The course of Graves' ophthalmopathy is not influenced by near total thyroidectomy: a case-control study

OBJECTIVE: The relationship between the method of treatment of hyperthyroidism due to Graves' disease and the course of Graves' ophthalmopathy is debated. Antithyroid drug therapy is associated with no change, or even amelioration, of ophthalmopathy. Although controversial, radioiodine may be followed by progression of eye disease, preventable by glucocorticoid administration. Whether thyroidectomy affects the course of ophthalmopathy is uncertain. DESIGN: In a case control study, the course of non-severe Graves' ophthalmopathy after thyroidectomy was investigated and the results compared with those observed in patients treated with methimazole. PATIENTS: Thirty patients with Graves' hyperthyroidism and non-severe/absent ophthalmopathy were treated with near-total thyroidectomy (Group 1, Tx), after achievement of euthyroidism with methimazole. After surgery, all patients started levothyroxine replacement therapy. Sixty patients treated with methimazole, matched for age, sex, duration of hyperthyroidism, degree of ocular involvement and smoking habits, were used as controls (Group 2, MMI). MEASUREMENTS: Patients were seen every 1-2 months for 12 months for thyroid tests and ocular evaluation. RESULTS: In Group 1, ocular parameters did not change in 17 of 18 patients with pre-existing ophthalmopathy, and in 12 patients without ophthalmopathy. Eye manifestations worsened only in one (3.3%) patient with pre-existing ophthalmopathy. In Group 2, ocular parameters did not change in 58 patients (33 with, and 25 without ophthalmopathy), while new ophthalmopathy occurred in two without pre-existing eye disease. One of the 30 patients treated by surgery (3.3%) had permanent hypoparathyroidism. CONCLUSIONS: Treatment of Graves' hyperthyroidism with near-total thyroidectomy in patients with non-severe or absent pre-existing ophthalmopathy is not associated in the short term with significant effects on the course of ophthalmopathy.     

Management of Graves' ophthalmopathy: reality and perspectives

Graves' ophthalmopathy is an debilitating disease impairing the quality of life of affected individuals. Despite recent progress in the understanding of its pathogenesis, treatment is often not satisfactory. In mild cases, local therapeutic measures (artificial tears and ointments, sunglasses, nocturnal taping of the eyes, prisms) can control symptoms and signs. In severe forms of the disease (3-5%), aggressive measures are required. If the disease is active, high-dose glucocorticoids and/or orbital radiotherapy, or orbital decompression represent the mainstay of treatment. If the disease is severe but inactive, orbital decompression is preferred. Novel treatments such as somatostatin analogs or intravenous immunoglobulins are under evaluation. Rehabilitative (extraocular muscle or eyelid) surgery is often needed after treatment and inactivation of eye disease. Correction of both hyper- and hypothyroidism is crucial for the ophthalmopathy. Antithyroid drugs and thyroidectomy do not influence the course of the ophthalmopathy, whereas radioiodine treatment may cause the progression of preexisting ophthalmopathy, especially in smokers. The exacerbation, however, is prevented by glucocorticoids. In addition, thyroid ablation may prove beneficial for the ophthalmopathy in view of the pathogenetic model relating eye disease to autoimmune reactions directed against antigens shared by the thyroid and the orbit.     

Relationship between management of hyperthyroidism and course of the ophthalmopathy

The relationship between treatment for hyperthyroidism and course of Graves' ophthalmopathy (GO) has been and still is a matter of debate. Literature often presents conflicting data, due to several influencing factors, such as selection bias, nonrandomized and uncontrolled or retrospective features of many studies, nonstandardized evaluation of ocular changes. However, it seems clear that neither antithyroid drug treatment nor thyroidectomy affect the natural course of GO, while radioiodine therapy may cause, in about 15% of cases, GO progression. The latter is more likely in patients who smoke, have pre-existing GO and more severe hyperthyroidism, or whose post-radioiodine hypothyroidism is not promptly corrected by L-thyroxine. GO progression after radioiodine therapy can be prevented by concomitantly treating patients with glucocorticoids, thus making radioiodine therapy a safe procedure also in GO patients. The presence of GO should not, therefore, influence the choice of treatment for hyperthyroidism. Should antithyroid drug treatment or thyroidectomy be selected for patients with mild ophthalmopathy, no treatment for GO is necessary, while a short course of moderate doses of glucocorticoids is advised if radioiodine therapy is chosen. In patients with severe GO, treatment of hyperthyroidism and management of GO proceed independently of each other, and either definitive (radioiodine or thyroidectomy) or conservative (antithyroid drugs) treatment for hyperthyroidism can be selected while treating GO. The authors' preference goes to the former, because it depletes intrathyroidal autoreactive T lymphocytes and removes thyroid antigens, which are likely to be involved in the pathogenesis of autoimmune reactions of the ophthalmopathy.     

Carotid cavernous fistula in a patient with Graves' ophthalmopathy

The clinical manifestations of carotid cavernous fistula, an abnormal arteriovenous connection between the cavernous sinus and the carotid artery, can closely mimic the cardinal signs of Graves' ophthalmopathy, an inflammatory disorder of the orbit usually associated with autoimmune thyroid disease. Therefore, carotid cavernous fistulas are generally considered in the differential diagnosis of Graves' ophthalmopathy, especially when the eye involvement is unilateral or asymmetric, and there is the need for exclusion of rarer etiologies of orbital disease. This is the first report of the simultaneous occurrence of Graves' ophthalmopathy and carotid cavernous fistula. The patient was a 67-yr-old woman who presented with a history of Graves' disease with mild bilateral ophthalmopathy treated with radioiodine following a 10-yr therapy with methimazole; after radioiodine treatment, ophthalmopathy deteriorated. At the time of our initial clinical evaluation the ocular involvement of the patient was symmetric, and no evidence of any associated condition was found. However, the response of eye disease to corticosteroid treatment was markedly unequal, resulting in evident asymmetry. This prompted a reconsideration of the diagnosis and a new evaluation of the patient with sensitive techniques, leading to the further diagnosis of carotid cavernous fistula.     

Epidemiology and prevention of Graves' ophthalmopathy.

Graves' ophthalmopathy is clinically relevant in approximately 50% of patients with Graves' disease, severe forms affecting 3%-5% of patients. Two age peaks of incidence are observed in the fifth and seventh decades of life, with slight differences between women and men. The disease is more frequent in women than in men, although the female-to-male ratio is only 1:4 in severe forms of eye disease. The natural history of Graves' ophthalmopathy is incompletely defined, but in many instances, especially in mild forms, the disease may remit or improve spontaneously. The onset of the ophthalmopathy is in most cases concomitant with the onset of hyperthyroidism, but eye disease may precede or follow hyperthyroidism. Cigarette smoking plays an important role in the occurrence of the ophthalmopathy, and is also associated with a higher degree of disease severity and a lower effectiveness of its medical treatment. Primary prevention (i.e., avoidance of the occurrence of the ophthalmopathy) is presently not feasible, but smoking withdrawal in relatives of patients with Graves' disease might be important. In terms of secondary prevention (i.e., avoidance of progression of subclinical eye disease into overt and severe ophthalmopathy) in addition to refraining from smoking, early and accurate control of thyroid dysfunction (both hyperthyroidism and hypothyroidism), as well as early diagnosis and treatment of mild eye disease are important. As to the role that management of hyperthyroidism may play in the course of Graves' ophthalmopathy, while antithyroid drugs and thyroidectomy are not disease-modifying treatments, radioiodine therapy causes a progression of the ophthalmopathy in approximately 15% of patients, especially high-risk patients, who smoke, have severe hyperthyroidism or uncontrolled hypothyroidism, high levels of thyrotropin (TSH)-receptor antibody, or preexisting eye disease. However, the risk of radioiodine-associated progression of the opthalmopathy can be eliminated by concomitant treatment with middle-dose glucocorticoids. In terms of tertiary prevention (i.e., avoidance of deterioration and complications of overt disease) early immunosuppressive treatment or orbital decompression, as appropriate, are essential tools. Smoking withdrawal may increase the effectiveness of immunosuppressive treatment.     

An update on medical management of Graves' ophthalmopathy

Graves' ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves' disease, is a disorder of autoimmune origin, the pathogenic mechanisms of which are still incompletely understood. Although GO is severe in only 3-5% of affected individuals, quality of life is severely impaired even in patients with mild GO. Management of severe GO can be either medical or surgical (orbital decompression, eye muscle or lid surgery). Medical management relies on the use of high-dose systemic glucocorticoids or orbital radiotherapy, either alone or in combination. Studies carried out in the last 5 yr have shown that glucocorticoids are more effective through the i.v. route than through the oral route. However, particular attention should be paid to possible liver toxicity of i.v. glucocorticoids. Recent randomized clinical trials have, with one exception, confirmed that orbital radiotherapy is an effective and safe therapeutic procedure for GO. At variance with previous encouraging data, recent randomized clinical trials have shown that currently available SS analogs are not very effective in the management of GO. Antioxidants might have a role, at least in mild forms of GO. Particular attention should be paid to correction of risk factors (cigarette smoking, thyroid dysfunction, radioiodine therapy) involved in GO progression.     

Management of Graves' ophthalmopathy

Management of Graves' ophthalmopathy is preferably done in a multidisciplinary setting. Smoking is associated with worse disease outcome. (131)I therapy for hyperthyroidism can also worsen ophthalmopathy, especially if administered during active disease or to patients who smoke or have severe hyperthyroidism, or those with high levels of TSH-receptor-binding inhibitory immunoglobulins. Coadministration of steroids and (131)I therapy is recommended for such high-risk patients. (131)I therapy is safe for patients with inactive Graves' ophthalmopathy. Subtotal thyroidectomy and antithyroid drugs show no benefit or harm to eye changes. There is no good evidence that total thyroid ablation has additional benefit. Artificial teardrops, dark glasses and prisms are very helpful. Dysthyroid optic neuropathy is best treated with intravenous pulsed methylprednisolone; if visual functions do not recover, urgent surgical decompression is indicated. A wait-and-see policy is recommended in mild Graves' ophthalmopathy because the natural history of this condition reveals a tendency to resolve spontaneously. Active, moderately severe Graves' ophthalmopathy qualifies for immunosuppression: intravenous pulsed methylprednisolone is more efficacious and has fewer side effects than oral steroids. Once the disease is inactive, rehabilitative surgery has much to offer. Quality of life is seriously limited in patients with Graves' ophthalmopathy, and remains restricted even after all treatments. Consequently, there is an urgent need for improved treatment modalities, and antibody therapy has shown promise in this respect.     

Patients with severe Graves' ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission

OBJECTIVE: To evaluate the relationship between severity of Graves' ophthalmopathy (GO) and relapse/remission rate of associated thyroid disease. PATIENTS AND METHODS: One hundred and fifty-eight patients with Graves' disease (GD) were seen within the first 6-12 months after the onset of GO and were followed for at least 18 months. During treatment, GO was classified as mild (n = 65) or severe course (n = 93) by severity and activity scores. All patients received standard anti-thyroid drug (ATD) treatment for 1 year, and in cases of relapse another cycle of ATD, thyroidectomy or radioiodine therapy. RESULTS: Following ATD treatment, 27 patients (42%) with a mild course of GO went into thyroid disease remission, while only seven (8%) patients with a severe course of GO achieved remission (P < 0.0001). Eventually, 32 patients (49%) with a mild course needed definitive thyroid therapy and the remaining 9% preferred another cycle of ATD. However, among patients with a severe GO course, 84% needed definitive therapy (P < 0.0001) and 8% opted for another course of ATD treatment. The probability of relapse could also be predicted by TBII levels 12 months after initiation of ATD therapy, as 96.8% of patients with TBII levels above 7.5 IU/l relapsed (odds ratio 24.3). CONCLUSION: Patients with severe GO and high TBII are unlikely to go into remission. This allows early decision-making regarding definitive treatment of the thyroid in GD patients with severe GO or very high TBII levels.     

The pathogenesis of Graves' ophthalmopathy

The pathology of the orbital changes in Graves' ophthalmopathy (GO) has been discussed in detail. The target tissue is the eye muscle and the damage probably results from autoimmune processes. Cell-mediated immune responses have been demonstrated and an antibody to eye muscle is detectable in 70% of patients. There is no direct evidence for an effect of thyroid hormones or TSH on orbital tissues in GO. The relation between GO and autoimmune thyroid disease is discussed. Present evidence suggests that in GO autoimmune responses are directed to orbital tissue antigens and do not cross-react with thyroid antigens. Clinical studies suggest that all patients with hyperthyroidism have some abnormality of eye muscle, whereas not all patients with ophthalmopathy have evidence of thyroid disease. It is not possible at the present time to be certain whether GO is an integral part of Graves' disease or a separate entity.     

Temporal relationship between onset of Graves' ophthalmopathy and onset of thyroidal Graves' disease

The temporal relationship between the onset of Graves' ophthalmopathy and the onset of thyroidal Graves' disease was evaluated in 125 consecutive patients with Graves' ophthalmopathy. Thyroidal Graves' disease--past or present--was clinically evident in 99 patients (79%): hyperthyroidism in 3 cases. Thyroid disease preceded the eye disease in 37 patients, it occurred simultaneously with the eye disease in 39 patients, and it developed after the eye disease in 23 patients (in 16 cases within one yr after the onset of eye disease). The age at the onset of thyroid disease (38.7 +/- 12.9 yr) was lower than the age at the onset of ophthalmopathy (41.8 +/- 12.5 yr; p less than 0.001). Among the 26 clinically euthyroid patients (21%) laboratory evidence of thyroidal Graves' disease was found in 14 cases (11%): abnormal TRH test, n = 9; normal TRH test but abnormal T3-suppression test, n = 4; normal TRH and T3-suppression tests but positive thyroid stimulating antibodies, n = 1). We conclude that Graves' ophthalmopathy as a rule develops at a time when thyroid autoimmunity also exists. This strongly suggests a common factor in the pathogenesis of thyroidal and ocular expressions of Graves' disease.     

Total thyroidectomy for the treatment of hyperthyroidism in patients with ophthalmopathy.

Total thyroidectomy was performed in 54 cases of Graves' ophthalmopathy from 1971 to August 2000. There were no surgical complications except for one case of mild hypocalcemia. The patients' postoperative lives were not disturbed. Ocular symptoms and signs were much improved after total thyroidectomy in most cases, but the ocular protrusion was reduced 0.9 mm on average (from 20.6 to 19.7 mm), and this improvement was not statistically significant. However, removal of the thyroid tissue was not complete in some cases in this series and the residual thyroid tissue may continuously support the progress of ophthalmopathy. Surgical influences on Graves' ophthalmopathy were compared between total and subtotal thyroidectomy in each of 50 gender- and age-matched cases from the same period. Average protrusion was reduced 0.9 mm after total thyroidectomy, but was increased 0.5 mm after subtotal thyroidectomy. In conclusion, total thyroidectomy can be performed as safely as subtotal thyroidectomy and is more effective for Graves' ophthalmopathy than subtotal thyroidectomy. However, this procedure would not be expected to completely inactivate aggressive ophthalmopathy, even if all thyroid tissue was removed. In severe cases, orbital decompression, corrective eye muscle, and lid surgery are necessary.     

Treatment of Graves' disease: the advantages of surgery.

The authors and others believe that surgery (thyroidectomy) is underused in the treatment for patients with Graves' disease. It is the most rapid and consistent method of making the patient euthyroid; it avoids the possible long-term risks of radioactive iodine; and it provides tissue for histologic examination. Children, young women, pregnant women, and patients with coexistent thyroid nodules are ideal candidates for thyroidectomy. It also is the treatment of choice for patients with Graves' ophthalmopathy. Patients should be rendered euthyroid before thyroidectomy. Although the operation is technically more difficult than operating on patients with nontoxic goiter or thyroid neoplasms because of the vascularity of the thyroid gland, this difference is small, and the complication rates are low. The authors recommend the Hartley-Dunhill operation (total thyroidectomy on one side and subtotal thyroidectomy on the other side, leaving about 4 to 5 g of thyroid tissue) for most patients and total thyroidectomy for patients with Graves' ophthalmopathy. In patients with recurrent or persistent thyroid cancer who fail to respond to surgery and radioactive iodine ablation, immunosuppressive therapy should be considered.     

Glucocorticoids do not influence the effect of radioiodine therapy in Graves' disease

OBJECTIVE: We evaluated, in a retrospective study, whether glucocorticoids given in order to avoid initiation or aggravation of ophthalmopathy during radioiodine (131I) therapy have an inadvertent effect on the final thyroid function. METHODS: Consecutive patients with Graves' disease (median age 50 years, range 21-82 years) treated with 131I therapy for the first time were included. Ninety-six patients (group 1) were given prednisolone (25 mg daily for 30 days beginning 2 days before 131I therapy) because of present or previous mild ophthalmopathy or the presence of risk factors (tobacco smoking and high concentrations of TSH-receptor antibodies) for developing this complication. One hundred and eleven patients received 131I therapy without prednisolone prophylaxis (group 2). RESULTS: The patients in group 1 were younger than those in group 2 (44.6+/-12.0 years versus 51.3+/-15.1 years; P = 0.001). At 1 year post therapy the patients were classified as hypothyroid, euthyroid or hyperthyroid. In group 1, the numbers of patients were 23, 35 and 38, respectively, while the corresponding numbers in group 2 were 26, 40 and 45, respectively (P = 0.99 between groups). The cure rate (attainment of euthyroidism or hypothyroidism) was 60% in group 1 and 59% in group 2 (P = 0.97). No significant between-group difference was found, neither in the median time-interval until development of hypothyroidism nor until recurrence of the hyperthyroid-ism. Using logistic regression the cure rate correlated negatively with age (P = 0.041) and the size of the thyroid gland (P = 0.010) and positively with serum TSH at treatment (P = 0.034), whereas no significant impact was found for the use of prednisolone, gender, smoking, presence of anti-thyroid peroxidase antibodies, use of anti-thyroid drugs or the presence of eye symptoms. CONCLUSIONS: Although glucocorticoids in some contexts seem to attenuate the radiation-induced oxidative stress this had no impact on the final outcome following 131I therapy of patients with Graves' disease.     

Serum antibodies against the flavoprotein subunit of succinate dehydrogenase are sensitive markers of eye muscle autoimmunity in patients with Graves' hyperthyroidism

Thyroid-associated ophthalmopathy is an autoimmune disorder of the extraocular muscles and orbital connective tissue, which is usually associated with Graves' hyperthyroidism. Well-studied markers of ophthalmopathy are eye muscle membrane antigens, reportedly of approximately 64-kDa molecular mass. One, originally identified only as the 64-kDa protein, has recently been shown to be the flavoprotein (Fp) subunit of mitochondrial succinate dehydrogenase, which has a correct molecular mass of 67 kDa. We have used purified beef heart Fp as antigen in an enzyme-linked immunosorbent assay for cross-reactive human autoantibodies. Sera have been screened from patients with thyroid-associated ophthalmopathy classified according to activity and presence or not of eye muscle disease, and from those with Graves' hyperthyroidism without eye involvement. Also examined were serum samples taken periodically from 20 patients with Graves' hyperthyroidism during 24 months of treatment of their hyperthyroidism with antithyroid drugs. Four of these patients had ophthalmopathy at the onset, 12 developed ophthalmopathy, and 4 did not develop any eye signs during treatment. Anti-Fp subunit antibodies were detected in 73% of patients with active ophthalmopathy and evidence of eye muscle involvement but only in 25% if there was only congestive ophthalmopathy. These values were 0% and 11% for patients with chronic ophthalmopathy, with or without eye muscle dysfunction, respectively. The antibodies were also detected in 14% of patients with Graves' hyperthyroidism without evident ophthalmopathy, 11% of patients with nonimmunologic thyroid disorders, 12% of type I diabetics, and 12% of age- and sex-matched normal subjects. Significantly, appearance of anti-Fp antibodies predicted the development of ophthalmopathy in 5 of the 6 patients with Graves' hyperthyroidism, who developed eye muscle dysfunction after treatment of the hyperthyroidism, and coincided with the onset of eye muscle signs in the other patient. Antibodies were not detected in any of 6 patients who developed congestive ophthalmopathy without evidence of eye muscle damage or in 4 patients who did not develop any eye signs. In conclusion, we have shown a close relationship between eye muscle disease and serum antibodies against the Fp subunit of succinate dehydrogenase in patients with Graves' hyperthyroidism.     

Increased frequency of euthyroid ophthalmopathy in patients with Graves' disease associated with myasthenia gravis.

We previously showed that myasthenia gravis (MG) has a mild clinical expression when associated with autoimmune thyroid diseases (AITD). In the present study we have investigated the frequency of thyroid-associated ophthalmopathy (TAO) in patients with Graves' disease (GD) associated with MG as compared with GD patients without MG. A total of 418 patients with GD were studied, 31 with MG and 387 without MG. TAO was evaluated by physical examination, exophthalmometry, computerized tomography, and computerized visual fields assessment. The overall prevalence of TAO was similar in GD patients with MG (61.2%) and in those without MG (56.4%). When the analysis was restricted to GD patients with ocular MG, a greater frequency of TAO was found (84.6%), compared with GD patients without MG or with GD patients with generalized MG, although the differences did not reach the statistical significance. GD patients with MG had a significantly greater prevalence (12.9%) of euthyroid ophthalmopathy (clinically overt ophthalmopathy without previous and/or current hyperthyroidism) than those without MG (3.1%; p = 0.003). The results suggest a preferential association between the ocular manifestations of GD and MG, which may be due to immunological cross-reactivity against common autoimmune targets in the eye muscle as well as to a common genetic background.     

Inducing Graves' ophthalmopathy

The majority of patients with Graves' disease (GD) have some degree of ocular involvement and this requires surgical or medical intervention in about 5% of cases. There are autoimmune and inflammatory processes operating in Graves' ophthalmopathy (GO), which together induce glycosaminoglycan production, edema and adipogenesis resulting in an increase in the volume of the orbital contents. GO is a heterogeneous disorder, i.e.: 1) whilst usually associated with hyperthyroidism it may occur in euthyroid (and even hypothyroid) patients; 2) expansion of orbital tissues may be due to 'big-fat' or 'big muscles'. The heterogeneity is further exemplified by the spectrum of protocols which have succeeded in inducing aspects of the disease both in animal models and in humans including: 1) Production of severe hypothyroidism in guinea pigs by thyroidectomy and administration of pituitary extract (TSH); 2) Induction of T cells autoreactive to the thyrotropin receptor (TSHR) in mice; 3) Depletion of regulatory T cells in humans susceptible to autoimmunity; 4) Modulation of adipose tissue metabolism in mice and men. In addition, identical induction protocols result in different pathological features depending on the environment, e.g. TSHR primed T cells produce thyroiditis and ocular pathology in BALBc mice in Brussels but thyroid stimulating antibodies accompanied by elevated thyroxine in these animals (from the same supplier) in Cardiff. Thus, experiences in the induction of GO have confirmed the polygenic, multifactorial nature of the disorder and highlight the importance of careful disease classification to promote further progress in understanding.     

Beneficial effects of intensive plasma exchange followed by immunosuppressive therapy in severe Graves' ophthalmopathy

Nine patients with severe Graves' ophthalmopathy were treated by intensive plasma exchange, followed by immunosuppression. Severity of ocular involvement and response to therapy were evaluated clinically by numerical scoring (ophthalmopathy index). Serum thyroid stimulating immunoglobulins (TSI) and urinary excretion of glycosaminoglycans (GAG) were measured immediately before and immediately after plasmapheresis. Plasma exchange was rapidly accompanied by marked clinical improvement in 8/9 patients. The most marked effects were on soft tissue involvement, proptosis, intraocular pressure, and visual acuity. The ophthalmopathy index decreased from 9.7 +/- 4.1 to 5.7 +/- 2.2 (P less than 0.001) after plasmapheresis. Serum TSI levels were initially elevated in 6 patients and remained positive in 3 patients after treatment. Urinary GAG excretion was initially 2- to 12-fold normal levels and was decreased by 60%. After plasmapheresis, patients received immunosuppressive drugs for 3-6 months. The follow-up period, after withdrawal of drugs, ranged from 5 to 38 months with a median of 17 months. The ocular condition remained stable in 6 patients. Three patients had a relapse 1 year after plasmapheresis: they were treated a second time by plasma exchange with subsequent improvement. In conclusion, intensive plasma exchange provided prompt and effective improvement in patients with severe progressive Graves' ophthalmopathy. This therapeutic procedure, followed by immunosuppression, gave long lasting results. Relapses were responsive to plasmapheresis therapy. The data suggest that plasma exchange may represent the best primary treatment for severe progressive Graves' ophthalmopathy.     

Diagnostic evaluation of Graves' ophthalmopathy

The important questions to be answered in the course of decision-making in patients with Graves' ophthalmopathy include the following: 1. Is the eye problem owing to Graves' ophthalmopathy? If not, the cause of the eye problem must be sought. 2. Does the patient have serious medical problems apart from the thyroid and the eyes? Define type and severity, and risk to life and well-being. Do they preclude anesthesia or steroid therapy? 3. Is the patient euthyroid? Define thyroid abnormality and treat. 4. Is the eye problem the highest medical priority for the patient and the physician? If not, treat the highest priority, then return to the eyes. 5. Which particular manifestations of Graves' ophthalmopathy are the most troublesome to the patient? Establish priorities according to need and rational order for surgical procedures. 6. How have the eyes been treated in the past? What has been successful? What side effects have resulted? In the evaluation of a patient with possible Graves' ophthalmopathy, no single clinical or laboratory feature is necessary or pathognomonic of the disorder. The sufficient findings for a diagnosis are a matter of clinical judgment. Several diagnostic tools including CT scanning, various ophthalmologic examinations, and studies of thyroid function are available. The physician must use these tools, along with clinical judgment, to establish the diagnosis with maximum certainty. Following this, the particular manifestations of the disease that are most troublesome to the patient must be carefully defined and assessed. Only then can the treatment be optimally tailored to the patient's needs.     

Studies on the occurrence of ophthalmopathy in Graves' disease

Eye disease was associated with hyperthyroidism in 202 of 221 patients with active Graves' ophthalmopathy (91.4%) and was not accompanied by thyroid hyperfunction (euthyroid Graves' disease) in the remaining 19 (8.6%). All the latter patients had some mild thyroid abnormalities (thyroid autoantibodies, negative TRH test, negative T3 suppression test, goitre). Sex distribution analysis evidenced a higher prevalence in females with a female/male ratio of 2.1 which was, however, significantly lower (P less than 0.05) than that observed in control (Graves' disease patients without overt ophthalmopathy (female/male ratio = 3.4]. Patients with euthyroid Graves' disease showed a female/male ratio of 0.7. Age distribution revealed a peak prevalence in the 5th decade of life, identical to that of Graves' disease without ophthalmopathy. A close temporal relationship between the onset of hyperthyroidism and the onset of ophthalmopathy was found, since in about 85% of the patients the first ocular manifestations occurred within +/-18 months around the onset of hyperthyroidism.     

Radioiodine therapy of Graves' hyperthyroidism in patients without pre-existing ophthalmopathy: can glucocorticoids prevent the development of new ophthalmopathy?

BACKGROUND: Radioiodine therapy (RIT) combined with glucocorticoids is an effective therapy for Graves' disease, but it is debatable whether glucocorticoids should be applied in patients without Graves' ophthalmopathy (GO). METHODS: The effect of 0.4 - 0.5 mg prednisone every second day over a period of 5 weeks after RIT was monitored over a follow-up period of at least 12 months after RIT. A questionnaire was sent to 186 consecutive patients without GO concerning eye symptoms after RIT. 148 patients (80 %) answered. If eye symptoms had occurred after RIT, additional clinical examination was carried out at our outpatient clinic. The primary endpoint was the absence or onset of GO within the first year after RIT. RESULTS: Within 12 months after RIT the examination confirmed GO in 5 out of 148 patients (3.4 %). In all cases the symptoms were transient. No adverse reaction to the use of prednisone after RIT was noted. CONCLUSIONS: The risk of new GO in the first year after RIT was low and the clinical course of GO was mild when RIT was combined with a low-dose glucocorticoid regimen. Preventive administration of glucocorticoids can therefore be recommended in patients with Graves' disease even without evident GO.