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Short Communication
Med Princ Pract 2003;12:266–268
DOI: 10.1159/000072296
Early Changes in Thyroid-Stimulating
Antibody Activity following Radioiodine
Therapy
Akheel A. SyedaCarol EvansaMarian LudgatebJohn H. Lazarus b
Departments of aMedical Biochemistry and bMedicine, University Hospital of Wales and University of Wales
College of Medicine, Cardiff, UK
Received: November 4, 2002
Revised: January 13, 2003
Akheel A. Syed
University of Newcastle upon Tyne
Department of Endocrinology, Diabetes and Metabolism, Queen Elizabeth Hospital
Gateshead NE9 6SX (UK)
Tel. +44 191 4032181, Fax +44 191 4036186, E-Mail a.a.syed@ncl.ac.uk
ABC
Fax +41 61 306 12 34
E-Mail karger@karger.ch
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© 2003 S. Karger AG, Basel
1011–7571/03/0124–0266$19.50/0
Accessible online at:
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Key Words
Graves’ disease W Hyperthyroidism W Thyroid
autoimmunity W Thyroid-stimulating hormone receptor
antibody stimulating activity W Thyroid-stimulating
antibody W Radioiodine therapy
Abstract
Objective: The aim of this study was to determine wheth-
er or not the titre of thyroid-stimulating hormone recep-
tor antibody with stimulating (TRAb-S) activity changes
in patients with Graves’ disease (GD) or toxic multinodu-
lar goitres (TMNG) 3 months after treatment with sodium
iodide (131I). Subjects and Methods: Serum specimens
were obtained from 21 hyperthyroid patients (15 with GD
and 6 with TMNG) at a median 0.5 months before and 3
months after 131I treatment using a standard ablative
dose of 555 MBq. TRAb-S activity was measured in a
sensitive and specific luminescent bioassay employing
the lulu cell line and expressed as a stimulation index (SI;
normal ^1.5). Results: The mean TRAb-S in the GD
patients was 2.72 SI (95% CI: 1.51–4.03) 0.5 months
before administration of 131I and 3.98 SI (95% CI: 1.20–
6.76) 3 months after administration of 131I. The difference
was not statistically significant at p ! 0.8. It was not ele-
vated in the TMNG patients before (0.57 SI; 95% CI: 0.41–
0.73) and after (1.00 SI; 95% CI: 0.74–1.26) treatment ei-
ther. Conclusions: Radioiodine therapy for GD or TMNG
did not induce a significant change in TRAb-S activity at 3
months after treatment with 131I, probably due to effec-
tive antithyroid therapy or the timing of samples.
Copyright © 2003 S. Karger AG, Basel
Introduction
Sodium iodide-131 (
131
I) is increasingly advocated as
the definitive treatment of choice in patients with hyper-
thyroidism [1]. Changes that occur in thyroid autoimmu-
nity after treatment of Graves’ disease (GD) with
131
I
include a rise in thyroid-stimulating hormone receptor
antibody with stimulating (TRAb-S) activity [2, 3]. Long-
term changes in the titre of TRAb-S that may influence
thyroid function have been noted years after
131
I treat-
ment [4]. Chiovato et al [5] observed a significant increase
in TRAb-S 6 months after
131
I treatment in patients who
later developed hypothyroidism, and they postulated that
the release of thyroid-stimulating hormone receptor
(TSH-R) molecules from follicular cells as a consequence
of radioiodine-induced thyroid cell damage may boost the
immune response and result in the increased TRAb-S
activity. Thus the TRAb-S status following
131
I treatment
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Changes in TRAb-S after
131
I
Med Princ Pract 2003;12:266–268
267
may be predictive of the clinical outcome of thyroid func-
tion and could influence the further management of the
patient.
The aim of this study was to determine whether or not
the autoimmune changes in TRAb-S activity in serum of
hyperthyroid patients treated with an ablative dose of
131
I
appear earlier than previously reported by using a highly
sensitive and specific human TSH-R bioassay.
Subjects and Methods
Twenty-one hyperthyroid subjects, 15 with GD and 6 with toxic
multinodular goitres (TMNG), were included in the study. GD was
diagnosed on clinical features plus the presence of elevated serum
thyrotropin-binding-inhibiting immunoglobulin (TBII) titres (115%
inhibition), and TMNG was also diagnosed on clinical features plus
undetectable TBII titres. A
131
I thyroid scan performed on the day of
ablative treatment was used as additional evidence for diagnosis and
to confirm a 4-hour uptake 14% as indicative of satisfactory iodide
trapping. Carbimazole was used as the antithyroid therapy of choice
to render patients euthyroid, maintained up to 5 days prior to
131
I
therapy, resumed 72 h after treatment and finally discontinued 6
weeks later. Each patient was given a standard ablative dose of
555 MBq (15 mCi). Paired serum samples were obtained at a median
0.5 months before and 3.0 months after
131
I treatment, and TRAb-S
activity was measured in a luminescent bioassay using the lulu cell
line (Chinese hamster ovary cells stably transfected with human TSH
receptor and a cyclic-adenosine-monophosphate-dependent lucifer-
ase-responsive reporter) [6]. Lulu cells were seeded in 96-well plates,
and serum was added at 10%. Luciferase expression was quantified
as emission of light in the presence of luciferin. Results were
expressed as a stimulation index (SI) of light output from a subject’s
serum to light output from control serum. The 97.5 percentile of
euthyroid serum (1.5 SI) was used as the cut-off. The Mann-Whitney
U test was used to assess statistical significance.
Results
The mean TRAb-S activity in the patients with GD
was 2.72 (1.51–4.03) and 3.98 (1.20–6.76) at 0.5 months
before and 3 months after
131
I therapy, respectively. The
corresponding SI values for patients with TMNG were
0.57 (0.41–0.73) and 1.00 (0.74–1.26; fig. 1). The differ-
ence in titre before and after treatment was not statistical-
ly significantly different (p ! 0.8). In the GD group, 8 of
the 15 subjects had elevated TRAb-S activity before
radioiodine treatment. Seven continued to have a raised
activity at 3 months whilst 1 returned to normal. Two
subjects with normal pretreatment TRAb-S developed
increased activity after treatment. None of the 6 patients
with TMNG had elevated TRAb-S activity either before
or after treatment.
Fig. 1.
Mean TRAb-S activity 0.5 months before and 3 months after
ablative radioiodine therapy in hyperthyroid subjects with GD and
TMNG. TRAb-S activity is expressed as an SI (normal ^1.5). Error
bars represent 95% confidence intervals.
Discussion
Three months after a standard ablative dose of
131
I had
been administered to patients with GD pretreated with
carbimazole, TRAb-S activity as measured in a sensitive
and specific human TSH-R bioassay showed no signifi-
cant change probably due to effective antithyroid drug
therapy and/or earlier sampling of serum than previously
reported [5]. It seems that changes in the titre of TRAb-S
do not occur 3 months after ablative treatment with
131
I;
however, further studies will be required to confirm this
observation.
An increase in TRAb-S titres has been reported follow-
ing
131
I treatment in some patients with TMNG and var-
iously interpreted as the induction of autoimmunity by
131
I-induced thyroid cell damage, the unmasking of pre-
existing GD or a temporary side-effect without further
clinical relevance [7, 8]. In this study, we did not observe a
similar effect on TMNG patients as the serum sampling
was done earlier than 6 months. It should also be noted
that the sample size of this study was small.
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268
Med Princ Pract 2003;12:266–268
Syed/Evans/Ludgate/Lazarus
Conclusion
In this study on 21 hyperthyroid patients, a significant
change in TRAb-S activity was not noticed 3 months after
treatment with
131
I, probably due to effective antithyroid
therapy or the timing of samples.
Acknowledgements
We are grateful to Barry Nix, Department of Statistics, Universi-
ty of Wales College of Medicine, for advice on statistical methods.
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