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.

Plasma testosterone, high density lipoprotein cholesterol and other lipoprotein fractions.

High density lipoprotein (HDL) cholesterol levels are strongly related to risk of heart attack. Identification of determinants of high density lipoprotein cholesterol may provide important information concerning the cause of heart disease. The relation between one possible determinant, testosterone, and high density lipoprotein cholesterol and other lipoprotein fractions was evaluated in 247 middle-aged men. The results indicate that testosterone levels (both free and total) were positively correlated with high density lipoprotein cholesterol (r = +0.24, p less than 0.01) and negatively correlated with triglycerides and very low density lipoprotein cholesterol. The association between testosterone and high density lipoprotein cholesterol could not be explained by intake of alcohol, obesity, age, smoking or physical activity. Furthermore, the relation of testosterone to HDL cholesterol was independent of the relation of testosterone to very low density lipoprotein (VLDL) cholesterol or triglycerides.

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.

Hyponatremia and natriuresis following subarachnoid hemorrhage in a monkey model.

A monkey model of subarachnoid hemorrhage (SAH) was used to study both the incidence of hyponatremia and natriuresis and the associated changes in antidiuretic hormone (ADH) secretion and salt and water balance. Following SAH, seven of nine monkeys became natriuretic and hyponatremic. The natriuretic period lasted an average of 4.4 +/- 0.4 days. The mean nadir of serum sodium content was 125.7 +/- 1.6 mEq/liter, and occurred on the average on the 5th day following SAH. The sodium balance after SAH was negative as compared to the preoperative positive sodium balance (p less than 0.001). The plasma vasopressin level was usually elevated for a day following surgery, but there was no significant difference in the levels during the preoperative period and during the period of natriuresis following SAH. The daily urine output and aldosterone levels were not significantly different, and the plasma volume was slightly, but not significantly, decreased after SAH. Four of the animals that had a hyponatremic and natriuretic response following SAH showed a normal regulation of vasopressin in response to both a water challenge and hypertonic saline challenge. The three monkeys that underwent sham procedures did not become hyponatremic and natriuretic postoperatively. The sham-operated monkeys did not show significant differences in their plasma vasopressin levels, urine volume, plasma volume, and aldosterone levels following surgery. These observations are more consistent with primary natriuresis as the cause of hyponatremia rather than the syndrome of inappropriate secretion of ADH. The cause of the renal loss of sodium is not known, but the possibility of a brain natriuretic factor or an alteration in the neural control of the kidney should be considered.

Reproductive history in relation to plasma hormone levels in healthy post-menopausal women.

OBJECTIVES: We sought to examine the relationship between reproductive history and measures of selected gonadotrophins and steroid hormones among post-menopausal women. Previous studies have suggested that there is a negative correlation between parity and post-menopausal serum estrogens, which may be a mechanism by which pregnancies protect women from the development of breast cancer. METHODS: We analyzed women who experienced a natural menopause within the Healthy Women Study cohort both 1 and 8 years after menopause. Lifetime reproductive history was obtained and blood was assayed for estrone, estradiol, androstenedione, testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) at 1 year post-menopause and for many of these steroid hormones at 8 years post-menopause. Also at 8 years post-menopause, a hip bone mineral density measure was obtained. RESULTS: Age at menopause related to a modest increase in estrone at 1 year but a decrease in estrone and estradiol at eight years. Adjustment for body mass index (BMI), oral contraceptive use, alcohol use, cigarette smoking, and education had little impact on these findings. There were no other internally consistent relationships between reproductive variables and steroid hormones or hip-bone mineral density. CONCLUSIONS: These observations do not support the hypothesis that parity acts to diminish endogenous levels of post-menopausal estrogens.

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.