One hundred and one eligible patients with a diagnosis of Graves’ disease were identified, 79 (79.2%) of whom were female (Table 1). The median duration from diagnosis of Graves’ disease to RAI treatment was 36 months (20-66 months), with 70 (69.3%) receiving their diagnosis less than five years prior to RAI therapy. Serum TRAb positivity was present in 86 (85.1%); 34 (33.7%) were documented as active or ex-smokers; 11 (10.9%) had a history of previous GO and 32 (31.7%) had eye features present at assessment, as depicted in Figure 1.
Table 1. Baseline characteristics of our cohort of 101 individuals.
n
|
101
|
Sex (male:female)
|
21:80
|
Smoking status, n (% cohort)
Current smoker
Never smoked
Ex-smoker
Unknown
|
18 (17.8)
13 (12.9)
16 (15.8)
54 (53.5)
|
Median duration of Graves’ disease, months (IQR)
Number with diagnosis duration <5 years, n (% cohort)
|
36 (20-66)
70 (69.3)
|
TRAb status, n (% cohort)
Positive
Negative
Unknown
|
86 (85.1)
3 (3.0)
12 (11.9)
|
Previous GO, n (% cohort)
|
11 (10.9)
|
Abbreviations: GO, Graves’ orbitopathy; IQR, interquartile range; TRAb, TSH-receptor antibodies; TSH, thyroid-stimulating hormone.
The median RAI dose given was 596Mbq (550-647Mbq), (Table 2). Eight of the 101 (7.9%) received steroid cover, four of whom had a previous history of GO. A single individual with prior GO continued to show signs of mild activity despite steroid prophylaxis. None of the remaining seven individuals experienced subsequent GO. One individual experienced a wrist fracture shortly after initiation of steroids, deemed by Endocrinology not to be a direct result of the steroids. For the 89 (88.1%) patients who were rendered hypothyroid in the year following RAI treatment, the median duration until this state was achieved was 3 months (2-4 months); 2 individuals subsequently developed recurrent hyperthyroidism in the same year. In total, recurrence of significant hyperthyroidism following radioiodine occurred in 8 (7.9%) of patients.
Table 2. RAI treatment factors and post-RAI events for our cohort of 101 individuals.
RAI dose
Median RAI dose, Mbq (IQR)
|
596 (550-647)
|
Steroid cover given, n (% cohort)
Previous GO, n (% total given steroid)
Side effects, n (% total given steroid)
Development of GO, n (% total given steroid)
|
8 (7.9)
4 (50.0)
1 (12.5)
1 (12.5)
|
Hypothyroidism achieved in year post-RAI, n (% cohort)
Median time taken to achieve, months (IQR)
Median time between hypothyroid and LT4, months (IQR)
|
89 (88.1)
3 (2-4)
0 (0-0)
|
Hyperthyroid flare, n (% cohort)
|
8 (7.9)
|
Development of GO, n (% cohort)
Median time taken to develop, months (IQR)
de novo GO, n (% total GO)
Reactivation GO, n (% total GO)
|
5 (5.0)
3 (2-5)
4 (80.0)
1 (20.0)
|
Treatment of GO, n (% total GO)
Conservative management only
Oral steroids only
IVMP only
IVMP and orbital radiotherapy
|
2 (40.0)
1 (20.0)
1 (20.0)
1 (20.0)
|
Abbreviations: GO, Graves’ orbitopathy; IQR, interquartile range; IVMP, intravenous methylprednisolone; LT4, levothyroxine; MBq, megabecquerel; RAI, radio-active iodine; TRAb, TSH-receptor antibodies; TSH, thyroid-stimulating hormone.
Following RAI treatment, GO developed in five (5.0%) of patients after an average interval of 3 months (2-5 months, Table 2). Four of these five individuals (80%) had developed de novo GO without any previous history; all had high-risk features for GO and had not received prophylactic glucocorticoid, as shown in Table 3. The fifth individual had a reactivation of GO despite receiving glucocorticoid on account of a previous GO history. Of all five total patients with development of GO: two of these individuals were classified as moderate GO requiring intravenous methylprednisolone therapy, with one requiring superadded orbital radiotherapy. A tapering regime of glucocorticoids was given to the individual who developed GO despite glucocorticoid cover. The remaining two individuals were treated with selenium supplementation and lubricating eyedrops. Although formal Graves’ Orbitopathy-Specific Quality of Life (GOQOL) scores were not collected, these patients had developed changes attributable to GO, such as proptosis, lid retraction, eyelid swelling with sub-brow fat hypertrophy and glabellar furrowing.
Table 3. Characteristics of the five individuals who developed post-RAI GO.
Patient
|
Characteristics
|
Steroids Prophylaxis Given
|
Treatment Given
|
1
|
123 months from Graves’ diagnosis
TRAb (normal range <0.4U/l)
- at diagnosis 4.8 U/l
- at time of RAI 1.7 U/l
Ex-smoker
No previous GO
|
No
|
IVMP, orbital radiotherapy
|
2
|
29 months from Graves’ diagnosis
TRAb (normal range <0.4U/l)
- at diagnosis >30 U/l
- at time of RAI >30 U/l
Non-smoker
No previous GO
|
No
|
Selenium supplements, lubricating drops
|
3
|
2 months from Graves’ diagnosis
TRAb (normal range <0.4U/l)
- at diagnosis 3.4 U/l
- at time of RAI 3.4 U/l
Ex-smoker
No previous GO
|
No
|
IVMP, lubricating drops
|
4
|
48 months from Graves’ diagnosis
TRAb (normal range <0.4U/l)
- at diagnosis >30 U/l
- at time of RAI 4.3 U/l
Ex-smoker
Pre-existent dry eyes, soft tissue swelling
|
Yes
|
Continued oral dexamethasone taper
|
5
|
1 month from Graves’ diagnosis
TRAb (normal range <0.4U/l)
- at diagnosis >30 U/l
- at time of RAI >30 U/l
Non-smoker
No previous GO
|
No
|
Selenium supplements, lubricating drops
|
Abbreviations: GO, Graves’ orbitopathy; IVMP, intravenous methylprednisolone; RAI, radio-active iodine; TRAb, TSH-receptor antibodies.