Biokinetics of ¹³¹I after endogenous and exogenous stimulation of TSH in patients with DTC.

Abstract

The effective radioiodine treatment of patients with DTC is possible only after raising the TSH value over 30 μUI/ml. This effect might be obtained by either endogenous or exogenous stimulation. The aim of this study was to evaluate differences in (131)I biokinetics of selected regions of interest (ROIs) in cases of endogenous and exogenous stimulation.
Two groups of 50 patients were enrolled in the study. All patients were treated with 3.7 GBq of ¹³¹I; the first group after thyroid hormone withdrawal (THW), the second group after rhTSH administration (rhTSH). On the basis of post-treatment images, the uptake ratios over selected ROIs (thyroid remnants, mediastinum, liver, stomach, abdomen, and whole-body) were compared between groups.
In the case of uptake over the whole-body and the liver, statistically significant higher values were received for the THW group. For the remaining regions, the differences between groups were statistically insignificant, but uptake ratios in the rhTSH group were generally numerically lower compared to the THW group.
The revealed difference in radioiodine biokinetics after thyroid hormone withdrawal or administration of recombinant human TSH may influence many important aspects of patients with DTC treatment, such as the choice of proper therapeutic scheme, the cost of therapy, and the dose assessment.

Full text

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Nuclear Medicine Review 2010
Vol. 13, No. 2, pp. 55–58
Copyright © 2010 Via Medica
ISSN 1506–9680
www.nmr.viamedica.pl
Original
Abstract
BACKGROUND: The effective radioiodine treatment of patients
with DTC is possible only after raising the TSH value over
30 μUI/ml. This effect might be obtained by either endogenous
or exogenous stimulation. The aim of this study was to evaluate
differences in 131I biokinetics of selected regions of interest (ROIs)
in cases of endogenous and exogenous stimulation.
MATERIAL AND METHODS: Two groups of 50 patients were
enrolled in the study. All patients were treated with 3.7 GBq of
131I; the first group after thyroid hormone withdrawal (THW), the
second group after rhTSH administration (rhTSH). On the basis
of post-treatment images, the uptake ratios over selected ROIs
(thyroid remnants, mediastinum, liver, stomach, abdomen, and
whole-body) were compared between groups.
RESULTS: In the case of uptake over the whole-body and the
liver, statistically significant higher values were received for the
THW group. For the remaining regions, the differences between
groups were statistically insignificant, but uptake ratios in the
rhTSH group were generally numerically lower compared to
the THW group.
Biokinetics of 131I after endogenous
and exogenous stimulation of TSH
in patients with DTC
Correspondence to: Alicja B. Hubalewska-Dydejczyk
Endocrinology Department
Jagiellonian University Medical College
ul. Kopernika 17, 31–501 Krakow
Tel: (+48 12) 424 75 20
e-mail: alahub@cm-uj.krakow.pl
CONCLUSIONS: The revealed difference in radioiodine bi-
okinetics after thyroid hormone withdrawal or administration of
recombinant human TSH may influence many important aspects
of patients with DTC treatment, such as the choice of proper thera-
peutic scheme, the cost of therapy, and the dose assessment.
Key words: endogenous stimulation, exogenous stimulation,
thyroid hormone withdrawal, recombinant human TSH,
radioiodine treatment, DTC
Nuclear Med Rev 2010; 13, 2: 55–58
Introduction
In patients with differentiated thyroid carcinoma (DTC),
efficient treatment with radioiodine complementary to radical
surgery is possible only on condition that the TSH value is over
30 μUI/ml. For many years, this effect was obtained by endog-
enous stimulation, which means that L-thyroxine (LT4) was with-
drawn for at least four weeks before the planned treatment with
131I. Recently, exogenous stimulation of TSH has become possible
after intramuscular injection of recombinant human TSH, rhTSH
(Thyrogen, Genzyme, Cambridge, MA) 24 h and 48 h before
radioiodine treatment.
At first, recombinant human TSH was only approved for the
stimulation of serum Tg and whole-body scintigraphy (WBS),
to be performed during post-surgical follow-up and for patient
staging. Next, many small clinical studies revealed that in low risk
patients (pT1-2 N0M0) thyroid remnant ablation using rhTSH and
thyroid hormone withdrawal (THW) methods had a similar rate of
effective ablation. These findings were finally confirmed by a large
multicentre controlled randomized study conducted in 2006 [1].
The aim of this study was to evaluate differences in the 131I
biokinetics of selected regions of interest (ROIs) in cases of endog-
enous and exogenous stimulation in patients from our Department.
Material and methods
A hundred patients were qualified for complementary treat-
ment with 131I in the Endocrinology Department of University Hos-
Monika Buziak-Bereza, Monika Tomaszuk, Dorota Pach,
Anna Sowa-Staszczak, Agata Bałdys-Waligórska,
Bogusław Głowa, Maciej Kołodziej,
Alicja B. Hubalewska-Dydejczyk
Nuclear Medicine Unit, Endocrinology Department, Jagiellonian
University Medical College, Krakow, Poland
[Received 04 II 2011; Accepted 21 II 2011]

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Original
pital in Krakow because of DTC in the low stage of the disease
(pT1aN0M0, pT1bN0M0, pT2N0M0). All patients received the same
radioiodine activity, 3.7 GBq (100 mCi).
The THW group consisted of 50 patients (mean age 57 years,
SD 13 years, min 29 years, max 79 years). Papillary thyroid car-
cinoma and follicular thyroid carcinoma were diagnosed in 83%
and 17% of patients, respectively. In this group of patients, thyroid
hormone treatment was withheld for 4–6 weeks before radioiodine
therapy, until the patient’s TSH was above the required level (mean
TSH level 68 μIU/ml, SD 35 μIU/ml).
The rhTSH group also consisted of 50 patients (mean age 54
years, SD 16 years, min 19 years, max 77 years). Papillary thyroid
carcinoma and follicular thyroid carcinoma were diagnosed in 86%
and 14% of patients, respectively. In this group, the patients con-
tinued receiving L-thyroxine therapy after radical surgery of the
thyroid. The Thyrogen was administered intramuscularly 48 h and
24 h before thyroid remnant ablation, in accordance with Polish
standards [2].
Post-treatment whole-body imaging was performed in all
patients seven days after 131I administration. All images were
acquired using a dual-head, large field of view E.CAM gamma
camera (Siemens, 2000) with high-energy (HE) collimators. The
camera settings were as follows: 1024 × 256 matrix, 8-cm/min
scan speed, with autocontour, without scatter correction.
Between the groups, on the basis of AP scans, counts over
selected regions of the body to counts over the background re-
gion ratios (uptake ratios) were compared. Such regions of inter-
est (ROIs) as: region over the thyroid remnants (thyroid/backg),
mediastinum (mediastinum/backg), liver (liver/backg),
stomach (stomach/backg), abdomen (abdomen/backg),
and whole-body (WB/backg), were chosen (Figure 1). The
background was estimated from counts over the right thigh
re-calculated on the same number of pixels as was assessed
in the selected ROI.
Statistical analysis was performed by U Mann-Whitney test at
a 95% confidence level.
Results
In the case of WB/backg ratios, statistically significant higher
values were received for the THW group, 0.90 ± 0.69, com-
pared with the rhTSH group, 0.52 ± 0.47 (Figure 2). Taking into
consideration the thyroid/backg ratios, the difference between
groups was statistically insignificant (THW group, 25.54 ± 36.21;
rhTSH group, 27.64 ± 30.14).
For mediastinum and stomach, differences between the
groups were statistically insignificant (mediastinum/backg — THW
group, 3.01 ± 1.50; rhTHS group, 2.57 ± 0.86; stomach/backg
— THW group, 4.70 ± 5.13; rhTSH group, 2.92 ± 1.02). For abdo-
men/backg ratios the same statistically insignificant results were
observed (THW group, 0.84 ± 0.32; rhTSH group, 0.75 ± 0.19).
In the case of liver/backg ratios, statistically significant higher val-
ues were also received for the THW group, 4.56 ± 1.66, compared
with rhTSH group, 3.60 ± 0.89 (Figure 3).
Figure 1. Localization of selected regions of interest. A. Endogenous stimulation, THW group; B. Exogenous stimulation, rhTSH group.
AB

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Monika Buziak-Bereza et al. Biokinetics of 131I in patients with DTC
Original
Discussion
This present study is focused on an assessment of the dif-
ferences in 131I biokinetics in cases of endogenous and exog-
enous stimulation of patients with DTC.
In previous publications concerned with the evaluation of
the biokinetics of radioiodine, mainly in thyroid remnant localiza-
tions and in the whole-body after the discussed DTC treatment
schemes, different sophisticated procedures were used. In this pa-
per, a new, simpler method for a number of different regions of
interest was described. The result obtained for whole body region
of interest is concordant with previous reports, finding that 131I
is excreted from the body significantly faster after an exoge-
nous stimulation of thyroid stimulating hormone level. Furthermore,
for the thyroid remnants region, the same level of tracer uptake
was found for both therapeutic schemes [3, 4]. Despite the lack
of statistically significant results for other regions (except the liver),
uptake ratios in the rhTSH group were always numerically lower
compared with the THW group. This might be interpreted such that
after an rhTSH administration most human organs demonstrated
faster radioiodine clearance because of the short-term influence
of a factor which stimulated the high TSH level in patients without
withdrawal of L-Tyroxine. So it is likely the patients’ hyperthyroid
state influenced the results. The only statistically significant dif-
ference between the groups was observed for the liver, which
is an organ with a very high metabolism. This may perhaps be
related to the fact that iodine contained in organic compounds un-
dergoes deiodination mainly in this organ. On the other hand, in
the THW group, after the withdrawal of L-Tyroxine, a slow rising of
the TSH level is observed with simultaneous slow passing of all
cells into a clinically manifested hypothyroid state.
Nowadays, the use of Thyrogen is only approved for pa-
tients with a low stage of the disease (pT1-2 N0M0). An observed
faster removal of radioiodine after rhTSH administration might be
a reason for delivering an insufficient radiation dose to metastases,
which is crucial for their effective sterilization. So, taking into ac-
count patients with higher stages of DTC, this issue should be
considered very carefully. Approval for exogenous stimulation
should undeniably be confirmed by positive results from a multi-
centre controlled randomized study with a large group of patients.
Our results might be also considered in respect of the treatment
cost. Faster elimination of radioiodine in the rhTSH group might
permit patients a shorter stay in hospital and thus a reduction in
the overall cost. Many factors might influence the profitability of the
treatment. To confront two therapeutic schemes, building a Mar-
cov model is a well-accepted statistical and economical technique
for comparing cost-effectiveness. In the literature, only three manu-
scripts considered this problem, and they all showed a preferable
overall cost for exogenous stimulation [5–7]. A simpler analysis,
which was performed in a French hospital, is also mentioned. The
parameter considered in order to discharge the patient from hos-
pital was a level of body residual activity lower than 400 MBq [8].
It was clearly shown that exogenous stimulation reduced patients’
average stay by one day. The cost of this therapeutic scheme is still
higher than endogenous stimulation, but a shorter hospitalization
allows for a 57% compensation of the Thyrogen cost for one patient.
Preparing patients with rhTSH might be cost-effective in developed
countries, but it should be stressed that this statement is only true
in the case of proper estimation of the remaining treatment costs.
The next problem connected with our result is the potential
difference in average absorbed dose for healthy organs, which
is delivered by 131I radiation during thyroid remnant ablation, after
endogenous and exogenous stimulation of the TSH level. Currently
just one paper has been published concerning a full estimate of
the radiation dose for healthy organs only in the case of rhTSH
stimulation [9]. However, this issue is very important from a radia-
tion safety point of view and should be considered more carefully
in future [10, 11].
Important information could be also obtained from compart-
ment models for radionuclide kinetics, an element of patient dose
estimates. The principle of utilizing compartment modelling is to
find solutions for the differential equations and calculate the trans-
fer coefficients between compartments. These constants describe
the degree and rapidity of compartment interactions. They are
estimated on the basis of each tracer biokinetic measurement. In
connection with our results, the difference in values of estimated
transfer coefficients might be observed for endogenous and ex-
ogenous therapeutic schemes. Hence it is crucial to know which
therapeutic scheme the compartment model was set for.
Conclusions
The revealed difference in radioiodine biokinetics after thyroid
hormone withdrawal or administration of recombinant human
Figure 2. WB/backg ratios for both groups.
Figure 3. Liver/backg ratios for both groups.

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Original
TSH may influence many important aspects of treatment for
patients with DTC.
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