CORTICOSTEROID BINDING GLOBULIN (CRG) IN FET- _ - - TSH HYPERSECRETION AND TSHa AND TSHB SUBUNIT MEASURE- 383 AL AND NEWBORNSHEEP. P.L. Ballard, w. 386 MENTS IN NEPHROPATHIC CYSTINOSIS. Barry B. Bercu and Platzker, R.D. Bland, J.A. Kitterman, E. Joseph D. Schulman. Neonatal and Pediatric Medicine clyman, P.D. Gluckman, S.L. Kaplan, and M.M. Grumbach. Branch, National Institute of Child Health and Human Development, DeDt. Ped., Childrens Hosp., LOS Angeles, and Dept. National Institutes of Health. Bethesda. M) 20205 ~ei.& Cardio. Res. Inst., Univ. Calif., San Francisco. We have previously reported partial pituitary resistance to To examine the ontogeny and regulation of CBG in the in cystinosis (J. Cl in. Endocr. Metab. 51 :1262, perinatal period, we determined plasma binding 1980). In 10 of these same patients and 3 others we measured capacity using a charcoal absorption assay. CBG capac- basal serum concentrations of Tq, T3, TSH, TSHa and TSHB. In ity increased progressively from 1.6 pg/dl at 75 days cystinotics, mean concentrations of TJ (204 5 9 SEM ng/dl) and to 7.1 ug/dl at 141 days (n=249), with the greatest TSH (19 + 5 uU/ml) were elevated compared to age matched controls increase from 121 days to term. There was a similar but mean-~4 (9.1 + 0.7 ugldl) was normal. In 7 patients the increase in CBG (+41.1%) and total (+36.7%) in TSHa was elevatehbeyond the normal range (> 1.8 ng/ml). TSHB 6 fetuses during the 4-6 days before spontaneous deliv- levels were minimally increased in 2 patients and were normal in ery. After birth, both CBG and proteins decreased dur- 11 others. All patients with elevated TSHa had increased TSH ing the first half day; thereafter CBG decreased (t+= levels and the molar ratio of TSHa to TSH (2.2 + 0.5) in their 5 days) to 1.0 pg/dl at 14 days while proteins did not serum was equivalent to that of normal children: All cystinotics change. In 7 fetuses with loss of pituitary function with increased TSHa were 5-10 years of age with moderate to there was no increase in CBG during the 22-35 days af- severe renal impairment; some younger patients had abnormally ter surgery. Infusions of hydrocortisone for 2 days, elevated TSH but all had normal TSHa. Kouridis g a. reported for 5 days, for 5-8 days and ACTH high TSHa in patients with pituitary tumors but not in patients for 3 days to intact fetuses did not affect CBG levels. with isolated pituitary resistance to thyroid hormone (J. Clin. We, conclude that the pituitary controls the major Endocr. Metab. 45:534, 1977). In contrast, most of the cystin- increase in CBG after 121 days; there is an additional otics with pituitary resistance had high TSHa levels. The prepartum increase in all serum proteins with labor. extent to which renal impairment or other factors may account for The pituitary hormone(s) which stimulate CBG production the increased TSHa levels in cystinotics remains to be defined. are not identified, but this hormonal influence appar- ently ceases with birth.

THE INFLUENCE OF THYROXINE (T ) CONCENTRATION IN Thyronine Metabolism in Fetal Pulmonary type I1 eells HUMAN MILK (HM) ON NEONATAL T~YROID SCREENING (NEO- 387 M. Segall-Blank, W.Douglas, R.Sanders, K.Hitchcock. 384 T4). Raul C. Banaqale (Spon. by A. P. Erenberq) Dept. Tspon. C.Anast.) Dept. ~nat.Tuftssch.~ed.Boston,MA of Ped., Univ. of Iowa Hospitals and Clinics, Iowa City, IA and The importance of thyroid hormone in fetal lung development Dept. of Ped., Iowa Methodist Medical Center, Des Moines, IA. and surfactant production is well known. Yet, triiodothyronine In HM T is excreted in significant amounts after the first (T3), the active hormone, is present in low concentrftjpns in post-partu# week and may delay the clinical recognition of a fetal rat serum. We therefore studied metabolism of I T in hypothyroid infant (Acta Paediatr Scand, Supp 277:54, 1979). The surfactant-producing type I1 cells maintained in organotypfc cul- same study has shown that the HM T4 concentration during the ture (Douglas, W.H.J. et al. In Vitro 12:373-381, 1976). The type first 5 days post-partum to be low (0.7 f 0.3 ug/dl). However, I1 cells were obtained from fetal rat lungs at 16 and 19 days of the T measurements in HM were accomplished on a limited number gestation (term, 22-23 df~j).Cultures were incubated@ 36 hrs. of artificially expressed samples. Prior to completion of the in medium enriched with I T4 at 37'~. Products of I T met- present study, speculation existed whether breast feeding inter- abolism in medium, cell homogenate and a subcellular fractiin en- fered with the results of our NEO-T (1251 T RIA) which is done riched with nuclear material were assayed by chromatography. Con- routinely on the 3rd day of life. ~fletable !bows results of a firmation by radioautography was performfq5 The distributiog of 1 year study comparing the NEO-T4 values of formula fed (FF) and radioactive compounds expressed as % of I T added to 10 day breast-fed (BF) infant. 19 cells and corrected for spontaneous degradation, follows: MALES FEMALES MEAN Subcellular fraction medium cell homogenate uq/dl n ug/dl n ug/dl n %T4 degraded 21.4212.6 12.528.5 11.9f 3 FF 15.88 340 16.77 340 16.32 (680) %Iodide formation 6.324.1 12.423.5 3.522.0 RF 16.32 15661 16.61 15131 16.46 (1079) %T3 of total activity 7.722.3 0.1820.2 4.621.5 MEAN i6.G (906j 16.67 (853j 16.41 i1759j The results obtained from day 16 cells were similar. This sug- The observed difference (p 40.01 between BF and FF (lower gests that f45al type I1 cells can deiodinate T4. The high per- values) males does not have a biological explanation. However, centage of I T present in the cells suggfqss intracellular the overall difference between BF and FF infants (0.14 ug/dl) T3 generation. Thire is a total net gain of Iodide in the does not approach statistical significance and confirms that HM system. This excess iodide formation suggests pathways of thyr- T concentration does not interfere with the NEO-T4 results done onine metabolism which could result in formation and degradation 0% the third day of life. pf qT3+ Suchflhenolic ring deiodination may terminate in 3,3'-T2 3 -T or To.

ABNORMALITIES IN SECRET ION AFTER PRIMARY HYPERPARATHYROIDISM (HPT) IN INFANCY. Casey CRANIAL IRRADIATION IN PRIMATES. B.B. Bercu, G. 388 Jason, Sara B. Arnaud, Michael R. Harrison, Dennis M. 385 Chrousos, T. Brown, D. O'Neill, J. Schwade, and Styne, and Selna L. Kaplan. University of California, D.G. Po lackman7NwIK Beethesda, MD 2amPON: J .D. Department of Pediatrics, San Francisco, CA. TCK,- - .. - I I. &i-- .. . - . ., Hypercalcemia (fCa) due to HPT in infancy is rare and its lab- Abnormalities of GH secretion have previously been reported in oratory diagnosis difficult. We report a case with unusual fea- children given cranial irradiation for CNS prophylaxis in acute tures in which the assay of (iPTH) aided in lymphocytic leukemia or for brain tumors. To better define these the diagnosis and in the evaluation of the novel therapeutic tech- neuroendocrine abnormalities, prospective 1ongitudi nal studies of nique of autotransplantation. An 18 no old female was noted to GH secretion were erformed in young adult male rhesus monkeys have 4Ca (16.7 mg/dl) and hypophosphatemia (2.5 mg/dl) during (N.4 in each group!. Two doses of cranial irradiation were given evaluation for retardation. She was the first child of 5th cous- (2400 or 4000 rad in 10 fractions over 2 weeks). Three consecu- ins, both of whom had asymptomatic 4Ca (11.4 and 10.4 mg/dl) and tive provocative tests of GH secretion were used (arginine infu- 'normal' levels of iPTH (31 and 35 p1 eq/ml). The infant's head sion, induced hypoglycemia and L-Dopa stimulation) prior circumference was small (44 cm) and skeletal films showed little to radiation and 10, 30 and 50 weeks after radiation. The 2400 evidence of increased bone resorption in spite of high serum iPTH rad group at 10 weeks had an excessive and prolonged GH response (125 ul eq/ml, normal, < 56). Treatment with dietary calcium re- to arginine (GH at 30, 60 and 90 min was 1595, 37~11and 30+11 striction, saline, furosemide, phosphate, and decreas- ng/ml vs 22t4, 15+4 and 6+1 ng/ml for 13 controls, mean + SET ed serum calcium to 12 mg/dl; steroids did not influence the and insulind(GH a7 30 anh60 min was 4693 and 49+7 ng/mT vs course. At surgery, 3 hyperplastic and one normal sized parathy- 40t9 and 8+1.5 ng/ml for 9 controls). In subsequent studies, GH roid glands were removed (140 mg, total wt). Portions of one responses To arginine and L-Dopa were normal, but GH response to gland were implanted into the brachial muscle. Normocalcemia was insulin was blunted. In the 4000 rad group the arginine and maintained by decreasing doses of Dihydrotachysterol postopera- L-Dopa tests were normal throughout, but the response to insulin tiBely. This is the first known instance of HPT due to parathy- was consistently blunted. In conclusion, there are abnormalities roid hyperplasia in infancy in which both parents were affected of GH secretion after cranial irradiation with doses frequently with milder forms of the disease and, we believe, the youngest in used in clinical practice, but their clinical significance is whom the disease was treated by autotransplantation. not yet clear. This may be a useful model for the study of neuroendocrine regulation of GH secretion.