We used the GnRH agonist (GnRHa) stimulation test (20 micrograms/kg leuprolide sc, followed by 24-h serial sampling) to investigate the relationship between gonadotropin and estradiol (E2) secretion in the early phase of female central precocious puberty (CPP). Girls with CPP and moderately increased (early pubertal) peak E2 concentrations after GnRHa stimulation (136 +/- 11 pmol/L; range, 92-176; group B; n = 7) were compared to girls with CPP and higher (midpubertal) peak E2 responses to GnRHa (mean +/- SE, 590 +/- 63 pmol/L; range, 235-1189; group C; n = 19) and to a group of subjects with no breast development and a prepubertal hypothalamic-pituitary-gonadal axis (peak E2 response to GnRHa, 39 +/- 7 pM/L; range, 18-62; group A; n = 6). Compared to group A subjects, patients in group B had similar (P > 0.2) peak GnRHa-stimulated LH concentrations (B, 4.8 +/- 1 IU/L; A, 2.3 +/- 0.5 IU/L) and peak nocturnal LH (B, 0.81 +/- 0.2; A, 0.25 +/- 0 IU/L), but higher peak GnRHa-stimulated FSH concentrations (B, 26 +/- 7; A, 11 +/- 2 IU/L; P < 0.05) and mean nocturnal FSH (B, 4.2 +/- 1; A, 1.1 +/- 0.3 IU/L; P < 0.05) concentrations. Compared to group B, group C patients had higher (P < 0.001) GnRHa-stimulated peak LH (67 +/- 19 IU/L) and higher (P < 0.05) peak nocturnal LH (9.7 +/- 2.9 IU/L) concentrations, but similar GnRHa-stimulated peak FSH (27 +/- 3 IU/L) and mean nocturnal FSH (3.8 +/- 0.5 IU/L) levels. Group C patients with a ratio of peak GnRHa-stimulated LH to FSH concentrations below or above 1, respectively, had similar peak E2 responses to GnRHa (516 +/- 80 vs. 644 +/- 92 pM/L; P > 0.1). Stepwise regression analysis indicated that the peak LH response to GnRHa (r = 0.76; P < 0.001), but none of the FSH secretory parameters (P > 0.10), affected the E2 response to GnRHa. These data suggest that girls with CPP in the early phase of activation of the hypothalamic-pituitary-gonadal axis are capable of clinically relevant E2 production, which may occur in the face of low LH secretion and low LH/FSH ratios and cannot be explained solely on the basis of increased FSH secretion. Thus, endocrine or paracrine factors other than gonadotropins may be important in amplifying E2 secretion in the early phase of CPP.

Intially corticotropin (ACTH) and cortisone were used only to induce diuresis in children with the nephrotic syndrome, though occasional remissions were produced.1-7 Most of these early trials were of short duration and the amounts of drugs administered were small because of limited supplies and the occurrence of side-effects such as edema, hypertension, and hypokalemia. The demonstration that such changes could be prevented or minimized by means of diets rigidly restricted in sodium and high in potassium 8 enabled us and others 9,10 to undertake more prolonged administration of large amounts of corticotropin and adrenocortical steroids in the hope of influencing the course of the underlying disease. Materials and MethodsDuring the past five years we have treated a total of 106 instances of nephrotic syndrome in children. All had persistent and usually massive proteinuria on admission. Each patient was treated in essentially the same way, and no attempt was made to exclude those with hypertension, formed elements in the urine, or azotemia. Data on 30 of these children have been reported earlier.8 Seventytwo were initial attacks ; the remainder represented exacerbations. From the information in Tables 1A and IB it can be calculated that the mean age at which the initial episode of nephrotic syn¬ drome occurred in the group of 72 children was 4 years 4 months, with \y2 to 2y2 years the com¬ monest age of onset and a range of 4 months to 13 years 7 months in the remainder. There were more boys than girls, 45 versus 27, and the latter were somewhat older at the first manifestation (4 years 9 months versus 4 years 2 months). Symptoms or signs of nephrotic syndrome, or both, had been present for one week to four years prior to hospitalization for the first course of corticotropin, with a mean duration of 27 weeks. This interval was much shorter, averaging four weeks, in patients who developed an exacerbation while under observation in the dispensary. A his¬ tory of an infection prior to or coincident with the first episode of nephrotic syndrome was obtained in 40 of the 72 patients, with upper respiratory in¬ fection in 34, unexplained fever in 3, varicella in 2, and rubeola in 1 (Table 1A). In the 18 patients admitted one to six times with a total of 34 exac¬ erbations, recrudescence followed an upper re¬ spiratory infection in 12 instances, bronchitis in 1 and was unassociated with any recognized infec¬ tion in the remaining 21 (Table IB). Beta-hemo¬ lytic streptococci were isolated from nose and throat cultures in only a minority of the initial and the subsequent attacks, 12% and 6%, respec¬ tively.

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The high nitrogen values for the washings are due to non-antibody protein of the serum. The progressive reduction in the values indicates the removal of this protein by successive dilution. The possibility that non-antibody protein was non-specifically taken up in the lattice of agglutinated ghosts cannot be excluded. Therefore a portion of the nitrogen in the resuspended antibody may not repre-sent antibody nitrogen.Summary. Study of a human cold hemagglutinin revealed:1. The cold hemagglutinin had the electrophoretic mobility of gamma globulin. 2. A cold hemagglutinin titer of 1/2560 at 4OC was equivalent to 1.473 mg per ml of antibody nitrogen.

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