Acquired von Willebrand disease in twins with autoimmune hypothyroidism: response to desmopressin and L-thyroxine therapy.

Because of menorrhagia, a 13-year-old girl was found to have type I von Willebrand disease and then chronic autoimmune thyroiditis with hypothyroidism. All clinical and laboratory evidence of von Willebrand disease resolved transiently after infusion of desmopressin, and permanently with L-thyroxine therapy. We recommend investigation for hypothyroidism in patients with newly diagnosed acquired von Willebrand disease.

A cohort study of thyroid disease in relation to fallout from nuclear weapons testing.

OBJECTIVE: To estimate individual radiation doses and current thyroid disease status for a previously identified cohort of 4818 schoolchildren potentially exposed to fallout from detonations of nuclear devices at the Nevada Test Site between 1951 and 1958. DESIGN: Cohort analytic study. SETTING: Communities in southwestern Utah, southeastern Nevada, and southeastern Arizona. PARTICIPANTS: Individuals who were still residing in the three-state area (n = 3122) were reexamined in 1985 and 1986, and information on the subjects' and their mothers' milk and vegetable consumption during the fallout period was obtained by telephone interview (n = 3545). After exclusions to eliminate missing data and confounding factors, 2473 subjects were available for analysis. MAIN OUTCOME MEASURES: Individual radiation doses to the thyroid were estimated by combining consumption data with radionuclide deposition rates provided by the US Department of Energy and a survey of milk producers. Relative risk models adjusted for age, sex, and state were fitted using maximum likelihood to period prevalence data for thyroid carcinomas, neoplasms, and nodules. RESULTS: Doses ranged from 0 mGy to 4600 mGy, and averaged 170 mGy in Utah. There was a statistically significant excess of thyroid neoplasms (benign and malignant; n = 19), with an increase in excess relative risk of 0.7% per milligray. A relative risk for thyroid neoplasms of 3.4 was observed among 169 subjects exposed to doses greater than 400 mGy. Positive but nonsignificant dose-response slopes were found for carcinomas and nodules. CONCLUSIONS: Exposure to Nevada Test Site-generated radioiodines was associated with an excess of thyroid neoplasms. The conclusions are limited by the small number of exposed individuals and the low incidence of thyroid neoplasms.

Natural history of thyroid abnormalities: prevalence, incidence, and regression of thyroid diseases in adolescents and young adults.

PURPOSE: This study reports the prevalence, incidence, and regression of thyroid abnormalities in a population observed from adolescence to adulthood. PATIENTS AND METHODS: Examinations for thyroid abnormalities were performed in 4,819 school-age children, ages 11 to 18, in 1965 to 1968; two thirds of this original cohort (3,121) were re-examined 20 years later (1985 to 1986). Each subject with a thyroid abnormality detected by physical examination was studied by means of a series of re-examinations, and tests of thyroid function, imaging, and biopsy to determine the exact nature of the thyroid abnormality. RESULTS: In the initial examinations (1965 to 1968), 185 thyroid abnormalities were found (3.7%). Diffuse hypertrophy with normal function (adolescent goiter) was the most common abnormality (19.3/1,000); 12.7/1,000 had chronic lymphocytic thyroiditis, and 4.6/1,000 had thyroid nodules, including two papillary carcinomas. Hyperthyroidism or hypothyroidism was found in 1.9/1,000. In the follow-up examinations in 1985 to 1986, 298 subjects had thyroid abnormalities (10.5%), of whom 81 (28.7/1,000) had simple goiters, 145 (51.3/1,000) had chronic thyroiditis, 45 (15.9/1,000) had hypothyroidism, 11 (3.9/1,000) had hyperthyroidism, and 66 (23.2/1,000) had nodules, which included 10 carcinomas. Of the 92 subjects with simple or adolescent goiter in 1965 to 1968, 60% were normal by 1985 to 1986, 20% were unchanged, and a few had developed thyroiditis (10%) or colloid goiters (3.0%). Of 61 subjects with thyroiditis, 27% had become normal, 33% remained unchanged, and 33% had become hypothyroid. Of the 22 subjects with thyroid nodules, two had complete disappearance of the nodules, and three had nodules considered to be variants of normal. The others exhibited a variety of nodular pathologic conditions. CONCLUSIONS: The natural history of thyroid disorders, including simple goiter, chronic thyroiditis, hyperthyroidism, hypothyroidism, and nodular diseases of the thyroid, indicates they are dynamic and changeable in form, function, appearance, and disappearance.

Development of a method to estimate thyroid dose from fallout radioiodine in a cohort study.

A cohort of 4831 persons aged 11-18 y in 1965 was identified among students in the schools of Washington County, UT; Lincoln County, NV; and Graham County, AZ. These children who had potentially been exposed to radioiodine from atomic weapons test fallout from the Nevada Test Site during 1951-1962 were selected for participation in a study of thyroid disease. The entire cohort was first examined during 1965-1968 for thyroid abnormalities. A total of 3,085 of these people were again reexamined during 1985-1986 to determine any subsequent occurrence of thyroid disease. In order to determine the relationship of the radiation dose to the thyroid with incidence of thyroid disease, we have developed a suite of models to calculate estimates of the internal dose received by the thyroid from fallout radioiodines. For completeness, the exposure to the thyroid from external radiation is also estimated. Dose estimates are made specific to each individual in the study using individual residential histories, the locality-specific exposure rate and radionuclide deposition, descriptions of dairy management for identified milk producers, and the subjects' sources of foods and intake rates of milk and leafy vegetables determined by interview. Other data such as the relationship of radioiodine deposition to measured exposure rate, environmental transfer parameters, and age-dependent factors for the conversion of radioiodine intake to thyroid dose were taken from work of other investigators. Dairy management information, milk distribution practices, the milk source for each study subject, as well as age-specific intake rates of milk and leafy vegetables, were determined by interview.

Cohort study of thyroid disease near the Nevada Test Site: a preliminary report.

The atmospheric testing of nuclear weapons in Nevada beginning in 1951 resulted in exposure of regions surrounding the Nevada Test Site (NTS) to fallout. A cohort of children born between 1947 and 1954 in two counties near the NTS, one in Utah and one in Nevada (UT/NV), were examined in 1965-1968 for thyroid abnormalities that might have been a result of exposure to radioiodine in fallout. The prevalence of thyroid abnormalities in these children (11-18 y) was compared to that in a control group selected from a county in Arizona (AZ) that was presumed to have received little or no fallout from the NTS. Thyroid nodules were found in 76 of the 4,819 children examined (15.8/1000). Of the 76 thyroid nodules, 22 were diagnosed as neoplasms. The rate of thyroid neoplasms among the UT/NV subjects was higher (5.6/1000) than among the AZ subjects (3.3/1000) (RR = 1.7), but because the number of neoplasms was small, the difference was statistically insignificant. In 1985-1986, 3,122 of the original study subjects were reexamined. In this reexamination, thyroid nodules were found in 125 individuals (44.2/1000). Of the 125 thyroid nodules detected during this later study period, 65 were considered to be thyroid neoplasms. Rates of thyroid neoplasms in UT/NV (24.6/1000) are again slightly higher than in AZ (20.2/1000) (RR = 1.2), but the difference is not significant (p = 0.65). Based on the rates of thyroid neoplasms in the two geographic locations, we conclude that living near the NTS in the 1950s has not resulted in a statistically significant increase of thyroid neoplasms in subjects from UT/NV when compared with subjects of the same age and gender living in AZ.

High-carbohydrate, high-fiber diet in children with type I diabetes mellitus.

The effects of a high-carbohydrate, high-fiber (HCHF) diet on glucose control was evaluated in 12 children with type I diabetes mellitus. The children had had diabetes for an average of 5.25 yr; their mean glycosylated hemoglobin was 12.4% (normal 5-9%), and C-peptide was virtually undetectable in all but one. They were followed on a regular diabetic diet for 10 days at home and in the hospital and then were studied on a HCHF diet for 14 days. The HCHF diet contained 60% carbohydrate and 30 g of fiber per 1000 cal provided through grains, fruits, vegetables, and high-fiber crackers. Capillary blood glucose levels were monitored at home before meals and at bedtime, and venous plasma glucose levels were measured in the hospital before and after each meal and during the night. Plasma glucose was measured serially after test meals with each diet. There was no significant difference in blood glucose levels preprandially, postprandially, and while fasting on the two diets. The 24-h glucose profiles and posttest meal profiles obtained during both diets were remarkably similar. We conclude that a diet high in fiber and carbohydrate has limited application in children with type I diabetes mellitus who have no residual beta-cell function.

Familial hyperphosphatasemia: diagnosis in early infancy and response to human thyrocalcitonin therapy.

Familial hyperphosphatasemia is an uncommon hereditary disorder of membranous bone with concurrent overproduction and overdestruction of bone and bone collagen by osteocytes. This process does not allow normal maturation into compact lamellar bone. Two cases of severely affected children are presented which demonstrate that the condition can be diagnosed in early infancy by abnormalities in the long bones. At this stage the skull may appear normal and the characteristic thickening of the calvarium appears later. The disease is treatable with human thyrocalcitonin; these and previously reported cases have responded favorably.

Thyroid nodularity in children.

Of 5,179 school children surveyed in Utah, Nevada, and Arizona for thyroid abnormalities because of possible exposure to radiation from fallout, nodularity of the thyroid was found in 98 (1.8%). In 34, the nodularity represented lobulation associated with adolescent goiter, and in 31, thyroiditis. Two malignant neoplasms were found. In a normal childhood population in which nodularity is incidentally discovered on physical examination, the risk of nodularity being malignant is approximately 2%. Factors that favor exploration of thyroid nodules in children are discreteness, growth of the mass, singleness, and absence of other thyroid disease.

Occurrence and natural history of chronic lymphocytic thyroiditis in childhood.

In a six-year survey of 5,179 school children in Arizona, Utah, and Nevada 62 cases of chronic lymphocytic thyroiditis were identified giving a prevalence of 1.2%. Thyroids were enlarged in 85%, firm in 60%, and had an irregular or lobulated surface in 75%. Antibodies to thyroglobulin were demonstrable in the serum at some time during the course of the disease in 76% by the tanned red blood cell technique and in 93% by radioimmunoassay. Serum TSH concentrations were elevated in seven of 15 subjects. Many of the cases were early or mild thyroiditis and, in most instances, subjects were asymptomatic and considered clinically euthyroid. Two subjects were hypothyroid, and two appeared clinically hyperthyroid. Spontaneous resolution of thyroiditis occurred in 15 of 32 individuals who received no treatment. Resolution occurred in 14 of 30 children treated with thyroid hormone supplement. The results suggest that lymphocytic thyroiditis in children may be present without symptoms and in many is a self-limiting disorder from which complete recovery occurs spontaneously.