_ in the older group appears to be in
line with this reasoning. The cases
of two stunted Marshallese boys
who showed almost complete atrophy of their thyroid glands with no
evidence of nodular development
are probably comparable to those

cases of hypothyroidism developing
in patients years after receiving
radioactive iodine therapy. It should
be pointed out that the thyroid exposures in the Rongelapese were
slightly different from patients
treated with '*'I because their thyroids were not hyperplastic when
exposed and at least part of the
radioactive iodine isotopes to which ©
they were exposed were of shorter
half life than '*'I. In addition their
exposure was complicated by gamma radiation.
There were some factors secondary to radiation exposure’ that

might have enhanced the develop-

ment of thyroid lesions in the Marshallese. Iodine deficiency or presence of goitrogens in the diet did
not appear to be among these. However, the physiological stresses. of
puberty and pregnancy may have
played a role in the development of
the lesions. For instance the development of ten cases of nodular
goiter in the children during or near
the time of puberty might indicate
that this stress may have enhanced
nodular development. In three women who developed thyroid nodules
later the demand of multiple pregnancies may have been related.

However, since the latent period

between exposure and nodule discovery varied only between 10 and
13 years it may be argued that development of thyroid nodules was
independent of these stresses. On
the other hand it is noteworthy that
all of the women who developed
malignant thyroid lesions had multiple pregnancies prior to the appearance of such neoplasms.
The development of thyroid nodules in the Marshallese showed
only a slight preponderance in favor
324

of the women (1.3 to 1.0). This is
similar to the near equal sex ratio
reported by Toyooka et al’* for thyroid nodules developing in persons
irradiated over the neck region in
infancy. However, in the case of
carcinoma of the thyroid the expected female preponderance occurred.*
The insidious development of
growth retardation in some of the
Marshallese children before clinical
evidence of thyroid abnormality or
deficiency was recognized demonstrates the apparent sensitivity of
growth and developmental proces-

ses to borderline or subclinical thy-

Med 66:1214-1242, 1967.
3. Sutow WW, Conard RA, Griffith KM:

Growth status of children exposed to fallout radiation on Marshall Islands. Pedtatrics 36:721-731, 1965,

4 Rall JE, Conard RA: Elevation of

serum protein-bound iodine level in inhabitants of Marshall Islands. Amer J Med

40:883-886, 1966.
& Sloan LW, Frantz VK: Thyroid can-

cer: Clinical aspects, In Werner SC (ed):
The Thyroid, ed 2. New York, Harper &

Row, Publishers Inc, 1962, pp 445-468.

6. Maloof F, Dobyns BM, Vicery A:
The effects of various doses of radioactive
iodine on the function and structure of the
thyroid of the rat. Endocrinology 50:612-

638, 1952.
7. Doniach I: Comparison of carcinogenic effect of x-irradiation with radioactive iodine on rat's thyroid. Brit J
Cancer 11:67-76, 1957.

roid deficiency. All possible steps
8. Lindsay S, Chaikoff IL: Effects of irradiation on thyroid gland with particular
are being taken so that the children
reference to induction of thyroid neowill adhere to the present thyroid
plasias: Review. Cancer Res 24:1099-1107.
treatment schedule so that they will
1964.
9. Sheline GE, Lindsay S, McCormack
achieve satisfactory growth and .
KR, et al: Thyroid nodules occurring late
maturation.
after treatment of thyrotoxicosis with radioCareful medical surveillance of
iodine. J Clin Endocr 22:3-18, 1962.
10. Hollingsworth DR, Hamilton HB.
these exposed people including
Tamagaki H, et al: Thyroid disease: A
those on Utirik will be essential in
study in Hiroshima, Japan. Medicine 42:
future years. The latent period for
47-71, 1963.
1L Pincus RA, Reichlin S, Hempe!the development of cancer was 7
mann LH: Thyreid abnormalities after
years in one case and 14 and 15
radiation exposure in infancy. Anan Intern
years in the other two. The fact
Med @8:1154-1164, 1967.
12. Tayooka ET, Pifer JW, Hempelthat there may be a longer latent
mann LH: Neoplasms in children treated
period for the induction of maligwith x-rays for thymic enlargement: III.
nant change is borne out by a reClinical description of cases. J Nat Cancer
Inat 31:1379-1405, 1963.
port by Goolden who noted the
13. Hempelmann LH: Risk of thyroid
development of thyroid cancer 40
deoplaams after irradiation in childhood.
years after radiation exposure.** It
Science 160:159-163, 1969.
14 Silver S: Radioactive Isotopes in
may be that we are just reaching
Medicine and Biology, ed 2. Philadelphia.
the critical period in the postradiaLea & Febiger, 1962, pp 138-148.
tion observations.
1& Upton AC: The dose-response relation im radiation-induced cancer. Cancer

This investigation was supported by the

US Atomic Energy Commission.
Keith Thompson, MS, assisted in carrying out statistical analyses.
CAPT Carl A. Broaddus, Jr., MC, USN;
Bentley P. Colcock, MD; and Brown M.
Dobyns, MD, performed the thyroid operations.
References

1. Conard RA, Rall JE, Sutow WW:
Thyroid nodules as a late sequela of radioactive fallout in a Marshal] Island population exposed in 1954. New Eng J Med 274:
1392-1399, 1966.
2. Robbins J, Rall JE, Conard RA: Late
effect of radioactive iodine in fallout: Combined clinical staff conference at the Na-

JAMA, Oct 12, 1970 # Volt 214, No 2

9017814

tional Institutes of Health. Ann intern

Printed and Published in the United States of America

Res 21:717-729, 1961.

16 Shellabarger CJ, Bond VP, Cronkite
EP: Studies on radiation-induced mammary gland neoplasia in the rat: VII. The
effects of fractionation and protraction of
sublethal total-body irradiaton. Radiat Res

17:101-169, 1962.

17. Marks S, Bustad LK: Thyroid neoplasms in sheep fed radioiodine. J Nat
Caneer Inst 30:661-673, 1963.
18 Goolden AWG: Carcinoma of the
thyraid following irradiation. Brit Med J
2:954-965, 1958.
.

Thyroid Neopiasia—Conard et al

Select target paragraph3