Thyroid Diseases: Baldeschi L

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

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Wakelkamp IM, Baldeschi L, Saeed P, Mourits MP, Prummel MF, Wiersinga WM. · Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Clin Endocrinol (Oxf). · Pubmed #16117821 No free full text.

Abstract: OBJECTIVE: Only a small percentage of Graves' ophthalmopathy (GO) patients develop optic neuropathy with impending loss of visual acuity. Therapy with methylprednisolone pulses is the treatment of first choice in severe and active GO patients. When the effect is insufficient, patients are usually treated with surgical decompression. We investigated whether surgery could become the first-line treatment, thus preventing treatment with steroids. DESIGN AND SUBJECTS: We performed a randomized trial in 15 patients with very active GO and optic neuropathy. Six patients were treated with surgical decompression, and nine with methylprednisolone i.v. pulses for 2 weeks, followed by oral prednisone for 4 months. The primary outcome was determined by changes in visual acuity. If the eye disease deteriorated despite treatment or did not improve sufficiently, patients were switched to the other treatment arm. RESULTS: The severity and activity of GO in both groups were similar at baseline. The Clinical Activity Score (CAS) was 6.3+/- 0.8 in the surgical group vs. 6.0+/- 0.5 in the steroids group and the Total Eye Score was 24+/- 6 vs. 25+/- 6. In the surgery group, 5/6 patients (82%) did not respond because of insufficient improvement in vision (n=3) or persistent chemosis (n=2), and all needed further immunosuppression. In the steroids group, 4/9 patients (45%) did not improve in visual acuity (P=0.132 vs. surgery group), and these needed decompressive surgery. All patients in whom therapy failed were switched to the other treatment arm and visual acuity improved in almost all patients. Visual acuity improved from 0.36 (0.02--0.40) to 0.90 (0.63--1.0) in the surgery group and from 0.50 (0.32--0.63) to 0.75 (0.32--1.0) in the steroids group at 52 weeks. At long-term follow-up in the surgery group 3/6 patients required squint surgery and 5/9 patients in the steroids group. Eyelid surgery was performed in 5/6 patients in the surgery group and in 4/9 patients in the steroids group. CONCLUSION: Immediate surgery does not result in a better outcome and therefore methylprednisolone pulse therapy appears to be the first-choice therapy.

Prummel MF, Terwee CB, Gerding MN, Baldeschi L, Mourits MP, Blank L, Dekker FW, Wiersinga WM. · Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. · J Clin Endocrinol Metab. · Pubmed #14715820 links to  free full text

Abstract: Radiotherapy is often used in Graves' ophthalmopathy, but its efficacy has been doubted. We compared its efficacy with sham irradiation in mild ophthalmopathy. In a double-blind randomized trial, 44 patients received orbital irradiation, and 44 were sham-irradiated. The primary outcome was assessed using major and minor criteria. As secondary outcome, we used a disease-specific quality of life questionnaire (the GO-QoL) and compared cost-effectiveness and need for follow-up treatment. The primary outcome was successful in 23 of 44 (52%) irradiated patients vs. 12 of 44 (27%) sham-irradiated patients at 12 months after treatment (relative risk, 1.9; 95% confidence interval, 1.1-3.4; P = 0.02). Radiotherapy was effective in improving eye muscle motility and decreasing the severity of diplopia. However, quality of life improved similarly in both groups. In the radiotherapy group there was less need for follow-up treatment; 66% vs. 84% of the patients needed further treatment (P = 0.049). Retrobulbar irradiation did not prevent worsening of ophthalmopathy, which occurred in 14% of the irradiated and 16% of the sham-irradiated patients. Radiotherapy is an effective treatment in mild ophthalmopathy. However, the improvement upon irradiation may not be associated with an increase in quality of life or a reduction in treatment costs.

Wiersinga WM, Bleumink M, Saeed P, Baldeschi L, Prummel MF. · Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands. · Thyroid. · Pubmed #18407753 No free full text.

Abstract: BACKGROUND: In agreement with the systemic nature of Graves' disease, Graves' ophthalmopathy (GO) presents as a symmetric bilateral eye disease in the vast majority of patients. However, asymmetric involvement of both eyes is frequently observed. We hypothesized that sleeping position might be involved in asymmetric GO; when, for example, the preferred sleeping position is on the right side, retrobulbar pressure might be somewhat higher in the right than in the left orbit, resulting in more severe eye changes in the right eye. METHODS: A prospective study in 75 consecutive untreated patients with GO, in whom eye changes and sleeping position were assessed independent of each other. Criteria for asymmetric eye changes were differences between both eyes in the presence of retrobulbar pain or of > or =1 grade in soft tissue involvement, and/or of > or =2 mm in exophthalmos, and/or > or =8 degrees in elevation. Preferred sleeping position was determined by questionnaire. RESULTS: All patients had bilateral GO. Eye changes were symmetrical in 50 patients, and asymmetrical in 25 patients based on differences in proptosis and elevation. Sleeping position did not differ between symmetric and asymmetric GO. Preferred sleeping position was on the left side in 23%; on the right side in 31%; and on the back, on the belly, or unknown in 46%. In patients with asymmetric GO, the most affected ("worst") eye was not related to preferred sleeping position on the right or left side. CONCLUSION: Slight asymmetry of eye changes between both eyes in patients with bilateral GO is not related to preferred sleeping position on either the right or left side.

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

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Baldeschi L, MacAndie K, Koetsier E, Blank LE, Wiersinga WM. · Orbital Center, Department of Ophthalmology, University of Amsterdam, Amsterdam, The Netherlands. · Am J Ophthalmol. · Pubmed #18191092 No free full text.

Abstract: PURPOSE: To investigate whether orbital irradiation influences the outcome of decompression surgery in Graves orbitopathy. DESIGN: Retrospective, comparative case series. METHODS: The medical records of all the patients with Graves orbitopathy treated with a three-wall orbital decompression through a coronal approach at our institution between January 1, 1990 and December 31, 2000 were reviewed. Only patients who underwent bilateral surgery for aesthetic rehabilitation, without preoperative diplopia, and who, in the active phase of the disease, had received orbital radiotherapy alone (20 Grays (Gy) in 10 daily fractions of two Gy over a period of two weeks; group R), systemic glucocorticoids alone (daily administration for more than three months independently from the dosage; group G), or both radiotherapy and glucocorticoids (group RG) were selected. Groups were compared for demographics, smoking habits, preoperative characteristics, and surgical outcome (mean reduction of exophthalmos, reduction of lid retraction, persistence of periorbital swelling requiring cosmetic eyelid surgery, onset of diplopia within 20 degrees of the central position of gaze, and variations in the peripheral field of diplopia). RESULTS: Sixty-one of 376 patients were selected for this study. There were no differences between group R (n=29), group G (n=15), and group RG (n=17) with respect to demographics or predecompression characteristics, whereas the number of smokers was significantly greater in group RG (P=.019). We could not find differences in surgical outcome by comparing the three groups. CONCLUSIONS: The total radiation dose, fraction size, and irradiated volume commonly used to treat active Graves orbitopathy do not adversely interfere with the outcome of rehabilitative decompression surgery.

Baldeschi L, Bisschop PH, Wiersinga WM. · Orbital Center, Department of Ophthalmology, University of Amsterdam, Amsterdam, The Netherlands. · Thyroid. · Pubmed #17542680 No free full text.

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Le Moli R, Baldeschi L, Saeed P, Regensburg N, Mourits MP, Wiersinga WM. · Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands. · Thyroid. · Pubmed #17465867 No free full text.

Abstract: BACKGROUND: Intravenous methylprednisolone pulses (IVMP) are more efficacious and better tolerated than oral prednisone in Graves' ophthalmopathy (GO) patients. However, acute and severe liver damage has been reported in sporadic cases during IVMP, resulting in fatal acute liver failure in four patients so far. The mechanism causing the liver damage is incompletely understood. DESIGN: We performed a prospective observational study in 13 patients with dysthyroid optic neuropathy (group A) and in 14 patients with moderately severe GO (group B) who were treated with high-dose (group A) or low-dose (group B) IVMP; cumulative steroid doses were 8.45 g in group A and 4.5 g in group B, and follow-up time was 24 weeks. MAIN OUTCOME: Slight increases in serum aminotransferases (in alanine aminotransferase [ALAT] more than in aspartate aminotransferase [ASAT]) were observed, in seven patients exceeding the upper normal limit of 40 U/L. These changes were more prominent in group A than in group B as was also evident from a decrease in ASAT/ALAT ratio in group A but not in group B. Changes in serum aminotransferases occurred especially in the first 6 weeks of IVMP, becoming smaller thereafter with the decrease in steroid dosage. Pretreatment liver steatosis or diabetes were not related to liver damage, but preexistent viral hepatitis was. CONCLUSION: IVMP in GO patients causes dose-dependent liver damage by a direct toxic effect of glucocorticoids on hepatocytes. Nevertheless, IVMP seems to be pretty safe if cumulative doses exceeding 8 g are avoided and liver function is checked before and at regular intervals during pulse therapy.

Baldeschi L, Lupetti A, Vu P, Wakelkamp IM, Prummel MF, Wiersinga WM. · Orbital Center, Department of Ophthalmology, University of Amsterdam, Amsterdam, The Netherlands. · Ophthalmology. · Pubmed #17320178 No free full text.

Abstract: OBJECTIVE: To present and discuss three cases of apparent reactivation of Graves' orbitopathy (GO) after orbital decompression and to evaluate the incidence of this phenomenon. DESIGN: Observational case series and retrospective follow-up study. PARTICIPANTS: A few weeks after surgery 2 patients with GO (patients 1 and 2), treated at our institution with rehabilitative bony orbital decompression during the static phase of the disease showed clinical and radiologic evidence of reactivated orbitopathy. After this observation, a sample of 249 patients who had consecutively undergone the same treatment for the same reason before the second of the 2 observed patients was selected for this study. METHODS: The records of the selected patients were retrospectively reviewed searching for cases presenting with clinical and radiologic evidence of GO reactivated as a consequence of any type of bony orbital decompression. Patients treated with perioperative systemic glucocorticoids or who had concurrent periorbital diseases, injuries, or surgeries, or who had immunocompromised conditions or a follow-up of < or =2 months, were excluded. MAIN OUTCOME MEASURES: Incidence of reactivation. Clinical history, clinical and radiologic characteristics, treatment modalities, and time course of the reactivation in patients presenting with this phenomenon. RESULTS: Decompression surgery took place between 1994 and 2000. Eleven patients were excluded for having been treated with perioperative glucocorticoids. Only 1 patient (patient 3) presented with reactivation. The incidence of the phenomenon that we regard as reactivation of GO after rehabilitative bony orbital decompression was therefore 1.3% (3/239). In all 3 patients, the reactivation took place a few weeks after surgery, after an early normal convalescence period and could be controlled with systemic immunosuppression or orbital radiotherapy. None of the patients we report developed further episodes of reactivation during the follow-up period (mean, 7.5 years). CONCLUSIONS: Based on its clinical characteristics, we suggest naming our observation delayed decompression-related reactivation and we propose using its acronym DDRR when referring to it. Although DDRR appears to be a rare event, it is important for physicians and patients to be aware of its possible occurrence with rehabilitative decompression surgery.

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.

Baldeschi L, Wakelkamp IM, Lindeboom R, Prummel MF, Wiersinga WM. · Orbital Centre, Department of Ophthalmology, University of Amsterdam, Amsterdam, The Netherlands. · Ophthalmology. · Pubmed #16530839 No free full text.

Abstract: PURPOSE: To determine if early rehabilitative orbital decompression in Graves' orbitopathy (GO) leads to a more effective postoperative outcome than the same intervention performed at a later, more likely, fibrotic stage. DESIGN: Retrospective comparative case series. PARTICIPANTS: The medical records of all GO patients treated with a 3-wall orbital decompression at our institution between 1990 and 2000 were reviewed retrospectively. Only patients operated bilaterally for aesthetic rehabilitation, without preoperative diplopia, were included. They were divided into group 1 (duration of GO < 4 years) and group 2 (duration > or = 4 years). METHODS AND MAIN OUTCOME MEASURES: The 2 groups were compared for demographics, smoking habits, preoperative characteristics (immunosuppressive treatments, Hertel values, score in NOSPECS [no signs or symptoms, only signs, soft tissue involvement with symptoms and signs, proptosis, extraocular muscle involvement, corneal involvement, sight involvement] class 2, degree of extraocular muscle enlargement), and surgical outcome (mean reduction of exophthalmos, symmetry of exophthalmos reduction, reduction in upper and lower lid retraction, any persistent periorbital swelling requiring cosmetic eyelid surgery, postdecompression diplopia). RESULTS: The medical records of 125 of 376 patients were selected for this study. There were no differences between group 1 (n = 70) mean GO duration (2.2+/-0.8 years) and group 2 (n = 55) mean GO duration (9.0+/-5.4 years) with respect to demographics, smoking habits, and preoperative characteristics except for the degree of extraocular muscle enlargement, which was significantly greater in group 1 (P = 0.039). There was no difference in surgical outcomes between the 2 groups, with the exception of postdecompression diplopia, which was significantly more frequent in group 1 than in group 2 (29% vs. 13%, P = 0.033). CONCLUSIONS: In GO, early rehabilitative orbital decompression does not improve surgical outcome and is associated with a higher risk of postdecompression diplopia.

Baldeschi L, MacAndie K, Hintschich C, Wakelkamp IM, Prummel MF, Wiersinga WM. · Orbital Center, Department of Ophthalmology, University of Amsterdam, Amsterdam, The Netherlands. · Am J Ophthalmol. · Pubmed #16140250 No free full text.

Abstract: PURPOSE: To evaluate the contribution of maximal removal of the deep lateral wall of the orbit to exophthalmos reduction in Graves' orbitopathy and its influence on the onset of consecutive diplopia. DESIGN: Case-control study. METHODS: The medical records of two cohorts of patients affected by Graves' orbitopathy with exophthalmos > or = 23 mm, without preoperative diplopia, were retrieved at random from the pool of patients decompressed for rehabilitative reasons at our institution (01/1990 to 12/2003), and retrospectively reviewed. They had been treated with an extended (cases, group 1, n = 15) or conservative (controls, group 2, n = 15) 3-wall orbital decompression performed through a coronal approach. The deep portion of the lateral wall had been removed in the extended decompression group while preserved in the conservative decompression group. Demographics, preoperative characteristics, and surgical outcome were compared. The difference in mean exophthalmos reduction between groups 1 and 2 was considered to be the contribution of the deep lateral wall to reduction of exophthalmos. RESULTS: Groups 1 and 2 were drawn from a pool of 37 and 335 patients, respectively. Demographics and preoperative characteristics of the two groups were not significantly different. The mean contribution of the deep lateral wall to exophthalmos reduction was 2.3 mm. The onset of consecutive diplopia was not significantly different between the two groups (case n = 2/15, controls n = 5/15; P = .203). Diplopia resolved spontaneously in all the patients of group 1, while all the patients of group 2 required surgery. CONCLUSIONS: Removal of the deep lateral orbital wall as part of a coronal-approach, 3-wall decompression, enhances the degree of exophthalmos reduction without increasing the risk of consecutive diplopia.

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.

Wakelkamp IM, Bakker O, Baldeschi L, Wiersinga WM, Prummel MF. · Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands. · Clin Endocrinol (Oxf). · Pubmed #12608932 No free full text.

Abstract: OBJECTIVE: From in vitro studies using cultures of orbital fibroblasts, it has become clear that cytokines play an important role in the orbital inflammation in Graves' ophthalmopathy (GO). Orbital fibroblasts seem to be the key target cells of the autoimmune attack, and they are able to express the TSH receptor (TSH-R). In vivo data on the presence of cytokines in orbital tissues are sparse, and mostly limited to samples obtained from patients with endstage, inactive GO; the same holds true for the presence of the TSH-R. The aim of the present study was to determine whether the cytokine profile and TSH-R expression differ in the active vs. the inactive stage of GO. DESIGN AND MEASUREMENTS: Orbital fat/connective tissue was obtained from six patients with active, untreated GO undergoing emergency orbital decompression, and from 11 patients with inactive GO subjected to rehabilitative decompressive surgery. The mRNA levels of various cytokines and the TSH-R were assessed by real-time polymerase chain reaction (PCR) using the LightCycler. Data are expressed as ratios (unknown mRNA/beta-actin mRNA). RESULTS: Active GO patients had much higher TSH-R expression than inactive patients: 4/0-24 (median value/range) vs. 0/0-9, P = 0.01. TSH-R expression was related to the Clinical Activity Score (r = 0.595, P = 0.015). Patients with active GO compared to those with inactive GO had higher mRNA levels of the proinflammatory cytokines interleukin-1beta (IL-1beta) (445/153-877 vs. 0/0-455, P = 0.001), IL-6 (1583/968-18825 vs. 559/0-7181, P = 0.01), IL-8 (1422/38-7579 vs. 32/0-1081, P = 0.046) and IL-10 (145/58-318 vs. 27/0-189, P = 0.002). In active GO there also existed a trend towards a predominance of T helper 1 (Th1)-derived cytokines as evident from higher IL-2 (37/0-158 vs. 0/0-68, P = 0.043), interferon-gamma (IFN-gamma) (20/0-79 vs. 0/0-16, P = 0.12) and IL-12 (2.3/0-14.8 vs. 0/0-1.6, P = 0.10) mRNAs. IL-1 receptor agonist (IL-1RA), IL-2 receptor (IL-2R), IL-3, IL-4, IL-5, IL-13, IL-18 and tumour necrosis factor-alpha (TNF-alpha) mRNAs were similar in both groups. CONCLUSIONS: These data show that at the mRNA level, TSH-R expression is largely present only during the active stages of GO. The active phase is characterized by the presence of proinflammatory and Th1-derived cytokines, whereas other cytokines, among them Th2-derived cytokines, do not seem to be linked to a specific stage of GO.

Terwee CB, Dekker FW, Bonsel GJ, Heisterkamp SH, Prummel MF, Baldeschi L, Wiersinga WM. · Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Institute for Research in Extramural Medicine, Amsterdam, the Netherlands. · Clin Endocrinol (Oxf). · Pubmed #12580935 No free full text.

Abstract: OBJECTIVES: The importance of facial disfigurement in many diseases necessitates a reliable and valid measure of disfigurement severity for clinical studies. The hypothesis is that a universal concept of disfigurement exists and can be measured in a reliable way. The objectives of this study were to investigate if persons, in particular patients and physicians, can agree on facial disfigurement severity; and to determine the relative contribution of predefined clinical characteristics of patients with Graves' ophthalmopathy (GO) to the overall rating of facial disfigurement severity. DESIGN: A panel study was carried out in four different panels, each consisting of four members. PATIENTS: We randomly selected 100 slide pairs of GO patients from four available study populations, involving mild, moderate and severe GO patients (mean age 49 years, 76% female) who were treated with either radiotherapy, sham-irradiation, prednisone or orbital decompression. MEASUREMENTS: All panel members individually scored the disfigurement severity of 100 GO patients shown on standardized slides on a Visual Analog Scale. In total, 1600 ratings were collected. We calculated within- and between-panel agreement of disfigurement severity and identified determinants of disfigurement. RESULTS: Agreement within a panel varied from 0.65 to 0.79 and was highest within the panel of ophthalmologists. Between-panel agreement was 0.67 and was highest between ophthalmologists and laypersons. Compared with the global average, patients overrated and endocrinologists underrated disfigurement severity. Female panellists rated the patients, on average, more disfigured than male panellists. Important determinants of disfigurement were eyelid retraction, severe eyelid swelling and proptosis. Their relative importance was consistent across panels and in contrast to current measures of GO severity. CONCLUSION: Facial disfigurement severity can be measured in a reliable way using panels of panellists. Except for some systematic differences between panellists, facial disfigurement does not seem to be in the eye of the beholder.

Terwee CB, Dekker FW, Mourits MP, Gerding MN, Baldeschi L, Kalmann R, Prummel MF, Wiersinga WM. · Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, the Netherlands. · Clin Endocrinol (Oxf). · Pubmed #11298093 No free full text.

Abstract: OBJECTIVE: The Graves' ophthalmopathy quality of life questionnaire (GO-QOL) is the first instrument available to measure health-related quality of life (HRQL) of patients with Graves' ophthalmopathy. The main objective of this study was to define a minimal clinically important difference (MCID) in score on the GO-QOL that can be considered an important improvement in HRQL by examining changes in GO-QOL scores in patients who subjectively report improvement from their treatment. A secondary objective was to test the longitudinal validity of the GO-QOL, using prespecified hypotheses about expected treatment effects. DESIGN: A prospective cohort study. PATIENTS: We included 164 patients who were scheduled for radiotherapy (23), orbital decompression (10 for sight loss, 38 for exophthalmos), eye muscle surgery (31), eyelid lengthening (43) or blepharoplasty (19). MEASUREMENTS: Patients completed the GO-QOL and three general HRQL questionnaires, before and three or six months after treatment, depending on the performed procedure. Clinical characteristics were collected from the medical records. Mean changes in GO-QOL scores and effect sizes were calculated after different treatments, and in subgroups of responders and nonresponders according to clinical characteristics and according to the patients themselves. RESULTS: A clinical response to treatment was associated with a change in GO-QOL scores of approximately 10--20 points after major treatments (radiotherapy or decompression), and with a change of approximately 3--10 points after minor surgery (eye muscle surgery, eyelid lengthening, blepharoplasty). Changes in GO-QOL scores of about 6--10 points were considered important improvements by the patients themselves. The direction and amount of change in GO-QOL scores after different treatments were in accordance with our prespecified hypotheses about treatment effects. Effect sizes in the GO-QOL subscales were generally higher than effect sizes of the general HRQL subscales, supporting the longitudinal validity of the GO-QOL. CONCLUSIONS: As a general guideline, one could consider a mean change of at least 6 points on one or both subscales an important change in daily functioning for patients. For more invasive therapies, a change of at least 10 points is recommended as a minimal clinically important difference.

Baldeschi L, Lupetti A, Wiersinga WM. · No affiliation provided · Ophthal Plast Reconstr Surg. · Pubmed #18030134 No free full text.

This publication has no abstract.