N. Lima, H. Cavaliere, E. Tomimori, et al.
lation and L-T4 are indicated individually. The 2 pa-
tients from group II (ꢀ) that had an increased serum
TG value post-RAI had a WBS demonstrating up-
take only in the thyroid bed. By contrast 5 patients
from group III (ꢁ), with the highest serum TG values
at the 3rd week post-surgery (3.6-16.8 ng/ml) had
evidence for nodal metastases in the WBS per-
formed after the therapeutic dose (Fig. 1).
surements performed 40 days after total thyroid-
ectomy for DTC, prior to the therapeutic use of 131I.
In 79 patients who later presented with lymph node
(no.=32) or distant metastases (no.=47), serum TG
at the 40th day post-thyroidectomy was significant-
ly higher (mean: 250 ng/ml) than in 255 patients
without metastases (mean: 15.9 ng/ml). Thus, an el-
evated serum TG level (>69 ng/ml) about 5 weeks
post-total thyroidectomy has a 90% predictive val-
ue for the presence of DTC metastases.
DISCUSSION
In this paper we have presented our data on week-
ly serum TG determinations after total thyroidec-
tomy for DTC. The patients were subdivided in 4
groups, based on the surgical and pathological
findings. Thus, group I represented patients with
DTC confined to a single solid nodule, whereas
group IV patients had a confirmed diagnosis of dis-
tant metastases. Also, we included within this spec-
trum of malignancy patients with invasion of cervi-
cal structures by the tumor (but without lymph
nodes metastases; group II) and patients with pa-
thological confirmation of lymph node metastases
(group III). As expected all patients (with one stage
II patient exception) in group I had undetectable
serum TG values 21 days after total thyroidecto-
my. One patient classified as stage III from group
II had detectable levels of serum TG at the 3rd
week post- surgery. This was interpreted as an ev-
idence of residual thyroid tissue, possibly infiltrat-
ing local structures. After thyroid ablation and WBS
there was no evidence for lymph node metastases.
Group III patients had higher mean SE serum lev-
els of TG; in 6 of these patients serum TG ranged
3.4-16.8 ng/ml at the 3rd week post-surgery (Fig.
1). After thyroid ablation and WBS, 5 of them had
evidence for lymph node metastases and in 3 of
these 5 patients metastatic nodes were removed
surgically.
TG is the main thyroid gland protein where it rep-
resents, approximately, 75% of all proteins. As a
precursor of thyroid hormone, it is synthesized ex-
clusively in the follicular cells of the thyroid. It has
long been believed that TG is present only in the
thyroid. About 40 yr ago it was demonstrated that
TG is present in the systemic circulation as well, be-
ing released via lymph from the thyroid (15).
In thyroid oncology, TG has been used as a tumor
marker for the detection of metastases or recur-
rence after total thyroidectomy in patients with DTC
for about 18 yr (5-8, 10, 11). In order to determine
the optimal timing of serum sampling for TG mea-
surements, information on TG half-life is of essential
importance. Like all glycoproteins, TG is eliminated
through the liver (16). The data on serum TG half-
life in the literature are scarse (16, 17) and the re-
ported values vary greatly, ranging from 6 to 96 h.
Following subtotal thyroidectomy, Feldt-Rasmussen
et al. (17) were able to demonstrate that TG with
different molecular sizes (ranging 100-600 kDa)
were detected in the systemic circulation. Accor-
dingly, for the heaviest TG molecule (19S) the mean
disappearance rate was 4.3 days whereas the over-
all half-life of smaller molecules had a mean disap-
pearance rate value of 3.7 h. More recently, Hoce-
var et al. (18) collected serum samples of patients
with DTC (no.=6) and nodular goiter (no.=5) at 24,
48, 72 and 168 h after total thyroidectomy. All mea-
surements were performed using the same assay in
order to eliminate interassay variations. Serum TG
levels were determined and TG half-life calculated
by the use of one-compartment kinetic mode.
Mean serum TG half-life was 65.2 h (SE=4.3 h) or,
approximately, 2.7 days. Individual values ranged
36.9-86.6 h for serum TG half-life (1.5-3.6 days, ap-
proximately). These results and the previous work
by Lo Gerfo et al. (16) suggest that serum TG sam-
pling should be carried out about 3 weeks after to-
tal thyroidectomy, in order to be indicative of the
presence or absence of metastatic or residual dis-
ease.
As previously mentioned, all patients in group IV
had evidence for distant metastases, which ex-
plained the higher levels of TG obtained at the 3rd
week post-surgery.
After 131I ablation, TG was undetectable in 31 pa-
tients (out of 36) from groups I, II and III while all
patients with distant metastases (group IV) exhibit-
ed TG concentrations ranging 2.5 to 8.6 ng/ml.
These detectable TG levels might be expected af-
ter thyroid ablation and L-T4 therapy, because of
the occurrence of distant metastases. More difficult
to explain is the presence of detectable TG values
in patients from group II (2 cases) and group III (3
cases) after 131I therapy and L-T4 suppressive dos-
es. One explanation could be that the time after
ablation (30 days) would be too short to evaluate
the therapeutic effectiveness of the 131I therapy.
Based on these experiments, Ronga et al. (11) eval-
uated the diagnostic significance of serum TG mea-
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