Clinical course of thyroid function and thyroid associated-ophthalmopathy in patients with euthyroid Graves’ disease

Figures & data

Table 1 Characteristics of the 58 patients initially diagnosed with EGD

Number of patients	58
Sex	Male: 13 (22.4%); female: 45 (77.6%)
Age (years)	43.6±13.3
Observation period (years)	5.8 (range 0.6–29.7)
Smoking rate	12/58 (20.7%)
Estimated thyroid volume (mL, n=35)	13.1 g (range 5.3–39.8)
TBII (IU/L) (Cosmic:Roche =31:25)	2.5 (range 0.6–47.2)
Positive rate	41/55 (74.5%)
Using Cosmic	21/31 (67.7%)
Using Roche	20/25 (80.0%)
TSAb (%, n=44)	257 (range 110–1,448)
Positive rate	31/44 (70.5%)
Sum of lid fissures* (mm)	34 (range 19–49)
Proptosis* (mm)	18 (range 11–36)
Eight extraocular muscles* (cm^2)	2.43 (range 1.11–5.80)
Course of thyroid function
Remained euthyroid	42 (72.4%), male: 7; female: 35; mean age, 43.2±12.4 years
Developed hyperthyroidism	14 (24.1%), male: 6; female: 8; mean age, 42.9±16.9 years
Developed hypothyroidism	2 (3.4%), male: 0; female: 2; ages 50 and 54 years
Duration until development of dysfunction (months)
Hyperthyroidism	28.5 (range 3–124)
Hypothyroidism	25 and 39

Notes:

* Right + left. Numerical values are reported as the median, with the exception of age (mean ± SD).

Abbreviations: EGD, euthyroid Graves’ disease; TBII, thyrotropin-binding inhibitory immunoglobulin; TSAb, thyroid-stimulating immunoglobulin.

Figure 1 Correlation between TRAb (TBII and TSAb) and eye symptoms.

Notes: Correlation between TRAb (TBII and TSAb) and ophthalmic observations (proptosis, lid fissure and sum of 8 ocular muscles) on the initial visit were analyzed using Spearman’s rank correlation coefficients. No statistical correlation was observed between the TRAb and eye symptoms.
Abbreviations: TRAb, thyrotropin receptor antibodies; TBII, thyrotropin-binding inhibitory immunoglobulin; TSAb, thyroid-stimulating immunoglobulin; L, left; R, right.

Figure 2 Kaplan–Meier curve describing the time remaining for normal thyroid function in 58 EGD patients.

Notes: Thyroid dysfunction occurred in 16 out of 58 EGD patients. Hyperthyroidism developed in 14 and hypothyroidism developed in 2 patients. Out of the 58 patients, 42 remained euthyroid. With the exception of 2 cases, thyroid dysfunction occurred within 6.7 years after the development of ophthalmopathy. The gray area shows the 95% confidence interval.
Abbreviation: EGD, euthyroid Graves’ disease.

Figure 3 Transition of the TBII and TSAb positive rates in EGD patients.

Notes: Upon initial presentation, 74.5% (41/55) and 70.5% (31/44) of the patients with EGD proved to be TBII and TSAb positive, respectively. The positive rate for both TBII and TSAb gradually decreased spontaneously, with the TRAb becoming negative at 7 years after the initial development in all the patients tested. Although there was only a small number of patients who were measured for TRAb throughout the observation period, the thyroid function continued to be checked in these patients during the entire study period. Specifically, there were 33 patients at 3 years, 18 patients at 5 years and 11 patients at 7 years, all of whom exhibited a normal thyroid function.
Abbreviations: TBII, thyrotropin-binding inhibitory immunoglobulin; TSAb, thyroid-stimulating immunoglobulin; EGD, euthyroid Graves’ disease; TRAb, thyrotropin receptor antibodies.

Table 2 Itemized ophthalmic initial treatments in 58 EGD patients

Treatment	Number of patients (58)
With treatment	29
Monotherapy
Local injection of steroid	11
Surgery	1
Radiation	8
Combined therapy
Radiation + surgery	2
Radiation + local injection of steroid	3
Radiation + local injection of steroid + surgery	2
Radiation + local injection of steroid + oral steroid	1
Surgery + local injection of steroid + oral steroid	1
Without treatment	30

Notes: As additional treatments, intravenous steroid pulse therapy, local injection of steroid and surgery were administered to 3 patients, respectively. One of these patients did not need any treatment at the initial visit, but then steroid pulse therapy was needed 2 years after the development of EGD.

Abbreviation: EGD, euthyroid Graves’ disease.

Figure 4 Clinical course of ophthalmic symptoms in 18 EGD patients without any eye treatments.

Notes: We examined 18 out of the 28 EGD patients without eye treatments in detail. Median observation time was 4.1 years (range 1.7–11.9). In most patients, the items observed spontaneously improved over time. In particular, a significant difference was observed for the improvements in the eye lid fissure.
Abbreviations: EGD, euthyroid Graves’ disease; L, left; R, right.