Kendall-Taylor P, Krassas GE, Lane CM, Lazarus JH, Marcocci C, Marino M, Mourits MP, Nardi M, Orgiazzi J, Pinchera A, Pitz S, Prummel MF, Wiersinga WM. · Department of Endocrinology, Freeman Hospital, Newcastle upon Tyne, UK, and Department of Ophthalmology, Orbital Center, Academic Medical Center, Amsterdam, The Netherlands. · Eur J Endocrinol. · Pubmed #16868132 links to  free full text

Abstract: OBJECTIVE: To determine management patterns among clinicians who treat patients with Graves' orbitopathy (GO) in Europe. DESIGN AND METHODS: Questionnaire survey including a case scenario of members of professional organisations representing endocrinologists, ophthalmologists and nuclear medicine physicians. RESULTS: A multidisciplinary approach to manage GO was valued by 96.3% of responders, although 31.5% did not participate or refer to a multidisciplinary team and 21.5% of patients with GO treated by responders were not managed in a multidisciplinary setting. Access to surgery for sight-threatening GO was available only within weeks or months according to 59.5% of responders. Reluctance to refer urgently to an ophthalmologist was noted by 32.7% of responders despite the presence of suspected optic neuropathy. The use of steroids was not influenced by the age of the patient, but fewer responders chose to use steroids in a diabetic patient (72.1 vs 90.5%, P<0.001). Development of cushingoid features resulted in a reduction in steroid use (90.5 vs 36.5%, P<0.001) and increase in the use of orbital irradiation (from 23.8% to 40.4%, P<0.05) and surgical decompression (from 20.9 to 52.9%, P<0.001). More ophthalmologists chose surgical decompression for patients with threatened vision due to optic neuropathy, who were intolerant to steroids than other specialists (70.3 vs 41.8%, P<0.01). CONCLUSION: Deficiencies in the management of patients with GO in Europe were identified by this survey. Further training of clinicians, easier access of patients to specialist multidisciplinary centres and the publication of practice guidelines may help improve the management of this condition in Europe.

Vaidya B, Shenton BK, Stamp S, Miller M, Baister E, Andrews CD, Dickinson AJ, Perros P, Kendall-Taylor P. · Department of Endocrinology, Newcastle University, Newcastle upon Tyne, United Kingdom. · Thyroid. · Pubmed #16187917 No free full text.

Abstract: Thyroid-associated ophthalmopathy (TAO) is thought to be a T-cell-mediated autoimmune disorder. We sought to characterize abnormalities in the peripheral blood T-cell subsets in patients with TAO, and examine whether the long-acting somatostatin analogue, octreotide-LAR, treatment affects these cells. We analyzed peripheral blood T-cell subsets by flow cytometry in 26 euthyroid patients with moderately severe active TAO and 24 controls. Twenty-five of the patients with TAO were enrolled in a randomized trial to receive either 30 mg of octreotide-LAR (n = 11) or placebo (n = 14) every 4 weeks for 16 weeks; all 25 patients subsequently received octreotide-LAR 30 mg every 4 weeks from week 16 to 32. T-cell subsets were analysed at baseline, week 16, and week 32. At baseline, the relative percentage of CD4+ helper T-cells (p = 0.0003) and the CD4+/CD8+ ratio (p = 0.008) were significantly higher in patients with TAO compared to controls. Patients with TAO had higher naïve active T cells (CD45RA+, CD45RA+ CD4+) and lower memory T cells (CD45RO+, CD45RO+ CD4+) than controls. At weeks 16 and 32, there were no significant differences in any T-cell subsets between the octreotide-LAR-treated and placebo groups. These results support a role of T cell in the pathogenesis of TAO, and show that octreotide-LAR has no effect on T-cell subsets during 32-weeks of treatment.

Haggerty H, Richardson S, Mitchell KW, Dickinson AJ. · Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom. · Arch Ophthalmol. · Pubmed #15767478 No free full text.

Abstract: OBJECTIVE: To assess the intraobserver and interobserver reliability of recording uniocular fields of fixation using a modified perimeter technique in healthy subjects and patients with Graves orbitopathy (GO). Patients with restrictive myopathies, particularly GO, require accurate measurement of monocular excursions. These ductions are recorded in 4 to 12 directions of gaze using a perimeter, producing a plot known as a uniocular field of fixation. While 4 direction plots give limited information on vertical muscles, recording 12 directions is time consuming and uncomfortable. This modified technique uses the 6 directions of gaze corresponding to the primary field of action of each muscle. METHODS: A single observer measured modified uniocular fields of fixation in 35 healthy subjects aged 20 to 60 years to establish normal and age-related ranges for all ductions. Fifteen subjects underwent measurement on 5 separate occasions by the same observer to establish intraobserver reproducibility. A second observer independently performed measurements in 10 of the subjects to determine interobserver reproducibility. Reliability was compared with that measured in 29 patients with GO. RESULTS: The technique was reproducible to within 4 degrees for healthy subjects undergoing assessment by a single observer. When results of 2 observers were compared, the coefficient of repeatability was 7.9 degrees . For subjects with GO, however, maximal variability was 7.8 degrees . For clinical purposes, only a change of 8 degrees or more can be assumed to be significant. CONCLUSIONS: This technique offers advantages for assessing any restrictive myopathy, including GO to within 8 degrees . This level of accuracy is likely to be similar in other centers, and has implications for interpreting GO outcome measures, where 5 degrees was previously taken to represent significant change.

Vaidya B, Oakes EJ, Imrie H, Dickinson AJ, Perros P, Kendall-Taylor P, Pearce SH. · Department of Endocrinology, University of Newcastle, Newcastle upon Tyne, UK. · Clin Endocrinol (Oxf). · Pubmed #12780750 No free full text.

Abstract: OBJECTIVE: Recent studies have shown that Graves' disease (GD) is linked to and associated with alleles of the cytotoxic T lymphocyte antigen-4 (CTLA4) locus. However, the true pathogenic polymorphism(s) at this locus remains uncertain. Moreover, the association studies of the promoter CTLA4(-318)C/T polymorphism in white GD populations have produced conflicting results. Therefore, we have analysed three CTLA4 single nucleotide polymorphisms, including promoter CTLA4(-318)C/T, exon 1 CTLA4(49)A/G and intron 1 CTLA4(1822)C/T in our GD cohort from the UK. PATIENTS AND METHODS: We studied 301 white patients with GD and 349 healthy ethnically matched local controls. Amongst GD probands, 129 had significant thyroid-associated orbitopathy (TAO; NOSPECS class III or worse). The CTLA4(-318)C/T, CTLA4(49)A/G and CTLA4(1822)C/T polymorphisms were genotyped by using the restriction enzymes MseI, Bst71I and HaeIII, respectively. RESULTS: We found no association between GD and alleles of CTLA4(-318)C/T. GD was found to be associated with the G allele of CTLA4(49)A/G[P = 5.9 x 10(-6), odds ratio (OR) 1.65] and the T allele of CTLA4(1822)C/T (P = 7.7 x 10(-6), OR 1.64). The frequencies of these alleles were significantly higher in GD probands with significant TAO than in those without TAO (G allele: P = 0.001, OR 1.68; T allele: P = 0.001, OR 1.70). CONCLUSIONS: The promoter CTLA4(-318)C/T polymorphism is not in linkage disequilibrium with the pathogenic polymorphism(s) at the CTLA4 locus. The alleles of both the exon 1 CTLA4(49)A/G and the intron 1 CTLA4(1822)C/T polymorphisms are associated with GD, which is stronger in patients with TAO.

Prummel MF, Bakker A, Wiersinga WM, Baldeschi L, Mourits MP, Kendall-Taylor P, Perros P, Neoh C, Dickinson AJ, Lazarus JH, Lane CM, Heufelder AE, Kahaly GJ, Pitz S, Orgiazzi J, Hullo A, Pinchera A, Marcocci C, Sartini MS, Rocchi R, Nardi M, Krassas GE, Halkias A. · Department of Endocrinology and Metabolism, F5-171 Academic Medical Center, University of Amsterdam, Meibergdreef 5, 1105 AZ Amsterdam, The Netherlands. · Eur J Endocrinol. · Pubmed #12720530 links to  free full text

Abstract: To improve management of patients with Graves' orbitopathy, a multi-center collaborative approach is necessary in order to have large enough sample sizes for meaningful randomized clinical trials. This is hampered by a lack of consensus on how to investigate the eye condition. The European Group on Graves' Orbitopathy aims to overcome this and has designed a preliminary case record form (CRF) to assess Graves' orbitopathy patients. This form was used in this first multi-center study. AIM: To investigate patient characteristics and treatment strategies in 152 new consecutively referred patients with thyroid eye disease seen in nine large European referral centers. METHODS: Newly referred patients with Graves' orbitopathy were included who were seen between September and December 2000. Demographic data and a complete ophthalmological assessment were recorded. RESULTS: One-hundred and fifty-two patients (77% females) were included. Diabetes was present in 9%, and glaucoma or cataract in 14% of patients. Forty percent were current smokers, 9% also had dermopathy, and only 33% reported a positive family history of thyroid disease. Mild eye disease was seen in 40%, moderately severe eye disease was seen in 33% and severe eye disease was seen in 28% of patients. Soft tissue involvement was the most frequent abnormality (seen in 75%), proptosis > or =21 mm was found in 63%, eye motility dysfunction in 49%, keratopathy in 16% and optic nerve involvement was found in 21% of patients. According to the clinical impression, 60% had active eye disease. Immunosuppressive treatment was planned more frequently in active patients (57/86; 66%) than in inactive patients (5/57, 9%; Chi-square 46.16; P<0.02). There were no important differences among the eight centers regarding the severity and the activity of their patients. CONCLUSIONS: In view of the large number of patients recruited in only 4 months, multi-center studies in the eight EUGOGO centers appear to be feasible.