ArticlePDF Available

Early Changes in Thyroid-Stimulating Antibody Activity following Radioiodine Therapy

Authors:
Akheel Syed at Salford Royal NHS Foundation Trust
Akheel Syed
Carol Evans at Cardiff and Vale University Health Board
Carol Evans
Marian Ludgate at Cardiff University
Marian Ludgate
John H Lazarus at Cardiff University
John H Lazarus
Download full-text PDF
Read full-text
Download citation

Abstract

The aim of this study was to determine whether or not the titre of thyroid-stimulating hormone receptor antibody with stimulating (TRAb-S) activity changes in patients with Graves' disease (GD) or toxic multinodular goitres (TMNG) 3 months after treatment with sodium iodide ((131)I). 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 (131)I 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). The mean TRAb-S in the GD patients was 2.72 SI (95% CI: 1.51-4.03) 0.5 months before administration of (131)I and 3.98 SI (95% CI: 1.20-6.76) 3 months after administration of (131)I. The difference was not statistically significant at p LT; 0.8. It was not elevated 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 either. Radioiodine therapy for GD or TMNG did not induce a significant change in TRAb-S activity at 3 months after treatment with (131)I, probably due to effective antithyroid therapy or the timing of samples.
Content uploaded by Akheel Syed
Author content
All content in this area was uploaded by Akheel Syed on Dec 18, 2014
Content may be subject to copyright.
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
www.karger.com
© 2003 S. Karger AG, Basel
1011–7571/03/0124–0266$19.50/0
Accessible online at:
www.karger.com/mpp
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
Downloaded by:
86.28.210.97 - 12/19/2014 12:33:27 AM
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.
Downloaded by:
86.28.210.97 - 12/19/2014 12:33:27 AM
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.
References
1 Lazarus JH: Guidelines for the use of radioio-
dine in the management of hyperthyroidism: A
summary. Prepared by the Radioiodine Audit
Subcommittee of the Royal College of Physi-
cians Committee on Diabetes and Endocrinol-
ogy, and the Research Unit of the Royal Col-
lege of Physicians. J R Coll Physicians Lond
1995;29:464–469.
2 Pinchera A, Liberti P, Martino E, Fenzi GF,
Grasso L, Rovis L, Baschieri L, Doria G:
Effects of antithyroid therapy on the long-act-
ing thyroid stimulator and the antithyroglobu-
lin antibodies. J Clin Endocrinol Metab 1969;
29:231–238.
3 Atkinson S, McGregor AM, Kendall-Taylor P,
Peterson MM, Smith BR: Effect of radioiodine
on stimulatory activity of Graves’ immuno-
globulins. Clin Endocrinol 1982;16:537–543.
4 Yoshida K, Aizawa Y, Kaise N, Fukazawa H,
Kiso Y, Sayama N, Mori K, Hori H, Abe K:
Relationship between thyroid-stimulating anti-
bodies and thyrotropin-binding inhibitory im-
munoglobulins years after administration of ra-
dioiodine for Graves’ disease: Retrospective
clinical survey. J Endocrinol Invest 1996;19:
682–686.
5 Chiovato L, Fiore E, Vitti P, Rocchi R, Rago T,
Dokic D, Latrofa F, Mammoli C, Lippi F, Cec-
carelli C, Pinchera A: Outcome of thyroid func-
tion in Graves’ patients treated with radioio-
dine: Role of thyroid-stimulating and thyrotro-
pin-blocking antibodies and of radioiodine-
induced thyroid damage. J Clin Endocrinol
Metab 1998;83:40–46.
6 Evans C, Morgenthaler NG, Lee S, Llewellyn
DH, Clifton-Bligh R, John R, Lazarus JH,
Chatterjee VK, Ludgate M: Development of a
luminescent bioassay for thyroid stimulating
antibodies. J Clin Endocrinol Metab 1999;84:
374–377.
7 Nygaard B, Faber J, Veje A, Hegedus L, Han-
sen JM: Transition of nodular toxic goiter to
autoimmune hyperthyroidism triggered by
131
I
therapy. Thyroid 1999;9:477–481.
8 Wallaschofski H, Muller D, Georgi P, Paschke
R: Induction of TSH-receptor antibodies in pa-
tients with toxic multinodular goitre by ra-
dioiodine treatment. Horm Metab Res 2002;
34:36–39.
Downloaded by:
86.28.210.97 - 12/19/2014 12:33:27 AM
... Thus, the TRAb titre after radioiodine could be useful in predicting the subsequent clinical outcome of thyroid function. However, effective anti-thyroid treatment with thionamides pre-and postradioiodine treatment may attenuate the immune response to radioiodine-induced thyroid cell destruction [30]. ...
The role of TSH receptor antibodies in the management of Graves’ disease
Article
  • Jun 2011
The central role of thyrotropin receptor antibodies (TRAbs) in the pathogenesis of Graves' disease has been recognised for several decades. However, the practical application of testing for TRAbs in clinical decision making remains the subject of controversy. The diagnosis of Graves' disease can be made in most cases simply based on a patient's clinical presentation. The TRAb test is therefore of most value in ambiguous clinical scenarios such as in the differential diagnosis of unilateral exophthalmos, euthyroid Graves' ophthalmopathy, subclinical hyperthyroidism, thyrotoxicosis associated with hyperemesis gravidarum, amiodarone-induced thyrotoxicosis and painless thyroiditis. It may also have a role in predicting the risk of a recurrence of Graves' disease following a course of antithyroid drug treatment. One further clinical utility of the TRAb test is in pregnancy where antibody titre measured during the third trimester is used to predict the risk of neonatal thyroid dysfunction. The TRAb titre not only aids in clinching a difficult diagnosis but can also help guide treatment in some patients. Although the TRAb assay has become more affordable in recent years, cost remains an important factor when considering its use routinely. Nonetheless, this is an underutilised blood test that could augment standard endocrine investigations in the differential diagnosis of hyperthyroidism.
View
... Thus, instead of an easy manageable hypothyroidism, the patient is now facing a high likelihood of recurrence of overt hyperthyroidism [9][10][11][12] . Although being the best therapeutic option in this context, the administration of radioiodine, in spite of her young age, was also only partly successful [13][14][15] , since post-iodine scintiscanning showed further enlargement of the thyroid tissue. Although presently both peripheral thyroid hormones and TSH are within the normal range, the final outcome of the disease in this patient remains uncertain 16,17 . ...
Zašto bolesnica s Gravesovom bolešću ostaje eutiroidna/blago hipertiroidna nakon totalne tiroidektomije - uloga antitijela na tirotropinske receptore (TRAb) i vestigalnih ostataka tiroglosalnog trakta
Article
Full-text available
  • Jan 2008
A young female patient suffering from Graves. disease is presented, who raised some diagnostic and therapeutic dilemmas after being diagnosed with subclinical hyperthyroidism following total thyroidectomy. This 20-year-old female patient, carrier of HLA B8 DR3 genes, was referred to our hospital for total thyroidectomy after developing severe leukopenia on both methimazole and propylthiouracil therapy. A high postoperative titer of thyrotropin receptor antibodies and positive scintigraphy finding of the pyramidal lobe and remnant thyroid tissue in the left thyroid lobe led to the administration of radioiodine. Despite further enlargement of the remnant thyroid tissue on post-radioiodine scintiscanning, the patient is currently euthyroid, with normal thyroid-stimulating hormone levels; however, her long-term prognosis remains uncertain.
View
131I-Induced Graves’ disease in patients treated for toxic multinodular goitre: systematic review and descriptive analysis
Article
  • Jan 2018
  • J ENDOCRINOL INVEST
Background Graves’ disease (GD) arising after the treatment of toxic multinodular goitre (TMNG) with radioiodine has long been described but it remained unclear whether GD was in fact iodine induced, its incidence, risk factors, natural history and treatment outcomes. Methods: A systematic search using The Cochrane Library, Medline and PubMed Central allowed the pooling of data from 3633 patients with thyroid autonomy, 1340 patients with TMNG, to fill gaps in knowledge, regarding the clinical expression of iodine-induced GD (131I-IGD) in adults. Results131I-IGD developed in 0–5.3% of those with thyroid autonomy (first year) and in 5–5.4% of those with TMNG, 3–6 months after treatment. Patients with toxic adenoma were less affected. 131I-IGD was more common in patients with pre-treatment direct or indirect signs of autoimmunity: positive anti-TPO (p < 0.05), glandular hypoechogenicity, TRAbs within reference range, diffuse uptake on 99mTc-pertechnetate scans (p < 0.05), findings that may increase the risk tenfold. 131I-IGD manifested 3 months after 131I, justifying 15.4–29% of cases of relapse. The rate of spontaneous remission was 17–20% (6 months) and the rate of relapse after a second 131I treatment 22–25%. The use of an uptake-based administered 131I activity led to a greater proportion of euthyroid patients (78% compared to 25–50% with the mass-based approach). ConclusionsGD may be triggered by 131I. The incidence of the condition is low. Several risk factors were consistently identified; some have shown to raise the risk significantly. 131I-IGD seems more treatment resistant than iodine-independent GD and the best resolution rates were achieved with uptake-based selected iodine activities.
View
Why does the patient with Graves' disease remain euthyroid/mildly hyperthyroid following total thyroidectomy - The role of thyrotropin receptor antibodies (TRAb) and vestigial remnants of the thyroglossal tract
Article
Full-text available
  • Oct 2008
  • ACTA CLIN CROAT
A young female patient suffering from Graves' disease is presented, who raised some diagnostic and therapeutic dilemmas after being diagnosed with subclinical hyperthyroidism following total thyroidectomy. This 20-year-old female patient, carrier of HLA B8 DR3 genes, was referred to our hospital for total thyroidectomy after developing severe leukopenia on both methimazole and propylthiouracil therapy. A high postoperative titer of thyrotropin receptor antibodies and positive scintigraphy finding of the pyramidal lobe and remnant thyroid tissue in the left thyroid lobe led to the administration of radioiodine. Despite further enlargement of the remnant thyroid tissue on post-radioiodine scintiscanning, the patient is currently euthyroid, with normal thyroid-stimulating hormone levels; however, her long-term prognosis remains uncertain.
View
A bioluminescence assay for thyrotropin receptor antibodies predicts serum thyroid hormone levels in patients with de novo Graves' disease
Article
  • May 2006
TSH receptor antibodies (TBII) in Graves' disease (GD) may be TSH receptor stimulating (TSAb) and blocking (TBAb) antibodies. In commercially available assays however, only total TBII titres can be measured, without discriminating between TSAb and TBAb. To design a TBII bioassay to detect of TSAb and to correlate TSAb activity with severity of hyperthyroidism in de novo GD patients. Thirty-five patients with de novo GD and 27 controls. The JP-26-26 cell line, which constitutively expresses the TSH receptor (TSHR), was stably transfected with a cyclic adenosine monophosphate responsive element--luciferase construct. The clone B1 exhibited a near linear increase in luminescence from 0.2 mU/l to 50 mU/l bovine TSH and was used as a TBII bioassay. TBII, free T4 and TSH were measured in the sera of all patients and controls. In the sera of 35 GD patients, TBII titres did not correlate with serum free T4 concentrations. In contrast, a strong and highly significant correlation was found between TSHR stimulating activity (luminescence) as measured with the TBII bioassay and serum free T4 levels (R = 0.80, P < 0.001). Interestingly, the luminescence/TBII ratio had a wide range at low TBII titres, whereas high TBII titres were associated with a low degree of TSHR activation. The TBII bioassay also detected TBAb in GD patients who spontaneously developed hypothyroidism. The B1-TBII-bioassay as developed in our laboratory has a high sensitivity for the detection of TSAb in GD and predicts the severity of hyperthyroidism in untreated GD patients. In addition, we found that high TBII titres are associated with weak TSHR activation.
View
Induction of stimulating thyrotropin receptor antibodies after radioiodine therapy for toxic multinodular goitre and Graves' disease measured with a novel bioassay
Article
  • Mar 2007
  • NUCL MED COMMUN
Radioactive iodine therapy (RaI) in toxic multinodular goitre (TMNG) has been associated with the occurrence of Graves'-like hyperthyroidism. It has been postulated that pre-existing autoimmunity may contribute to this phenomenon. To study whether RaI induces thyrotropin receptor stimulating antibodies (TSAbs) in the short term in TMNG and whether pre-existing autoimmunity is relevant. Thirty-one patients with relapsing Graves' disease and 17 patients with TMNG, all eligible for RaI. Before and 6 weeks after RaI, sera were collected and analysed for the presence of thyroglobulin (Tg), thyroid peroxidase antibodies (TPO-Abs) and thyrotropin receptor binding antibodies (TBIIs). TSAbs were analysed with a novel high-sensitive luciferase-based bioassay based on the JP-26-26 cell line, which constitutively expresses the TSH receptor. In Graves' disease, RaI did not induce or increase the levels and proportion of patients with measurable levels of any of the antibodies measured, despite a significant increase in Tg. In contrast, in TMNG, RaI induced TBIIs in three TMNG patients, which was accompanied by measurable TSAbs on one occasion. We conclude from the present study that induction of TBIIs and TSAbs may occur shortly after RaI in TMNG and that pre-existing autoimmunity may not be a requirement for the induction of TBIIs, as evidenced by the lack of effect of RaI on TBIIs in Graves' disease.
View
Autoimmunization and multinodular large toxic goiter therapy using repeated doses of 131I
Article
  • Jul 2006
The radioiodine therapy can favour and induces of autommunological reaction in thyroid gland. The aim of the study was evaluation of antithyroid autoantibodies in patients with multinodular large toxic goiter treated with repeated doses of 131I before and after therapy. Studies were conducted in 24 women (age range: 65-84 yrs) with multinodular large toxic goiters--goiter volume assessed by USG over 100 ml. Serum TSH, fT4, antithyroid antibodies (anti-TPO, anti-Tg, TSHR-Ab) levels were estimated in all patients parallel with radioiodine uptake test (after 5 and 24 hours), 131I thyroid scintigraphy and fine needle biopsy. These studies and therapy with 22 mCi 131I were repeated every 3 months. Before therapy median of thyroid volume was approximately 195 ml and during therapy gradually decreased to 110 ml after 12 months. After 12 months we found 11% of patients with hyperthyrodism, 62% of patients with euthyroidism and 27% of patients with hypothyroidism. Before radioiodine treatment aTg and aTPO presence were detected in the most of patients, but only in 5 cases above normal value. TSHRAb were detected (normal, very low values) in 16 patients. During therapy statistically significance increase of TSHRAb levels (median: from 0,27 to 0,65 after 6 months and to 0,71 IU/l after 9 months) was observed; aTPO and aTg antibodies levels showed marked tendency to rise, but without significant differences (aTPO median: from 40 IU/ml to 48 IU/ml; aTg - median: from 27 IU/ml to 46 IU/ml). During these observations we didn't find evident correlation between the levels of antithyroid antibodies, radioiodine uptake, proved reduction of goiter volume and TSH, FT4, FT3 values.
View
Guidelines for the use of radioiodine in the management of hyperthyroidism: a summary. Prepared by the Radioiodine Audit Subcommittee of the Royal College of Physicians Committee on Diabetes and Endocrinology, and the Research Unit of the Royal College of Physicians
Article
Full-text available
  • Nov 1995
  • J Roy Coll Phys Lond
Radioiodine (131I) therapy is indicated in patients with nearly all causes of hyperthyroidism. It may safely be given to patients of all age groups but is less often given to children under 10 years old. It is completely contraindicated in pregnancy and while breast feeding, but there is no increased risk of thyroid cancer, leukaemia or solid tumours. Administration of radioiodine must conform to regulations and definitions laid down by ARSAC And POPUMET. Medical staff authorising therapy must hold an ARSAC licence. The recommended strategy is to give an activity sufficient to render the patient rapidly euthyroid and maintain that state or achieve no more than a low rate of hypothyroidism in subsequent years. A range of activity (300-800 MBq) is suggested depending on the clinical state. Antithyroid drugs may be given before or after (or both) radioiodine if necessary. Full written information should be given to the patient and written consent obtained. A structured follow-up should be used ensuring regular measurement of TSH or FT4. Close cooperation with the patient's general practitioner is recommended throughout the assessment, treatment and follow-up. Shared care with a computer based follow-up system is recommended.
View
Outcome of Thyroid Function in Graves’ Patients Treated with Radioiodine: Role of Thyroid-Stimulating and Thyrotropin-Blocking Antibodies and of Radioiodine-Induced Thyroid Damage 1
Article
Full-text available
  • Jun 1998
We investigated the interrelationship and the influence of thyroid-stimulating antibodies (TSAb), TSH-blocking antibodies (TSHBAb), and of radioiodine (131I)-induced thyroid damage in the early (within 1 yr) outcome of thyroid function in hyperthyroid patients with Graves' disease (GD) treated with 131I. TSAb, TSHBAb, and ultrasound thyroid volume (as an index of thyroid damage) were simultaneously measured before and at 1, 3, 6, and 12 months after 131I in 31 GD patients. One year after radioiodine, 9.7% of patients were hyperthyroid (Hyper-group), requiring methimazole; 12.9% were euthyroid (Eu-group); and 77.4% were hypothyroid (Hypo-group). Pretreatment thyroid volume in the Eu-group and Hyper-group was significantly greater (P = 0.009) than in the Hypo-group. Pre-131I TSAb levels were higher in the Hyper-group vs. the Hypo-group (P = 0.01) or the Eu-group (P = 0.03). A significant post-131I increase in TSAb levels occurred in 66% of patients developing hypothyroidism but not in those remaining hyperthyroid. After 131I, TSHBAb appeared in 7 patients, in all but one associated with high levels of TSAb. One year after radioiodine: 1) the mean percent reduction in thyroid volume was greater in the Hypo-group (80.7%) or the Eu-group (83.5%) than in the Hyper-group (35.7%) (P = 0.007 and 0.0033 respectively); 2) hypothyroid patients had smaller (P = 0.0058) post-131I thyroids than hyperthyroid patients; and 3) TSAb were still elevated in 75% hypothyroid patients, but all of them had a thyroid volume < or = 8 mL, indicating major postradioiodine gland damage. In conclusion: 1) the early outcome of thyroid function after 131I for GD is mainly related to pretreatment thyroid volume and to the degree of its reduction after therapy; 2) high TSAb levels before 131I are associated with a relative resistance to therapy; 3) a postradioiodine increase in TSAb levels is related to the development of hypothyroidism; and 4) the concomitant appearance of TSHBAb and disappearance of TSAb are not frequent after 131I and play a role in the development of early postradioiodine hypothyroidism only in a minority of patients.
View
Development of a Luminescent Bioassay for Thyroid Stimulating Antibodies
Article
Full-text available
  • Feb 1999
The hyperthyroidism of Graves Disease (GD) is due to thyroid stimulating antibodies (TSAb) which are thyrotropin (TSH) agonists. They are detected routinely by measuring their ability to inhibit TSH binding to the receptor (TBII), which does not reflect their true biological activity. Current bioassays which measure cAMP by RIA, are not suitable for routine use. We have developed a luminescent bioassay for TSAb, by introducing a cAMP responsive luciferase construct into CHO cells stably expressing the human TSH receptor (TSHR). Clone lulul displays dose dependent TSH response detectable from 10 microU/ml and maximal at 10 mU/ml when a >25 fold increase in light output is obtained. 34 euthyroid sera were tested to determine a reference range, with values >1.5 relative light units (R.L.U.) being considered positive. An international TSAb standard responded in a dose dependent manner with 10 mIU/ml giving an R.L.U. of >10. The assay was adapted to a 96 well format for automatic readout and 100 treated GD samples (50 TBII negative and 50 TBII positive) were tested, 73% being positive. In contrast only 4% of 79 control sera from individuals with Hashimoto's, non-thyroid autoimmunity or multinodular goitre produced R.L.U. >1.5. When 44 of the GD sera were compared in a traditional salt-free bioassay, 61% were positive compared with 75% in the new luminescent assay. In conclusion, we have developed a luminescent bioassay for TSAb, using unfractionated serum which is capable of high throughput suitable for routine use.
View
Transition of Nodular Toxic Goiter to Autoimmune Hyperthyroidism Triggered by 131I Therapy
Article
Full-text available
  • Jun 1999
The use of 131I treatment in nodular toxic goiter is widely accepted. In this article, we describe transition of nodular toxic goiter into an autoimmune toxic goiter with development of thyrotropin receptor antibodies (TRAb) as a side effect of 131I treatment. In this retrospective study, 149 patients with nodular toxic goiter (100 with multinodular goiter, 49 with a solitary autonomously functioning toxic nodule) were studied. Of these 149 patients 100 became permanently euthryoid after 1 dose of 131I, and due to persistent hyperthyroidism, 32 patients needed 2-5 doses to became euthyroid. After becoming euthyroid, none of these 132 patients had relapse of hyperthyroidism in the follow-up period. Based on evaluation of the thyroid hormone variables, 17 of 149 patients had a distinctly different pattern in the changes in thyroid hormones. They developed an increase in FT4I 3-6 months posttreatment after an initial fall in FT4I. Twelve of these 17 patients were treated with antithyroid drugs before the initial 131I dose. On samples of frozen sera (-20 degrees C) anti-thyroid peroxidase (TPO) and TRAb were followed for 6 months after 131I treatment in these 17 patients. A similar follow-up was done in 20 patients (10 with and 10 without antithyroid drug pretreatment), randomly selected from the patients who did not relapse. In the remaining 112 patients, anti-TPO and TRAb levels were measured only before the 131I treatment. Of the 17 patients with relapse, 6 developed TRAb concomitant with recurrence of hyperthyroidism (4% of the study group). In 5 of the 17 patients TRAb values remained absent throughout the follow-up period. The remaining 6 patients had elevated TRAb values before 131I treatment. Among the 132 patients who did not relapse, an additional 7 cases with presence of TRAb were found. A total of 9% of the study group was found to have TRAb before 131I pretreatment. Anti-TPO was found in 20 of 149 patients (13%) before 131I treatment. Complications, either hypothyroidism or TRAb-associated hyperthyroidism, were seen in 8 of 20 patients (40%) with anti-TPO before 131I treatment, compared to 9 of 129 (7%) without (p<0.005). In conclusion, TRAb and a Graves' like hyperthyroidism can be triggered by 131I treatment in patients with nodular toxic goiter. The presence of anti-TPO seem to be a marker of an increased risk of development of TRAb-associated hyperthyroidism as well as hypothyroidism, but both side effects can be seen despite the absence of anti-TPO autoantibodies.
View
Effects of Antithyroid Therapy on the Long-Acting Thyroid Stimulator and the Antithyroglobulin Antibodies 1
Article
  • Mar 1969
Serial tests for long-acting thyroid stimulator (LATS) and antithyroglobulin antibodies were performed in 32 patients with toxic diffuse goiter submitted to ¹³¹I therapy and in 29 patients receiving antithyroid drugs. The level of detectable LATS and the incidence of positive assays tended to increase transiently following ¹³¹I therapy and to decrease during the administration of antithyroid drugs. Statistical analysis of the LATS changes detected at the time interval of 46–180 days after treatment showed that the differences between the 2 therapeutic groups were significant. A transient rise of circulating antithyroglobulin antibodies occurred in several patients treated with radioiodine, but individual changes showed no parallelism with the course of LATS. No definite pattern was noted in the behavior of antithyroglobulin antibodies during the administration of antithyroid drugs. Twentysix patients with toxic adenoma previously treated with radioiodine and 26 untreated controls were tested for LATS and all of them had negative assays. The possibility that thiocarbamides interfere with the immune response was investigated in mice immunized with sheep red blood cells. No immunosuppressive effect of methimazole was found. The implications of these findings are discussed.
View
Effect of radioiodine on stimulatory activity of Graves’ immunoglobulins
Article
  • Jul 1982
The effects of 131I therapy on the activity of thyroid stimulating antibody (TSAb) and thyrotrophin binding inhibiting immunoglobulin (TBII) in nineteen patients with Graves’disease have been studied. Prior to 131I administration TSAb was detected in 84%, and TBII in 68% of patients. Following 131I administration TSAb and TBII were detectable in 100% of patients. The elevation 3 months after treatment of the means of both the TSAb and TBII indices for the group of nineteen patients was highly significant compared with pre treatment values. All the patients went into remission during the course of the study and the TSAb index declined in all patients, becoming undetectable in eleven; TBII also declined in most patients but remained detectable in thirteen. The study furthermore afforded the opportunity for a direct comparison of binding with stimulatory activity. These results show that after 131I therapy for Graves’hyperthyroidism there is a transient increase in TSAb as well as TBII, followed by a decline, and that the measurement of binding and stimulatory activities are in good general agreement.
View
Relationship between thyroid-stimulating antibodies and thyrotropin-binding inhibitory immunoglobulins years after administration of radioiodine for Graves' disease: Retrospective clinical survey
Article
  • Nov 1996
Thyroid-stimulating antibody (TSAb) activity and the TSH-binding inhibitory immunoglobulin (TBII) index were assessed in 158 patients with Graves' disease who had been treated with 131I 6-14 years earlier. Twenty-one patients (13%) were still hyperthyroid, 45 (28%) were euthyroid, 44 (28%) were subclinically hypothyroid, and 48 (30%) were overtly hypothyroid. Positive results were obtained in 10 (48%) of the 21 patients with hyperthyroidism for both TSAb and TBII assays, and in 3 patients (14%) in one of the assays. In contrast, only two (5%) patients with subclinical hypothyroidism and 1 (2%) patient with overt hypothyroidism tested positive in both assays, and 11 (25%) subclinically hypothyroid patients and 15 (31%) overtly hypothyroid patients tested positive in one of the assays. The correlation coefficients between TSAb and TBII were 0.88 (p < 0.01) in hyperthyroid patients, 0.49 (p < 0.01) in euthyroid patients, 0.34 (p < 0.05) in subclinically hypothyroid patients, and 0.12 (p > 0.05) in patients with overt hypothyroidism. Findings indicate the presence of long-term changes in the population of TSH receptor antibodies years after 131I treatment, which may influence thyroid function.
View
Induction of TSH-Receptor Antibodies in Patients with Toxic Multinodular Goitre by Radioiodine Treatment
Article
  • Feb 2002
Previous studies have indicated pre-existing subclinical Graves' disease (GD) in many patients with the scintigraphic diagnosis of disseminated thyroid autonomy (DISA) or toxic multinodular goitre (TMG) type A. After radioiodine (RAI) treatment, an increase or the induction of TSH-receptor antibodies (TRAbs) in patients with GD or TMG has been repeatedly reported. In the present study, we investigated whether RAI could induce TRAbs in patients with TMG in whom pre-existing GD was excluded with highly sensitive TBII and TSAB assays. Therefore, TRAbs, anti-thyroperoxidase antibodies (anti-TPO-Abs) and anti-thyroglobulin antibodies (anti-TG-Abs) were determined in 43 consecutive patients at the nuclear medicine outpatient clinic with the scintigraphic diagnosis of toxic adenoma (TA; n = 20) or TMG type A (n = 11) or type B (n = 12) before and after RAI treatment. After RAI therapy, we detected TRAbs in 36 % (4 of 11) of patients with TMG type A only, whereas TRAbs were not detectable in patients with TMG type B or in patients with TA. Furthermore, 3 of the 4 patients with detectable TRAbs after RAI showed positive anti-TPO-Abs before RAI therapy. These findings provide further evidence for pre-existing GD in patients with TMG type A or DISA as previously suggested. Therefore, patients with TMG type A and high anti-TPO-Abs seem to be at increased risk of developing TRAbs or side-effects such as relapse of hyperthyroidism or thyroid associated ophthalmopathy. These patients therefore require more frequent evaluation after RAI treatment.
View