Serum concentrations of TSH, freeT4 (f-T4) and freeT3 (f-T3) were determined simultaneously in 199 fullterm newborn babies from 12 to 168 hours after birth. In addition, cord sera from 29 fullterm neonates were analyzed similarly. Cord blood concentrations of TSH were higher, and of f-T3 were lower than seen in adults and f-T4 was similar to the adult range. Serum concentrations of TSH showed a marked increase during the first day of life followed by a decline to the adult range on day four. The free thyroid hormone values increased to the maximum levels within 24 to 48 hours followed by a decrease, but remained higher than in adults even at 168 hours. The f-T3/f-T4 ratio was found to be lower than in adults except between 12 hours and 24 hours. These data allow us more detailed discussion with regard to hormonal dynamics in the newborn. Furthermore, our study is the first to successfully establish the reference intervals for TSH, f-T4 and f-T3 during the first seven days of life utilizing the most widely used kits and sufficient numbers of samples. These references will be of great assistance for prompt and proper evaluation of neonates at risk for thyroid dysfunction.

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Estrogen plays an important role in bone maturation and bone mineralization. To elucidate the physiological roles of estrogen in the regulation of bone growth, we investigated the relationship between bone mineral status and the estrogen receptor (ER) gene polymorphism in subjects with precocious puberty, where excess estrogen is exposed to the bone. Thirty-six patients with central precocious puberty or early puberty were enrolled in the study. The relationships between PvuII and XbaI restriction fragment length polymorphisms of the ER gene and the lumbar spine bone mineral density (BMD), BMD SD score adjusted for either chronological age or bone age, were evaluated. The mean BMD value for bone age (-0.52 ± 0.83 SD) was significantly lower than the BMD value for chronological age (0.30 ± 0.96 SD) (p<0.01), indicating that bone maturation (advancement of bone age) was not associated with bone age-matched mineralization (increase in BMD). Furthermore, the PP genotype for the PvuII polymorphism appeared to be associated with an increased BMD (p<0.05), suggesting that the ER gene genotype may be related to bone mineral accretion during estrogen exposure. ER gene polymorphisms might thus account for the varying degrees of increase in BMD after estrogen exposure, leading to the dissociation of bone maturation and bone mineralization.

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We present the cases of two girls with ovarian hyperandrogenism. They had clinical signs of hyperandrogenism: deep voice, hypertrichosis and amenorrhea. Case 1 was a 13-year-old girl with insulin receptor dysfunction suspected, because of a low dose of insulin utilization in the glucose clump test. Case 2 was an 11-year-old girl with polycystic ovary syndrome. In the two cases, OGTT showed impaired glucose tolerance and high serum concentration of IRI. HCG stimulation test revealed hypersecretion of testosterone probably from the ovary. A polycystic ovary or an enlarged ovary was detected by magnetic resonance imaging. We suggest that in these two cases the hypersecretion of testosterone from the ovary was associated with high serum IRI.

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A 17 9/12-year-old female with familial diabetes insipidus (FDI) and idiopathic hypoparathyroidism is described. We analyzed the arginine vasopressin-neurophysin II (AVP-NPII) gene in her family, and a novel heterozygous mutation in exon 2 of the AVP-NPII gene was noted in the patient and her mother. This deletion mutation results in a frame shift beginning at codon 70 and a premature termination at codon 80. Only two cases of non-FDI and idiopathic hypoparathyroidism have been reported so far, but there has been no report on the association of FDI and idiopathic hypoparathyroidism. The causes of this association are not known and it is not known whether it is accidental or not.

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Pallister-Hall syndrome was first described by Hall et al. in 1980. This syndrome is characterized by hypothalamic hamartoblastoma, hypopituitarism, polydactyly, imperforate anus and other anomalies. We report a case of a male infant with hypothalamic tumor, hypopituitarism, dysplastic metacarpals, micropenis and remarkable hypoglycemia. He has been treated with hydrocortisone, thyroid hormone, NaCl, fludrocortisone acetate and GH. He has grown well on this therapy.

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We report here a girl (the proband) and her mother with del(X)(p11.2) showing few somatic stigmata of the typical Turner syndrome. The proband exhibited short stature, cubitus valgus, short 4th metacarpal, multiple pigmented nevi and epicanthal fold, while her mother exhibited short stature, cubitus valgus, and short 4th metacarpal. Pubertal changes occurred in both of them. The mother had menarche at 12 years and menopause at 37 years 7 months, indicating premature ovarian failure. The grandmother of the proband had cubitus valgus but normal karyotype. There were many patients with thyroid disease on both their paternal and maternal sides. The proband and her mother had overt hypothyroidism, compensated hypothyroidism, and euthyrodism respectively, though all of them showed positive antithyroid antibodies. In Turner patients with del(Xp), there are many important issues, including determination of the loci of some genes on the X chromosome and genetic counseling.

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We studied the clinical characteristics of Japanese children with idiopathic type 1 diabetes who had had a remarkably rapid onset, severe metabolic disorder and absolute insulin deficiency at diagnosis. In 85 Japanese children with type 1 diabetes, 14 (16.5%) were classified as idiopathic type 1 diabetes mellitus with no evidence of anti-islet autoantibodies. Among the 14 patients with the idiopathic form, three were identified as having a fulminant onset form. These three patients had had a remarkably rapid onset with a short symptomatic period of less than seven days prior to the onset of overt diabetes. They exhibited severe ketoacidosis and had low levels of HbA1c despite high concentrations of blood glucose at diagnosis. Their initial serum C-peptide levels were extremely low or undetectable. Most of the patients experienced viral infections prior to the onset of the disease. These findings suggest that the nonautoimmune, fulminant onset form of type 1 diabetes may be not rare in the Japanese population. This form is characterized by a remarkably rapid onset with severe metabolic disorder and absolute deficiency of insulin secretion at onset. Viral infections may be associated with the rapid destruction of beta-cells without an autoimmune mechanism.

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To reveal the relationship between birth weight and type II diabetes mellitus (DM) in obese children. Obese children (128 boys and 52 girls) with a mean age of 10.3 years were examined. The mean percent relative weight was 48.3% in boys, and 53.7% in girls. The fasting serum level of insulin and fasting plasma glucose were measured, and the homeostasis model assessment (HOMA) was calculated. Maternity record books were used to determine the weeks of gestation and the standard deviation score (SDS) for birth weight was calculated. The relation between insulin and HOMA, and birth weight and birth weight SDS were analyzed by simple regression. In boys, no relationship was found between serum insulin and birth weight. HOMA showed a negative correlation with birth weight SDS (r=-0.175, p<0.05). In girls, serum insulin showed a negative correlation with birth weight and birth weight SDS (r=-0.287, p<0.05, r=-0.316, p<0.05). HOMA showed a negative correlation with birth weight and birth weight SDS (r=-0.289, p<0.05, r=-0.315, p<0.05). Also, percent relative weight showed a negative correlation with birth weight and birth weight SDS (r=-0.301, p<0.05, r=-0.307, p<0.05). This study suggested a relationship between low birth weight and hyperinsulinemia. Fetal malnutrition in utero may lead to insulin resistance. We consider that low birth weight is one of the risk factors for type II DM in obese children.

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We investigated the incidence of diabetic retinopathy and nephropathy in juvenile-onset type 1 diabetic patients and the impact of metabolic control and other risk factors on the incidence of retinopathy and nephropathy. A clinic-based observational longitudinal study was performed. Patients visited our outpatient clinic at the Diabetes Center, Tokyo Women's Medical University from 1980 to 1998. Participants for the study were 533 patients with type 1 diabetes. Fukuda's classification for fundoscopic findings grade (A1, A2, and B1) corresponded to non-proliferative retinopathy and the other grades to proliferative retinopathy. Incipient nephropathy was defined as that in which the albumine-creatinine ratio (ACR) was 30-300 mg/g.Cr, and overt nephropathy was defined as that in which ACR was over 300 mg/g.Cr. The predictive effect of independent variables was explored using Cox's proportional hazard regression analysis. Independent predictors were HbA1c, total-cholesterol, triglyceride, duration of diabetes, systolic blood pressure (BP) for non-proliferative retinopathy, HbA1c, diastolic BP, and total-cholesterol for proliferative retinopathy, HbA1c and duration of diabetes for incipient nephropathy, and HbA1c and onset age for overt diabetic nephropathy. Systolic BP was a significant independent risk factor for non-proliferative retinopathy, and diastolic BP was an independent risk factor for proliferative retinopathy. Once retinal vascular injury has been initiated, greater diastolic pressure may promote progression. Duration of diabetes was an independent risk factor for both non-proliferative diabetic retinopathy and incipient diabetic nephropathy, but was not a risk factor for either proliferative diabetic retinopathy or overt diabetic nephropathy. Strict control of blood glucose, BP, and lipid metabolism are mandatory for reducing the risk of progression of diabetic complications.

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