Course Of Ophthalmopathy Research Articles

Effect of thyroid hormone status on complete blood cell count-derived inflammatory biomarkers in patients with moderate-to-severe Graves' ophthalmopathy.

To evaluate the systemic inflammation in moderate-to-severe Graves' ophthalmopathy patients with abnormal thyroid function by using complete blood cell count-derived inflammatory biomarkers and compare to moderate-to-severe GO patients with regulated thyroid function and healthy controls. The second aim is to evaluate the relationship of complete blood cell count-derived inflammatory biomarkers with clinical findings in moderate-to-severe GO. In this retrospective study, 90 GO patients with abnormal thyroid function composed Group 1, 58 patients who had normal thyroid function for at least 3months composed Group 2, and 50 healthy individuals composed Group 3. Demographic data, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and systemic immune-inflammatory index (SII) were evaluated. There was no statistically significant difference between groups in terms of age, sex, and smoking habits (p > 0.05). There was a statistically significant difference in NLR (p = 0.011), MLR (p = 0.013), MPV (p < 0.001), and SII (p < 0.001) values among 3 groups. For NLR, MLR, and SII the highest values were detected in Group 1. MPV levels were higher in Group 3 than Groups 1 and 2 (p < 0.001). None of the hematological parameters were found to be a risk factor for any clinical severity findings of GO. The higher levels of NLR, MLR, and SII levels may show systemic inflammation in GO patients with abnormal thyroid function, and this may have an impact on the clinical course of ophthalmopathy. These findings may suggest that cautious control of thyroid hormone levels is important in the management of GO.

SUN-LB87 De-Novo Graves Ophthalmopathy After Total Thyroidectomy With Exacerbation Following Rifampicin Therapy for Latent Tuberculosis: A Call for Attention to Disease Modifying Interventions

Introduction Factors influencing development and course of ophthalmopathy, the most common extrathyroidal manifestation of Graves’ disease, remain poorly defined. Clinical Case A 46 year old healthy, non-smoking, medical secretary, presented with Graves’ disease. Laboratory investigation showed thyrotoxicosis with high thyroid stimulation immunoglobulin (TSI) levels (1608 %, normal <140%). At presentation there was no evidence of thyroid eye disease on clinical exam and orbital MRI. Treatment with Methimazol and PTU induced severe pruritus and she underwent total thyroidectomy. One month after surgery she presented with retroorbital pain, eyelid edema and chemosis, as well as bilateral limitation in abduction; a clinical activity score (CAS) of 3/7. She received IV pulse methylprednisolone 4.5 gr with minor improvement. MRI showed bilateral thickening of all rectus muscles with orbital fat infiltration. TSI increased concomitantly to 3600%. Three months later, she underwent standard retrobulbar radiotherapy (20 Gy), again with only minor improvement. She continued treatment with oral prednisone 20mg with small fluctuations in disease activity in the following months during which TSI remained high (3145%) and latent tuberculosis was detected (elevated interferon-gamma release assay). Therefore, rifampicin 600mg/d was started. A month later the ophthalmopathy worsened (a CAS score of 5/7 without optic neuropathy). Laboratory tests showed new perturbation in thyroid function tests (TSH increased from 5 to 15 mIU/l, normal: 0.5-5; FT4 decreased from 16 to 11 pmol/l, normal: 10-20) and TSI increased to 3879%. Euthyrox dose was increased by 50% from 800 to 1200 microgram/week. It was postulated that prednisone was also being rapidly metabolized by rifampicin mediated induction of the CYP450, and therefore the dose was increased from 20 to 40 mg/d. Six weeks later, normalization of thyroid function tests was followed by improvement in the ophthalmopathy (CAS-3). Conclusion (Clinical lesson) A) De-novo severe Graves’ ophthalmopathy after thyroidectomy requiring multiple forms of treatment is rare but close surveillance is advisable, perhaps particularly in the presence of high TSI. A plausible mechanism may be transient increase in antigenic exposure/dissemination during surgery. B) Rifampicin, through induction of cytochrome P450-mediated metabolism of levothyroxine, steroids and mycophenolate (the latter not used in our patient) can lead to disease flare-up. Tight clinical and laboratory monitoring of thyroid function tests with individualized dose escalation might be needed. In the future, pharmacogenomics may serve to personalize treatment protocols.

Результати хірургічного лікування хворих на дифузний токсичний зоб з автоімунною офтальмопатією

Лікування дифузного токсичного зоба з автоімунною офтальмопатією є однією з проблем сучасної ендокринології через складний механізм патогенезу захворювання та його тяжкий перебіг, що в деяких випадках призводить до інвалідизації пацієнтів. Одним із методів лікування цієї патології є хірургічне втручання, а саме тиреоїдектомія, яка забезпечує швидку ліквідацію не лише тиреотоксикозу, а й «мішені» для антитиреоїдних антитіл (АТ рТТГ). У подальшому для лікування автоімунної офтальмопатії застосовують пульс-терапію глюкокортикоїдами згідно з рекомендаціями EUGOGO 2016 року. Але вибір оптимального часу для початку пульс-терапії після тиреоїдектомії остаточно не з’ясовано. Метою дослідження було вивчення концентрації АТ рТТГ та перебігу автоімунної офтальмопатії у хворих на дифузний токсичний зоб з автоімунною офтальмопатією в різні терміни після тиреоїдектомії. Матеріал і методи. Виконано проспективне дослідження, до якого було включено 70 пацієнтів (60 жінок і 10 чоловіків; середній вік 46,0±3,4 року), хворих на дифузний токсичний зоб з автоімунною офтальмопатією. Досліджували стан очей і клінічний перебіг автоімунної офтальмопатії (огляд офтальмолога, екзофтальмометрія, ультразвукове дослідження орбіт), а також концентрації АТ рТТГ перед операційним втручанням і через 6, 12, 24 і 36 місяців після нього. Результати. Отримані результати дослідження дозволяють стверджувати, що після тиреоїдектомії поступово зменшується активність автоімунного процесу, підтвердженням чого є зменшення концентрації АТ рТТГ. Рівень АТ рТТГ вірогідно (р&lt;0,05) зменшувався вже через 6 місяців після тиреоїдектомії, далі ця тенденція зберігалася протягом 36 місяців. Паралельно зі зниженням рівня АТ рТТГ протягом року після тиреоїдектомії значно зменшувалися клінічні прояви офтальмопатії в 14,3% випадків. У цілому по групі також зменшилась активність офтальмопатії (за САS), але вірогідних змін розмірів екзофтальму, товщини хоріоретинального комплексу та ретробульбарної клітковини не виявлено. Висновки. Після хірургічного втручання (в обсязі тиреоїдектомії) з приводу дифузного токсичного зоба з автоімунною офтальмопатією рівень АТ рТТГ вірогідно зменшується вже через 6 місяців, а мінімального рівня досягає через 36 місяців. У 14,3% випадків значно зменшилися клінічні прояви офтальмопатії — зникли спонтанний ретробульбарний біль, періорбітальний набряк, гіперемія кон’юнктиви та хемоз. Доцільно починати пульс-терапію глюкокортикоїдами через 6 місяців після тиреоїдектомії, коли досягнуто стану еутиреозу на тлі замісної терапії левотироксином і вірогідного зменшення концентрації АТ рТТГ.

ОЦЕНКА ЭФФЕКТИВНОСТИ ЛЕЧЕНИЯ ЭНДОКРИННОЙ ОФТАЛЬМОПАТИИ

Background. The achievements of modern medicine contribute to the timely diagnosis of endocrine ophthalmopathy (EOP). However, treatment continues to be a complex task, the results of which do not satisfy the physician and the patient. Purpose of the study – to evaluate the effectiveness and safety of pulse therapy with methylprednisolone in the treatment of active forms of endocrine ophthalmopathy. Material and methods. The analysis of the efficacy of treatment of 36 patients with moderate intensity of pulsed EEG by methylprednisolone therapy was carried out. The minimum cumulative dose of the drug was 4.5 grams. Results. Reduction of the activity of the image intensifier on the CAS scale and reduction of the intensity of inflammatory changes in soft tissues of the orbit was observed 1 month after the start of the drug administration. After the abolition of pulse therapy, the positive effect was preserved in 29 of 36 positively responding patients, which was 80.6%. Deterioration of the course of ophthalmopathy at the end of the course of treatment was recorded in 7 patients (19.4%), of which tobacco smoking was noted in 5 (71.4%) patients, the hormone condition was not stable in 2 (28.65%) patients, who required correction by endocrinologist. Conclusions. The therapy used enabled to reduce the inflammatory process in the orbit within a short period of time, and the subsequent scheme of the drug administration improved the effect and created a long-term remission. To treat patients with EOC in order to provide a therapeutic effect, it is necessary to use the safest doses of glucocorticoids. The definition of the prescribed therapy should be based on the degree of severity and activity of the process.

Effect of Near‐Total Thyroidectomy on Thyroid Orbitopathy Due to Toxic Goiter

The relative merit of surgery in the treatment of Graves' ophthalmopathy as well as the extent of surgical resection are still matters of debate. This study aimed at reporting an assessment of the impact of near-total thyroidectomy on the course of ophthalmopathy including exophthalmos. A total of 20 patients with thyrotoxic goiters who were suffering from mild to moderate exophthalmos were enrolled in this prospective study. Preoperative evaluation of ophthalmopathy was accomplished through the NOSPECS classification, magnetic resonance imaging (MRI) for measuring the extraocular muscle diameters, and measurement of the exophthalmos using Hertel's exophthalmometer. Ophthalmopathy including exophthalmos was reevaluated 6 months after operation using the same parameters. Clinical activity evaluation, exophthalmometry, and extraocular muscles measurement by MRI revealed that most of the patients experienced improvement of their ophthalmopathy (65%). This improvement was statistically significant. In addition, no major postoperative complications were observed. However, the study, unlike a number of reported retrospective ones, failed to specify any statistically significant prognostic factors affecting the course of ophthalmopathy; this may have been due to the limited number of patients. In addition, all of the patients were of relatively young age and thyrotoxic, and most were female and nonsmoking. In addition to the fact that near-total thyroidectomy adds the advantages of total thyroidectomy (no recurrence) to those of subtotal thyroidectomy (low incidence of temporary and permanent hypoparathyroidism), it has a significant positive impact on thyroid-associated orbitopathy.

A systematic review of drug therapy for Graves’ hyperthyroidism

We assessed the effects of dose, regimen and duration of anti-thyroid drug therapy for Graves' thyrotoxicosis on recurrence of hyperthyroidism, course of ophthalmopathy, adverse effects, health-related quality of life and economic outcomes. We undertook a systematic review and meta-analyses of randomised controlled trials (RCTs). We identified RCTs regardless of language or publication status by searching six databases, and trial registries. Dual, blinded data abstraction and quality assessment were undertaken. Trials included provided therapy for at least 6 months with follow-up at least 1 year after drug cessation. Fixed or random effects meta-analyses were used to combine study data. Twelve trials compared a Block-Replace regimen (requiring a higher dose of anti-thyroid drug treatment) with a Titration regimen. Overall, there was no significant difference between the regimens for relapse of hyperthyroidism (relative risk (RR) = 0.93, 95% confidence interval (CI) 0.84 to 1.03). Participants were more likely to withdraw due to adverse events with a Block-Replace regimen (RR = 1.89, 95% CI 1.25 to 2.85). Prescribing replacement thyroxine, either with the anti-thyroid drug treatment, or after this was completed, had no significant effect on relapse. Limited evidence suggested 12-18 months of anti-thyroid drug treatment should be used. The titration regimen appeared as effective as the Block-Replace regimen, and was associated with fewer adverse effects. However, relapse rates over 50% and high participant drop-out rates in trials mean that the results should be interpreted with caution, and may suggest that other strategies for the management of Graves' disease, such as radioiodine, should be considered more frequently as first-line therapy. There were no data on the course of ophthalmopathy, health-related quality of life and economic outcomes.

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.

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

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. 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. 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). Patients were seen every 1-2 months for 12 months for thyroid tests and ocular evaluation. 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. 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.

Treating severe Graves' ophthalmopathy

Most patients with Graves' disease have some evidence of ocular involvement, but this is commonly mild, requiring only local measures. A minority of patients (3-5%) have severe Graves' ophthalmopathy, for which the three main treatment procedures are represented by high-dose glucocorticoids, orbital radiotherapy and orbital decompression. Favourable results with medical treatment have been reported in approximately 60% of patients, with particular regard to inflammatory changes, newly developed eye muscle dysfunction and optic neuropathy. Orbital decompression is indicated in severe eye disease not responsive to glucocorticoids and/or irradiation, particularly in the presence of marked proptosis and optic neuropathy. Not conclusive or unsatisfactory results have been obtained with other medical treatment procedures, including immunosuppressive drugs, intravenous immunoglobulins and plasmapheresis. Recently favourable responses have been reported with somatostatin analogues. Rehabilitative surgery involving either the eye muscles or the eyelids is not infrequently required after medical treatment or decompression. Permanent control of thyroid hyperfunction by radioiodine or thyroidectomy is advisable when severe ophthalmopathy is present. Exacerbation of ophthalmopathy following radioiodine may occur but can be prevented by concomitant administration of glucocorticoids. Smoking deleteriously influences the course of ophthalmopathy and its response to treatment.

Radioiodine and thyroid-associated ophthalmopathy

Particular attention has recently been paid to the relationship between radioiodine administration and the course of thyroid-associated ophthalmopathy (TAO). Conflicting results have been reported in the literature, and radioiodine therapy has been associated either with aggravation, improvement, or no relevant changes of eye disease. Retrospective observations and recent prospective studies suggest that radioiodine can worsen preexisting ophthalmopathy and that these untoward ocular effects can be prevented by concomitant glucocorticoid administration. In the authors' experience, subtotal thyroidectomy can sometimes be associated with an exacerbation of ophthalmopathy; antithyroid drugs per se do not cause relevant changes in eye disease, but drug withdrawal is frequently followed by a relapse of hyperthyroidism which adversely affects the course of ophthalmopathy. Based on these considerations, the authors suggest that in Graves' disease patients with significant eye manifestations, a rapid and permanen...

Treatment of Graves' disease and the course of ophthalmopathy

Contradictory results have been obtained with regards to the effect of various treatment modes on the exacerbation of Graves' ophthalmopathy, probably because the number of patients in each study was small and some studies were analyzed only in relation to one type of treatment. To circument these problems, we studied the course of Graves' ophthalmopathy after various modes of therapy for thyrotoxicosis among 537 patients with Graves' disease. A total of 537 patients with Graves' disease were prospectively studied over an 11-year period. Thirty-one patients were lost to follow-up during the first six months after treatment and were excluded from the study. Of those remaining, 426 received one form of treatment, 79 received two kinds of therapy, and one received three kinds of therapy. Thus, surgical treatments numbered 164, radioactive iodine-131 (131I) treatments numbered 241, and medical treatments numbered 182. Ocular signs were considered improved or exacerbated by the following criteria: decrement or increment of the exophthalmos of 2 mm or more, improvement or deterioration of visual acuity, and regression or progression of extraocular muscle involvement causing diplopia. Among patients who did not have infiltrative ophthalmopathy before treatment, there was no difference in the occurrence of posttreatment exophthalmos in the surgically, medically, and 131I-treated patients (7.1%, 6.7%, and 4.9%, respectively). The incidence and the degree of progression of ophthalmopathy in patients who already had exophthalmos before treatment were similar in the medically, surgically, and 131I-treated groups (19.2%, 19.8%, and 22.7%, respectively). Most of the progression occurred in the posttreatment euthyroid stage. The incidence of improvement of ophthalmopathy was also similar (14.1%, 12.6%, and 12.3% in the medically, surgically, and 131I-treated patients). In conclusion, we found no influence of type of therapy for thyrotoxicosis on the clinical course of Graves' ophthalmopathy in this retrospective study of 537 patients.

Relationship of long-acting thyroid stimulator to the clinical features and course of Graves' disease

Long-acting thyroid stimulator (LATS) determinations were performed in the serum of 439 subjects. A positive LATS response was found in 1 per cent of those without thyroid disease, in 9 per cent of those with thyroid disorders other than Graves' disease and in 53 per cent of those with active Graves' disease. Only 16 per cent of the patients with inactive Graves' disease had LATS in their serum and there was a significant negative correlation between the presence of LATS and the duration of inactivity of the disease. Analysis of the association of LATS with each of the three major manifestations of Graves' disease (hyperthyroidism, ophthalmopathy and dermopathy), individually and in various combinations, revealed that LATS was most closely associated with the number of manifestations present, rather than with any individual manifestation. The incidence was lowest (47 per cent) in patients with only one of the three organ systems involved; it was 63 per cent in those with two organs actively involved and 89 per cent in those with all three involved. The presence or absence of hyperthyroidism was statistically associated with the presence of LATS only when it was the sole active manifestation of the disease, and the addition of ophthalmopathy was similarly unrelated to the incidence of LATS when ei her other manifestation was present and active. Only dermopathy showed a statistically significant association with LATS regardless of the presence or absence of other features. Sixty per cent of the patients with dermopathy had very high concentrations of LATS. The incidence of LATS was higher in patients previously treated for hyperthyroidism than in those never treated. Serial LATS determinations were performed in seventy-four patients and results compared prospectively with the clinical course of the patient's disease, including dermopathy and ophthalmopathy. In the majority of patients LATS decreased during the period of study, including those who received no specific treatment. Ophthalmopathy either stabilized or improved in most patients, either following treatment or spontaneously. The course of ophthalmopathy usually paralleled the course of LATS. Patients with persistently very high or moderately high levels of LATS, or those who showed a change from no detectable LATS to very high levels, had a relatively poor prognosis in regard to ophthalmopathy. The course of hyperthyroidism did not parallel the course of LATS. There was no prognostic significance in a single LATS determination, even when the serum concentration of LATS was very high. Serial LATS determinations were of prognostic value. Eighteen patients were treated with glucocorticoids for severe, progressive ophthalmopathy. Following treatment LATS decreased markedly in seven of the eight patients who had LATS in their serum. However, the presence or absence of LATS prior to therapy was not helpful in determining whether a patient would respond to glucocorticoid therapy. In thirteen of the eighteen patients ophthalmopathy improved. The possible role of LATS in the pathogenesis of Graves' disease is discussed in the light of the observed in errelationships.

Ophthalmopathy associated with Graves' disease. Unusual clinical manifestations and their management.

The clinical features and course of ophthalmopathy associated with Graves' disease may be exceedingly diverse and unpredictable. The ophthalmopathy may be characterized by exophthalmos of varying degrees, retraction of the eyelids, edema of the contents of the orbit and adnexa, chemosis and congestion of the surface of the eye, and, not infrequently, ophthalmoplegia. These protean manifestations may occur in various combinations or as isolated findings. Severe progressive ocular changes may occur at any time during the course of Graves' disease. However, it is noteworthy that they often accompany extremely mild Graves' disease and may become more severe during the period of recovery from hyperthyroidism regardless of the method of treatment used. In fact, the characteristic ophthalmopathy of Graves' disease may occur in patients who do not show any other clinical or laboratory evidence of the disease. Frank manifestations of Graves' disease subsequently develop in some of these patients. It is