Atrial natriuretic factor in patients with congenital heart disease: correlation with hemodynamic variables.

To investigate the alpha-atrial natriuretic factor in congenital cardiac malformations, three groups of children, aged 7 months to 16 years, with different hemodynamic situations were studied during routine cardiac catheterization. Twenty-one (group I) had tetralogy of Fallot, 24 (group II) had a left to right shunt with pulmonary hypertension and 12 (control group) had a minor cardiac lesion. Alpha-atrial natriuretic factor levels were determined by a radioimmunoassay on blood samples from the inferior vena cava, right atrium, pulmonary artery, left atrium and aorta. To evaluate the effect of an acute volume load, measurements of hormone and pressures were repeated after right ventriculography. Alpha-atrial natriuretic factor levels varied over a wide range in all groups and in all chambers investigated. Nevertheless, children with pulmonary hypertension had significantly higher levels of the hormone (p less than 0.01) and were well separated from the control group, but less well from those with tetralogy of Fallot. A 50% increase of alpha-atrial natriuretic factor from the inferior vena cava to the right atrium occurred in patients with shunt lesions with pulmonary hypertension and in patients with tetralogy of Fallot (p less than 0.001) and a further 30% increase from the right atrium to the pulmonary artery (p less than 0.05). After right ventriculography, a 100% to 200% increase of alpha-atrial natriuretic factor was observed in the total sample (p less than 0.001). A positive correlation was observed between right atrial mean pressure and right atrial alpha-atrial natriuretic factor (r = 0.63) and between pulmonary artery mean pressure and pulmonary artery alpha-atrial natriuretic factor (r = 0.61).(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of dehydroepiandrosterone enanthate to promote growth.

Adrenal androgens may promote pubertal growth. To assess this possibility, we administered dehydroepiandrosterone (DHEA) enanthate in monthly im injections in a dose of 70 mg/m2 for 1 yr to five boys with constitutional short stature (aged 11-13 4/12 yr) and one boy (aged 13 4/12 yr) with panhypopituitarism (coincidentally receiving T4 and human GH). All had bone age delay of at least 3 yr and subnormal levels of DHEA and DHEA sulfate (DHEA-S) for their chronological age. Pretreatment growth velocity ranged from 3-5 cm/yr. After DHEA enanthate injection, plasma DHEA levels were increased 10-fold after 8 days, 2.6-fold after 15 days, and 1.8-fold after 22 days. At the same times, plasma DHEA-S concentrations were 14-, 6-, and 4-fold increased, respectively. There was no rise in plasma testosterone and delta 4-androstenedione, which remained at prepubertal levels. During the year of therapy and for 1 yr after therapy, there was no significant change in growth velocity, and the rate of skeletal maturation assessed by x-ray was not affected. Three of the five boys with constitutional short stature entered puberty within 1 yr after discontinuation of therapy. These results demonstrate that this long-acting form of DHEA administered for 1 yr did not raise plasma testosterone above prepubertal levels and did not accelerate either growth or skeletal maturation. These findings do not support the possibility that DHEA plays a role in normal growth.

Hormonal changes in puberty III: Correlation of plasma dehydroepiandrosterone, testosterone, FSH, and LH with stages of puberty and bone age in normal boys and girls and in patients with Addison's disease or hypogonadism or with premature or late adrenarche.

In 104 normal boys, aged 7 to 14 years (bone ages 5 to 15 years), plasma dehydroepiandrosterone (DHEA) rose from 52.7 at 7 years, to 112.0 ng/100 ml at 10 years. A further rise occurred at 12 years (188 ng/100 ml). In relation to the bone age, DHEA increased from a mean plasma level of 31.1 at a bone age of 5 years to 77.1 ng/100 ml at one of 7 years. Further increases were observed with mean values of 163.2 at a bone age of 11 years, and of 221.2 at a bone age of 12 years, with a maximum of 333.4 ng/100 ml at bone ages of 14-15 years. The first significant increase of plasma testosterone (T) was noted at a bone age of 12 years (54.8 ng/100 ml). The major rise of T was preceded by the rise of plasma LH and was accompanied by the rise of plasma FSH. Plasma DHEA and T were also measured in 123 normal girls, ages 6 to 13 years (bone ages 5 to 15 years). DHEA rose significantly from a mean level of 44.7 at 6 years, to 80.9 ng/100 ml at 8 years, with further increases between 9 and 10 years and between 10 and 11 years. In relation to bone age, DHEA increased significantly from a mean plasma concentration of 30.9 at a bone age of 5 years, to that of 58.6 ng/100 ml at 7 years. Further increases were observed with values of 191.1 at a bone age of 10 years and 485.6 ng/100 ml at a bone age of 13 years. The first significant rise of testosterone (T) occurred at 10 years of both chronological and bone age. DHEA rose before the increase of gonadotropins. The major rise of T at a bone age of 10 years occurred concurrently with increases in plasma FSH and LH. Low levels of DHEA were observed in Addison's disease. In hypogonadotropin hypogonadism and in anorchia, DHEA levels were normal, suggesting that DHEA is produced primarily in the adrenal gland. In seven girls with early adrenarche, plasma concentrations of DHEA were in the upper range of normal values, whereas T levels were within the normal range. Conversely in girls with late adrenarche, plasms DHEA was lower than normal but T was within the normal limits. The elevation of DHEA prior to the first signs of puberty suggests that DHEA may play a role in the maturation of the hypothalamic-hypophysealgonadal axis. However, the mechanism that triggers the secretion of DHEA is not known.

Melatonin radioimmunoassay.

A radioimmunoassay for melatonin has been developed after the raising of anti-melatonin antibodies in rabbits. The radioimmunoassay is specific and the sensitivity range is greater than the tadpole bioassay.?Author

Hormonal changes during puberty: V. Transient pubertal gynecomastia: abnormal androgen-estrogen ratios.

The plasma profiles of 8 hormones were followed over the course of prepuberty and puberty in 30 adolescent males who developed gynecomastia and 24 who did not. Throughout puberty, ratios of delta 4-androstenedione to estrone (E1) and estradiol (E2) were significantly lower in the gynecomastia group than in the control group. Similarly, ratios of dehydroepiandrosterone-sulfate to E1 and E2 were significantly lower in the gynecomastia group. In contrast, ratios of plasma testosterone to E1 and E2 as well as plasma progesterone and PRL concentrations, were similar in both groups. Because of the adrenal origin of dehydroepiandrosterone and its sulfate, and of peripheral conversion of adrenal androgens to E1 and to E2, it appears that either decreased adrenal production of androgens and/or increased conversion of dehydroepiandrosterone-sulfate and delta 4-androstenedione to estrogens cause transient gynecomastia in adolescent boys.

Radioimmunological determination of urinary melatonin in humans: correlation with plasma levels and typical 24-hour rhythmicity.

To study melatonin secretion by a gentle noninvasive method, a simple and quick RIA procedure to analyze melatonin in small urine volumes has been developed. Urinary extracts were prepurified by alkaline washes, and melatonin content was determined by RIA. The specificity of urinary melatonin determinations was confirmed by both thin layer chromatography and by gas chromatography-mass spectrometry. In the present study, we compared the amount of melatonin excreted in urine with plasma levels in 140 specimens from 13 adult volunteers. Comparisons showed a very good correlation between plasma levels at midnight and nocturnal excretion of urine, indicating the biological relevance of melatonin determination in urine. Our studies show further that urinary melatonin excretion displays the characteristic circadian rhythm usually observed in plasma. On the average, melatonin excretion is greatest between 2300--0300 h. The total 24-h excretion of melatonin varies considerably among different individuals.

Human serum melatonin changes during the menstrual cycle.

Serum melatonin concentration in early morning during the menstrual cycle, studied in five healthy women, showed that melatonin was elevated at the time of menstrual bleeding and had its nadir at the time of the menstrual cycling in humans.

Effects of cardiac surgery on renal function in children.

In order to determine whether cardiac surgery with cardiopulmonary bypass (CPB) affects renal function in children, glomerular filtration rate (GFR and renal plasma flow (RPF) were determined preoperatively and on the second postoperative day by a single-injection, urineless technique in a randomly selected group of 10 children. The GFR was 126.7 +/- 6.8 ml. per minute per 1.73 sq. M. (mean +/- S.E.M.) before the operation and 127.4 +/- 16.2 on the second postoperative day (p = 0.95). The RPF was 541.7 +/- 80.6 ml. per minute per 1.73 sq. M. preoperatively and 536.0 +/- 82.1 on the second postoperative day (p = 0.8 to 0.9). The results in this group of 10 children indicate that renal function is not markedly altered 2 days after cardiac surgery with CPB and deep hypothermia with circulatory arrest. The study also revealed a falsely decreased creatinine clearance. This was due to an increase in postoperative plasma creatinine values, probably related to an increase in plasma noncreatinine chromogens.

Atrial natriuretic factor after heart operations in children. Relation to hemodynamic and renal parameters.

The purpose of this study was to measure changes in serum atrial natriuretic factor concentrations immediately after heart operations in children under baseline conditions and in response to continuous infusion of dopamine (2.5 and 5.0 micrograms/kg/min). During control periods, levels of atrial natriuretic factor were elevated at 190 +/- 24 and 199 +/- 36 pg/ml. The cardiac index was 2.6 L/min/m2 and the renal plasma flow was decreased to 269 +/- 41 ml/min/1.73 m2, indicating a state of renal vasoconstriction (mean renal fraction of cardiac index of 10.0% +/- 1.0%). The mean sodium fractional reabsorption was 99.0% +/- 0.2%. During dopamine infusion, atrial natriuretic factor concentrations increased to 259 +/- 57 pg/ml and to 280 +/- 56 pg/ml, with dopamine 2.5 and 5.0 micrograms/kg/min, respectively (p = not significant), whereas left atrial pressure decreased from 11.7 +/- 0.9 mm Hg during the control period to 10.1 +/- 0.9 and to 9.9 +/- 1.0 mm Hg (p less than 0.05). No correlation was found between changes in left atrial pressure and atrial natriuretic factor levels. Dopamine at 5 micrograms/kg/min increased the cardiac index to 3.0 +/- 0.2 L/min/m2 (p less than 0.001) and the renal plasma flow to 406 +/- 61 ml/min 1.73 m2 (p less than 0.001), alleviating the renal vasoconstriction. The mean urinary sodium excretion increased to 0.33 +/- 0.08 mmol/kg/hr (p less than 0.01). The atrial natriuretic factor plasma concentrations were not related to the urinary sodium excretion, renal plasma flow, or glomerular filtration rate during the control period or during dopamine treatment. These data indicate that after heart operations in children, low urinary sodium excretion occurs despite high circulating atrial natriuretic factor levels. Atrial natriuretic factor concentrations were related neither to left atrial pressures nor to the renal changes induced by dopamine.

Metabolic studies in primary tubular hypomagnesaemia-hypokalaemia.

13 1/2 year old boy with short stature and pubertal delay had infrequent episodes of tetany. Biochemical determinations demonstrated low plasma and high urinary magnesium and potassium levels, hypocalciuria, slightly increased plasma bicarbonate, slightly reduced fractional distal reabsorption of chloride and sodium, high plasma renin activity and high urinary excretion of prostaglandins (E2, F2 alpha). The other parameters of renal functions were normal. Endocrine evaluation of short stature and pubertal delay was normal. Intracellular magnesium and potassium levels in lymphocytes and erythrocytes were within normal limits. Cyclooxygenase blockade with Indomethacin 2.5 mg/kg daily during 4 weeks normalized urinary excretion of prostaglandins and corrected in part low plasma and high urinary potassium levels, but had no effect on magnesium, calcium, sodium and chloride handling. These data raise the possibility that tubular hypomagnesaemia-hypokalaemia could be solely explained by a low renal threshold for magnesium.

[Osteogenesis imperfecta and localized involvement of the spine: a peculiar form? Apropos of a familial case]. / Osteogenesis imperfecta et atteinte localisée au rachis: forme particulière? A propos de l'observation d'une famille.

The authors report a particular type of Osteogenesis Imperfecta (O.I.), where the symptoms of bony fragility affected only the spine in three members of the same family, a father and his two daughters. This type of O.I. represents a type IA variety according to the classification of D. Silence. The authors while underlining the wide variety of this condition think that it is very likely that non recognition of the condition is in part due to the mild symptoms attributable to this lesion in the spine. This diagnosis has to be considered for all symptomatic osteoporosis of the vertebrae in children and adults. After eliminating other osteopenic conditions, diagnosis may be established on the basis of clinical signs and family history. Although this condition is related to a collagen metabolism deficiency particularly in type I, for the present condition there was no specific biochemical test available.