NATIONAL INSTITUTES OF HEALTH CLINICAL STAFF
case in these children, who had enlarged
clinically to be solitary thyroid nodules in
thyroid glands when treated, and it may be
these children. That is the problem of
that the nodule formation was induced in
radiation-induced thyroid carcinoma. Two
sorts of evidence have led to the clear dem-
the children by whatever stimulus there is
that causes the thyroid to grow to its adult
size. Radiation injury in general may be
onstration that irradiation is a contribut-
ing cause in the development of thyroid
expressed as the product of the degree of
cell damage times the mitosis rate of the
cancer. Although thyroid cancer can be
produced in animals simply by prolonged
thyroid stimulation resulting from iodine
cells (26), and the child’s thyroid grows
from about 2 g at age | year to 17 g in the
deficiency or chronic administration of antithyroid drugs (29), there is abundant ex-
adult (27).
The role of thyroid stimulation by TSH
in the nodule formation after irradiation
is clearly indicated by the findings of Maloof (28). In rats treated with 1], hypo- physectomy or treatment with thyroxine
prevented the cellular hypertrophy that
was otherwise observed. It was of considerable interest that this treatment also
greatly reduced the development of abnormalities in the thyroid cell nuclei (characterized by increase insize, irregularity, and hy-
perchromatism), thus indicating that these
changes were dueto cell stimulation rather
than to irradiation per se. When thyroxine
therapy was stopped, the lesions reappeared. This underscores the fact that thyroid radiation not producing obvious atrophy, inflammation, and fibrosis does not
appear to cause any specific cell abnormality recognizable by ordinary histological examination.
Last, I shall discuss the subject that was
uppermost in the minds of those who ob-
perimental
Treatment
that
the
roid irradiation (19, 20) just as it is by con-
comitant treatment with a carcinogen such
as acetaminofluorene (19, 29). As demonstrated by the experiments of Doniach (19),
summarized in Table 11], the effect of 30 pc
of 152] 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
Island children were exposed. It is of interest, also, that the radiation in Doniach’s
rats increased the prevalence of multinodularity of the thyroid glands in response to
maining in the operated cases, as well as in
those not operated upon, unless this is prevented by the administration of suppressive doses of thyroid hormone. The ability
Induction of Thyroid Tumors in Rats*
Rats
With
Adenomas
+
41
30 uc @I + MTU
1,100 rads X rays to thyroid
48
13
1,100 rads X rays + MTU
to show
goitrogen.
The failure to find thyroid carcinoma in
any of the Marshallese children can beattributed, it seems, to a happy chance. There
remains a high likelihood that carcinoma
would develop in the thyroid remnants re-
None
Methylthiouracil (MTU)
30 xc I (1,500 rads to thyroid)
evidence
prevalence is increased by antecedent thy-
served the development of what appeared
TABLE 11.
Internal ‘Medicine
no.
0
50
52
39
21
22
21
* From Doniach, I: Brit. Med. Bull. 14: 181, 1958 (19).
With
Adenomatous
Replacement
47
4
With
Carcinomas
—
0
0
_ 27
1
11
1
0
0
17
0
0
7
Paap men eaethe
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