Measuring disease activity to predict therapeutic outcome in Graves' ophthalmopathy

OBJECTIVE: The concept of disease activity in Graves' ophthalmopathy (GO) might explain why as many as one-third of patients do not respond to immunosuppressive treatment, because only patients in the active stage of disease are expected to respond. The hypothesis was adopted that a parameter used to measure disease activity should be able to predict a response to immunosuppressive treatment. The aim of this study was to develop a multivariate prediction model in which all previous tested activity parameters are integrated. DESIGN AND PATIENTS: We included 66 consecutive patients with untreated moderately severe GO who had been euthyroid for at least 2 months. All patients were treated with radiotherapy. Measurements Treatment efficacy after 6 months follow-up was used as the primary outcome measure. Disease severity and 15 different disease activity parameters were assessed before treatment. Univariate and multivariate logistic regression models were used to predict response (model 1) or no change (model 2). RESULTS: In multivariate analyses, we found that duration of GO, soft tissue involvement, elevation, soluble interleukin-2 receptor (sIL-2R), soluble CD30 (sCD30), eye muscle reflectivity and octreotide uptake ratio were significant predictors of a response to radiotherapy. Gender, duration of GO, soft tissue involvement, eye muscle reflectivity, IL-6 and urinary glycosaminoglycan (GAG) excretion were significant predictors of no change upon radiotherapy. Prognostic score charts were developed for use in clinical practice to calculate the probability of response (model 1) and the probability of no change (model 2) for each new patient. Finally we used a combination of both models to define a recommended treatment modality for each individual patient, based on both the predicted probabilities of response and no change. We were able to identify the correct treatment (based on a comparison with the observed response) in 89% of the patients. CONCLUSIONS: Although we strongly recommend that our results should be confirmed in other studies, our findings are the first evidence for the idea that disease (in)activity should determine which kind of treatment should be use

Clinical activity score as a guide in the management of patients with Graves' ophthalmopathy

OBJECTIVE: Approximately 35% of patients with Graves' ophthalmopathy do not respond to immunosuppressive treatment. A possible explanation for this finding is that only patients with active ophthalmopathy respond to immunosuppressive treatment, whereas patients with fibrotic end stage disease do not. To distinguish between these two groups and to predict the outcome of immunosuppressive treatment, we developed a clinical activity score (CAS) based on four of the five classical signs of inflammation and tested its efficacy in a double-blind, prospective study. DESIGN, PATIENTS AND MEASUREMENTS: The CAS was determined by an opthalmologist before, on the day of, and after the start of either oral prednisone or retrobulbar irradiation in 43 patients with moderate to severe Graves' ophthalmopathy. The therapeutic outcome was determined by a second ophthalmologist unaware of the CAS stores given. Success of treatment was defined as an improvement in NOSPECS class or grade. RESULTS: Responders (22) and non-responders (21) did not differ in age, sex, duration or severity of their Graves' ophthalmopathy. The pretreatment CAS, however, was significantly higher in responders than in non-responders. Twelve of 22 responders and three of 21 non-responders had a CAS > or = 4 (55% vs 14%; P or = 4 had a similar duration of Graves' ophthalmopathy as patients with a CAS <4. CONCLUSIONS: The clinical activity score has a high predictive value for the outcome of immunosuppressive treatment in Graves' ophthalmopathy. Disease activity, and not disease duration, is the prime determinant of therapeutic outcom

Development of a disease specific quality of life questionaire for patients with Graves'ophthalmopathy: the GO-QOL

To develop a reliable and valid disease specific quality of life questionnaire (the GO-QOL) for patients with Graves' ophthalmopathy (GO), that can be used to describe the health related quality of life and changes in health related quality of life over time as a consequence of disease and treatment. 70 consecutive GO patients (age > 18 years) who were referred for the first time to the combined outpatient clinic of the orbital centre and the department of endocrinology completed the 16 questions of the GO-QOL. Additional information on general quality of life and disease characteristics was obtained. Construct validity and internal consistency of the disease specific questionnaire was determined, based on principal component analysis, Cronbach alphas and correlations with MOS-24, three subscales of the SIP, demographic, and clinical measures. The a priori expected subdivision of the questionnaire in two subscales, one measuring the consequences of double vision and decreased visual acuity on visual functioning, and one measuring the psychosocial consequences of a changed appearance, was confirmed in the principal component analysis. Both scales had a good reliability and high face validity. Correlations with other measures supported construct validity. Mean scores (range 0-100) were 54.7 (SD 22.8) for visual functioning and 60.1 (24.8) for appearance (higher score = better health). The GO-QOL is a promising tool to measure disease specific aspects of quality of life in patients with GO and provides additional information to traditional physiological or biological measures of health statu

[Subclinical hypothyroidism; the start of a clinical trial into the usefulness of treatment with radioactive iodine]

Item does not contain fulltextSubclinical hyperthyroidism is defined as the presence of serum free thyroxine (T4) and triiodothyronine (T3) levels within the reference range and a reduced serum thyrotrophin (TSH) level. Evidence is accumulating that it has important clinical effects. Randomised clinical trials are needed to answer the question whether or not treatment of subclinical hyperthyroidism prevents cardiac problems, especially atrial fibrillation, and preserves bone mineral density. A randomised, Dutch multicentre trial has recently been started. Its goal is to study whether radioiodine treatment prevents the development of atrial fibrillation and prevents decreases in bone mineral density

Circulating cortisone levels are associated with biochemical markers of bone formation and lumbar spine BMD: the Hertfordshire cohort study

Objective: Cortisone is an endogenous corticosteroid that has negligible intrinsic glucocorticoid activity but can be converted to the active corticosteroid cortisol by the enzyme 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1). 11?-HSD1 is expressed in osteoblasts and may play a role in determining susceptibility to glucocorticoid-induced osteoporosis. In intact osteoblasts enzyme activity, and thus cortisol generation, is dependent on substrate concentration with an almost linear increase in activity across the physiological range. We have therefore attempted to measure the impact of 11?-HSD1 activity on bone in vivo by examining the association of circulating cortisone with bone markers, bone mineral density (BMD) and bone loss in a cohort of women and men.Design and subjects: Baseline cross-sectional association study involving 135 women and 171 men aged 61–73 years from the Hertfordshire Cohort Study and a 4 year follow-up study examining changes in BMD.Measurements: Serum cortisone, cortisol and osteocalcin, and urinary type I collagen cross-linked N-telopeptide (NTX) were measured at baseline. BMD at spine and hip was measured at baseline and 4 years later.Results: In men serum cortisone levels were negatively correlated with serum osteocalcin (r = ?0·20, P = 0·01); a similar relationship was seen in women (r = ?0·16, P = 0·06). No correlation was seen between serum cortisone and urinary NTX (r = 0·03, P = 0·74 for women; r = ?0·03, P = 0·72 for men). A negative correlation was observed between serum cortisone and spine BMD in women (r = ?0·18, P = 0·04); a similar relationship was also seen in men (r =?0·14, P = 0·07). However, cortisone did not correlate with BMD at the femoral neck or total hip or changes in BMD at any site over time. In analyses adjusted for adiposity, osteoarthritis grade and a range of life-style variables, these relationships did not change substantially. All these relationships were independent of cortisol concentrations.Conclusions: The most plausible explanation for the association of circulating cortisone levels with osteocalcin is the presence of 11?-HSD1 activity within osteoblasts. The measurement of serum cortisone may independently give insights into the action of glucocorticoids on bone