Endogenously radioiodinated thyroglobulin (Tg) and the serum concentration of Tg have been measured in patients with metastatic thyroid carcinoma after therapeutic doses of radioiodine. Serial samples of blood were analyzed for both these parameters over a period of 10 to 22 days. The specific activity of Tg (cpm/ng) was calculated for each sample. Among the six patients studied, three showed constant specific activity. The specific activity of the other three fell, indicating the entering of newly synthesized Tg into the circulation. The respective amounts of Tg entering into the circulation in these three patients were 120, 852, and 20,935 ng/ml serum/day

Ajay Kumar, B. S.

Ganatra, R. D.

Jeevanram, R. K.

Shah, D. H.

Sharma, S. M.

English

Publications of the IAS Fellows

Synthesis of Thyroglobulin in Thyroid Carcinoma 
Patients After Radioiodine Therapy 
R. K. JEEVANRAM, MSC, D. H. SHAH, BSC (HONS), BSC (TECH), PHD (USA), B. S. AJAY KUMAR, BSC, 
S. M. SHARMA, MBBS, DMRT, AND R. D. GANATRA, MBBS, FCPS, MSC, FASC 
Endogenously radioiodinated thyroglobulin (Tg) and the serum concentration of Tg have been measured 
in patients with metastatic thyroid carcinoma after therapeutic doses of radioiodine. Serial samples of 
blood were analyzed for both these parameters over a period of 10 to 22 days. The specific activity of 
Tg (cpm/ng) was calculated for each sample. Among the six patients studied, three showed constant 
specific activity. The specific activity of the other three fell, indicating the entering of newly synthesized 
Tg into the circulation. The respective amounts of Tg entering into the circulation in these three patients 
were 120, 852, and 20,935 ng/ml serum/day. 
Cancer 5232240-2244. 1983. 
T IS NOW well known that serum thyroglobulin (Tg) can I be used as a reliable biochemical marker for detection 
of presence of metastases of recurrence of disease in pa- 
tients with differentiated thyroid carcinoma after surgical 
removal of primary It is also has been shown 
that Tg is undetectable after successful ablation of thyroid 
cancer.’.’ In addition, Tg levels are shown to be lower in 
patients who have undergone thyroid ablation as com- 
pared with patients with partial thyroidectomy or normal 
subjects. Very recently, Ashcraft and Van Herle have 
further pointed out that the Tglevel, less than 1 ng/ml 
during thyroxine (T4) therapy or 10 ng/ml off T4 therapy, 
is suggestive of a successful therapy, and a routine scan 
could be avoided unless clinically indicated.’ This avoids 
the potential risk of stimulation of thyroid cancer cells 
by thyroid stimuluating hormone and morbidity of in- 
duced hypothyroidism. In the current study, we made an 
attempt to study the specific activity of radioiodinated 
Tg in thyroid carcinoma patients after radioiodine therapy 
as a guideline for the effectiveness of radioiodine therapy. 
Materials and Methods 
Study Subjects 
Six patients with thyroid carcinoma who had undergone 
thyroidectomy, but who had functioning metastases, were 
From the Radiation Medicine Center, Bhabha Atomic Research Cen- 
ter, Tata Memorial Center Annexe, Jerbai Wadia Road. Parel. Bombay 
400 012, India. 
Address for reprints: R. K. Jeevanram, Radiation Medicine Center. 
Bhabha Atomic Research Center, Tata Memorial Center Annexe, Parel. 
Bombay 400 012, India. 
Accepted for publication September 27, 1982. 
studied. Of the six patients, two (N, Rx) had already 
undergone radioiodine treatment in the past and one 
patient (P) had undergone deep x-ray therapy. Thyroxine 
therapy was started in all six patients on fifth day after 
radioiodine treatment. 
The sera of these patients were found to be negative 
for the presence of antithyroglobulin and antimicrosomal 
antibody by tanned red cell agglutination technique using 
kits from Fugizoki Pharmaceutical Co., Ltd., Japan. 
Of the six patients studied, three were followed up later 
when they came for the successive therapeutic treatments. 
Measurement of radioiodinated serum Tg: Serial blood 
samples were obtained with an interval of 1 to 2 days 
after radioiodine treatment from these patients. The per- 
cent radioactivity associated with Tg/ml serum and the 
disappearance rate of radioiodinated serum Tg were mea- 
sured according to the procedure described earlier. l o  
Measurement of Tg by radioimmunoassay (RIA): The 
amount of total circulating Tg referred as stable Tg, was 
measured by RIA as described by Van Herle et al.’ Since 
the presence of I3lI in the serum interferes with the RIA 
procedure, all radioiodinated sera were stored at -20°C 
until decay of radioactivity. 
Specific activity: The specific activity of Tg in each 
sample was calculated as follows: 
Specific activity (counts/50 sec/ng Tg) 
- Radioactive counts with Tg per ml serum 
- 
Amount of Tg in ng per ml serum 
Results 
In all patients studied, the levels of radioiodinated and 
stable Tg rose initially, attained a maximum value be- 
0008-543)</83/ 12 I5/2240 $ I .05 0 American Cancer Society 
2240 
No. I2 TG SYNTHESIS AFTER I3'I  THERAPY - Jeevunrurn et uf. 224 I 
10000 
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FIG. I .  Disappearance rate of radioiodinated Tg (X) as measured by 
column chromatography and stable Tg (0) as measured by radioim- 
munoassay. 
. 
I 
tween 2 and 8 days, and then declined. The disappearance 
rate of stable Tg, however, differed in these patients (Figs. 
I and 2). 
SpecL'iJic activity: The specific activity of radioiodinated 
Tg in these six patients is shown in Figure 3. Three patients 
who had parallel decline of both radioiodinated Tg and 
stable Tg, showed constant specific activity (represented 
by horizontal line in Figure 3), thus indicating a negligible 
amount of newly synthesized Tg entering the circulation. 
The remaining three patients who had a slower disap- 
pearance rate of stable Tg. showed a fall in specific activity, 
FIG. 2. Disappearance rate of radioiodinated Tg (X) as 
measured by column chromatography and stable Tg (0) 
as measured by radioimmunoassay. 
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FIG. 3.  Specific activity of radioiodinated Tg after ra- 
dioiodine therapy (six patients). Three patients (N. R and 
RM) show constant specific activity and remaining three 
patients (P. M and SI) show decline in specific activity. 
Days after radiolodine therapy 
indicating possibly the newly synthesised Tg entering the 
circulation. 
Discussion 
The data presented here show that there is a parallel 
rise in stable and radioiodinated Tg in circulation, in all 
of the six patients studied, after radioiodine treatment. 
The increase in the level of stable and radioiodinated Tg 
between 2 and 8 days, indicate that the effect of radioio- 
dine is seen within a short period. This is in contrast to 
the delayed effect of radioiodine observed for controlling 
thyroid activity of Graves' disease." The purpose of ra- 
dioiodine for the treatment of Graves' disease and thyroid 
cancer is different, i.e.. a large amount of radiation dose 
is given in thyroid cancer patients, with 80 to 250 mCi 
I3 ' l ,  for total destruction of functioning thyroid tissue, 
while comparatively small amount of radiation dose is 
given in Graves' disease, with 3 to 10 mCi l 3 ' 1 ,  for partial 
destruction of thyroid. 
Thyroxine therapy was started on the fifth day after 
radioiodine treatment in all patients studied. The cir- 
culating Tg level showed a decline in some patients even 
prior to Tg therapy, whereas in some other patients, the 
Tg level continued to show an increasing trend even after 
T4 therapy, indicating at this stage that the radiation dose 
to the tumor has a primary role on the level of circulat- 
ing Tg. 
Although the stable and radioiodinated Tg showed a 
parallel rise after radioiodine treatment; they were not 
parallel during the decliningphase in all the patients stud- 
ied, i.c.., the disappearance rate of stable Tg was longer 
than that of radioiodinated Tg in three of the six patients. 
Theoretically, one would expect both radioiodinated and 
stable Tg to have similar kinetics resulting into a constant 
specific activity if complete ablation of tumor had been 
achieved with radioiodine. The decline in specific activity 
thus indicates the presence of functioning tumor. which 
releases the Tg and thus lowers the specific activity. The 
amount of Tg entering the circulation might have direct 
relation with the mass of functioning tumor present. It 
is pertinent to note that a direct correlation between cir- 
No. 12 TG SYNTHESIS AFTER I3 'I  THERAPY - Jeevanrarn ef af .  2243 
culating Tg and amount of tumor mass is not yet estab- 
lished. 
We have attempted to calculate the amount of Tg en- 
tering in circulation in the patients who show a decline 
in specific activity. As the level of stable Tg is not at a 
steady state, i.e., the stable Tg is declining as a function 
of time but at a much slower rate than that of radioiodi- 
nated Tg. the rate of disappearance of stable and ra- 
dioiodinated Tg were plotted on linear graph paper (Fig. 
4) for the purpose of calculation Tg synthesis. If the dis- 
appearance rate of both stable and radioiodinated Tg 
were similar, the two curves could be superimpose; how- 
ever, when there is a difference in disappearance rate or 
addition of Tg into circulation, the curves could be dif- 
ferent. The first possibility could be ruled out, as the 
disappearing Tgs (stable and radioiodinated) are one and 
the same basically. Therefore, the area between the two 
curves is considered due to the addition of newly syn- 
thesised Tg. Thus, the net synthesis of Tg was calculated 
directly by measuring the area which gives ng/ml/days 
which then divided by the number of days for which the 
area was calculated gave the amount of Tg added per ml 
serum per day. The amounts of Tg entering the circulation 
in the three patients (P, M, SI) who showed a decline in 
specific activity were 120, 852, and 20,935 ng/ml serum/ 
day; respectively. 
The predictions made by the specific activity studies 
were further verified when three of the six patients came 
for subsequent follow-up. The Patient R who had shown 
constant specific activity was followed for a period of 6 
months while the patient was on T4, by collecting blood 
sample each month. The Tg level was 35 ng/ml and this 
remained almost constant in the 6-month period. The 
patient came for successive treatment after 14 months 
and thyroxine therapy was withdrawn prior to therapy, 
and the Tg level was 204 ng/ml. The Tg level could have 
gone up because of withdrawal of T4 as it is clearly known 
that Tg level is dependent on thyroid stimulating hor- 
mone.'* Following therapy the Tg level, came down to 
25 ng/ml and the patient was on T4. 
The second patient, RM. who also showed constant 
specific activity had a Tg level of 43,000 ng at the time 
of the first treatment. The patient came for successive 
treatment after ten months and Tg level was 270 ng/ml. 
The level of Tg could have been lower than 270 ng/ml 
if the measurement was made prior to stopping T4. 
The third patient, M, who did not show constant spe- 
cific activity had a Tg level of 2200 ng/ml at the time 
first treatment. The patient came for successive treatment 
six months after therapy and the Tg level was 1140 ng/ 
ml. This is in accordance with the observed decline in 
specific activity. 
1 1 1 I 1 1  
5 7  9 II 13 14 
Days after radioiodine therapy 
FIG. 4. Synthesis of Tg after radioiodine therapy. Amount of Tg 
entering the circulation between 5th and 14th day is shown by a shaded 
area between the two curves, radioiodinated Tg (X)  and stable Tg (0). 
As far as the new synthesis of Tg is concerned, it is 
adequate if serial determination of stable Tg in circulation 
is made. However, it would be difficult to assess the num- 
ber of samples to be collected, as it is not possible to set 
up the assay for Tg immediately after the collection of 
sample because of the presence of radioiodine in serum. 
I t  is, therefore, desirable to determine the disappearance 
of radioiodinated Tg as a guideline for collecting the 
number of samples. 
In conclusion, the specific activity determination may 
therefore serve as a guideline of effectiveness of therapy. 
The data on six patients is limited: nonetheless one can 
classify the patients into two groups on the basis of specific 
activity: patient should be called at the earliest possible 
day for the next therapy, and the patient may be kept 
safely on thyroxine for a prolonged period of time with 
a regular checking of circulating Tg. 
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3. Schlossberg AH,  Jacobson JC, lbbertson HK. Serum thyroglobulin 
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Synthesis of thyroglobulin in thyroid carcinoma patients after radioiodine therapy

Indian Academy of Sciences

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Synthesis of thyroglobulin in thyroid carcinoma patients after radioiodine therapy

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