Hemodynamic changes have been observed in patients with Graves' disease. The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index (CVI) in patients with ...thyroid-associated ophthalmopathy (TAO).
In this cross-sectional observational study, 40 patients affected by TAO were recruited. Forty healthy individuals, matched for age and sex, served as controls. Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants. Images were binarized using the ImageJ software and luminal area (LA) and total choroidal area (TCA) were measured. CVI was calculated as the proportion of LA to TCA. The relation between CVI or subfoveal choroidal thickness (SFCT) and clinical activity score, exophthalmometric value, diplopia status, gender, and age was evaluated.
CVI was significantly higher in patients with TAO (P = 0.004). No significant difference was observed in SFCT (P = 0.200) and TCA (P = 0.153) comparing TAO patients and healthy controls. LA was significantly higher in TAO group (P = 0.045). On multiple regression analysis, CVI was associated with TCA (P = 0.043). No association was found between SFCT or CVI and TCA, clinical activity score, exophthalmometric value, Inami value, diplopia status, gender or age (P > 0.05).
This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.
Limited data suggest that treatment with statins is associated with a reduced risk of Graves' orbitopathy (GO) in patients with Graves' disease (GD), attributed to the anti-inflammatory rather than ...to the hypolipemic effects of these medications. The aim of the present study was to investigate whether there is an association between high cholesterol and GO. The primary outcome was the relation between GO and low-density lipoprotein (LDL)-cholesterol. The secondary outcomes were the relation between severity or activity (the clinical activity score CAS) of GO and LDL-cholesterol.
A cross-sectional investigation was conducted in consecutive patients with GD who came under the authors' observation to undergo radioiodine treatment, a stratification aimed at forming two distinct groups of patients under the same conditions. A total of 250 patients were enrolled, 133 with and 117 without GO. Ophthalmological assessments and serum lipids measurements were performed.
In multivariate analyses with correction for the duration of hyperthyroidism, a variable that differed between patients with respect to the presence or absence of GO, a correlation between the presence of GO and both total (p = 0.01) and LDL-cholesterol (p = 0.02) was observed. In patients with hyperthyroidism lasting <44 months, total and LDL-cholesterol were higher (p = 0.01 and p = 0.008, respectively) among GO patients. In this subgroup, based on the presence/absence of GO, cutoff values were established for total (191 mg/dL) and LDL-cholesterol (118.4 mg/dL), above which an increased risk of GO was observed (total cholesterol relative risk: 1.47; p = 0.03; LDL-cholesterol relative risk: 1.28; p = 0.03). GO severity and CAS did not correlate with serum lipids. However, CAS was found to be higher (p = 0.02) in patients with high total cholesterol. When the analysis was restricted to untreated GO patients, a correlation was found between CAS and both total (p = 0.04) and LDL-cholesterol (p = 0.03), after adjustment for GO duration.
In patients with a short duration of hyperthyroidism, total and LDL-cholesterol correlate with the presence of GO, suggesting a role of cholesterol in the development of GO. Depending on GO duration, total and LDL-cholesterol correlate with GO activity, suggesting a role of cholesterol in the clinical expression of GO.
High-dose intravenous glucocorticoid (ivGC) pulse therapy, which is commonly used for Graves' orbitopathy (GO), has been associated with acute liver damage (ALD), resulting in a fatal outcome in a ...few cases. No certain risk factors for ALD have been established. Consequently, a large retrospective cohort study was performed.
The relationship between ALD and several potential risk factors was assessed in 1076 consecutive patients with GO given ivGC. ALD was defined as an increase of alanine aminotransferase ≥300 IU/L.
Fourteen cases of ALD were recorded, resulting in a morbidity of 1.3%. Thirteen patients recovered and one died, resulting in a mortality of 0.09%. There was a significant, positive correlation of ALD with age and methylprednisolone acetate (MPA) cumulative dose, and ALD was more common (relative risk RR=2.8; p=0.05) in patients aged ≥53 years (9/420; 2.14%) than in those aged <53 years (5/656; 0.76%). In patients aged ≥53 years, there was a significant positive correlation of ALD with MPA cumulative dose, and with MPA dose per infusion. Thus, the frequency of ALD in this age group was greater (RR=3.48; p=0.04) in patients with a MPA dose per infusion ≥0.7 g (5/111, 4.5% vs. 4/308, 1.29%). Regardless of age, no cases of ALD were observed for MPA doses per infusion <0.57 g.
Age and MPA dose are significant risk factors for ALD, with the following practical implications. First, the total MPA cumulative dose should not exceed 8.5 g (the average dose in patients without ALD). Second, in patients aged ≥53 years, selection and observation should be quite strict. However, being aged ≥53 years should not be seen as an absolute contraindication to ivGC, especially in patients with severe GO, considering that the risk of ALD, although statistically significant, was relatively low. Third, the MPA dose should not exceed 0.57 g per infusion, a measure to be applied regardless of age.
Clinically overt Graves' orbitopathy (GO) is associated with Graves' disease (GD) in approximately 95% of cases, whereas the remaining 5% is observed in patients with hypothyroid autoimmune ...thyroiditis (AT) or without overt thyroid dysfunction (euthyroid GO). However, it is not known whether there is a difference in terms of GO phenotype between patients with GD and those with hypothyroid AT or without thyroid dysfunction, and hence this is investigated here.
The study design was to evaluate retrospectively all consecutive patients with a recent manifestation of GO, seen at their first visit to a tertiary referral center over a period of 10 years. In total, 358 GO patients were studied, and all of them underwent GO assessment.
Of the 358 patients studied, 341 had hyperthyroid GD, 10 had AT with hypothyroidism, and seven had euthyroid GO. Age, sex, and smoking habits were similar in the three groups, as was the time since GO was first noticed (GO duration). The vast majority of patients had moderate to severe, active GO, as expected in a tertiary referral center. Exophthalmometry, eyelid width, clinical activity score (CAS), diplopia, and visual acuity did not differ between patients with GD and those with AT or euthyroid GO, suggesting that the GO phenotype was similar. Accordingly, the NOSPECS score did not differ between the three groups.
The phenotype of GO is similar regardless of the underlying thyroid disease. Because this study was performed in a tertiary referral center, this conclusion can be restricted only to patients who develop moderate to severe GO.
ObjectiveIntravenous glucocorticoid (i.v.GC) pulse therapy for Graves' ophthalmopathy (GO) can be associated with acute liver damage (ALD), which was roughly estimated to occur in ∼1% of patients, ...with an overall mortality of 0.4%. The aim of this study was to evaluate the frequency of ALD after the introduction of a series of exclusion criteria and preventive measures.DesignRetrospective evaluation of all consecutive patients candidate to i.v.GC over a period of 5 years.MethodsThe study includes 376 GO patients candidate to i.v.GC. Several liver tests were performed before, during, and after i.v.GC. To prevent ALD morbidity and mortality, the following measures were applied: i) exclusion of patients with active viral hepatitis and/or severe liver steatosis; ii) reduction in the GC dose, frequency, and number of pulses; and iii) administration of oral GC after i.v.GC, and also during i.v.GC in patients positive for nonorgan-specific autoantibodies (to prevent autoimmune hepatitis due to immune rebound). ALD was defined as an increase in alanine aminotransferase ≥300 U/l.ResultsA total of 353 patients were given i.v.GC and 23 were excluded for various conditions. ALD was detected in 4/376 patients candidate to i.v.GC, resulting in a morbidity of 1.06%. One patient recovered spontaneously and three after additional treatment with oral GC, given to re-establish immune suppression in the suspect of an autoimmune hepatitis.ConclusionsALD related to i.v.GC is a relatively rare adverse event. Provided an accurate selection of patients and a series of preventive measures are applied, i.v.GC is a safe treatment for the liver.
Context:
In a previous study, we found that total thyroid ablation (thyroidectomy plus 131I) is associated with a better outcome of Graves' orbitopathy (GO) compared with thyroidectomy alone, as ...observed shortly (9 months) after glucocorticoid (GC) treatment.
Objective:
The objective of the study was to evaluate the outcome of GO in the same patients of the previous study over a longer period of time.
Design:
This was a follow-up of a randomized study.
Setting:
The study was conducted at a referral center.
Patients:
Fifty-two of 60 original patients with mild to moderate GO participated in the study.
Interventions:
Patients randomized into thyroidectomy (TX) or total thyroid ablation and treated with GC were reevaluated in 2010, namely 88.0 ± 17.7 months after GC, having undergone an ophthalmological follow-up in the intermediate period.
Main Outcome Measures:
The main outcome measures included the following: 1) GO outcome; 2) time to GO best possible outcome and to GO improvement; and 3) additional treatments.
Results:
GO outcome at the end of the follow-up was similar in the two groups. However, the time required for the best possible outcome to be achieved was longer in the TX group (24 vs. 3 months, P = 0.0436), as was the time required for GO to improve (60 vs. 3 months, P = 0.0344). Additional treatments were given to a similar proportion of patients in each group (TX, 28%, total thyroid ablation, 25.9%), but they affected GO beneficially more often in the TX group (28 vs. 3.7%, P: 0.0412).
Conclusions:
Compared with thyroidectomy alone, total thyroid ablation allows the achievement of the best possible outcome and an improvement of GO within a shorter period of time.
Context: Graves’ orbitopathy (GO) is probably caused by autoimmune reactions against autoantigen(s) shared by thyroid and orbital tissues sustained by intrathyroidal autoreactive T-lymphocytes ...infiltrating the orbit. Total thyroid ablation (TTA) may be beneficial for GO through removal of shared antigen(s) and autoreactive T-lymphocytes, but randomized studies are lacking.
Objective: Our objective was to evaluate the effects of TTA in patients with GO treated with iv glucocorticoids (GC).
Design/Setting: A prospective, single-blind, randomized study was conducted at a referral center.
Patients/Interventions: Sixty patients with mild to moderate GO were randomized into: 1) near-total thyroidectomy (TX); or 2) TX plus 131I (TTA) groups, and then treated with iv GC. Patients were evaluated 3 and 9 months after iv GC.
Main Outcome Measure: Overall improvement of GO at 9 months was the main outcome measure.
Results: The distribution of GO outcome at 9 months was significantly more favorable in TTA than in TX patients (P = 0.0014 by χ2 test). A cumulative significant (P = 0.0054) difference between the two groups at 3 and 9 months was found using a generalized linear model. Radioiodine uptake test and thyroglobulin assay in a patient sample showed complete ablation in the majority of TTA, but not of TX patients.
Conclusions: Compared with thyroidectomy alone, TTA is followed by a better outcome of GO in patients given iv GC. Whether TTA maintains this advantage in the long-term remains to be established.
Patients with moderate to severe Graves' orbitopathy (GO) rather frequently require rehabilitative surgery after medical therapy. Diplopia is the most common side effect of orbital decompression ...(OD). The aim of this study was to evaluate the occurrence of postoperative diplopia in primary gaze after OD, and the influence of the surgical approach on this outcome. Moreover, we investigated the results in terms of proptosis reduction, and the long-term subjective satisfaction of patients treated with OD with regard to their appearance and ocular function.
A retrospective evaluation of 247 patients with GO treated with medial and lateral decompression (MLD) or lateral decompression (LD) OD between January 2002 and December 2009 was performed.
The overall prevalence of postoperative diplopia in primary gaze was 55/247 (22.3%), with a statistically significant difference (p<0.001) between patients with (36/113, 31.2%) and those without (19/134, 14.2%) preoperative diplopia in secondary gaze. The surgical procedure influenced the outcome in patients without preoperative diplopia (17.8% after MLD and 0% after LD, p=0.02), but not in patients with preoperative diplopia in secondary gaze (33.3% after MLD and 26.1% after LD, p=0.5). Overall, proptosis reduction was 5.7±2.2 mm (1-11 mm), after MLD and 4.0±1.6 mm (1-8 mm) after LD (p<0.001). Fifty-one out of 55 patients with constant, postoperative diplopia in primary gaze after OD underwent squint surgery, which was successful in all but two. Four patients refused squint surgery. Patients were also interviewed for satisfaction in terms of recovery of their appearance and ocular function after a mean of 6 years from surgery (range 2-9 years): more than 85% of patients reported a good to excellent postoperative satisfaction for both items.
Preoperative diplopia in secondary gaze is a risk factor for the development of diplopia in primary gaze after OD, independently of the surgical approach (MLD vs. LD). In absence of diplopia, MLD, but not LD, seems to be associated with its development in primary gaze. The reduction in proptosis after MLD is greater than that after LD. Most patients were satisfied with the results of both appearance and ocular function after OD.
Purpose
To compare optic disc, retinal and choroidal measurements in patients with Graves’ disease with or without orbitopathy, and healthy controls.
Methods
Optical coherence tomography and ...Heidelberg retinal tomography were performed in 40 patients with Graves’ orbitopathy (GO), 40 subjects with Graves’s disease (GD) with no sign of orbitopathy and 40 healthy controls. Degree of exophthalmos, ocular alignment, clinical activity score (CAS), choroidal thickness, retinal thickness, ganglion cell layer (GCL) thickness, disc area, cup area, rim area, cup/disc area ratio, linear cup/disc ratio and mean peripapillary retinal nerve fibre layer thickness were analysed.
Results
GO patients and healthy controls significantly differ regarding mean central retinal thickness (275 ± 19 µm and 285 ± 20 µm,
P
= 0.017); mean central GCL thickness (14.87 ± 3.0 µm and 17.92 ± 5.02 µm,
P
= 0.001); mean disc area (2.00 ± 0.44 mm
2
and 1.72 ± 0.37 mm
2
,
P
= 0.003); mean cup area (0.53 ± 0.52 mm
2
and 0.31 ± 0.20 mm
2
,
P
= 0.003); cup/disc area ratio (0.22 ± 0.10 and 0.17 ± 0.08,
P
= 0.010); and linear cup/disc ratio (0.47 ± 0.15 and 0.40 ± 0.13, respectively,
P
= 0.011). No difference was found between patients without orbitopathy and healthy controls. No significant difference was found regarding the choroidal thickness between the three groups. There was no statistically significant relationship between retinal thickness, ganglion cell layer thickness, mean disc area, mean cup area, cup/disc area ratio, linear cup/disc ratio, CAS, exophthalmometric value and ocular alignment.
Conclusion
GO patients showed significant changes in foveal and GCL thickness, and optic nerve head morphology suggesting a possible influence of the orbital inflammatory process.
There is a general belief that Graves' orbitopathy (GO) is a "chronic" disease, namely that patients' eyes do not return to how they were before GO appeared. Here, we investigate this issue from both ...the patient's and the physician's point of view.
We studied the disappearance of GO, regardless of treatment, in all consecutive patients with a GO history of at least 10 years who came for a follow-up visit over a period of 5 years. Patients underwent an ophthalmological examination and were asked to answer a questionnaire on self-perception related to GO.
We studied 99 consecutive patients with a GO duration ≥10 years. Between the first and the last observation, patients received several types of treatment for their thyroid disease and/or for GO. At the end of follow-up, GO was considered disappeared based on objective criteria in 8 patients (∼8%) and based on subjective criteria in 24 patients (∼24%). When we considered both subjective and objective criteria, only 2 patients (∼2%) had all criteria fulfilled and could be considered as GO-free.
GO is a chronic disease in the vast majority of patients. Even after a very long time since its onset, complete disappearance is rare, although a minority of patients believe they do not have GO anymore and an even lower proportion do not have relevant GO signs. Our findings have obvious implications in patient management and counseling.
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