the unexposed group does tend to support the results of the statistical analysis using data from Olmsted County. Prolactin Survey.—Serum prolactin levels were determined on nonfasting blood specimens obtained in 1982 from 174 of the 178 remaining persons with a history of radiation exposure in 1954. (Prolactin radioimmunoassays were performedin the laboratory of P. R. Larsen, MD, Brigham and Women’s Hospital, Boston.) The mean prolactin level plus or minus 2 SDs was 6.9+11.8 ng/mL for men and, after exclusion of values obtained during pregnancyor lactation, 9.0+12.8 ng/mL for women. Seven persons had levels exceeding 2 SDs of the mean; six were not elevated when rechecked on a subsequent sample. One persistent and unexplained elevation (serum prolactin level, 42 ng/ mL) was discovered in an asymptomatic but childless 82-year-old woman. Skull roentgenograms showed a normal sella turcica. Because (1) there was no evidence of a masslesion (including the findings of an ophthalmologist’s examination), (2) prolactin elevation was minimal, and (3) the patient was of an advanced age, further evaluation was not carried out.It is not certain, therefore, that she has a pituitary tumor. Comment Subclinical tumors of the pituitary gland are common, being found in up to 27% of consecutive necropsies.*’ Nevertheless, clinically diagnosed tumors are infrequent, although CT and newer assays for pituitary hormones, especially prolactin, may be increasing the frequency of the diagnosis.’° The reason for the apparent increase in relative risk of clinically significant pituitary tumors in radiationexposed Marshallese is unknown. Sixteen percent of the more heavily exposed Rongelap-Ailingnae population have had subclinial thyroid hypofunction develop.’ The possibility of an endocrine “domino” effect is suggested by human and animal data indicating that dysfunction and hyperplasia-adenoma formationof pituitary cells can result from thyroid hypofunction."” In addition, hypothyroidism is sometimes associated with hyperprolactinemia or galactorrhea or both.’ Hypothyroidism in ated with an increase in pituitary tumors in humans. Furthermore, our two patients were clinically and biochemically euthyroid when tested in the years preceding their diagnoses (see Table 1 for exceptions), although subclinical thyroid hypofunction in the early years after fallout exposure cannot be excluded because sensitive thyroid-stimulating hormone assays were unavailable at that time. External gamma irradiation of experimental animals has produced pituitary tumors.'* There have been no prior reports implicating the same mechanism in humans. Noincrease in incidence of pituitary tumors has been noted among survivors of the atomic bombings in Japan or among children who received cranial radiation, although the incidence of other intracranial tumors is elevated.'*” Internally deposited, short-lived radioisotopes of iodine are considered the cause of the high incidence of thyroid neoplasia in the exposed Marshallese, but there is no equivalent concentration of fallout nuclides that mightlead to a high absorbed dose in the human pituitary. Nevertheless, pituitary tumors have been found in offspring of pregnant mice intravenously injected with strontium 90 and in rats given intraperitoneal injections of strontium 90 or cerium 144,°” and orally administered yttrium 90 concentrates in the pituitary of guinea pigs.” While the relevance to humans of such animal research is clearly important, differences in species responses and circumstances of exposure do not permit the inference of a causal association between the radiation received by the subjects of this report and subsequent pituitary neoplasia. In conclusion, the development of two pituitary tumorsin this relatively small population may be evidence that certain types of radiation can induce pituitary neoplasia in humans. The link is not a strong one, however, being a statistical phenomenon unassociated with a knownbiologic basis. Jacob Robbins, MD, and D. Lynn Loriaux, MD, gave permission to use clinical data on their patients, and Paul E. McKeever, MD, provided the photograph and histologic interpretation of the prolactinoma in case 2. Geraldine Callister provided secretarial services, and William A. Scott and Peter M. Heotis provided the administrative management of patients and data. Claire J. Shellabarger, PhD, reviewed the manuscript. ca es Ce gu | QF +i JAMA, Aug 3, 1984—Vol 252, No. 5 fs, 666 general, however, has not been associ- Printed and Published in the United States of America References 1. Conard RA, Paglia DE, Larsen PR, et al: Review of Medical Findings in a Marshallese Population 26 Years After Accidental Exposure to Radioactive Fallout, Brookhaven National Laboratory report 51261. Upton, NY, Brookhaven National Laboratory, 1980. 2. Lessard E, Miltonberger R, Cohn S, et al: Exposure to fallout: The radiation dose experi- ence at Rongelap and Utirik atolls, Brookhaven National Laboratory abstract 32510. Presented at the Seventh International Congress of Radiation Research, Amsterdam, July 3-8, 1983. 3. 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