VARIABLES AFFECTING THE LONG-TERM OUTCOME OF GRAVES ORBITOPATHY FOLLOWING HIGH-DOSE INTRAVENOUS GLUCOCORTICOID PULSE THERAPY IN PATIENTS NOT TREATED WITH ORBITAL RADIOTHERAPY.

OBJECTIVE: Intravenous (iv) glucocorticoids (GC) (ivGC) are used for active Graves orbitopathy (GO), but factors affecting GO outcome are poorly understood. We performed a retrospective study to investigate the variables affecting GO after ivGC. METHODS: We evaluated 83 consecutive GO patients treated with ivGC but not orbital radiotherapy (ORT) and re-examined them after a median of 47 months. The endpoints were the relationships between GO outcome or additional treatments with age, sex, smoking habits, thyroid volume, thyroid treatment, time since thyroid treatment, antithyroid-stimulating hormone receptor antibodies (TRAb), GO duration, GO features, and follow-up time. RESULTS: GO features improved after treatment, resulting in moderate and marked amelioration in ~75% and ~41% of patients respectively. By multivariate analysis, a moderate GO improvement correlated with diplopia at first observation, which was more severe in responders. A marked GO improvement correlated with time between first and last observation and time after thyroid treatment, which were longer in responders. This likely reflected the combination of an early effect of GC and a late, spontaneous improvement of GO, as shown by analyses of GO outcome at various time points. Additional treatments after ivGC correlated by multivariate analysis with eyelid aperture, diplopia and NOSPECS score (NOSPECS stands for no GO signs [N], only eyelid sign [O], soft tissue involvement [S], proptosis [P], extraocular motility restriction [E], corneal involvement [C], and sight loss [S]) at first observation, which were more severe in responders. CONCLUSION: Our study shows that response to ivGC increases with time, likely reflecting the known tendency of GO to improve spontaneously, and is more pronounced when GO is more severe to begin with, which is associated with more additional treatments. ABBREVIATIONS: ANOVA = analysis of variance CAS = clinical activity score GC = glucocorticoids GO = Graves orbitopathy 131I = radioactive iodine iv = intravenous ivGC = high-dose intravenous glucocorticoid pulse therapy MMI = methimazole OD = orbital decompression ORT = orbital radiotherapy TRAb = antithyroid-stimulating hormone receptor antibodies.

Efficacy and safety of radioiodine therapy for mild Graves ophthalmopathy depending on cigarette consumption: a 6­month follow­up.

INTRODUCTION    Graves ophthalmopathy (GO) is an autoimmune disease associated with Graves disease. Its treatment is largely dependent on the severity and activity of ocular lesions. Particular attention should be given to radioiodine (RAI) therapy. Although its use is a valuable therapeutic option for hyperthyroidism, it may be followed by worsening of GO.  OBJECTIVES    The aim of the present study was to analyze how the severity of nicotine addiction affects the response to RAI treatment in patients with GO. PATIENTS AND METHODS    A total of 106 patients (58 smokers and 48 nonsmokers) with mild GO treated with 800 MBq of RAI were included to the study. We assessed the serum levels of thyroid­stimulating hormone (TSH), thyroid hormones, autoantibodies against thyroperoxidase, thyroglobulin, and TSH receptor (TSHR­Abs), as well as urinary cotinine levels and severity of ophthalmopathy. Analyses were conducted at baseline (before RAI treatment) and 2 and 6 months after the therapy. RESULTS    Significant differences in serum levels of TSHR­Abs were found between nonsmokers and smokers at 2 and 6 months after RAI therapy, whereas there were no differences at baseline. In smokers, there were significant differences in the severity of ophthalmopathy and the concentration of serum TSHR­Abs assessed at baseline and at 6 months of follow­up. Six months after RAI therapy, 46.2% of smokers and 4.3% of nonsmokers (P <0.001) progressed from mild to moderate GO.  CONCLUSIONS    High urinary cotinine levels in smokers were associated with the deterioration of ocular lesions after RAI treatment. A high dose of RAI did not induce an exacerbation of GO in nonsmokers who were administered oral steroid prophylaxis.

Graves' ophthalmopathy treated with protracted hypofractionated low-dose adaptive radiotherapy: case report and review of the literature.

Graves' ophthalmopathy (GO) is the most common extra-thyroidal manifestation of Graves' disease. The treatment options for GO are high-dose glucocorticoids, selenium, rituximab, cyclosporine, orbital radiotherapy (RT), and surgery. A 43-year-old male patient was referred to our clinic with complaints of severe bilateral proptosis, diplopia, and orbital pain at both globes for 1 year. Pretreatment magnetic resonance imaging revealed bilateral proptosis, the expansion of bilateral optic nerves sheath, the increase of right medial muscle thickness, and a mass at the right eyehole. Patient was treated with 1 Gy per fraction per week with a total dose of 10 Gy over 10 weeks with adoptive intensity-modulated radiotherapy technique. During RT at 3rd and 6th weeks, a moderate shrinkage of the lesions was observed. The patient has been disease free, has had no complaints for 36 months, and has not required any surgical intervention. No late side effects such as retinopathy or cataract were observed. Orbital RT with innovative techniques may be considered as an initial local treatment for GO. With adoptive protracted low dose RT, a good clinical and radiological response could be seen without increasing early and late reactions.

Current trends in the management of thyroid eye disease.

PURPOSE OF REVIEW: The present review summarizes the body of literature concerning the medical and surgical treatment of thyroid eye disease (TED) from 1 January 2014 through 30 March 2015. RECENT FINDINGS: Corticosteroids continue to be the primary medical therapy for TED. Recent research has offered insight into potential differences between oral corticosteroid and intravenous corticosteroid treatment regimens in terms of efficacy and side-effect profiles. Steroid-sparing medications, for example, rituximab and others, are an area of active study. There has been renewed interest in the role of radiation therapy as a nonmedical treatment for TED with some promising data. The use of balanced orbital decompression techniques have become popular, although the data regarding postoperative diplopia are mixed, and 'fat decompression' offers an alternative or an augmentation to bony decompression. Stereotactic image guidance is a useful adjunct to orbital decompression surgery. SUMMARY: TED continues to be a difficult condition for the patient to cope with and for the clinician to treat, and recent research builds on the present foundation of knowledge and treatments, but unfortunately does not offer paradigm-shifting information at the present time.

[Thyroid orbitopathy, an overview with special attention to the role of radiotherapy]. / Orbitopatía tiroidea, una visión global con atención especial al papel de la radioterapia.

Thyroid orbitopathy is the most prevalent non-thyroid symptom in Graves' syndrome. It has a high incidence and particularly affects young women. Smoking is clearly involved in its development and progress, and in its response to different treatments. This autoimmune condition usually has a benign course, independent from hyperthyroidism, but its severe, progressive forms represent a major therapeutic challenge. Clinical evaluation poses great difficulties, as there is no truly objective rating scale representing disease activity. New molecular or inflammation markers may prove to be useful in this regard. This review reports new findings about its pathophysiology and the different techniques used for treatment over time. Discussion particularly focuses on the immunomodulatory role of radiotherapy, as well as on its role together with corticosteroids.

Orbital radiotherapy in the management of Graves' orbitopathy--current state of knowledge.

The treatment of Graves' orbitopathy (GO) remains a diagnostic and therapeutic challenge for clinicians worldwide. The elimination of risk factors, such as encouraging smoking cessation and achieving euthyroidism, are the most important and usually sufficient treatment methods in most mild cases. A course of selenium may also be beneficial. High-dose systemic corticosteroid therapy remains the first-line therapy in moderate-to-severe orbitopathy; however in some patients such treatment may be insufficient. Radiotherapy for GO has been used for decades and is considered to be effective in active GO, although less than systemic corticosteroids. Unfortunately, there are only eight randomised studies that may be analysed to assess its true effectiveness and applicability. It has been indicated that radiotherapy affects mainly eye motility and soft tissue changes, with almost no influence on exophthalmos. The combination of these two therapies has proven to be even more effective than either treatment alone, especially in subjects with resistant or recurrent GO. Orbital radiotherapy seems to be a safe procedure with few adverse effects observed long after the therapy. It should be avoided in patients with retinopathy, due to diabetes mellitus and hypertension, and in young subjects (< 35 years old). Orbital radiotherapy, as a safe and generally effective second-line therapy, is used in some countries as a supporting method during the second course of systemic corticosteroid therapy, if the response to the first course is unsatisfactory. Further randomised, double-blind studies are needed to confirm fully its clinical usefulness.

Treatment of mild, moderate-to-severe and very severe Graves' orbitopathy.

Treatment of Graves' orbitopathy (GO) is better performed through a multidisciplinary approach. Euthyroidism should be promptly restored. Antithyroid drug and thyroidectomy are not disease-modifying treatments, whereas radioiodine may be associated with worsening of GO. This risk is eliminated by glucocorticoid prophylaxis. Treatments for GO differ depending on its severity and activity. Mild forms should be treated with local measures. In addition a course of selenium may be beneficial. Glucocorticoids (oral or intravenous) represent the main treatment of moderate-to-severe GO, the intravenous route being more effective. Weekly pulses of methylprednisolone are used and the cumulative dose should not exceed 8 g. Severe adverse events have been reported, particularly with higher doses. Orbital radiotherapy can be used either alone or associated with glucocorticoids. In very severe sight-threatening GO high dose intravenous glucocorticoid should be the initial treatment, orbital decompression being considered in nonresponding patients. Rehabilitative surgery should be deferred until GO becomes inactive.

Radioiodine treatment in autoimmune hyperthyroidism: analysis of outcomes in relation to dosage.

BACKGROUND: Controversy exists regarding the optimal dose of radioiodine ((131)I) therapy in autoimmune hyperthyroidism (i.e., Graves' Disease). METHODS: In order to evaluate the efficacy and safety of high dose (131)I therapy in autoimmune hyperthyroidism, a retrospective review of patients who received (131)I therapy for Graves' disease from 1980 to 2000 in the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City was carried out. RESULTS: The study population consisted of 596 autoimmune hyperthyroid patients with a mean age of 35 years. The mean follow-up period was 10.31 +/- 2.37 years. Remission of hyperthyroidism occurred in 81.9%, persistent hyperthyroidism was recorded in 14.4% and recurrence in 3.7%. (131)I doses of 5-9 mCi (185-333 MBq) and > or =20 mCi (> or =740 MBq) were associated with remission rates of 65.5% and 87.7% respectively. Remission occurred earlier and more often with high doses of (131)I. The high-dose group (20-30 mCi [740-1110 MBq]) had the lowest rate of persistence (9.7, 27.5 and 34.3%, for 20-30 [740-1110 MBq], 10-14 [370-518 MBq] and 5-9 [185-333 MBq] mCi, respectively p <0.05) and hypothyroidism occurred earlier in this group (p = 0.05). CONCLUSIONS: Remission of autoimmune hyperthyroidism is more likely with doses of 20-30 mCi (740-1110 MBq).