2/1996
The importance of repeated plasma thyroglobulin measurements in follow-up
studies of differentiated thyroid cancer
Jan Nemecą'˛, P. Vlceką'˛, R. Bílek˛, P.
Chytrý˛, V. Zamrazil˛'ą, P. Racek˛
Clinic of Nuclear medicine, 2nd School of Medicine, Charles' University,
Praha Motolą
Institute of Endocrinology, Praha, Czech Republic˛
Supported by grant IGA 3418-3, Ministry of Health, Czech Republic
Introduction
It was found that plasma thyroglobulin levels are very important markers
of differentiated thyroid cancer which in athyroid status could give much
information on the activity of the disease, and are also an important prognostic
factor (Nemec, Bílek, Zamrazil et al., to be published). Moreover,
it is generally believed that plasma thyroglobulin levels are TSH dependent
and lower in suppressed patients, and rise following thyroid hormone suppression
withdrawal (Ashcraft and Van Herle, 1975, Baskin 1994, Mizukami et all
1995, Van Herle and Uller 1975). Here we present results of our longitudinal
study on 2648 patients repeatedly examined in the follow-up by measuring
plasma thyroglobulin levels in various phases of the disease and treatment.
Methods
Plasma Tgl was measured by own radioimmunoassay (Bednár et all 1981)
repeatedly, Tgl value 1 during suppressive treatment following previous
radioiodine patients in a group of 2648 differentiated cancer patients,
plasma Tgl 2 5 weeks following thyroxine withdrawal in order to prepare
the patient for possible radioiodine treatment. Reference levels during
suppression were up to 10 µg/l, without suppression up to 30 µg/l.
Results
are given in Tables. Table 1 shows that in only about 53 % of patients
the withdrawal was really followed by an increase in plasma thyroglobulin
levels. This might be in our patients attributable to the fact that for
the comparison of both plasma Tgl levels patients were taken out of our
group of patients previously treated with thyroablative amounts where remaining
thyroid secretion was present in 618 patients who had acually been treated
with radioiodine (25% of examined patients).
The probablility (in %) of active tumor disease
in differentiated thyroid cancer patients in relation to the plasma thyroglobulin
levels repeated in 6 to 12 month during suppressive treatment with thyroid
hormones was studied in 1223 patients, active disease being present in
123 patients (10 %). Plasma thyroglobulin levels were measured following
suppressive treatment after radioiodine administration (Tgl a) and were
repeated 6 to 12 month later (Tgl b). In individual fields containing results
of at least 100 patients each, the probablility of disease is given in
patients with Tgl a and Tgl b levels higher than the value given in Table
2.
It is quite clear that higher plasma thyroglobulin levels, repeated in
the course of 6 to 12 months could predict the activity of the tumor disease
even during continuing suppressive treatment in quite a high percentage,
increasing from 11 % in all patients to 30 % in repeatedly high values.
It must be stressed that plasma thyroglobulin levels during suppresslon
should not exceed 10-15 µg/l in athyroid patients.
In the next calculations, 2649 patients, 495 of them with active disease
were evaluated according to the plasma thyroglobulin levels during suppressive
treatment and after discontinuation of. Intervals of plasma thyroglobulin
levels were set at different values so that the number of patients was
similar in each field, about 550 in each. The mean percentage of primary
tumor or metastatic lesions is given in each table and numbers higher than
the mean in individual fields were printed in both characters, see Tables
4-6. The total number of patients with active tumor disease is lower Table
4 than the sum of patients in Tables 5-6 as many patients had more than
one active site of the disease.
All tables show that high probability is always
connected with high plasma Tgl levels and the percentage of active tumors
in fields of low Tgl level is very low and thus the risk of false-negative
results is low namely in distant metastases.
Discussion
The long follow-up studies with a large number of patients allowed us very
intensive study. In Table 1, the rising number of patients is documented
with a peak in 1992 as many patients were studied using whole body radioiodine
scans to define the actual stage of the disease. In 1993, the number of
these studies decreased because positive whole body scintigraphy using
99mTc MIBI or Myoview rendered a huge proportion of 131I whole body scans
with withdrawal of suppressive treatment unnnecessary (Nemec et all 1995
and 1996). Most of our patients in this study had previously received radioiodine
treatment and in most of them no further active secretion of thyroglobulin
was present. This is probably the cause of the less prominent TSH-dependency
in our material as documented by a relatively low correlation coefficient
between supressed and nonsuppressed plasma Tgl values. The TSH dependency
is, however, present and it is important to take different reference values
for patients in these two groups. It is documented in Tables 4-6, where
the ranges for Tgl a (on suppression) and Tbgl b (without suppression)
differ considerably to achieve symmetric distributions of patients in the
net.
From our material it is clear that the evaluation of patients using
a combination of 2 plasma Tgl levels is important even with 2 suppressed
values; however, much better distribution would be achieved using the combination
of one suppressed and one unsuppressed value. The distribution is roughly
similar in any type of tumor disease but best results are achieved in patients
with distant metastatic lesion compared to patients with primary tumor
and lymph node metastases. These differences are not clinically relevant
in the combined follow-up studies as lesions in the neck could be evaluated
by ultrasonography in combination with plasma thyroglobulin evaluation
without the necessity of withdrawing thyroxine treatment.
We believe that in the near future most patients will be evaluated using
plasma tgl, ultrasonography for detection of local disease, and by whole-body
scans with 99mTc tagged radiopharmaceuticals as MIBI and/or Myoview. Only
in suspected tumor recurrence whole-body radioiodine scans would be indicated
as a preparation for repeated radioiodine therapeutic administrations.
Summary
Own experience with plasma thyroglobulin levels in the follow-up studies
of patiens with differentiated thyroid cancer was reviewed. The TSH dependency
of plasma Tgl is in our material lower than expected, probably due to the
type of study where most patients were examined following previous radioiodine
treatment with little remaining functionally active tissue able to secrete
thyroglobulin. Important information could be extracted by studying even
the suppressed Tgl levels, but better information is obtained by comparison
of supressed and nonsuppressed values (considering, however, the different
reference ranges). The best results were seen in the evaluation of patients
with distant metastatic dissemination with a very low incidence of falsenegative
levels.
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