42
ectomy in the rat has been reported to cause ade-
nomaformation in the remaining thyroidtissue 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_underthe influence of TSH
first undergoes diffuse hyperplasia and hyper-
trophy and adenomaformation. In the cases of
iodine deficiency and partial thyroidectomy, it is
probabie that no drugor carcinogenic agentis in-
volved. The incidence of carcinomasafter a com-
bination of carcinogenic agents (such as radiation
or acetylaminofluorene) and any factor that causes
hypothyroidism is much higher.** Radiation by
either x rays or '*'I is particularly effective, since
it simultaneously acts as a carcinogen and,by im-
pairing the functional capacity of the gland, in-
duces TSH secretion and thyroid stimulation.
The high incidence of adenomatousgoiters 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, leaveslittle doubt aboutthe etiological relationship of these lesions with irradiation exposure. The higher incidence in children maybe re-
lated to increased sensitivity of the child’s thyroid
to irradiation butis probably related more directly
to the relative magnitudesof 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 considerseri-
ously radiation exposureas the etiological factor.
In Appendix 7 statistics on thyroid malignancies
in the Marshall Islands and the Trust Territory
are presented. A low incidence ofsolitary nodules
was noted in older (>50 years of age) unexposed
Marshallese of both Rongelap and Utirik Islands.
Thesingle nodule case in the less exposed 46-year-
old 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 adequate. 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.
Thesensitivity of children’s thyroid glands to
the development of neoplastic changes from radia-
tion 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
changesin the glands of the Marshallese may be
related to a greater dose ofradiation received by
their thyroid glands. Lesions similar to those seen
in the Marshallese have been reported in children
5 to 11 years old after treatment with '*'T for
thyrotoxicosis.**:** Doniach** points out that cell
division in the growing thyroid glandof the child
may bea factor in the increased sensitivity to irradiation. There appears to be an increased incidence of 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 assumedthat theslight growth re-
tardation 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 developmentof hypothyroidism in two of the most growth-.
retarded boys and evidence of mild hypothyroidism in several other children with thyroid nodules
and growth retardation, a hypothyroid etiology
seems mostlikely. Elevated TSH levels indicate
that the hypothyroidism is primary. Minimal
hypofunction of the gland may have been missed
in the past, since the apparently normal PBTlevels
may have been spuriously high, the true thyroxine
level being masked by the elevated iodoprotein
component characteristic of the Marshallese.
*in March 1966, twocases of goiter with large, nodular glands
were seen at the Majuro Hospital. One may have had mild hyperthyroidism. These cases were not part of the population under
study.