Mark F. Prummel

Risk factors for and prevalence of thyroid disorders in a cross‐sectional study among healthy female relatives of patients with autoimmune thyroid disease

objective Autoimmune thyroid disease (AITD) is a common disorder especially in women, and both genetic and environmental factors are involved in its pathogenesis. We wanted to gain more insight into the contribution of various environmental factors. Therefore, we started a large prospective cohort study in subjects at risk of developing AITD, for example healthy female relatives of AITD patients. Here we report on their baseline characteristics.

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

AIM 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. METHODS 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. RESULTS 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). CONCLUSION 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 status.

Bone-alkaline phosphatase as indicator of bone formation

Bone-alkaline phosphatase was determined in patients at risk of osteoporosis due to treatment with oral corticosteroids, and in patients at risk of increased bone synthesis because of treatment with cyclosporin. Both a significant decrease of bone-alkaline phosphatase during corticosteroid treatment, and a significant increase of bone-alkaline phosphatase during cyclosporin treatment could be demonstrated. It is concluded that bone-alkaline phosphatase is a useful parameter for monitoring changes in bone formation.

Clinical Features of Dysthyroid Optic Neuropathy: A European Group on Graves Orbitopathy (EUGOGO) Survey

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.

A new ultrasonographic method to detect disease activity and predict response to immunosuppressive treatment in Graves ophthalmopathy

Purpose: To determine whether the internal reflectivity of the eye muscles on Amode ultrasonography serves as indicator for disease activity in Graves ophthalmopathy, thereby predicting response to immunosuppressive treatment. Methods: Eye muscle reflectivity, expressed as percentage of the initial scleral spike, was measured in the superior, medial, and lateral recti, and normal values were determined in 23 healthy controls. These were compared with values in 16 consecutive patients with untreated, moderately severe Graves ophthalmopathy. The accuracy of the measurement was assessed by calculating the intra- and interobserver coefficient of repeatability. Baseline eye muscle reflectivity in the 16 patients was correlated to the therapeutic outcome 24 weeks after start of immunosuppressive therapy. The response to treatment served as indicator for pretreatment disease activity. Results: Eye muscle reflectivity could be measured reliably, with an intraobserver coefficient of repeatability of 8.2% in controls and 10.2% in patients. Patients had lower reflectivity than controls (54.6 ± 17.4% versus 70.7 ± 6.6%; P P = 0.02). From the individual data, a cut-off value of 40% was derived, which appeared as an accurate predictor of outcome (positive predictive value 73%; 95% confidence interval 39%–94%). Conclusions: Measuring eye muscle reflectivity in Graves ophthalmopathy appears to be a reliable new method to determine disease activity, with a promising accuracy in predicting therapeutic outcome of immunosuppressive treatment.

Effects of Graves’ ophthalmopathy on quality of life

General health-related quality of life is markedly impaired in patients with Graves’ ophthalmopathy (GO), and even worse than in patients with other chronic conditions like diabetes, emphysema or heart failure. A disease-specific quality-oflife questionnaire for GO has been developed, the so-called GO-QOL, consisting of two subscales: one for visual functioning (8 questions referring to limitations due to decreased visual acuity and/or diplopia) and one for appearance (8 questions referring to limitations in psychosocial functioning due to changes in appearance). The GO-QOL was found to be a valid and reliable instrument. A minimal clinically important difference (MCID) in the GO-QOL score was derived from data obtained before and after specific eye treatments. Based on the patient’s opinions, changes of ≥ 6 points (minor surgery) or ≥ 10 points (surgical decompression, immunosuppression) are recommended as MCID. It is concluded that the GO-QOL is an useful instrument for measuring changes over time in visual functioning and appearance of GO patients. The GO-QOL is available in six languages, and can be used as a separate outcome measure in clinical studies.

Measuring Eye Movements in Graves Ophthalmopathy

Background: The current grading of class IV (extraocular muscle involvement) of the NO SPECS classification for Graves ophthalmopathy is subjective and, in practice, virtually limited to three grades (grade c rarely occurs). The subjectiveness results in a high degree of observer disagreement, as illustrated by kappa values of 0.48 to 0.64 for the agreement between the authors in grading of class IV changes in 13 patients. Methods: The authors investigated the significance of a quantitative approach in assessing eye motility and modified a hand perimeter to measure the monocular eye movements in degrees. Results: The mean maximal excursions in the four main directions of gaze, obtained with this device in 40 healthy control subjects (5 men and 5 women from each decade between 20 and 60 years of age), were as follows: elevation=34°, depression=58°, adduction=48°, and abduction=46°. The ductions showed an age-related decline. The intraobserver and interobserver variations were assessed in 12 and 18 patients with Graves ophthalmopathy, respectively, by calculating the coefficients of repeatability, which varied from 5° to 8°. The authors compared the current grading of NO SPECS class IV with quantitative measurements of elevation in 11 patients by calculating the kappa values for agreement. These were found to be 0.57 and 0.80, respectively. Conclusions: The quantitative measurement of eye movements with a modified perimeter appears to be precise and reproducible. In addition, it should replace the current grading of the extraocular muscle movements of Graves ophthalmopathy patients in the NO SPECS classification, which is less reliable, as evidenced by a higher degree of observer disagreement.

The effect of long-term prednisone treatment on growth hormone and insulin-like growth factor-I

Due to a lack of longitudinal data the precise effect of long-term corticosteroid treatment on serum levels of the anabolic hormones Growth Hormone (GH) and Insulin-like Growth Factor-1 (IGF-1) is unknown. Therefore, we prospectively followed GH and IGF-1 levels over a six month period in 18 euthyroid patients with Graves’ ophthalmopathy. Ten patients were treated with a three month course of prednisone; eight patients receiving retrobulbar irradiation served as controls. Baseline serum GH and IGF-1 levels were similar in both groups. Whereas no changes were seen in controls, prednisone induced a rapid increase in serum IGF-1 levels, which was sustained during the entire treatment period: 18.2±5.2 at baseline vs 24.1±6.7 nmol/l after 12 weeks of treatment (p<0.001). After discontinuation of prednisone IGF-1 returned to baseline levels. Basal GH levels were frequently undetectable, but during treatment GH values were lower in the prednisone group (median of detectable values 4.0 mU/L [range 2.0–26.0]) than in controls (11.8 [2.8–44.0]; p<0.01). In conclusion, long-term prednisone treatment is associated with suppressed GH levels and with an increase in total IGF-1 levels. This suggests that prednisone can disrupt the GH/IGF1 axis.

Facial disfigurement: is it in the eye of the beholder? A study in patients with Graves' ophthalmopathy.

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.

Assessment of disease activity of Graves’ ophthalmopathy

The concept of disease activity originates from observations of the natural course of the eye signs in patients left untreated for the ophthalmopathy, and from a small number of histologic studies performed on orbital tissues from patients with variable duration of the eye disease.