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A sensitive, simple, and rapid semiautomated sandwich enzyme immunoassay (EIA) was developed for measuring thyrotropin in dried blood samples on filter paper for use in screening for neonatal hypothyroidism. Good correlation was found between values for thyrotropin determined by this method and those determined by radioimmunoassay (RIA) (r=0.94). In pilot tests on 17,160 newborn infants in the general population, five cases of primary hypothyroidism were detected by both EIA and RIA. The recall rate was slightly highter in EIA than in RIA.

As a part of studies concerning clinical application of the measurement of urinary iodide with an iodide-selective ion electrode, we report here the reference values for the iodide content or concentration in morning spot urine specimens from normal subjects of varying ages and studies with patients with thyroid diseases in Japan. The number distribution of the iodide content or concentration in the morning specimens appeared logarithmic normal in adults, children and infants. Normal ranges found in 95 per cent of populations of healthy subjects were 5.3 to 62.0 mumoles/g Creatinine (Cr) for adults, 5.3 to 42 mumoles/g Cr for children, and 1.9 to 56 microM for infants, respectively. Urinary iodide concentrations in breast-fed infants varied widely compared with those in bottle-fed infants. Mean values were 16.4 microM for breast-fed infants and 8.6 microM for bottle-fed infants, and they were not statistically different. Urine samples from the infants with transient hypothyroidism, who had undergone amniofetography showed extraordinarily high iodide concentrations, even though they were measured at 20th, 29th and 30th days after birth. Although urinary iodide excretion in patients with simple goiter was within normal limits, the mean was statistically lower than that in normal controls (p less than 0.001). Because of the simplicity and rapidity of the electrode method, we strongly recommend it for use in examining iodide excretion in patients with various thyroid diseases.

A total of 663 children with various underlying diseases were immunized with a live varicella vaccine at the vaccine clinic of Osaka University Hospital during a period of seven years from October, 1975. Clinical reactions after vaccination occurred in 32.4% (24/74) of the children with malignancies and in 0.3% (2/591) of those in other groups. Vaccine-induced immunity was detected for more than 6 years, by FAMA (fluorescent antibody to membrane antigen) and IAHA (immune adherence hemagglutination) tests, and a skin-test for varicella-zoster virus (VZV). During an observation period of more than 7 years, clinical varicella developed in 12 children, 8 of whom were in the group with malignancies. Zoster occurred in only 4 (9.1%) of 44 vaccinees with acute leukemia, this incidence being significantly less (p less than 0.05) than that (21.6%, 8/37) in un-vaccinated leukemic children.

Ammonia metabolism was studied in an 8-year-old girl with ornithine transcarbamylase (OTC) deficiency, using 15N-tracer. Changes in the incorporation of 15N into amino acids and urea were examined after 15NH4Cl administration. The recovery of total 15N in the urine of the patient in 3 days was 28.5% of the administered 15N whereas that of a control was 69.3%. They were mostly urea. The recovery of 15N-urea in the patient was 28.8% of the control in 1 day, 32% in 2 days and 33.3% in 3 days after the administration of 15NH4Cl. A larger amount of 15N was incorporated into glutamine (alpha-amino N) and glutamate and 15N was incorporated more rapidly into alanine, asparagine and serine in the patient than in the control. The incorporation into ornithine was less in the patient than in the control.

Seventy-three infants born to HBeAg positive HBV carrier mothers were protected from neonatal HBV infection with our standard prevention schedule consisting of two doses of HBIG (0,2 mo) and three doses of HBV vaccine (2, 3, 5 mo). In 62 infants who successfully responded to HBV vaccine with a titer of anti-HBs greater than 2(3), anti-HBs titer was monitored for as long as 48 months (25.6 +/- 11.0 mo) and found to decrease as follows: 5.1 +/- 1.7 at 12 mo., 4.5 +/- 1.8 at 18 mo., 4.2 +/- 1.8 at 24 mo., 4.0 +/- 1.6 at 30 mo., 3.7 +/- 1.7 at 36 mo., 3.2 +/- 2.0 at 48 mo. During the follow-up period, eight HBV events (11.9%) were demonstrated: one case showed an increase of anti-HBs, three showed a reappearance of anti-HBc alone, three showed a reappearance of anti-HBc with increase of anti-HBs, and one became a chronic HBV carrier. All infants were further divided into three groups by their maximal response of anti-HBs to HBV vaccine: Group I (greater than or equal to 2(6)), Group II (2(3)-2(5)), and Group III (2(2) greater than or equal to). Group I sustained a higher titer from 12 to 30 months of age and had less HBV events than G-II and G-III. Our study suggests that acquisition of a high titer of anti-HBs is important in long-term prevention of HBV infection as well as in the neonatal period in infants born to HBeAg positive HBV carrier mothers.

Somatotropic, thyrotropic, gonadotropic and corticotropic functions in 10 patients with idiopathic hypopituitary dwarfism (IH) were investigated. The patients were divided into two groups: Group I (5 patients) had normal plasma T4 levels, and Group II (5 patients) had T4 levels of less than 4.6 microgram/dl. In Group I three cases had isolated growth hormone (GH) deficiency and two cases had GH and gonadotropin (Gn) deficiencies; in Group II the 5 cases showed multiple anterior pituitary hormone deficiencies. In Group II, the plasma thyroid stimulating hormone (TSH) was 4.1-9.4 muU/ml and the response to thyrotropin releasing hormone (TRH) was greatly delayed and prolonged, with a maximum after 120 min instead of 15 min. The basal prolactin (PRL) level in Group II was 12-31 ng/ml, which was significantly higher than normal (P less than 0.001). In 4 cases in Group II, the plasma cortisol level increased 120 min after the infusion of lysine-vasopressin, whereas oral administration of metyrapone and hypoglycemia induced by insulin did not increase the plasma cortisol levels. From these findings it is concluded that hypothalamic lesions caused the pituitary hormone deficiencies in 4 Group II cases, and Group I may tentatively be differentiated from Group II by T4 determinations.

An effective method of prediction of neonatal transient hypothyroidism was examined in 105 neonates (including a pair of twins) born to mothers with chronic thyroiditis (92 mothers with goitrous Hashimoto's disease and 12 with primary atrophic hypothyroidism). Antithyroid microsomal antibody was measured by a hemagglutination technique (MCHA), and antithyroid-stimulating hormone (TSH) receptor antibody by both radioreceptor assay (TBII) and biologic thyroid-stimulation blocking assay (TSBAb). For generalization of predictive criteria, the expression of TBII activity was standardized using standard serum made taking units of MRC-LATS-standard B as a reference, and that of TSBAb activity was standardized as the degree of dilution with normal pooled serum to attain 50% inhibition of TSH (100 microU/ml)-induced cyclic adenosine monophosphate increase (TSBAb50). The MCHA titer in maternal serum at delivery correlated well with that of the corresponding cord serum, but not with the free thyroxine (T4) index or the TSH level in cord serum. TBII activity was positive in only 4 of 12 mothers with primary atrophic hypothyroidism, TSBAb activity was also positive only in these four mothers, and neonatal thyroid dysfunction was observed in three of their neonates. Two of these neonates developed transient hypothyroidism requiring T4 treatment, and the t third developed mild transient hyperthyrotropinemia with normal T4 and triidothyronine levels. The mothers whose neonates showed transient hypothyroidism had TBII activities of more than 300 U/ml and TSBAb50 activities of more than 300. Ninety-two mothers with goitrous Hashimoto's disease had neither TBII nor TSBAb activity, irrespective of their thyroid function, and delivered euthyroid babies.(ABSTRACT TRUNCATED AT 250 WORDS)

A simple and reliable method of paired TSH assay was developed and used in screening for neonatal primary hypothyroidism. In this method, a paired assay is first done. Equal parts of the extracts of dried blood spots on filter paper (9 mm diameter) from two infants 4-7 days old are combined and assayed for TSH by double antibody RIA. If the value obtained is over the cut-off point, the extracts are assayed separately for TSH in a second assay to identify the abnormal sample. Two systems, A and B, with different cut-off points were tested. On the basis of reference blood samples (serum levels of TSH, 80 microU/ml in system A and 40 microU/ml in system B), the cut-off point was selected as follows: upper 5 (A) or 4 (B) percentile in the paired assay and values of reference blood samples in the second individual assay. Four cases (2 in A and 2 in B) of neonatal primary hypothyroidism were found among 25 infants (23 in A and 2 in B) who were recalled from a general population 41,400 infants (24,200 in A and 17,200 in B) by 22,700 assays. This paired TSH neonatal hypothyroidism.

In children with biliary atresia, defective intestinal absorption of vitamin D and impaired hepatic uptake and 25-hydroxylation of vitamin D lead to a deficiency of vitamin D and rickets. We recently observed severe rickets in a 3-year-old boy with corrected biliary atresia resulting in jaundice, despite oral treatment with 1 alpha-hydroxyvitamin D3 (1 alpha-OHD3) or 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. He had low 25-hydroxyvitamin D (25-OHD) and high 1,25-(OH)2D serum levels. Intramuscular vitamin D2 administration produced radiological and biochemical evidence of recovery. Oral 1,25-(OH)2D3 (0.1 microgram/kg) and 25-OHD3 (10 micrograms/kg) tolerance tests were done to assess the ability to absorb vitamin D and the effectiveness of using these drugs orally. Eleven children with corrected biliary atresia, aged 9 months to 7 years, were studied. In oral 1,25-(OH)2D3 tolerance tests, the increments above the baseline serum levels of 1,25-(OH)2D were 140.7 +/- 27.4 pg/ml in nonjaundiced patients (n = 5). In jaundiced patients (n = 3), 1,25-(OH)2D3 absorption in two patients with high basal 1,25-(OH)2D values was lower than that of nonjaundiced patients; however, the absorption in the third patient with a low basal value was similar to that of nonjaundiced patients. In oral 25-OHD3 tolerance tests, the mean increase of serum 25-OHD was 48.9 +/- 30.6 ng/ml in nonjaundiced patients (n = 5) and 23.7 +/- 9.5 ng/ml in jaundiced patients (n = 4), the peak serum 25-OHD levels being reached 6-12 h after 25-OHD3 loading.(ABSTRACT TRUNCATED AT 250 WORDS)