Racial differences in metabolic control of children and adolescents with type I diabetes mellitus.

OBJECTIVE: This study evaluated racial differences in the metabolic control of children and adolescents with insulin-dependent (type I) diabetes mellitus and examined the interactive effects of race with age and sex. RESEARCH DESIGN AND METHODS: Data on several demographic and clinical variables were obtained for 102 black and 108 white children, including the percentage of total HbA1, age, age at diagnosis, duration of diabetes, pubertal status, insulin dose (U.kg-1.day-1), body mass index, number of clinic visits kept and missed, number of hospitalizations for diabetic ketoacidosis (DKA) for the year, and socioeconomic status (SES). RESULTS: Black children had higher insulin dosages (P less than 0.05) and lower SESs (P less than 0.001) than white children. HbA1 was higher in black than white children (P less than 0.01) after statistically adjusting for the effects of insulin dose, diabetes duration, and SES. With HbA1-based criteria, more black than white children were in poor and fewer in good metabolic control (P less than 0.001). Older children (greater than or equal to 13 yr) had higher HbA1 levels than younger (less than 13 yr) children (P less than 0.002), but there were no differences in HbA1 between males and females nor were there interactive effects of race, sex, and age-group. Black children were hospitalized for DKA more frequently than white children (P less than 0.04). More black than white children missed clinic visits (P less than 0.01), but they did not differ in number of visits kept. CONCLUSIONS: Black youths with type I diabetes mellitus are in poorer metabolic control than white youths.

Androgens in pubertal males with Addison's disease.

The time of onset and progression of pubertal development has been documented in seven male patients with Addison's disease. Two patients developed associated autoimmune problems before puberty and were excluded from further study. The mean age of the onset of puberty among the remaining five patients was 12.3 +/- 0.4 yr, not different than the 11.4 +/- 0.4 yr reported for normal American boys. Integrated plasma levels of testosterone, androstenedione, 17-hydroxyprogesterone, progesterone, and dehydroepiandrosterone were also determined in three Addisonian patients who had no associated autoimmune disease before puberty and their study date. Results were compared with integrated plasma levels from three other groups: four agonadal males, four normal adult males, and three pubertal boys. Integrated plasma levels of these steroids confirm that in a male, testosterone is essentially testicular in origin, dehydroepiandrosterone is mainly adrenal in origin, and androstenedione and 17-hydroxyprogesterone are derived from both sources.

Twenty-four hour integrated concentrations of progesterone, 17-hydroxyprogesterone and cortisol in normal male subjects.

The 24 h integrated concentrations of progesterone, 17-hydroxyprogesterone (17-OHP) and cortisol were determined in 5 male subjects ranging in age from 25 to 36 years. Using a nonthrombogenic catheter and a constant withdrawal pump, blood was collected for a period of 24 h in 30 min aliquots. All five subjects had similar 24 h integrated concentrations of cortisol (9.2 +/- 5.4). One subject had elevated 24 h integrated concentrations of progesterone (55.2 +/- 18.7) and 17-OHP (352 +/- 122) when compared to the mean integrated concentrations (progesterone: 24.9 +/- 4.7; 17-OHP: 109 +/- 33) of the 4 other subjects. The 30 min integrated concentrations showed a diurnal variation for both 17-OHP and cortisol but not for progesterone. The best correlation between cortisol and 17-OHP occurred when the concentration of 17-OHP 90 or 120 min earlier. No significant correlation occurred between cortisol and progesterone.

Usefulness of sex steroid hormone levels in predicting coronary artery disease in men.

The relation between sex hormone levels and subsequent risk of a major coronary event was studied in a nested case-control study among 163 men in the Multiple Risk Factor Intervention Trial who later had a major coronary event and in 163 controls. Cases and controls were matched for age, serum cholesterol level, randomization group, randomization date and clinic. Blood samples were collected at baseline before randomization and frozen at -70 degrees C. Follow-up extended over 6 to 8 years. Sixty-one patients had a nonfatal acute myocardial infarction and 102 fatal infarction. Total and free testosterone, total and free estradiol, androstenedione and estrone concentrations were measured. There were no significant differences between cases and controls for any sex hormone level. There was also no difference in the ratio of testosterone to estradiol. Controlling for other cardiovascular risk factors did not change these results. These results do not support previous case-control studies of a relation between sex hormone levels and risk of heart attack among men.

Relation between plasma high-density lipoprotein cholesterol and sex hormone concentrations in men.

High-density lipoprotein (HDL) cholesterol is inversely associated with risk of heart attack. Sex hormones have been suggested as possible factors contributing to the gender difference of coronary heart disease risk. Little is known about how endogenous sex hormone concentration might be related to HDL cholesterol. The relation was examined in 225 men participating in the Multiple Risk Factor Intervention Trial. Plasma testosterone concentration was positively correlated with HDL cholesterol and the change in testosterone concentration was also positively correlated with change in HDL cholesterol. The relation between testosterone and HDL cholesterol could not be fully explained by age, relative weight, alcohol consumption and cigarette smoking in the cross-sectional study. However, when this relation was examined longitudinally, the partial correlation between changes in testosterone and HDL cholesterol did not quite achieve statistical significance (0.05 less than p less than 0.10). The biologic process that relates HDL cholesterol to testosterone is not known. The results suggest an inverse relation between plasma estradiol concentration and low-density lipoprotein cholesterol, but no statistical significant correlation with HDL cholesterol. In addition, there was no association noted in the current research between estradiol concentrations and the known determinants of HDL cholesterol.

Genetic linkage and HLA association in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Twenty-eight families of patients with congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency were studied to evaluate the specific HLA linkage relationship and HLA antigen association to the 21-OH deficiency gene. Genotype assignment, based on hormonal studies (ACTH stimulation) and HLA genotyping, correlated very well (p less than 0.01) in 23 unaffected sibs of children with 21-OH deficiency further supporting the genetic linkage of the 21-OH deficiency gene to the HLA complex. One family was informative for the placement of the 21-OH deficiency gene outside the HLA complex on the HLA-DR locus side. In this family HLA-A, B, C, DR, MT, MB, and glyoxylase typing and mixed lymphocyte culture was performed. An association of 21-OH deficiency and the HLA-A3 antigen was noted in the 28 families. This association is not secondary to the association of the 21-OH deficiency gene with HLA-BW47.

Epidemiologic studies of menopause: changes in risk factors and disease.

There have been important studies of changes in risk factors and psychosocial variables during peri- and postmenopause. Most of the studies have been done in whites. Studies have clearly documented changes in behavior and biological variables related to menopause. The most critical questions bear on the interrelationships between sex steroid hormone levels, life-styles, including diet, exercise, alcohol consumption, obesity, and changes in key risk factors that are associated with the major causes of morbidity and mortality among postmenopausal women. The best study designs should be longitudinal and include frequent, accurate, and reproducible measurements of biological and psychosocial variables. Importantly, studies should be done in heterogeneous populations. The most critical variables may be measures of the degree of obesity and fatness, diet, and exercise and their relationship to hormonal changes occurring during the peri- and postmenopausal period.

Graves' ophthalmopathy in childhood and adolescence.

Thirty-four patients with childhood Graves' disease were examined to determine the incidence and severity of Graves' ophthalmopathy in children and adolescents. Twenty-three of the 34 patients formed a population of childhood Graves' disease unselected for ocular disease; 11 were unaffected and 12 (52.2%) had findings considered to be of mild functional importance. The remaining 11 patients were referred for evaluation because of a history of Graves' ophthalmopathy; eight (72.7%) exhibited findings of mild severity and three the more meaningful complications of ophthalmoplegia. There were no cases of dysthyroid optic neuropathy or sight-threatening corneal involvement. Both the presence of asymmetric ocular manifestations and increasing severity of disease seem to correlate with increasing age. Although ophthalmoplegia does occur infrequently, Graves' ophthalmopathy in children and adolescents seems to be a substantially more benign process than that seen in adults.

Metrizamide computed tomographic cisternography for the diagnosis of occult lesions of the hypothalamic-hypophyseal axis in children.

In children, hypothalamic-hypophyseal syndromes such as diabetes insipidus, precocious puberty, growth retardation, and panhypopituitarism can be due either to structural lesions or to functional disorders of the cerebral endocrine complex. When clinical and endocrinological parameters fail to distinguish between these etiologies, neuroradiographical diagnosis becomes extremely important. Although conventional intravenously enhanced computed tomography (IVCT) is satisfactory for the diagnosis of lesions larger than 1 cm, metrizamide CT cisternography (MCTC) greatly improves the diagnostic yield for smaller juxtapituitary masses in the suprasellar cistern, clearly defines their sizes and relationships with contiguous structures, and definitively confirms the diagnosis of empty sella syndrome. Six patients with endocrinopathies and normal or ambiguous IVCT findings are presented to illustrate how MCTC can influence their management and outcome without the patient discomfort and technical complexity associated with pneumoencephalography.

The detection of the heterozygous carrier for congenital virilizing adrenal hyperplasia.

The response of plasma progesterone, 17 alpha-hydroxyprogesterone (17-OHP), and cortisol to intravenous ACTH was determined in 16 control subjects and seven sets of parents of children with congenital virilizing adrenal hyperplasia. The baseline and poststimulation concentrations of hormones (of each group) were similar except for those of 17-OHP in the parents which were significantly greater following administration of ACTH. When rates of increase were determined, those of progesterone and 17-OHP but not cortisol were significantly greater in the parents. The combined rate of increase of progesterone and 17-OHP was calculated; 10 of the 14 parents had a combined rate of increase greater than the mean plus two standard deviations of the control group. This test provides a simple method for the detection of some heterozygous carriers for CVAH.

Stress management training for adolescents with diabetes.

Evaluated the effects of stress management training (SMT) for adolescents with diabetes in a 9-month controlled treatment-outcome study. Nine patients were randomly assigned to a stress management group while another 10 patients served as controls and received standard outpatient treatment. The treatment program consisted of 10 sessions over 3 months, 3 additional sessions over 3 months, and a 3-month follow-up without treatment. Diabetes-specific stress decreased significantly for patients in the SMT group over the course of the intervention and follow-up. However, metabolic control, regimen adherence, coping styles, and self-efficacy about diabetes were unchanged. These findings suggest a SMT program for adolescents with diabetes may be helpful in reducing diabetes-specific stress, but additional procedures are necessary to improve adherence, coping styles, and metabolic control.

Reliability and interrelations among serum sex hormones in postmenopausal women.

Serum sex hormones may be related to the risk of several diseases in postmenopausal women including osteoporosis, heart disease, and breast and endometrial cancer. For assessment of the relation of sex hormones to disease, the measurements should be reliable, valid, and practical. In this paper, the authors evaluated the short-term (4-week) and long-term (2-year) reliability of serum sex hormones and interrelations among serum sex hormones in white postmenopausal women recruited in Pittsburgh, Pennsylvania, 1981-1986. For comparison, the authors simultaneously evaluated the short- and long-term reliability of other commonly measured risk factors, i.e., lipids, lipoproteins, and blood pressure. Serum concentrations of estrone, estradiol, testosterone, and androstenedione were measured by extraction, column chromatography, and radioimmunoassay. Reliability was estimated by calculating the intraclass correlation coefficients (R) and their 95% confidence interval. About 50% of the estradiol levels were below the sensitivity of the assay and, therefore, these results should be interpreted with some caution. The intraclass correlation coefficient for testosterone was 0.92 (95% confidence interval 1.0-0.82), suggesting that a single measure may be reliable in characterizing women for epidemiologic research. Over 4 weeks, estrone could be measured more reliably (R = 0.72) than over 2 years (R = 0.56), but the variability over the long term was similar to that observed for other biologic variables, suggesting that, in situations where the relation between estrone and disease is fairly substantial, a single measure may be used. For estradiol and androstenedione, the intraclass correlations were small, indicating poor reproducibility and the need for more measurements. Estrone concentrations were 11 pg/ml or 46% higher in women with measurable estradiol. Estrone was also positively related to androstenedione concentrations (r = 0.33, p less than 0.001). Concentrations of estradiol are extremely low in postmenopausal women, and accordingly, there is a greater possibility of laboratory error. Since the data suggest that estrone levels can be more reliably measured and are, in fact, related to estradiol levels, it is possible that estrone levels may be used to indicate the total estrogen status of postmenopausal women.

Cigarette smoking and serum sex hormones in men.

The relation between cigarette smoking and serum sex hormone concentrations was examined in two samples of the Multiple Risk Factor Intervention Trial (MRFIT) population. One sample consisted of 121 men at the Pittsburgh, Pennsylvania MRFIT center who were followed longitudinally for four years. The other sample was drawn from the entire MRFIT cohort and consisted of 163 MRFIT participants who subsequently developed coronary heart disease and 163 matched controls. The results indicated a positive correlation between cigarette smoking and serum total androstenedione concentration. The association was independent of age, relative weight, alcohol drinking, blood pressure, and high density lipoprotein (HDL) cholesterol. Serum total and free testosterone concentrations were positively correlated with cigarette smoking among the longitudinal sample and the controls, but not for the baseline sera from the coronary heart disease cases. This positive correlation was also independent of age, relative weight, alcohol drinking, blood pressure, and HDL cholesterol. There was no association between either serum estradiol or estrone concentrations and cigarette smoking in this population. These observations may have important implications for epidemiologic studies of diseases with significant smoking relations.

Plasma progesterone, 17-hydroxyprogesterone, androstenedione and testosterone in prepubertal, pubertal and adult subjects with congenital virilizing adrenal hyperplasia as indicators of adrenal suppression.

To determine whether a single morning plasma level of 17-hydroxyprogesterone (17OH-P), androstenedione, testosterone and progesterone reflected the degree of control of 21-hydroxylase congenital virilizing adrenal hyperplasia (CVAH) as indicated by 24-hour urinary 17-ketosteroid and pregnanetriol excretion, 142 simultaneous 24-hour urine and morning blood collections were made from 65 patients with CVAH. Patients were grouped into five categories on the basis of age, skeletal age, and sex. Paired blood and urinary data were analyzed. The results suggest that androstenedione is the most reliable indicator for all patient categories. Testosterone is an excellent indicator for children of both sexes and for adolescent and adult females. Levels of 17OH-P are difficult to interpret, as they can be several fold higher than the normal values when adrenal suppression appears adequate on the basis of urinary data. In general, progesterone is a poor indicator.

Pituitary cellular hypersensitivity in idiopathic hypopituitarism.

Lymphocyte transformation in response to a saline extract of human pituitary was used to evaluate anti-pituitary immunity in patients with idiopathic hypopituitarism. Nine normal subjects and three children with idiopathic hypopituitarism were studied. Lymphocytes of one patient were significantly reactive to pituitary extract (beyond the 95% tolerance limits of the normal subjects) at five and eleven months after the diagnosis of hypopituitarism. The anti-pituitary hypersensitivity appeared organ specific since there was no lymphocyte reactivity to human thyroid extract in this patient. The presence of alopecia universalis, dystrophic nails and a primary immunodeficiency state suggests an autoimmune basis of his hypopituitary state. Due to hypogammaglobulinaemia and the lack of pituitary cell antibodies in this child, a humoral role in the development of his hypopituitarism is not supported.