NEONATAL HYPOGLYCEMIA ASSOCIATED WITH ANTERIOR STUDIES OF PLASMA CALCITONIN IN HYPOPITUITARISM AND 2831 HYPOPITUITARISM. David R. Brown and David B. Klain HYPOTHYROIDISM. Dennis E. Carey, Kenneth Lee Jones, Children's Health Center and Deot. of Peds. Univer- Jacqueline G. Parthemore, and Leonard J. Deftos. sity of Minnesota, Minneapolis. (spon. by Robert A. Ulstrom.) of California San Dieno- 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 92093 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 radioimmunoassay in the basal All infants were products of complicated pregnancies and deliver state and following infusion of pentagast#n (0.5 pg/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 studie3 before and TSH, T4, ACTH, cortisol and growth hormone, in addition to meta- after one year of human growth hormone (HGH) therapy 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 ? 5.1 pg/ml 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 prolactin levels further support pg/ml to a peak of 107 + 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 + 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 + 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 1 CT responses than the cretins, especially to calcium infusion. be related to birth hypoxia or anatomic malformation of the ant- 8 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 adults to events at birth than previously appreciated and consequently and that CT secretion is abnormal in patients with athyreotic Ithis system should be more agressively evaluated in newborns. cretinism.

ANTIBODIES TO LUTEINIZING HORMONE IN A PATIENT TREAT- ED WITH GROWTH HORMONE. S. Burstein, F.A. Conte. S .L. ROWTH RETARDATION S. Castel Is, A. Brown, N. Kaplan, and M.M. Grumbach. Dept. Pediatrics, Univ. of E. Dunn, and N. Muthukrishnan. Depts. of- an Francisco, San Francisco, Ca. ology, SUNY, Downstate Med. Ctr., G'klyn, N.Y 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 chlorpromazine stimulation, port the development of antibodies to hLH in a patient treated and normal adrenal functions measured by circadian variation of with 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 insulin-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 respons plasma testosterone and 3 females had low plasma estradiol. 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 hypofunction associated in some cases with hGH deficiency. revealed an "apparent" basal plasma LH of 25.4 ng/ml. Further Ethylestrenol, a synthetic androgen, was administered for one ;tudies indicated that his serum had antibodies to hLH which hav year at 2 to 4 rng daily. Range of growth rate before therapy >ersisted for over 2-112 years on growth hormone therapy without was 1.2-4.9 cm/yr; during therapy was 3.6-15.6 cm/yr. There waz :he development of significant GH antibodies. l251-h~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 51~rRBC 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 he binding reaction are sufficiently great to be physiologically disappearance rate. Ethylestrenol, was found to stimulate ignificant. growth without accelerating bone maturation, and to increase rec cell mass without prolonging red cell survival. I Supported by NIH Grant RR-318

A Virilizing A renocortical Tumor in a Female Infant: SteroidogenesidS In Vivo and In Vitro. Lucienne A. Cahen, Dorothy B. Villee, M. Linda Powers, and John F. Crigler, Jr., Harvard Med. Sch., Children's Hosp. Med. Cen., Endocrine Division, Boston, Mass. The peripheral Aetaholisn of TI, has heen notcd to h~ altered Normal adrenal and adrenal tumor cells from a female infant in a number of non-thvroiclal illnesses. The known relationsl~ip with a virilizing adrenal tumor were grown in tissue culture £01 of thyroid hormones and oxvRen consumption led to these studies a period of 7 weeks with and without ACTH (0.1 unit/ml). The investigatinp the effects of hvnoxia on nerinllcrnl 7-t.taholi5n or cells grew well and continued to produce steroid hormones, as TI,. TI,,T2, rT? and TT.11 levels were c!rtcrmine status astl~maticosand cvanotic Ilenrt ,lisr,n4~,nnne nf r.!'lnr WPrr measured by radioimmunoassay of individual steroids in the cul- ture medium. Compared to normal cells, tumor cells with no ACTH cachectic or malnor~risl,rd. 'lean renul ts(+Sr'')?rr tabulated '~eln!il added produced equivalent amounts of cortisol, 180H corticoster- "('7 T/, 7 rT TC!' one, and 180H deoxycorticosterone, but lesser amounts of dehydrc mnli~ up/rll nr/dl ny?~1 uU/i.l lnh .qth.7 ?l.6+1.To /#.Qtn. 1 epiandosterone (DHA), androstenedione (A), testosterone (T) and Controls Q.15t0.5 (17 h.752n.9 77.6+7.5 ?/I .7+fi .07 5./~5+!.^ progesterone. Normal cells exposed to ACTH showed an increase ir Chronic 'lvpoxia O7.7th.I 17.7tC.1 1.77t.l.h all steroids measured whereas ACTH-exposed tumor cells showed ar Acute Ilynoxia 66 7.hQf1.1 - 3 sianificant decrease in T7 levels wit!^ a sipnifi- increase principally in DHA, consistent with a deficiency in 3b There &-as hydroxysteroid dehydrogenase. Concentrations of DHA, A and T in cant incrca7e in rT7 in the patient? ~.ithr'ironic hv~oxin.i'ven the patient's serum were elevated before the adrenal tumor was hvnoxia of short duration raused a significant increase in rT7. removed. The relative concentration of the three androgens in T4 levels were also lower in the c'lrnnic hvpoxic proun. These media of tumor cells in vitro resembled that in patient's serum data are similar to the finrlin~sohtatner? drlrinp catnhnlic non- in vivo. These studies demonstrate that both normal and tumor thyroidal illnesses. Tbese alterations in t!i-rroirl Fllnction tcnts cells of adrenal can be maintained for a long time in vitro, nav reflect an afiantive nllenonenon at tile cellular level, i.e.,a that they retain their ability to respond to ACTH and that they ~rotectivemechanism vhich ran divert Tq to rT7, or convernelv, produce their characteristic steroids. The tumor cells appear t( as during cold exposure, can increase nrnductinn of T?. Tn lipht of these data correlatinp hvnnxia and Chvrnid hormones. the suo- have a 36-hydroxysteroid dehydrogenase deficiency. Supported by the National Foundation, the Grant Foundation, qestions that the low thvroid function levels in 'lnS infants mav be etiolosicallv related to R?S mav need to he reevaluated. and USPHS Grant RR00128, Div. Research Resources, NIH.