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subjects. In others, there appeared to be
partial destruction with the result that
TSH secretion was increased;
and
the
glands, although maintaining normal oral-
most normal hormone production, were
operating at their maximal ability. They
could not respond to further TSH stimulation. The possible relationship between
this state of affairs and the formation of
thyroid nodules will be considered in the
next discussion.
RADIATION EFrects on THE Toyrow GLAND
The foregoing presentation has clearly
shown radiation of the thyroid gland by
isotopes of radioiodine to be a major feature of the late results of exposure to radioactive fallout. I shall now discuss the subject of thyroid radiation. This subject takes
on practical importance in the etiology of
certain thyroid tumors and in theclinical
use of iodine isotopes for diagnosis and
therapy of thyroid diseases. Roughly during
the period over which the Marshall Island
observations have extended and to some
extent before that time, a considerable
number of experimental andclinical observations on this problem have been published and have been the subject of several
reviews, notably by Doniach (19) and by
Lindsay and Chaikoff (20). This work has
led to at least a general understanding of
radiation-induced thyroid abnormality.
As demonstrated by the Marshall Islanders, the abnormalities fall into two cate-
gories—one related to interference with
thyroid cell function and the other concerned with the development of neoplastic
changes. The Marshall Island findings also
demonstrate very well the interplay between these two radiation effects.
In clinical practice, one of the major uses
of radioiodine is to produce destruction of
thyroid tissue—either the normal gland in
patients with intractable angina pectoris,
the hyperplastic gland in hyperthyroidism,
or neoplastic tissue in metastasizing thyroid
carcinoma. Since retention of iodine in the
Internal Medicine
thyroid gland is unique among mammalian
tissues, complete destruction can be readily
attained by administering a suitably large
dose of the isotope. This is achieved with
a dose delivering about 50,000 to 75,000
rads. The thyroid tissue is then subject to
acute radiation injury, with subsequent in-
flammation, tissue destruction, and fibrotic
healing. This is the desired end result in
heart disease and in thyroid carcinoma. In
hyperthyroidism, however, the usual aim is
to leave the patient with sufficient thyroid
function to achieve euthyroidism. By properly adjusting the isotope dosage, this aim
can be achieved in a high percentage of
patients given about 10,000 rads to the
gland.
Studies of these patients after partial thyroid destruction have led to some interesting observations. Injury to the various
thyroid metabolic processes may not be uniform. Thus, in some of the patients the
accumulation of radioiodine by the thyroid
gland remains greater than normal although hormonesecretion falls to normal
or below. This is due to an injury to the
iodine organification mechanism exceeding
that to the iodide transport system (17, 18).
As discussed earlier, the trapped but nonorganified iodine can be demonstrated by
discharging it with an ion such as perchlorate, which competes with iodide for
membrane transport. Other examples of uneven metabolic injury have not been described but probably exist.
On the other hand, thyroid function with
respect to iodine metabolism and hormone
production may appear to be normal in
every respect, although the cell is gravely
injured. This phenomenon has aroused
considerable interest in recent years because
only long after successful radiotherapy does
this injury become manifest by the late
onset of hypothyroidism (21, 22). One possible explanation for this phenomenon is
that the radiation has led to lethal mutations in the chromosomes of the thyroid
epithelial cells without damageto the rela-
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