- 1 EVALUATION OF THE RENIN-ALDOSTERONE SYSTEM DURING 862 : HYPO- AND HYPERGLYCEMIA IN CHILDREN AND ADOLESCENTS. Zeev Hochberg, Zvi Dickerman, Hayutah Kaufman and Zvi Laron (Spon. by Frank A. Oski) Inst. of Pediatric and Adoles, 'cent Endocrinology. Beilinson Med. Ctr.. Petah Tikva, Israel. The effect of insulin-induced hypoglycemia and load- ing on the renin-aldosterone system was studied in 10 normal children and adolescents, aged 8 to 16 years in an attempt to find a simple tool for the evaluation of this system. The nadir ormal serum PTH. During pregnancy, serum HPL and other hormones of insulin induced hypoglycemia was followed 15 min. later by a re increased, but during lactation only HPL remains elevated. 371 + 139% (m + SEM) elevation of plasma renin activity (PRA). e studied lactating mothers and non-lactating controls for froma basal level of 2.9 + 0.4 ng/ml/hour (m + SEM) to 7.9 + 4,25(OH)2D, 250HD, PTH, HPL, calcium and magnesium at 6 weeks 1.9 (p< 0.025). Plasma aldosterone levels increased 243 + 21% ost partum. In nursing mother 24,25(OH)zD was significantly (m + SEM) from a basal level of 7.3 + 0.7 ngldl to 19.9 + 2.3 (~(0.005). A standard oral glucose load (1.75 glkg body weight) was followed by an insignificant elevation of PRA. Plasma aldos- terone levels decreased 53 + 11%(m + SEM) 15 min. after the glucose peak, from 10.6 + 1.1 to 3.9 + 0.2 ngldl (p< 0.005). The theoretical basis by which insulin-induced hypoglycemia results y enable the lactating woman to maintain normal serum calcium in the elevation of PRA and aldosterone could be a combination of K+ shift, ACTH secretion, catecholamine surge and glu- cagon rise. All of these are known to be stimulated by insulin hypoglycemia and to stimulate the renin aldosterone system. The 19.3 -+ 1.3 aldosterone suppression by the oral glucose load was independent The mechanism of this suppression is still unknown. 7.4?0.4(n=47) 7.9 t .48 6.6 ? 1.3 of the PRA. It is suggested that the ease of administration makes the insulin tolerance and oral glucose tolerance tests useful in the investigation of the renin aldosterone system.

MARKED ELEVATIONS OF OCTANOIC ACID AND OTHER THE QUANTITATIVE EVALUATION OF NUTRITIONAL RICKETS MEDIUM CHAIN FREE FATTY ACIDS UNASSOCIATED USING URINARY EXCRETION. Zeev Hochberg WITH CEREBRAL SYMPTOMS. Richard E . Hillman, and Daniel Hardoff (Spon. by Frank A. Oski), Dept. Darryl C . DeVivo , James P . Keatin . (Spon . by Jean Holowach) . of Peds, Rothschild University Hospital, Haifa. Israel. Washington Univ . Sch . of Medicine, Ft . Louis Children's Hospital, Phosphaturia is a prominent feature of nutritional rickets. Dept . of Pediatrics, St. Louis, Missouri. This investigation was designed to study the application of Octanoic and other short and medium chain free concen- phosphaturia in the quantitative assessment of nutritional trations (FFA) have been noted to be elevated in Reye syndrome and rickets. Seventeen infants aged 4-7 months with nutritional infusion of these substances has produced a similar syndrome in rickets were studied. The severity of the rickets was deter- animals. Thus, these substances have been implicated as causal mined using clinical, radiological and chemical criteria. A factors for some of the symptoms in this problem. MCT's are used to scoring method was designed with 9 parameters, each scored from treat a variety of children. They have been demonstrated to produce 0 to 3. The additive score defined the severity of the disease. elevations of FFA in . We measured medium chain FFA in pa- This was correlated with the degree of phosphaturia, measured tients receiving MCT's chronically. A patient with type IB glyco- by tubular reabsorption of phosphorus (TRP) and the phosphate genosis had extreme elevations of C7-C10 FFA. She also had elevat- excretion index (PEI). TRP and PEI were calculated from a ed butyrate and isobutyrate but not propionate or valerate levels. single blood and concomitant urine specimen. TRP was negatively Patients receiving MCT's as part of a ketogenic diet had mildly ele- correlated with the severity of nutritional rickets r - 0.914 vated concentrations of C8 and C9 FFA and variable concentrations o pt0.005. The infants who were most severely affected, as C7 FFA . None of these patients had cerebral symptoms. Thus, ele- expressed by higher scores, had the lowest TRP (32-702). The vations of medium chain FFA may be a secondary phenomenon in PEI correlated positively with the scores (r - 0.873, p< 0.01). Reye syndrome. The more rachitic infants had higher PEI's, in the range of M 0.25-0.61. These data indicate that the severity of nutritional u rickets can be assessed by calculating the TRP and PEI from a C7 C8 C9 C 10 single blood and urine specimen obtained simultaneously. Type IB (1) 229 56 39 23 Ketogenic diet (4) var. 9-18 4.4-5.7 0.6 Normal (10) <1.5 0.7-2.8 <1.3 0.6-1.2

VALPROIC ACID (DIPROPYLACETIC ACID)-AN INHIBI- 861 1 TOROF BRANCHEDCHAINFATTYACIDDEHYDROGEN- I ELLITUS, Sheldon D. Horowitz, Wa ne ASE . Richard E . Hillman, Leonard Berg, Darryl C . orcherdlny, berala J. narrnn.&ersity o DeVivo . (Spon . by Jean Holowach) . Washington Univ . Sch . Med., Center for Health Sciences, Department of muisChildren's Hospital, Dept . of Pediatrics, St. Louis, MO. I Pediatrics, Madison. Sodium , a new anticonvulsive agent, has been noted to Autoaggression against pancreatic islet cells has produce hyperglycinemia and hyperglycinuria. Measurement of been described in patients with mellitus. free short chain fatty acids in patients receiving this drug demon- Based on the hypothesis that a loss of immune regula- strate elevations of isobutyric , 2-methyl butyric , and isovaleric tory suppressor T cells could be important in the acids but not . Thus, this drug appears to be an acyl- development of these autoaggressive reactions, we CoA dehydrogenase inhibitor. However, unlike hypoglycin , it ap- examined suppressor function in 14 children pears to have a greater effect on branched chain than straight chain with insulin-dependent diabetes mellitus. Suppressor fatty acids. Since this drug appears to produce a secondary "hyper cell activity was determined by assessing the effectc glycinemia syndrome", it may provide a model for studying some as. concanavalin A-treated lymphocytes on the one-way pects of diseases of branched chain amino acid which are mixed leukocyte culture reaction. Suppressor cell associated with altered metabolism. activity was demonstrated in 15 of 15 normal controls Serum concentrations (IIM) However, 11 of 14 patients with insulin-dependent dia I I betes mellitus lacked suppressor T cell function. In IsoButyr Butyr 2-MeButyr Isovaler our sample, age, sex, duration of diabetes mellitus nd control of the disease did not correlate with the Patients (3) 9.1. 5.6 0.9, 0.6 11.5, 4.1 20.9, 7.9 resence or absence of suppressor cell activity. Our 6.2 0.6 3.8 8.9 ata suggest that decreased suppressor T cell functio. Controls (27) 0.8c0.4 0.7c0.5 trace 1.6t0.7 lay be important in the pathogenesis of some forms of 3iabetes mellitus. The relationship of HLA (HLA-A,B,C 3) and suppressor T cell function in diabetes mellitu is being investigated.