T.M.Strom*, J. Weil*, A. Timnic*, D. Knorr, C.G.D.Brook F..A.~ivese~': F. Bidlingmaier 38 The Middlesex Hospit~l,Mortimer Street, London W1. Depart. of Paediatrics, University of Munich and CROW'LII AND CROWD1 IIOIIMONE (CII) TRMTMENT FOI.I.OIIING IUUlOTIICIL$PY 35 Institute of Clinical Biochemistry, University of Bonn OF BRAIN TUEIOURS. FRGl EIND~NCSITES FOR ATRIAL NATRlURETlC PEPTIDE Of a cohort of 132 children .,live and well following treatment of brain (ANP) ON PLATELETS IN PATIENTS WITH HIGH tumours renlote from the hypothalasus or pituitaly with radrotherapy, 96% tiad PLASMA ANP LEVELS. evidence of GI1 abnornwlity. 32 had campleLctl their Growth. 14 who had received craniospinal irradiation, had final height SDS -2.03 (range, -3.7 to +O.O9), In our first study we found binding sites for ANP on human sitting height (SH) SbS -3.22 and subischinl leg letlgtl; (SILL) SDS -0.61. 18 platelets. Binding studies on these easily accessible cells could treated with cranial irradiation aloac liad final height SDS -0.93 (range, -7.6 be a useful model to investigate receptor-status in patients with to +2.07), SH SUS -1.24 and ST1.L SDS -0.53. llius the crfect of spin.il elevated ANP plasma levels. We reported high ANP levels in irradiation on final height was considerable. neonates and in patients with heartfailure. Therefore we studied 40 children were treated with GH for periods of 1-4 years. 32 had the number of binding sites on platelets in venous umbilical blood received craniospinal irradiation and 8 cranial irradiation alone. 17 cliildren of term infants (n = lo), in adults (n = 15) with heartfailure and who had received craniospinal irradiation were treated with Cll when in controlsubjects (n = 18). For the bindin2 studies 40 x 106 prepubertal. Over the first 12 months of treatment mean height velocity SDS platelets were incubated with 10.000 cpm J ANP and increasing increased +2.52 (range -0.9 to +4.84). Mean height SDS Lor CA increased t0.27 concentrations of unlabeled ANP. Time of incubation was 120' at (range -0.3 to +1.55) and height SDS ror LIA +0.09 (-0.89 to +0.99). Mean SILT. room temperature. Separation of bound and free tracer was SDS increased +0.33 (-0.41 Lo +1.13) but SII SDS was not improved. GI1 giver, ro performed by filtration through Whatman CFIC filters. 23 children in puberty was without significant effect on growth. In neonates we found 18-32 and in patients with heart failure We conclude: 1. Spinal irradiation adversely aifected spinal growth and 8-30 binding siteslplatelet. In comparsion with control subjects this did not respond to GI1 in the doses used. 2. After craniospinal (15-30 binding sitesiplatelet) there was only in patients with irradiation, GH could only nonnalise leg growth and must therefore be heartfailure a trend for reduction of binding sites (p< 0.1). instituted before puberty. 3. After cranial irradiation alone Gtl mainl~ined The Kd (14 + 8 pM) was similiar in all subjects studied. height SDS. 4. Delay in instituting GI1 treatment leads to nn irrevcsiblc lass In our results there was no convincing evidence of "receptor uf final helght prognosis. down regulation" in the presence of high ANP levels as described in in-vitro experiments.

T.Kaethner*, C.Emmerich*, S.Gajowski*, OV.Duda*, R. Brauner, F. Malandry*, R. Rappaport, 3M. Zucker*, C. Kalifa*, "OK.Ehlenz*, OOOW.Rascher*,M.Brandis (1ntrod.b~H. ATXfe-Kahn*, P. Bataini*, JL. Dufier*, A. Tar*. Helge) Deparwnt of Pediatric Endocrinology and Diabetes and INYRM U30 36 Dept .of Pediatrics, "Obstetrics and Internal Med., 39 Hdpital des Enfants-Malades, Paris, France. Phillpps -University ,355 Marburg/L. ,FRG SEQJENTIAL OCCURRENCE CF ENDXRIM DISTURBANCES IN CHILDREN OOODept.ofPediatrics, Unlv.of Heidelberg, FRG TREATED FOR OPTIC CCIM (CG). LEVELS OF ALDDSTERONE AN0 VASOPRESSIN IN THE Children with 02 are at mqjor risk for short final stature because of the ccn- AMNIOTIC FLUID AND IN THE URINE OF NEWBORNS: bind effects of GH deficiency (1313) and central precocious puberty (PP) . In Recently we reported about a highly stimulated renln-anglotensln- order to better establish our therapeutic strategy, the course of the endocrine aldosterone-system (RAAS) in newborns without elevation of vaso- disturbances was reevaluated in 48 cases (28 boys, 20 girls), before and after pressln (ADH) levels. In the following study we examined cranial irradiation. 25 of then had neurofibrmtosis. All received cranial irra- aldosterone (ALDO) .ADH, electrolytes, creatlnine and osmoiality diation at the dose of 50-55 Gy over 5-6 w at man age of 6.2 t0.5 yr (I+ sm) . In 53 amnlotlc fluld samples and In urlnes of premature and Before irradiation OQ), with 01 peakst 8 ng/ml after AITT, was found in 4 cut of mature newborns. ~2~~stEttZ33Pwith grcwth acceleration was present in 22/48 patients. After Results: In all amniotlc fluld samples ALDO and ADH were irradiation 1) GC occurred in a1 1 patients within 2 yr ((peak ( 5 ng/ml in 5~Lof detectable.ADH levels were ln the same range In amniotlc flulds thfm,2?-bily 2 patients developped PP, 3) partial or ccrrplete gonadotropin defi- as In urines collected at the first day of llfe. (17 pg/ml vs. ciency occurred in 6 patients, of whm 3 had already PP, with a wan follm up or' 10 pg/ml) In contrast ALDO levels ~n the amnlotlc fluid were 40 4.8 + 0.6 yr, 4) grazrth, as expressed by SD changes over the 1st two yr was -1.3 times lower than levels in urlnes. (37ng% vs.1280 ng%). Hormone ? 0.2 9 in prepubertal patients (n= 91 and -0.1 !0.1 SD in pubertal patients concentrations were not correlated to fetal age,electrolytes, (n= 9, pt0.031) with a parallel BA progression of 3.4 * 0.45 yr in the 2d group, creatlnlne and osmolality ln amn~oticfluld. 5) final height reached in 16 cases was - 2.2 9. Conclusion: In the 17th week of gestation the buman fetus 1s In conclusion: 1) radiation dose adninistered in CG invariably produced W, able to produce AOH In a simlllar amount as in the early postnatal 2) j~hindked a decreased grovrth rate in prepubertal children, 3) children llfe. But Aldo levels in the amnlotlc fluid are slgnlficantly with PP maintained a sufficient grcwth rate although BA progressed excessively, lower than ln the urlnes of newborns. This may reflect the onset 4) this radiation dose induced gonadotropin deficiency. of stlmulatlon of RAAS ln the early postnatal llfe This study provides usefull guidlines for the homonal treabrent of these patients using 01 alone or in carbination with LHRH analogue/or sex steroids according to the course of the endocrine disturbances.

JW Honour,MJ Dillon, JM Cowen, HB Val~nan .M. Fontoura*, R. Brauner, R. Rappaport, A. Fischer*, E. Quintana*, Col)bold Laboratory ,Middl csex Ilospital, I.ondon , &I.Zucker*, F. Bernaudin*, E. Vilwr*, A. Devergie*. 37 England: institute of Child Ilealtli, London, England DeparWnt of Pediatric Endocrinology and Diabetes and 1NYFO.I U30 and Northwick Park tiospital, Harrow, Enaland 40 HBoital des Enfants-Malades, Paris, France. THI: AETIOLOGY OP AI.DOSTERONC SECRI;T~& AND SODIUE: GRWH AND ENCOCRIM FUNCTION PFTER BOM MOrl TRANSPMATION IIOMEOSTASIS IN PRETCRM INFANTS (BMT) WITH OR WITHOUT TOTAL BODY IRRADIATION (lBI). Late hyponatraeniia with negative sodium balance was previously TBI preparing to BW is frequently follaed by grovrth retardation. As 01 seen in preterm infants in our hospital (Honour et a1;1979;Actn deficiency (W)is a well knam ccnplication of cranial irradiation, the purpose Paed Scand 63:813). Contributory factors were a low salt int,ike of this study was to evaluate the risk of GW after TBI and its possible relation- and re~iolinsensitivity to the high aldosterone production (APR) ship to this failure of grcwth. 20 children received 8MF for ALL (n= 81, inmmo- which followed 2-3 weeks with low APR. By increasing sodium deficiency (n= 6) or other disease (n= 6). 15 of them (group I) had TBI at 9-12 Gy intakes we maintained sodium balance in 15 preterm infants. We doses after conditionning by chmtherapy. They were ccnpared to 5 children (group found p1nsm;i 1-cnin activity 20920 + 5650 ng/l/l~around day 7 11) who had cnly chmtherapy. None of the children received additional cranial falling to 6472 + 4500 ng/l/l~around day 33. Corresponding irradiation. Results were as follms (dian - range) : plasma aldosterone concentrations were 4893 + 2483 pmol/l and GRWP ,'IEAT TBI FOLLOrl-UP KIM CM GH-AITI 3960 + 3135 pmol/l. In 15 infants of 27 - 357 mean 31.3 weeks (yr) (yr) (9) ( < &1g/ml) gestation tetraliydroaldosterone (THAldo) excretion rates were I (15) 5.6 3.5 -1 1 normal at 29.2 + 24 pg/24h. The ratio of urinary 18-hydroxy-THA (1.5-12.71 (1- 6.5) (1- -3) (principal metabolite of 18-hydroxycorticostero11e ) to THAldo 11 (5) 2.2 2.2 0 0 was 0.35 + 0.22. These data (1)exclude a defect in aldosterone (0.6-2.8) (1.6-4) (1.5- -1) biosyntliesis (2) show PRA does not relate to sodium balance .ind Grovrth retardation was significantly superior in group I than in group I1 (3) the adrerial zona glomerulosa response to angiotensin in tlic (p~0.05). In group I, out of 5 patients with grovrth failure (>I%) one had CK neonatal period may be inhibited by other factors such as atrial and the 4 others had non~l01 secretion as sham by plam h-C and 12 hr GH nntriuretic peptide. nocturnal profile. No significant grovrth retardation occured in group 11. Elevated TSH was found in 5 cases of group I with T4 normal (3) or deratly decreased (2). In conclusion, after a wan interval tine of 3.5 yr GW) does not appear as a Mjo?Ccrrp@ion of mI. Thyroid deficiency is mre frequent. Grovrtti retardation often severe, is probably mre frequently the consequence of the cartilage irra- diation. A mre prolonged follw-up of these patients is still necessary.