Effect of 131I treatment on the outcome of Graves ophthalmopathy

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Graves ophthalmopathy (Graves' ophthalmopathy, GO) is an organ specific autoimmune thyroid disease is closely related to autoimmune disease,

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Graves ophthalmopathy (Graves' ophthalmopathy, GO) is an organ specific autoimmune thyroid disease is closely related to autoimmune disease, also known as thyroid associated ophthalmopathy or autoimmune thyroid disease, endocrine exophthalmos and other [1]. The symptoms can be associated with hyperthyroidism at the same time or before the symptoms of hyperthyroidism, can also occur after the remission of hyperthyroidism symptoms. At present, there is no effective treatment for the disease and the side effect is small. This paper summarized retrospectively in our hospital during January 2000 -2010 December 131I treated 652 cases of patients with Graves hyperthyroidism with GO clinical data, analysis of correlation between the prognosis of hyperthyroidism efficacy and GO after 131I treatment, to explore the effect of 131I treatment on GO outcome.

1 materials and methods

1.1. case data: from January 2000 to December 2010, 652 patients with Graves hyperthyroidism complicated with GO were treated in our department from to. Among them, there were male and female, with an average age of 38.5 + to 9.6 years (range, ranging from 15 to 67 years). The course of disease was from 2 months to 12 years. All cases were consistent with the endocrinology branch of Chinese Medical Association diagnostic criteria for Graves hyperthyroidism [2], it is suitable for 131I treatment. In addition to this group of patients have different degrees of unilateral or bilateral exophthalmos, ocular symptoms were associated with different degrees, including bulging eyes, photophobia, tearing, foreign body sensation, visual fatigue, eye pain, vision loss, diplopia, blurred vision; ocular signs are: exophthalmos, orbital, eyelid edema, Zhou Shuizhong chemosis, eye movement disorders, hypophasis, ptosis, etc.. According to the 2008 European GO expert group (EUGOGO) grading standards and events on the severity of GO evaluation of [3], this group of patients 522 cases of mild GO and moderate GO; 130 cases (19.9%); 554 cases of non active GO, active GO 98 cases (15%).

1.2. preparation before treatment: (1) all patients were treated with FT3, FT4, TSH, TRAb, TG-Ab and Tpo-Ab. (2) no severe hepatic and renal dysfunction. (3) the highest uptake rate of 131I and the effective half-life of thyroid gland, thyroid scintigraphy, excluding inflammatory hyperthyroidism, and can be used as a reference to determine the dose of 131I therapy. (4) estimation of thyroid weight: using ultrasound to measure thyroid size, calculate the total volume (double length, width and thickness of the thyroid and the product of), and in accordance with the formula will be converted into the weight of thyroid volume. =0.479 (V) [4] (cm3) of thyroid weight. (5) before the treatment with exophthalmometer exophthalmos, a detailed record of ocular symptoms and characteristics of patients, excluding ophthalmic orbital lesions and other factors causing exophthalmos.

1.3. treatment: all patients were treated with 131I according to routine procedures. The formula for calculating the dose of 131I is as follows: [4]:

131I dose

=

Thyroid weight (g) * estimated thyroid tissue absorbed dose (Gy/g) * 0.67

The highest 131I uptake rate (%) * effective half-life (d)

The calculation of the theoretical treatment combined with the patient's own factors to adjust the individual treatment dose, and after the effective half-life of the end of the test, the patient was given a one-time treatment of 131I. According to the EUGOGO GO management [3, 5] of consensus, in the active stage of moderate exophthalmos (the group of patients were 54 cases, accounting for about 8.3%) combined with glucocorticoid treatment course, an average of about 3 months. After treatment, the patients were followed up regularly to evaluate the therapeutic effect.

1.4. efficacy evaluation criteria: all patients were followed up for more than six months,

Evaluation of the curative effect of 1.4.1 Graves hyperthyroidism: (1) recovery: hyperthyroidism symptoms and signs completely disappeared, serum T3, T4, FT3, FT4 returned to normal. (2) the improvement: hyperthyroidism symptoms, signs disappeared, serum T3, T4, FT3, FT4 decreased significantly, but did not fall to normal level. (3): Patients with hypothyroidism hypothyroidism symptoms and signs, serum thyroid hormone levels lower than normal, higher than normal TSH. (4) invalid: the symptoms and signs of patients did not improve or worse, serum T3, T4, FT3, FT4 levels were not significantly reduced. (5) recurrence: after 131I treatment, the symptoms and signs of hyperthyroidism appeared again, and the serum thyroid hormone levels increased again.

[7] 1.4.2 Graves disease curative effect evaluation: (1) markedly: eye swelling, foreign body sensation, photophobia and pain symptoms disappeared, periorbital edema and hyperemia of bulbar conjunctiva edema subsided, ptosis and eyeball movement disorder returned to normal, the degree of exophthalmos decreased more than 3 mm. (2): ocular symptoms, eye symptoms and the degree of exophthalmos detection were improved, but did not reach the target. (3) invalid: no significant improvement before and after treatment. (4): deterioration of ocular symptoms, eye symptoms and the degree of exophthalmos were aggravated.

1.5 statistical analysis: the SPSS13.0 statistical software package for the 2 test (P< 0.05 for a statistically significant difference), and analysis the relationship between R * C classification data, the correlation coefficient of R.

2 Results

2.1652 cases of patients with Graves hyperthyroidism with GO, Graves hyperthyroidism clinical cure in 426 cases (65.3%), improved in 125 cases (19.2%), 64 cases of hypothyroidism (9.8%), invalid in 22 cases (3.4%), 15 cases of recurrence (2.3%), the total efficiency is about 94.3% GO; 71 cases (10.9%), effective 407 (62.4% cases), 146 cases (22.4%), 28 cases (4.3%), deterioration of the total improvement rate is about 73.3%; while Graves and GO are effective in hyperthyroidism in 467 cases, accounting for 71.6% of the total number of cases.

2.2 131I Graves after treatment of hyperthyroidism is effective or not and GO outcome relationship: 131I Graves after treatment of hyperthyroidism effective group 615 cases, the improvement rate of GO, efficiency and degradation rate were 75.4%, 21% and 3.6%; and 37 cases of recurrence of Graves' disease treatment, the improvement rate of GO, the efficiency and rate of turn evil as of 37.8%, 46% and 16.2%. The effect of GO between the two groups had statistical differences (P< 0.05), namely Graves hyperthyroidism invalid or relapsed patients GO improvement rate was significantly lower than that of group GO and the effective treatment of hyperthyroidism, invalid and deterioration of about 62.2%, significantly higher than that of Graves hyperthyroidism effective group 24.6%. Thus, after 131I treatment, the prognosis of GO with hyperthyroidism is effectively alleviated significantly correlated (=26.439 x 2, P< 0.05, r = 0.302) (see Table 1).

Table 1 the relationship between the effectiveness of 131I and the outcome of GO after treatment

Graves hyperthyroidism

Curative effect of GO (case)

Improvement (%)

Invalid (%)

Deterioration (%)

Total (%)

effective

464 (75.4%)

129 (21%)

22 (3.6%)

615 (100%)

Ineffective or recurrent

14 (37.8%)

17 (46%)

6 (16.2%)

37 (100%)

Total

478 (73.3%)

146 (22.4%)

28 (4.3%)

652 (100%)

2 =26.439, P< 0.05, r = 0.302;

Comparison of 2.3 131I Graves after treatment of hyperthyroidism group and hypothyroidism group clinical cure effect of GO: 131I Graves after treatment of hyperthyroidism cure rate was 65.3%, the cure of GO in patients with no improvement rate, efficiency and degradation rate were 77.9%, 18.8% and 3.3%; 64 cases of hypothyroidism occurred in 131I patients after the treatment. The improvement rate of GO, efficiency and degradation rate were 78.1%, 17.2% and 4.7%. The deterioration rate of hypothyroidism group GO is slightly higher than the cure group, but no significant differences between the two groups (P> 0.05). The results show that the prognosis of 131I after treatment of hyperthyroidism or hypothyroidism and the cure of GO has no obvious correlation (=0.296 x 2, P> 0.05). In other words, after the treatment of 131I hyperthyroidism or hypothyroidism achieve clinical cure, there is no obvious effect on the outcome of patients with GO.

Comparison of curative effect group and hypothyroidism group GO cure hyperthyroidism 2 131I after treatment

Graves hyperthyroidism

Curative effect of GO (case)

Improvement (%)

Invalid (%)

Deterioration (%)

Total (%)

Cure

332 (77.9%)

80 (18.8%)

14 (3.3%)

426 (100%)

hypothyroidism

50 (78.1%)

11 (17.2%)

3 (4.7%)

64 (100%)

Total

382 (80%)

91 (18.6%)

17 (3.4%)

490 (100%)

2 x =0.296, P> 0.05

2.4 131I GO after treatment is invalid or deterioration of the relationship between prognosis and Graves hyperthyroidism: can be seen from table 3, the probability of Graves hyperthyroidism is invalid or recurrence after 131I treatment in patients with GO is also invalid for 45.9%, although Graves hyperthyroidism treatment is effective but not complete remission in patients with GO is as high as 30.4%, two are Graves was significantly higher than that of hyperthyroidism cure group and hypothyroidism group (P< 0.05). 131I and GO after treatment in 28 patients deteriorated in Graves hyperthyroidism invalid or recurrent patients accounted for 6 cases, accounting for about 16.2% of all patients in this group; deterioration of hyperthyroidism clinical cure group, effective group and hypothyroidism group of patients with GO only were 3.3%, 4% and 4.7%, were significantly lower than those of hyperthyroidism is invalid or the recurrence group (P< 0.05).

Table 3 the relationship between the failure of GO after treatment with 131I and the prognosis of Graves hyperthyroidism

Graves' hyperthyroidism outcome

GO effect

Total (%)

Inefficiency (%)

Deterioration rate (%)

recovery

18.8 (80/426)

3.3 (14/426)

22.1 (94/426)

effective

30.4 (38/125)

4 (5/125)

34.4 (43/125)

hypothyroidism

17.2 (11/ 64)

4.7 (3/646)

21.9 (14/64)

Ineffective or recurrent

45.9 (17/ 37)

16.2 (6/ 37)

62.2 (23/37)

Total

22.4 (146/652)

4.3 (28/652)

26.7 (174/652)

3 discussion

The incidence of GO is high, data show that about 13 ~ 45% of hyperthyroidism patients with different degrees of GO[7]. GO patients with ocular signs vary in Ophthalmoptosis, but also showed eyelid edema, conjunctival edema, eyelid retraction, eyelid lag, extraocular muscle involvement, corneal involvement and optic nerve involvement, there may be severe compressive optic neuropathy and even loss of vision. The pathogenesis of GO is not very clear, and it is generally believed that it is related to autoimmune factors. Most scholars believe that CO exists with thyroid tissue antigen orbital tissue, the antigen stimulated lymphocytes produce antibodies, antigen antibody complexes are formed, and in the role of complement, the orbital massive infiltration of T lymphocytes and T lymphocytes of orbital fibroblast cells to release various cytokines, oxygen free radicals and fibroblast growth factor, synthesis of glycosaminoglycan (GAG), causing the ball to GAG after the accumulation, the eye edema, resulting in [8, 9].

131I is one of the most classic, the most mature and the most widely used clinical treatment methods for the treatment of hyperthyroidism. Hertz is equal to 1942 reported that 131I can be used for the treatment of hyperthyroidism has been nearly 70 years of history, has been more and more domestic and foreign medical workers and patients accepted. 131I therapy is becoming the first choice for the treatment of Graves hyperthyroidism because of its advantages of simplicity, convenience, economy, safety, effectiveness and less side effects. The results of this study show that a single 131I Graves after treatment of hyperthyroidism was 94.3%, the cure rate was 65.3%, and the incidence of hypothyroidism was only 9.8%. The results are consistent with the results of previous studies in our department, which suggest that 131I has obvious advantages in terms of efficacy and side effects.

In this paper, the data showed that 652 patients after a single 131I treatment, Graves hyperthyroidism and GO were effective relief of a total of 467 cases, accounting for the total number of cases of, suggesting that 131I is an effective means of treatment of hyperthyroidism with GO. 131I Graves after treatment of hyperthyroidism patients with GO effectively. The improvement rate was 75.4%, significantly higher than the 37.8% group is invalid or recurrence of hyperthyroidism and hyperthyroidism; ineffective treatment or recurrence, approximately 66.2% of patients with GO is also ineffective or even worse. After 131I treatment, the outcome of GO was significantly correlated with the therapeutic effect of hyperthyroidism (r = 0.302). Thus, for patients with hyperthyroidism combined with GO, the effective control of hyperthyroidism is to ease the fundamental GO. This conclusion is consistent with the results of Baldys-Waligorska et al. [10]. May be due to reduction of thyroid volume after 131I treatment, and can lead to the reduction of autoreactive T lymphocyte depletion of thyroid - orbital cross reactive antigens, further through immune regulation and reduce production of GAG, the ball after inflammation, edema gradually subsided, ocular symptoms will be alleviated or eliminated.

The results of this study confirmed that 131I treatment in about 22.4% of patients with GO did not change significantly, but in contrast to the 4.3% of patients. 131I treatment of hyperthyroidism leading mechanism of GO is increased the concentrations of FT3, FT4 in blood decreased too fast, negative feedback effect on the pituitary gland greatly weakened, especially the occurrence of hypothyroidism TSH increased rapidly in orbital tissue sites, promote fibroblast proliferation and GAG synthesis, the hydrophilicity of GAG due to the orbital tissue the swelling, thereby increasing the exophthalmos. We further analysis showed that the clinical cure of hyperthyroidism 131I in patients after GO invalid rate and deterioration rate were 18.8% and 3.3%; while in hypothyroidism patients, invalid rate and deterioration rate of 17.2% and 4.7% GO, no significant difference between the two groups. That is to say, after 131I treatment did not significantly increase GO hypothyroidism. The results of previous studies may be due to a slightly different [11] in our patients were closely followed up in the process of subclinical or early hypothyroidism patients timely enough thyroid hormone replacement therapy, stable feedback regulation function of hypothalamus pituitary thyroid axis, so as to effectively control the progress of 131I GO after treatment the.

Our study showed that after 131I treatment of Graves' disease is invalid or recurrent group (non hypothyroidism group) in patients with exacerbation rate of GO was significantly higher than that of other groups; Graves' hyperthyroidism is invalid, although recurrence or effective treatment but did not heal with probability GO invalid than cure group and hypothyroidism group. In short, the treatment of hyperthyroidism by 131I is the fundamental measure to control GO. To strengthen the follow-up service after the 131I, timely detection and correction of hypothyroidism can effectively avoid the aggravation of GO.

In addition, it is worth mentioning that, before the 131I treatment in the active phase of moderate GO patients, 131I before and after treatment with corticosteroids can effectively prevent the progress of [3, GO, 12]. This study selected 652 patients in 54 patients treated with 131I and the application of glucocorticoid, the only 4 cases of 131I GO (7.4%), deterioration of no significant change in 17 cases, the patients with GO were improved in different degree, the effective rate is about 61.1%.

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