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Intravenous application of 100 micrograms synthetic ovine corticotropin releasing factor (CRF) led to stimulation of ACTH-secretion in nine normal controls, with a maximum 30 min after CRF. Cortisol, corticosterone, cortisone and 11-deoxycortisol increased with a maximum at 60 min after CRF, whereas no rise was seen in aldosterone, 11-deoxycorticosterone, 17-alpha-hydroxyprogesterone, progesterone, DHEA-S and testosterone. The specificity of CRF-stimulation was also shown by unchanged TSH, LH, FSH, hGH, prolactin and thyroid hormone levels, als well as unchanged insulin and gastrin levels. No serious side-effects were observed during the test period and afterwards. CRF-tests were performed in ten patients with disturbances of the hypothalamo pituitary adrenal axis (HPAA). Preliminary findings show hyperresponsiveness of ACTH in all situations of ACTH-hypersecretion (two patients with Cushing's disease, one patient with Nelson's syndrome, and one with Addison's disease). In contrast, one patient with successful microadenomectomy showed no response of ACTH to CRF, whereas in another patient with a macroadenoma ACTH and cortisol-levels still increased postoperatively. Divergent patterns in ACTH-responsiveness to CRF were seen in four patients with secondary adrenal insufficiency, allowing the localization of the defect. These data point to the possible importance of the "CRF-test" as a differential diagnostic tool and prognostic factor in diseases of the HPAA.

We reported previously reference values for seven corticosteroids in the plasma of term neonates and their mothers, including values for aldosterone (Aldo) that appeared high compared to the values in the literature. Plasma 11-deoxycortisol (S) was not measured in that longitudinal study. Using an improved technique of chromatographic separation of Aldo and S, the Aldo levels were measured again, and S levels were newly determined in stored plasma samples of the 12 newborn infants of our original report. The mean concentrations were: (Formula: see text). These plasma Aldo values should replace those of our original report. Thus, both plasma Aldo and S levels decline in the first week of life in normal infants.

The small adrenal cortex of SGA infants may play a role in the pathogenesis of their frequent postnatal problems. We therefore evaluated adrenocortical function of SGA infants at birth and during postnatal adaptation. In 22 vaginally delivered term infants (SGA

Influence of the Mode of Delivery on Umbilical and Postnatal Plasma Levels of 7 Corticosteroids in the Newborn

85 SIGNIFICANCE OF THE ADRENALS AND THE TESTES FOR THE PRODUCTION OF TESTOSTERONE (T) AND ANDROSTENEDIONE (A) DURING MALE INFANCY

Increased mortality with long-term E infusions in intensive care patients has been reported and evidence is accumulating that E causes reversible adrenocortical suppression with decreased serum cortisol levels. A direct inhibition of adrenal steroidogenesis has been suggested, but so far data on the mechanism of this action are lacking. A 6 1/2 year old boy with convulsions due to encephalitis was treated with constant E infusions (1 - 2 mg/kg/h). Prior to E administration, adrenocortical function was normal as tested by an ACTH-test. 5 days after institution of therapy and 14 days after discontinuation, plasma levels of 11-deoxycorticosterone (DOC), corticosterone (B), 11-deoxycortisol (S) and cortisol (F) were measured by RIAs after Sephadex LH-20 chromatography. During E therapy DOC and S levels were highly elevated, while B was in the lower normal range and F was markedly decreased. Likewise the ratios of B/DOC and F/S, which reflect adrenocortical 11 β-hydroxylase activity, were extremely decreased (B/DOC:0.06 vs 27 in controls; F/S:0.009 vs 230 in controls). After discontinuation of therapy, the absolute values as well as the ratios returned to normal. These results show, that E is a potent inhibitor of adrenal 11 β-hydroxylation.Increased precaution seems to be necessary when this drug is used in patients who are under considerable amount of stress.

To clarify the origin of estrogens in infant blood, we measured E1 and E2 in the gonads of 50 girls and 64 boys deceased by sudden death between birth and 2 years of age. In both sexes, E2 was the major gonadal estrogen which exceeded E1 almost tenfold in the ovaries and twice in the testes. Thus, there was a clear sex difference in gonadal estrogen concentrations. On an average, girls had 8 times higher E2 and twice as high E1 concentrations in their gonads than boys. As in plasma, E2 concentrations were highest in ovaries of 2 to 4 months old girls (2 - 55 ng/g) and in testes of 1 to 3 months old boys (0.6 - 6.4 ng/g). Ovarian E2 concentrations decreased to values below 3 ng/g until the end of the 1st year of life, testicular E2 reached values below I ng/g already by 6 months of age. The gonadal steroidogenic activity paralleled changes in gonadal morphology. Ovarian weights showed a similar pattern of rise and fall as the E2 concentrations, the biggest ovaries consisting of multiple macroscopic cysts. In boys, testicular E2 closely correlated with Leydig cell development and testicular testosterone concentrations. We conclude that the surge of E2 in the blood of infant girls and boys originates from ovarian follicles and testicular Leydig cells, respectively, which develop under the influence of the characteristic post-natal gonadotropin surge.

81 DEMONSTRATION OF MINERALOCORTICOID RECEPTOR DEEICIENCY IN TWO SIBLINGS WITH PSEUDOHYPOALDOSTERONISM(PH)

We are reporting the first case of combined ectopic ACTH syndrome and “humoral hypercalcemia of malignancy” in a child with a liver tumor: A 6 9/12 y o girl presented with Cushing's syndrome, hypercalcemia and a large liver tumor. Serum CRF was undetectable. ACTH ranged from 184 to 819 pg/ml and was unresponsive to CRF and dexamethasone (2 and 8 mg). All urinary steroids, except for THAldo, were greatly elevated. By contrast, serum multisteroid analysis revealed high levels of only Cortisol, corticosterone and DHAS, whereas progestins (Prog, 17-OHProg) and mineralocorticoids (DOC, Aldo) were normal. Serum Ca was 14.2 ng/dl, P 2.2 mg/dl, 1,25-(OH)2D 61 pg/ml (normal: 20-40), urinary cAMP 6.7 nmol/dl GF (normal: T.6-4.9) and P reabsorption 1.6 mg/dl (normal: 4.5-6.8). Serum PTH(44-68), 25-(OH)D, AP, osteocalcin and urinary Pro-OH were normal, and PTH(intact) was suppressed, suggesting the presence of a PTH-like factor distinct from PTH. The tumor was surgically removed and proved to be a hepatoblastoma. Extraction yielded 8.3 ng/gm of ACTH and 0.04 ng/gm of CRF. Histochemical staining was positive for ACTH and CRF. By electron microscopy, multiple hormone granules were demonstrated in individual tumor cells. Postoperatively, ACTH and Ca levels rapidly reverted to normal. 4 m later, basal and CRF-and ITT-stimulated ACTH and Cortisol results were normal, and the girl was clinically doing well.

The apparent inability of elevated atrial-natriuretic peptide (ANP) levels to cause natriuresis and diuresis in children with heart failure may be related to a reduced response of target organs to ANP. The cellular effects of ANP seem to be mediated by cGMP as the second messenger of ANP. Simultaneous measurement of ANP and cGMP has been shown to be a useful tool to study the cellular response to ANP. Therefore, plasma ANP and cGMP levels were measured by radioimmonoassay in 168 healthy children and in 47 children with congenital cardiac diseases. In healthy children ANP and cGMP plasma levels were measured in the range of 5-109 pg/ml (mean 45.5) and 0.2-2.8 pmol/ml (mean 1.3) respectively. In children with cardiac diseases significantly higher ANP (range 30-980, mean 280 pg/ml) and cGMP levels (range 0.2-6.0, mean 2.8 pmol/ml) were determined. There was a highly significant correlation between the two in children with cardiac diseases (p

The adrenal cortex seems to play an important role in the newborn's adaptation to extrauterine life. Since systematic studies on multiple CS in the same human newborn have not yet been reported, progesterone (P), deoxycorticosterone (DOC), 17α-hydroxyprogesterone (17α), corticosterone (B), aldosterone (A), cortisone (E) and cortisol (F) were followed in a single 250 μl peripheral plasma sample in 12 vaginally delivered full-term infants of either sex. Mean concentrations (after automated LH-20 multi-column chromatography and specific radioimmunoassays) were in ng/ml: Besides marked materno-fetal CS differences, P, 17α and DOC (predominantly of placental origin) disappear rapidly with varying half lives. A, B, E and F, however, remain elevated in comparison with later infancy, reflecting high adrenal biosynthetic activity. *(Approved by parents and Hospital's Ethical Committee)