Sex-specific sensitivity of the hypothalamic pituitary axis to estradiol benzoate in normal children

142 R. GUREWITZ*, Z. DICKERMAN. S. PELEG*. R. KERET*. A. GIDALI* and Z. LARON. Inst. of Pediat. &Adolesc. Endocr., Beilinson Medical Ctr., Petah Tikva, Israel. Sex-specific sensitivity of the hypothalamic pituitary axis to estradiol benzoate in normal children . The i nfl uence of i .m. estradiol benz . (EB)(10-15 meg/kg) basal plasma E • LH and FSH and their response to LRH (50 meg/m i. v.) in children was studied. In all pubertal (n=10). early (n=15) and late pUbertal (n=6) boys the single EB inj. suppressed basal LH and FSH and their response to LRH . Pre- (n=5) and early pUbertal (n=6) girls had suppression of basal LH and FSH but in late puberty (n=14) the basal LH rose from 1.2+0.5 to 3.0+1.6 mIU/ ml (p < 0.05) whereas FSH remained suppressed.-The mean peak response of LH to LRH following EB (single inj.) was increased in all pubertal stages (to 1.7+0.4, 17.0+14.8 & 27 .3+23.6 mIU/ml respectively) . FSH response was increased only i n early and late puberty (to 13.4+6.0 and 10.5+1.8 mIU/ml respectively). Following 4 daily EB inJ. basal plasma LH and FSH levels and their response to LRH in boys (n=22) and girls (n=17) were inconsistently variable in all stages . In conclusion EB modulates the hypothalamic pituitary regulation of gonadotropin secretion, particularly the pituitary response to LRH, which was found to differ at various pubertal stages in normal boys and girls. The sex-specific sensitivity to physiological plasma estrogen levels may be of importance in the maturation of the hypothalamic pituitary axis during puberty. 143 Z.HOCHBERG* A.M.MOSES* A.BENDERLI* M.MILLER* and R.A.RICHMAN* (Intr. by M.Karp). SUNY Upstate Medical Center, Syracuse, NY, and Techn ion-I srael Institute of Technology , Haifa , Israel . Abnormal osmore ceptors in Kallman's syndrome ( KS) . We have previousl y described high set osmot ic threshold (OT) for vasopressin release and deficient thirst i n a patient with KS (ESPE-meet ing 1980) . In the present study the OT was evaluated by an isovolemic i nfus i on of 5\ NaCl in 7 patients with KS. The OT was defined at the plasma osmolality (Posm) at which the free water cl ear ance (CHzO) abruptl y fell. The OT was abnormally high in 5 patients, 291-Z96mOsm/kg. It was normal i n one , 287mOsm/kg, and abnormally low in one patient, Z70m0sm/kg. These values are compared to the OT in 73 normal volunteers previously reported (A.M.M &M.M). 287 .3 ! 0.9(SD) mOsm/kg . The 5 patients with high set OT den ied thirst at Posms as high as 296- 316mOsm/kg. Normal response of volume regulation of vasopress in release was demonstrated by an appropriate fall in CHzO during water deprivation. Normal response of baroreceptors was shown by a fall in CH 0 and a r ise i n plasma ADH during infusion of the hypotensive trimethaphan i n 2 patients. It is concluded that the hypothalamic involvement i n KS include deficient thirst sensation and abnormal setting of the osmoreceptors, that can be at an abnormal high or low setting. 144 L.G. Linarelli, M.D. Pediat r ic Department, University of California, San Diego and Mercy Hospital, San Cal ifornia U.S .A. 145 OWEIIS, J.: MARTIN, H.: AND ORSON, J., BROWN University Program in Medicine, PrOVidence, HI, USA. The effect of Phenytoin (OPH) on t he Conversion of Testosterone(T) to Dihydrotestosterone (OUT) in vitro. Oiminisned or sbsent virilization of male external gen italia is a n occasional feature of t he fetal hydantoin SYD<lrOlllC. We have studied the effect of DPR on t he conversion of- l 4C-testoaterone to its 50Lreduced metabolites in skin of IIIllle infants. Neonatal foreskkns obtained at circumcision were incubated for two hours With 1 C-testosterone in buffer, with glucose, penicillin, and supra-pharmacological concentrations of OPR. Using thin layer chromatography, the incubation mixture was assayed for T and androstenedione plus the 5ot.reduced metabolites, OUT, androstanedione, androstanediol, and androsterone. Testosterone metabolites formed were expressed as nanomoles/loo mg tissue/hour with and Without OPR. There was a significant nonlinear decrease in the amount of both ORT and total 50/. reduced metabolites formed with increasing amounts of OPR, with minillllli production at 4,400 nanomoles of OPR. This result was comparable to that obtained under identical experimental conditions follOWing addition of progesterone, a known inhibitor. These in 'Y1tro results may explain the mechanism of abnormal phenotypic sexual differentiation of the male fetus exposed to OPR in utero. 146 ABDOllAH SADEGHI-NEJAD, JOSEPH I . WOlFSDORF, AND BORIS SENIOR. Ped iatr i c Endocrine Metabol ic Service, Tufts New En91and Med ic a l Center, Boston. RARE ACQU IRED NEUROLOGICAL DISORDERS IN TWO PATIENTS ON LONG-TERM HUMAN GROWTH HORMONE (hGH) THERAPY . Acquired neurological disorders are not known to occur i n associat ion with either GH def ic iency or hGH therapy . Two of our group of over 50 pat ients receiv ing hGH developed unusual and rare neurological disorders. A 13 year old boy treated for isolated GH deficiency from t he ag e of 4 years developed the Gu illain-Barre syndrome (GBS) while stilI on therapy, and required assisted ventilation. Recovery was prolonged but complete. A 17 year old boy with anterior hypopitu itarism receiving thyroxine and co rti sone and on hGH s ince the age of 4 developed dyspha9ia and dys a rthr ia. Cran ial nerves were affected and there was atrophy and fasc iculat ion of the ton gue . After extensive stud ies the d ia9nosis of bulbar amyotrophic lateral sclerosis (ALS) was made. The neurol09 ical deficit pr09ressed and he requ ired 9astrostomy and ass isted vent ilat ion . Both GBS and ALS are rare diseases in children. The cause of ne ither is known. GBS may follow v ira l i nf ecti o ns o r inject ion of a foreign protein. A slow v iru s i nf e c ti o n and autoimmunity have been postulated for ALS. The occurrence of these rare neurol09ical disorders, possibly having sim ilar etiol09ies, in two children treated with hGH for years may well be f o r t u i t ous . Nevertheless , s ince hGH is obtained from cadavers . one cannot dismiss the possibility of a causal associat ion . 147 T.Sato, Y.Uchigata, N.Uwadana and Y.Suzuki.(lntr.by H. Takahashi).Department of Pediatrics , School of Medicine, Kanazawa Univ ersit y. Kanazawa, J apan . A syndrome of periodic ACTH and ADH di scharge . Neonata l Diabetes Insipidus Assoc i ated with Opt ic AtrophY ,Cerebral Atrophy and Gastroschisis . Congenital diabetes i nsipi dus has not previously been reported in assoc iation with gastroschi sis and its' associated an omali es . This is an unusual case of an in utero cerebral vascular acc ident caus ing diabetes ins ipidus, optic atrophy and left cerebral hemisphere atrophy. A 36 week gest ation i nf ant with a birthweight of 2.7 Kg. was noted to have herniation of the abdominal wall expo s in g intestinal contents at birth r equiring surgery in the fi rst hours of life . On the 10th (...truncated)