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NATIONAL INSTITUTES OF: HEALTH CLINICAL STAFF
ma
case in these children, who had enlarged
thyroid glands when treated, and it may be
.
*
=
Annals of
Internal Medicine
The role of thyroid stimulation by TSH
clinically to be solitary thyroid nodules in
these children. That is the problem of
radiation-induced thyroid carcinoma. Two
sorts of evidence have led to the clear demonstration that irradiation is a contributing cause in the development of thyroid
cancer. Although thyroid cancer can be
produced in animals simply by prolonged
thyroid stimulation resulting from iodine
deficiency or chronic administration of antithyroid drugs (29), there is abundant experimental evidence to show that the
prevented the cellular hypertrophy that
roid irradiation (19, 20) just as it is by concomitant treatment with a carcinogen such
as acetaminofluorene (19, 29). As demonstrated by the experiments of Dontach (19),
that the nodule formation was induced in
the children by whatever stimulus there is
that causes the thyroid to growto its adult
size. Radiation injury in general may be
expressed as the product of the degree of
cell damage times the mitosis rate of the
cells (26), and the child’s thyroid grows
from about 2 g at age | year to 17 g in the
adult (27).
in the nodule formation after irradiation
is clearly indicated by the findings of Maloof (28). In rats treated with 17, hypophysectomy or treatment with thyroxine
prevalence is increased by antecedent thy-
was otherwise observed. It was of considerable interest that this treatment also
greatly reduced the development of abnormalities in the thyroid cell nuclei (character-
summarized in Table 11, the effect of 30 uc
of 181] in the rat is similar to that of 1,100
rads of X-ray radiation. This is in the range
of radiation dosage to which the Marshall
ized by increase in size, irregularity, and hy-
Island children were exposed. It is of interest, also, that the radiation in Doniach’s
perchromatism), thus indicating that these
changes were due to cell stimulation rather
than to irradiation per se. When thyroxine
therapy was stopped,
rats increased the prevalence of multinodularity of the thyroid glands in response to
goitrogen.
the lesions reap-
peared. This underscores the fact that thy-
The failure to find thyroid carcinoma in
any of the Marshallese children can he attributed, it seems, to a happy chance. There
remains a high likelihood that carcinoma
would develop in the thyroid remnants re-
roid radiation not producing obvious atrophy, inflammation, and fibrosis does not
appear to cause any specific cel] abnormality recognizable by ordinary histological examination.
Last, I shall discuss the subject that was
uppermost in the minds of those who observed the development of what appeared
TABLE 11.
maining in the operated cases, as well as in
those not operated upon, unless this is prevented by the administration of suppres-
sive doses of thyroid hormone. The ability
Induction of Thyroid Tumors in Rats*
Treatment
Rats
None
Methylthiouracil (MTU)
30 we IT (1,500 rads to thyroid)
30 pe MII + MTU
1,100 rads X rays to thyroid
41
50
52
48
13
With
Adenomas
With
Adenomatous
Replacement
With
Carcinomas
“10.
22
* From Doniach, I: Bret. Med. Bull. 14: 181, 1958 (19).
3G4}2840
21
0
0
0
27
I
17
0
0)
0
11
1
7
Te ee FFee ee
1,100 rads X rays + MTU
0
39
21
47
4