C.A. SKLAR and R.A. ULSTROM, University of Minnesota 133 U. Vetter, J. Hornoki, W.M. Teller 130 Hospitals, Minneapolis, Minnesota Department of Pediatrics, University of Ulm, PRG Growth and Adrenal Secretion The effect of growth hormone (GH) on adrenal androgen secretion 17a-Hydroxylase-deficiency with unimpaired formation was assessed in 7 patients (5 males, 2 females) with GH deficiency in a male but normal ACTH- function. Patients ranged in age from Case report: This is the first report of a male neonate with g 3/12-148/12 years. Plasma concentrations of dehydroep!androst­ 17a-hydroxylase deficiency with micropenis, hypospadia and normal erone (OHEA), its sulfate (OHEA-S) and A), as aldosterone secretion. Diagnosis was based on elevated excretion well as urinary 17-ketosteroids and free cortisol were determined of PD, DOC, TH-DOC, THE, alla-THB and decreased excretion of before, during short-term (2U/dx3j and after long-term (6 months) Cortisol, l1-desoxy-cortisol, THF, THE and . Serum treatment with GH. The baseline, pretreatment plasma levels of levels of ACTH, LH, FSH, DOC were elevated whereas cortisol, OHEA-S were appropriate for the degree of skeletal testosterone and FRA were decreased. Serum levels and urinary maturation, whereas plasma DHEA and A were undetectable «42ng/d1 excretion of aldosterone were normal. and < 27ng/d1, respectively) in 5/7 subjects. No significant Discussion: 17a-hydroxylase deficiency is a rare disorder of change was noted in the plasma androgen values or in the urinary metabolism. The clinical pattern in adults presents 17-ketosteroid and free cortisol concentrations during the short­ with hypokalaemic hypertension associated with metabolic term administration of GH. Despite a significant increase in alcalosis and pseudohermaphrodism in males. Low aldosterone growth velocity after 6 months of GH therapy, the pre- and post­ levels indicate that the 17a-hydroxylase deficiency is linked treatment plasma and urinary ster·oid concentrations were not to a dehydrogenase deficiency in the conversion of 18-0H­ statistically different. These results fail to substantiate a to aldosterone. Our case presenting with unimpai­ role for GH in the secretion or metabolism of adrenal . red aldosterone formation may be a unique entity or due tv Thus, the delayed adrenarche and subnormal plasma adrenal androgen unexpressed enzyme deficiency dpring tte newborn period. levels sometimes seen in GH deficient patients are not due to the absence of GH per se.

E.H.SOBEL and B.Zumoff*. Departments of Pediatrics and J.S.D. WINTER and DEAN*, 131 Medicine, Albert Einstein College of Medicine,Bronx, 134 Department of Paediatrics, University of Manitoba, New York, U.S.A. Winnipeg, Manitoba, Canada. Interactive effects of ACTH and growth hormone on adrenocortical l]a-Hydroxylase and Sa-Reductase Deficiencies in a Newborn Male. hormone secretion. In a 46XY normotensive infant with micropenis, perineoscrotal The effects of ACTH and growth hormone (GH) on adrenocortical hypospadias and a bifid scrotum with histologically normal testes, mone secretion were studied in a 13-year-old girl with GH and thy­ l]OH-deficiency was diagnosed from increased serum corticosterone rotropin deficiency but normal ACTH function. Cortisol secretion (B) and (p) plus inadequate cortisol (Fl, testosterone was measured by the sum of the urinary excretions of tetrahydro­ (T) and DHA responses. Urine B metabolites were raised 100-fold; cortisol (THF). allotetrahydrocortisol (ATHF). and tetrahydrocorti­ sone(THE). Adrenal androgen secretion was measured by the sum of the Sa/56-reduced metabolite ratio was normal before and after andro.terone(Al and (E). The patient took a constant cortisol loadin • Plasma Na K, aldosterone and renin were normal. dally dose of desiccated thyroid1150mg) during 5 successive periods: B P ng% F T ng% DHA ng% control, 3 days of 1M ACTH (0.5mg/kg daily), 12-day post-ACTH Basal 22.0 475 8.8 25 .20 control, 6 days of 1M human GH (3.5mg daily), and 3 days of ACTH + Post-hCG 16.0 59 ·20 GH at the previous doses. Control excretion of THF + ATHF + THE Post-ACTH 25.0 765 II. I 37 <20 was 6.0mg/g creatinine and of A+E was 2.9mg/g creatinine; these Pos t-r dexa 2.8 <35 4.5 .10 ·20 values confirm normal endogenous ACTH function. Taking these levels Normal basal <0.8 <100 20.0 20 90 as 100, excretion of and androgen metabol ites rose to 240 Normal ost-ACTH 3.4 177 65.0 20 150 and 190 respectively during ACTH and decreased to 107 and 105 re­ Genital skin fibroblast T receptors were normal in vitro 23 fmol/ spectively during the last 3 days of the post-ACTH control period. mq) but surprisingly 5a-reductase activity was reducedl'0.4 pM/pg During the GH period, they fell to 66 and 72 respectively. When ACTH DNA/hr}, although Km for T (0.12 and NADPH (170 were nor­ was added to GH, they rose to 170 and 103 respectively. Thus GH mal. T therapy corrected the micropenis but not the Sa-reductase given alone depressed secretion of both cortlsol and adrenal andro· deficiency. Fami Iy study suggested reduced 170H activity in the gens; this could be due to depression of endogenous ACTH secretion father and reduced Sa-reductase activity in the mother. Although or to interference with the effect of ACTH on the adrenal. The data the data suggest this boy may be a double heterozygote, a more from the combined GH-ACTH period are compatible with either mechan­ direct link between l]OH-deficiency and target cell Sa-reductase ism. cannot be excluded.

J. s6LYOM /Intr. by J. Perheentupa!. M. Zachmann , E. A. Werder, B. Manella * and A. Prader 132 2nd Department of Paediatrice, Semmelweie 135 DepLof Pediatrics. U.of Zurich. Switzerland. Medical Univereity, Budapeet, Hungary 17.20-Desmolase deficiency - clinical and biochemical heterogeneity. 71uctuation of blood-epot 17-oH-progeeterone level in infante with congenital adrenal hyperplaeia. 3 XV-individuals were studied at a pubertal age. No.1 and 2 Serial eampling for determination of 17-0H-progee­ were the original patients (Zachmann et al .• Clin. Endocr. 1.369, terone by radioimmunoaeeay ueing dried capillary blood 1972) with intersexuality. raised as boys. No.3 (unrelated) had epote were rerformed throughout the day in eight in­ female external genitalia and was raised as girl. 1 and 2 had male fante with congenital adrenal hyperplaeia due to 21­ puberty. but 3 not. Serum testosterone (T) before and after HCG hydroxylase deficiency in order to check the value (5000 IU/m2) was (ng/dl): of a eingle random eample for identification of pati­ No. age (y) bone age (y) basal day 2 day ij day 6 ente and in monitoring therapy. The eamplee were ta­ l1Z.7 13.25 331 S9ij 5H ij60 ken in different part of the country and eent into 2 13.0 lij.O 121 3B6 2Bij ij03 the laboratory by mail. Marked variation of dot-17­ 37 25 OHP valuee in a range of diagnostic high level wae 3 15.0 12.0 36 H obeerved before starting therapy without any sign of Androstenedione was low (62.76.29 ng/dll. 170H-progesterone was diurnal rhythm. Repeated sampling for dot-17-0HP du­ normal or high (182.212.5Bl ng/dl) and increased after HCG (31ij. ring the firet weeke of treatment 381.13B6 ng/dl). most in 3 with the lowest T. DHA before and after ehowed persietent fluctuation at pathological high HCG was low in 1 and 2 (170-119.178-160 ng/dl). but normal in 3 levels. While receiving glucocorticoid therapy for (530-ij05 ng /dl). In urine. pregnanetriolone was present (0.62. 0.32. some monthB 17-0HP concentrations were suppressed Z.2mg/Hh) and the 17-ketosteroids were normal or low (S.8.ij.l,1.ij ehowing moder.ately elevated levele in the morning mg/2ijh). It is concluded that the degree of the defect may vary from and low levele in the evening. The blood-epot 17-oHP method can be used both for early identification and partial (1 and 2) to marked (3) and that it may concern both, the Aij­ follow-up of congenital adrenal hyperplasia caeee, andA 5-pathways (1 and 2). or theih-pathway only (3). however, 17-oHP profile over 24h are needed for Supported by the Swiss National Science Foundation (Grant No. monitoring therapy. 3.959.0BO).

1560