NEONATAL HYPOGLYCEMIA ASSOCIATED WITH ANTERIOR , 283j HYPOPITUITARISM. David R. Brown and David B. Klain . Dennis E. Carey, Kenneth Lee Jones, Children's Health Center and Dept. of Peds. Univer- Jacqueline G. Parthemore, and Leonard J. Deftos. sity of Minnesota, Minneapolis. (spon. by Robert A. Ulstrom.) of California San Diego School of Medicine and San We have observed the association of profound hypoglycemia and Diego VA Hospital. Departments of Pediatrics and Medicine. La anterior hypopituitarism in four newborns. All presented with Jolla, California. Q'nQ?*--<- hypoglycemia during the first 30 hours of life, which reached The secretion of calcitonin (CT) was studied in 17 children, levels less than 10 mg.%. Rates of 20-30 mg./kg./min. of 20% 10 with hypopituitarism and 7 with agoitrous hypothyroidism. dextrose were required to maintain glucose levels above 30 mg.%. Plasma CT levels were measured by radioimunoassay in the basal All infants were products of complicated pregnancies and deliver. state and following infusion of pentagast#n (0.5 &/kg) and 10 ies and had APGAR scores of five or less at one and five minutes minute infusions of calcium (2.3 mg/kg Ca as CaCl ). Of the Measurements of anterior pituitary function including serum 10 children who have hypopituitarism, 5 were studiej before and TSH, T4, ACTH, cortisol and growth , in addition to meta- after one year of human growth hormone (HGH) and 5 were pyrone and cosyntropin stimulation, revealed anterior panhypo- studied before treatment only. Basal and peak response CT level: pituitarism in three infants and isolated ACTH deficiency in the were essentially unchanged by HGH. In the patients with hypo- other. Posterior pituitary function was normal in all cases. pituitarism, CT levels increased from 41.9 Z 5.1 pglml to a Unresponsiveness of TSH to intravenous thyrotropin releasing peak of 67.4 + 10 pg/ml after pentagastrin and from 38.8 t 5.2 hormone (TRH) and normal serum levels further support pg/ml to a peak of 107 f 14.9 pg/ml after calcium infusion. In anterior pituitary dysfunction in contrast to a hypothalamic the cretins, CT levels increased from 33.8 ? 6.5 pg/ml to 35.8 etiology. Autopsy on one infant revealed no anterior pituitary f 7 pg/ml following pentagastrin and from 31.4 ? 5.9 pg/ml to tissue. The three surviving patients are all doing well on 40 f 4.9 pg/ml following calcium. Although basal levels of CT appropriate hormone replacement. Micropenis was present in the seemed to be lower in cretins, these values could not be rigor- one male and all infants showed a widening of the midfacies. ously validated. The patients with hypopituitarism had greater This unappreciated cause of early neonatal hypoglycemia may CT responses than the cretins, especially to calcium infusion. be related to birth hypoxia or anatomic malformation of the ant- These studies suggest that children with hypopituitarism have erior pituitary and its rudiments. These may be more susceptibl a greater CT response to calcium infusion than do normal adult: to events at birth than previously appreciated and consequently and that CT secretion is abnormal in patients with athyreotic this system should be more agressively evaluated in newborns. cretinism.

ANTIBODIES TO LUTEINIZING HORMONE IN A PATIENT TREAT- 5 I CLLUS WIIH ED WITH GROWTH HORMONE. S. Burstein, F.A. Conte. S .L. G~~W~OAT~O~??Brown,N. Kaplan, and M.M. Grumbach. Dept. Pediatrics, Univ. of Solomon, E. Dunn, and N. Muthukrishnan. Depts. of- an Francisco, San Francisco, Ca. Pediatrics and Radiology, SUNY, Downstate Med. Ctr., G'klyn, N.' Many clinical grade preparations of hGH (human growth hormone) Eight sickle cell patients, 9-15 yr., with severe growth re- are contaminated with hLH and hFSH. However, no evidence of a tardation, retarded bone age and delayed puberty had normal ser clinical effect of such contamination has been described. We re- um concentrations of T4,T3,PRL after stimulation port the development of antibodies to hLH in a patient treated and normal adrenal functions measured by circadian variation of rith hGH for isolated GH deficiency. plasma cortisol, plasma cortisol during hypoglycemia, ACTH and J.C. was first investigated for short stature at 7-11/12 years metyrapone tests. hGH response to -induced hypoglycemia and GH therapy was begun at 8-9/12 years for a diagnosis of iso- was abnormally low in 4/8. Four males and 3 females had ele- lated GH deficiency. On LRF (luteinizing hormone releasing factor: vated plasma concentrations of LH and FSH; 4 males had low testing, the LH rose from 0.8 to 1.2 ng/ml (LER 960); FSH responsc plasma and 3 females had low plasma . The slso was normal. At 11-11/12 years the patient was still prepu- severe growth retardation seems to result from a primary gonadal ~ertalwith undetectable testosterone levels. A repeat LRF test hypofunct ion associated in some cases with hCH deficiency.

revealed an "apparent" basal plasma LH of 25.4 ng/ml. Further , a svnthetic androoen.d, was administered for one ;tudies indicated that his serum had antibodies to hLH which ha\ year at 2 to 4 mg daily. Range of growth rate before therapy ,ersisted for over 2-112 years on without was 1.2-4.9 cm/yr; during therapy was 3.6-15.6 cmlyr. There was :he development of significant GH antibodies. 1251-hLH was bound no acceleration in bone age. No significant changes in Hgb., :o his serum in a displacable fashion; hFSH and hTSH displaced Hct., reticulocyte count and fetal Hgb occurred. A striking :his tracer only at doses compatible with contamination of these finding was a consistent increase in red cell mass measured by itandards by hLH. Radioiodinated hFSH, hTSH and hLH-a were not 51Cr tagging of the RBC. There was a tendency towards a further ~ound;the antibody is directed against the LH-6 subunit. The shortening of an already short 51Cr RBC survival in 4/6. There ,inding capacity of the serum and the equilibrium constant for were no consistent changes in an already very low plasma 59~e the binding reaction are sufficiently great to be physiologicall) disappearance rate. Ethylestrenol, was found to stimulate growth without accelerating bone maturation, and to increase red cell mass without prolonging red cell survival. Isupported by NIH Grant RR-318

- - A Virilizing Adrenocortical Tumor in a Female Infant: E EFFECT ()F HYPOXIA ON PERIPHERAL METAROI.TSM OF Steroidogenesis In Vivo and In Vitro. Lucienne A. HYROXINE . ,. .Cliance, 'l.i:a?lan, T.'los!!an~ Jr . .? .l'ti per 285 288 and O.Talahashi,-- Qept. of Der', , l'ahnenan; 'led .Coil . Cahen, Dorothy B. Villee, M. Linda Powers, and John F and Vept. of red., l'niv. of Pa., "I~iln.,Pa. F. Crigler, Jr., Harvard Med. Sch., Children's Hosp. Med. Cen., The peripheral etah holism of TI, has heen noted to he ~lterrd Endocrine Division. Boston, Mass. in a number of non-thvroiclal illnesqe?. The known relationsl~ip Normal adrenal and adrenal tumor cells from a female infant with a virilizing adrenal tumor were grown in tissue culture for of thyroid and oxvpen consumption lrd to tl~escstuc'irs

investigatinc. the~ effects. --- of )~vnoxinon nerinllcr?l 7-t.taholi\n or a period of 7 weeks with and without ACTH (0.1 unitlml). The cells grew well and continued to produce steroid hormones, as TI, TI,,T2, rT? and TT.17 levels were c!rtcrminr tah~~lat~rl1,rlmi ture medium. Compared to normal cells, tumor cells with no ACTH rT TC!' added produced equivalent amounts of cortisol, 180H corticoster- "('7 T/, I-? mnll~ up/