42
ectomy in the rat has been reported to cause adenoma formation in the remaining thyroid tissue 2

years later.**-°’ All these procedures produce hypothyroidism which serves as an effective stimulant

to the secretion of TSH by the pituitary gland.
The thyroid gland under the influence of TSH
first undergoes diffuse hyperplasia and hvpertrophy and adenoma formation. In the cases of
iodine deficiency and partial thyroidectomy, it is
probable that no drug or carcinogenic agent ts in-

volved. The incidence of carcinomasafter a combination of carcinogenic agents (such as radiation

or acetylaminofluorene) and anyfactor that causes
hypothyroidism is much higher.** Radiation by

either x rays or **'T is particularly effective, since
it simultaneously acts as a carcinogen and, by impairing the functional capacity of the gland, induces TSHsecretion and thyroid stimulation.
The high incidence of adenomatous goiters and
hypothyroidism in the more heavily irradiated
children exposed at <10 years of age, compared
with no abnormalies in some 100 children in the
same age rangein the less exposed and unexposed
groups, leaves little doubt about the etiological relationship of these lesions with irradiation exposure. The higher incidence in children maybe related to increased sensitivity of the child’s thyroid
to irradiation butis probably related more directly
to the relative magnitudes of the radiation doses
received, the small child’s gland probably having
received 5 to 10 times the radiation dose received
by the adult’s gland. Since most of these lesions
appeared in teen-age children, puberty may have
been a contributing factor. The incidenceof the
lesions in female childrenis only slightly greater
than in male children (1.27 to 1). A greater prevalence of thyroid abnormalities in that sex is correctly noted. The increased incidence of thyroid
abnormalities, including one case of malignancy,

in the adults of the more heavily exposed Rongelap population makes it necessary to considerseriously radiation exposure as the etiological factor.
In Appendix 7 statistics on thyroid malignancies
in the Marshall Islands and the Trust Territory
are presented. A low incidenceofsolitary nodules
was noted in older (>>50 years of age) unexposed
Marshallese of both Rongelap and Utirik Islands.
The single nodule case in the less exposed 46-yearold Ailingnae woman, on the other hand, may

well fall into the category of the sporadic type,

since the nodule was well encapsulated, and the

remainderof the thyroid gland appeared normal.

Urine analyses indicate that iodine intake is ade-

quate. The incidence of nodules and sporadic
cases of goiter seen at the Majuro Hospital* is low,
and the Marshallese population showsno evidence
for goitrogenic factors in their environment.
The sensitivity of children’s thyroid giands to
the development of neoplastic changes from radiation exposure has been amply demonstrated. A
series of retrospective and prospective studies have
clearly shown the causalrelation of irradiation of
the neck region in infants and later development
of thyroid cancer.°?-** Althoughthe calculation of
the dosage in the Marshallese is subject to large
uncertainties, the greater incidence of pathological
changes in the glands of the Marshallese mav be
related to a greater dose of radiation received by
their thyroid glands. Lesions similar to those seen
in the Marshallese have been reported in children
3 to 11 years old after treatment with **'I for

thyrotoxicosis.**°* Doniach** points out thatcell
division in the growing thyroid gland ofthe child
may bea factor in the increased sensitivityto irradiation. There appears to be an increasedincidenceof thyroid carcinoma in inhabitants of Hiroshima and Nagasaki exposed to radiation from the
atomic bomb explosions.** These people were exposed to varying doses of external radiation to the
thyroid gland but not to internal exposure from
radioiodine.
It has been assumed thatthe slight growth retardation previously noted in someof the exposed
children was due to radiation, but the mechanism
has been obscure. The growth hormonestudies

suggested that pituitary function was normal. X
rays of the sella turcica showed no evidence of
pituitary abnormality. With the recent development of hypothyroidism in two of the most growthretarded boys and evidence of mild hypothyroidism in several other children with thyroid nodules
and growthretardation, a hypothyroid etiology
seems most likely. Elevated TSH lteveis indicate
that the hypothyroidism is primary. Minimal
hypofunction of the gland may have been missed
in the past, since the apparently normal PBI levels
may have been spuriously high, the true thyroxine
level being masked by the elevated iodoprotein
componentcharacteristic of the Marshallese.
*In March 1966, two cases of goiter with large, nodular glands
were seen at the Majuro Hospital. One may have had mild hy-

perthyroidism. These cases were not part of the populauon under
study.

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