This slide kit covers more complex thyroid eye disease.

Transcription

1 An imbalance in the normal level of thyroid hormone in the body can cause thyroid eye disease. If you wish to explore information on the basics of thyroid eye diseases, please first see: This slide kit covers more complex thyroid eye disease. 1

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3 In 2008, the European Group on Graves orbitopathy (EUGOGO) issued a consensus statement aiming to provide practical information for the management of patients with Graves orbitopathy (GO), which, at the time, was often suboptimal. GO is often mild and self-limiting, with 3-5% of cases posing a threat to eyesight. Bartalena L, et al. Thyroid. 2008;18(3): Bartalena L, et al. Eur J Endocrinol. 2008;158(3):

4 Care of those with thyroid eye disease is often best served in a multidisciplinary environment, with access to experts from a variety of specialties. 4

5 Active and/or severe GO, orbital pain, diplopia and stressful life events were all found to decrease scores in measures of quality of life, suggesting that GO patients are not just physically ill, but they also exhibit emotional distress. Social isolation, psychological burden and professional disadvantages were all key impacts on patients with GO. Ponto KA, Kahaly GJ. Pediatr Endocrinol Rev & Suppl 2:

6 EUGOGO recommends that patients with GO should be managed in a multidisciplinary clinical with input from endocrinologists and ophthalmologists. Survey of patterns of referral within Europe in 2006 revealed that 65% of referring doctors had access to joint thyroid-eye clinics, which was a noticeable improvement from the situation 10 years previously. However, overall, there was insufficient referral of cases with suspected optic neuropathy, and a need for practice guidelines. Perros P, et al. Eur J Endocrinol 2006;155:

7 EUGOGO uses the grades of the US Agency for Health Care Policy and Research (AHCPR) published in 1992, to describe studies. 7

8 The Agency for Healthcare Research and Quality published grading recommendations in

9 Only patients in the active phase of GO are expected to respond to immunosuppressive treatment. A clinical activity score, based on the parameters in the slide above, was developed to identify the one third of patients who present in the active phase of the disease. Terwee CB, et al. Clin Endocrinol (Oxf). 2005;62:

10 Graves orbitopathy is assessed based on clinical examination of the key areas outlined on this slide. Forms to aid initial assessment of patients are available to download from the EUGOGO website. 10

11 The management of patients with GO depends on the degree of severity of the ophthalmology, established by assessing the impact of the disease on that patient s quality of life and the risk of vision loss. All patients who do not have mild or sight-threatening disease are considered moderate-to-severe. Barrio-Barrio J, et al. J Ophthalmol 2015;2015:

12 A comparison of features for mild versus moderate-to-severe disease to distinguish those patient requiring active intervention. Barrio-Barrio J, et al. J Ophthalmol 2015;2015:

13 Patients with the signs and symptoms outlined above should be referred for specialist care immediately. Barrio-Barrio J, et al. J Ophthalmol 2015;2015:

14 A number of signs and symptoms are unpleasant for the patient and should be referred for specialist assessment, but the referral for these patients is not urgent. 14

15 This study followed 443 patients with Graves hyperthyroidism and slight or no ophthalmopathy, randomly assigned to receive radioiodine, radioiodine followed by a 3-month course of prednisolone or methimazole for 18 months. Those receiving radioiodine therapy alone had worsening of their ophthalmopathy more often than those treated with methimazole. Those treated with radioiodine followed by prednisolone fared best of the three groups. Bartalena L, et al. N Eng J Med 1998;338:

16 253 patients with recent onset Graves hyperthyroidism were assessed for at least one year. Results showed that smoking was associated with a 1.3-fold increase in the overall incidence of symptomatic endocrine ophthalmopathy and a 2.6- and 3.1-fold increase in the incidence of proptosis and diplopia, respectively. The relative risk increased relative to the number of cigarettes smoked per day. Former smokers had a significantly lower risk for the occurrence of proptosis and diplopia than active smokers. Pfeilschifter J, et al. Clin Endocrinol (Oxon) 1996;45:

17 Disease activity was measured to see if therapeutic outcome could be predicted via a multivariate prediction model integrating previously tested activity parameters. Duration of GO, soft tissue involovement, elevation, soluble interleukin-2 receptor (sil-2r), soluble CD30, eye muscle reflectivity and octreotide uptake ratio were significant predictors of a response to radiotherapy. Terwee CB, et al. Clin Endocrinol (Oxon) 2005;62:

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19 EUGOGO questionnaire revealed the treatment used most regularly for severe orbitopathy was IV steroids. Wiersinga WM et al. Eur J Endocrinol 2006;155:

20 70 euthyroid outpatients with untreated, active and severe GO received either once weekly iv methylprednisolone (0.5g then 0.25 g for 6 weeks each) or oral prednisolone starting with 0.1 g/d, then tapering the dose by 0.01 g/week. Kahaly GJ et al. J Clin Endocrinol Metab 2005;90:

21 Assessment at 3 months revealed that in patients with active and severe GO, iv glucocorticoids were more effective and better tolerated that oral steroids. Kahaly GJ et al. J Clin Endocrinol Metab 2005;90:

22 In addition, thyroid stimulating hormone receptor antibody titers decreased during iv steroid administration (P<0.001), and smoking had a strong inpact on the therapy response (P<0.001) Kahaly GJ et al. J Clin Endocrinol Metab 2005;90:

23 This meta-analysis of 15 studies, evaluated the efficacy of corticosteroids in the treatment of Graves Ophthalmopathy in comparison with other treatments. Results showed that the combination of oral corticosteroid treatment and radiotherapy was markedly more effective than either modality alone (pooled RRR 70%). The number of patients who should be treated with the combination to prevent one treatment failure was between 3 and 8. Intravenous corticosteroids, with and without radiotherapy had the best documented efficacy. Pulse therapy with intravenous corticosteroids helped overcome side effects. Abalkhail S, et al. Med Sci Monit 2003;9:CR

24 A study comparing treatment of Graves ophthalmopathy found that both orbital cobalt irradiation combined with systemic methylprednisolone and systemic methylprednisolone therapy alone are valuable methods of treatment, but the combined therapy was more effective. Bartalena L et al. J Clin Endocrinol Metab 1983;56:

25 The T2 relaxation times of intraocular muscles and orbital fat, areas of extraocular muscles and degree of ophthalmos were measured by magnetic resonance imaging (MRI) in 23 patients with Graves ophthalmology who underwent radiation therapy. This study revealed that patients with primarily elevated extraocular muscle T2 times (probably suggestive of acute inflammatory changes), showed a better therapy response regarding muscle thickening than patients with primarily normal T2 times. Just M, Kahaly GJ, et al. Radiology 1991;179:

26 This study tested whether steroids, irradiation or both were optimal treatments for moderately severe Graves orbitopathy. For the irradion, external beam radiation was compared with sham irradiation. Treatment was successful in 18/30 irradiated patients and 9/29 shamirradiated patients. The difference was caused by improvements in diplopia grade, but not by reduction of proptosis nor of eyelid swelling. Quantitatively, elevation improved significantly in the radiotherapy group. Mourits MP, et al. Lancet 2000;355;

27 The safety of long-term orbital radiotherapy has been investigated in several studies: Marcocci followed 204 patients for between 5 and 25 years and found there was no increase in the incidence of cataract nor in the incidence of tumours. Hypertension, especially if associated with diabetes, was suggested as a contraindication, as it may cause retinopathy. Wakelkamp considered the long-term safety of orbital radiation in 245 GO patients, compared with patients not receiving radiation but treated with glucocorticosteroids. Mortality rate was similar between the groups. Ophthalmic follow-up after approximately 11 years, found possible retinopathy in 15% of patients, 22 of those irradiated and 1 of the nonirradiated patients. In 5 patients (all of whom had been irradiated) definite retinopathy was present. Of these, 3 had diabetes, and 1 had hypertension. Gorman et al concluded in their 12 month follow up of 42 patients with mild-to-moderate ophthalmopathy receiving orbital radiotherapy that there was limited evidence for clinically significant improvement due to the therapy. Marcocci C, et al. J Clin Endocrin Metab 2003;88: Wakelkamp IM, et al. Ophthalmology 2004;111: Gorman CA, et al. Ophthalmology 2005;109:

28 Patients with moderately severe GO were randomly assigned to receive orbital radiotherapy as 20 divided fractions of 1 Gray weekly over 20 weeks, or 10 fractions of 1 Gray or 2 Gray daily over 2 weeks. Result showed that the 1 Gray/week protocol was more effective and better tolerated than the other regimens. Kahaly GJ, et al. J Clin Endocrinol Metab 2000;85: Kahaly GJ, et al. J Clin Endocrinol Metab 2001;145:

29 A meta-analysis of the treatments for active and severe GO found that the optimum first-line treatment was a 12-week course of high dose iv glucocorticoid pulses. This regimen has a response rate of almost 80% and causes fewer adverse events than oral treatment. Zang S, et al. J Clin Endocrinol Metab 2011;96:

30 Despite evidence supporting the use of iv steroids for GO, there are a number of issues to consider before and during therapy. There is a morbidity and mortality rate associated with iv therapy for GO, of approximately 6.5% and 0.6%. 1 Before therapy, patients should be screened for recent hepatitis, liver dysfunction, cardiovascular morbidity, severe hypertension, inadequately managed diabetes and glaucoma. The cumulative dose should not exceed 8 Gray. 1. Zang S, et al. J Clin Endocrinol Metab 2011;96:

31 Medical management options for GO suggest that immunoglobulin is a good choice for active and severe disease, combining a good response rate with a low rate of side effects. 31

32 In vitro study of retro-orbital fibroblasts found that pentoxiphylline inhibited cytokine-induced HLA-DR expression and glycosaminoglycan (GAG) synthesis. This drug was then tested in 10 patients with moderately severe ophthalmopathy. Patients were examined after 12 weeks, when 8/10 patients had responded to the treatment with reductions in serum GAG and TNF alpha. Pentoxyphilline had a beneficial effect on the inflammatory symptoms of thyroid-associated ophthalmopathy. Balazs C et al. J Clin Endocrinol Metab 1997;82: Balazs C, et al. Horm Metab Res 1998;30:

33 In summary, treatment of patients with GO depends on whether disease is active or inactive. Key factors that help the symptoms of GO - normalise thyroid function and stop smoking. 33