The changes in the leptin and ghrelin concentrations during the perinatal period are reviewed and their possible roles are discussed. In humans, leptin concentrations in cord blood were positively correlated with the birth weight and Kaup index. Most leptin was derived from fetal adipocytes, although the placenta has also been shown to make a contribution. An apparent gender difference in these concentrations (male<female) has been observed. After birth, these concentrations rapidly decreased and then gradually increased during the neonatal period. The developmental changes in the expression and localization of OB-Rb in the rat brain suggested that the setting point of leptin signal transduction changes with age during the neonatal period. The ghrelin concentration in cord blood was inversely correlated with birth weight, placental weight and the IGF-I concentration. IGF-I was a predominant factor that was correlated with the ghrelin concentration. The placenta seemed to contribute the ghrelin concentration in cord blood. During the early neonatal period, the ghrelin concentration significantly increased. The present results suggest that they might cooperatively regulate the energy balance during the perinatal period, and their expression in the placenta might contribute to the regulation of feto-maternal energy transport.

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We report a case of diabetic ketoacidosis with acute renal failure and elevation of pancreatic and muscle enzymes due to excess ingestion of sugar-containing soft drinks. A 12-yr-old boy suffering from consciousness disturbance was admitted to our hospital. He had had flu-like symptoms and had been consuming 1000-2000 ml of soft drinks everyday before the onset of ketoacidosis. Laboratory data on admission revealed marked metabolic acidosis, hyperglycemia, hyperosmolarity, hypernatremia, myoglobinuria, and elevated levels of creatine phosphokinase, myoglobin, blood urea nitrogen, creatinine, and pancreatic enzymes. Conventional fluid and insulin therapy were effective for these complications. Insulin therapy was discontinued within one month of hospital stay. Until this admission, there was no active intervention to resolve the problem of his family's lifestyle or to treat his obesity, therefore this neglect caused this unfortunate episode. Both medical doctors and school teachers should consider the importance of effective education and follow-up for young obese patients and intervene in childhood obesity actively.

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We present the case of a 3-year-old girl with McCune-Albright Syndrome (MAS). She was referred to our clinic for mammary gland enlargement and vaginal bleeding. A right ovarian cyst was detected by abdominal MRI and pelvic ultrasound examination, and it was followed up as a functional cyst. Endocrine studies showed gonadotropin-independent precocious puberty. A bone scintigram, revealed polyostotic fibrous dysplasia. These data confirmed the diagnosis of MAS without skin pigmentation (café-au-lait spot). We treated the patient with the aromatase inhibitor, anastrozole (Arimidex^R), because of repeated vaginal bleedings. After 6 mo of treatment, the frequency of vaginal bleeding was clearly decreased and the level of estradiol was down to within normal limits. The aromatase inhibitor, anastrozole, appears to be an effective treatment for precocious puberty caused by MAS.

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The effects of testosterone (T) for pubertal induction on bone mineral density (BMD) and biochemical markers of bone turnover were evaluated in three boys with testicular dysfunction. Testosterone enanthate (50 mg) was administered every 4 weeks for 1 year intramuscularly in all subjects. BMD and markers of bone turnover including serum osteocalcin, bone-specific alkaline phosphatase (bALP), urinary deoxypyridinoline (Dpyr), and N-terminal telopeptide of type I collagen, were measured before and during T treatment. BMD steadily increased during treatment. All markers of bone turnover were increased at 6 months of treatment, although increases were statistically significant only in bALP and Dpyr. An initial increase in markers of bone turnover has not been described in adults, but the observed changes resemble spontaneous puberty. The effects of exogenous T administration on bone turnover appear to differ depending on age.

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Serum IGF-I levels are one of the important clinical parameters in the evaluation of GH secretion. Almost all previous reports on the clinical utility of serum IGF-I levels in the evaluation of GH secretion have been based on the comparison between IGF-I levels and GH peaks of the GH provocation test. GH provocation tests have limitations such as a relative lack of normal values. There has been no report on serum IGF-I levels in short children whose heights were monitored over a range of years and whose diagnosis was made not based on GH peaks of the GH provocation test. The purpose of this study was to evaluate the clinical utility of IGF-I levels based on clinical and auxological data without using GH peaks of the GH provocation test. Here, 125 subjects with short stature were seen at least twice for more than a year from 1985 to 2000 at our hospital. Four populations were selected from the 125 subjects without using GH peaks of the GH provocation tests. The first group (CGHD, N=15), complete GH deficiency, consisted of prepubertal patients with growth velocity less than -1.5 SD, invisible/thin stalk on MRI or CNS lesion such as brain tumor. The second group (HV-N, N=22), subjects of prepubertal and growing children with short stature (Ht < -2 SD), had normal height velocity for at least one year (height velocity > +0 SD). The third group (FH-N, N=8) subjects had short height (Ht < -2 SD) in childhood but normal final height (Ht > -2 SD). The fourth group subjects were prepubertal short children (Ht < -2 SD) with a decrease in height velocity (HV-D, N=10) who were diagnosed as familial short stature (FSS) or constitutional delay of growth and adolescence (CDGA). Measurements of serum IGF-I levels were carried out from the age of three to nine years in females, three to ten years in males in CGHD, HV-N and HV-D, and before reaching final height in FH-N. IGF-I levels of 13 out of 15 CGHD were low values under the cut-off line (< -2 SD). IGFBP-3 levels of CGHD were all low values under the cut-off line (< -2 SD). IGF-I levels of HV-N, FH-N and HV-D were all within the normal range (> -2 SD), except for one subject in group HV-D. In conclusion, IGF-I measurements are useful for screening patients who need GH treatment and probably for diagnosing GHD. Additional IGFBP-3 measurements are valuable in diagnosing GHD especially at the age of less than five years.

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Several types of transient thyroid dysfunction in infants born to mothers with Graves' disease have been described, ranging from completely unaffected infants to those with hyperthyroidism or hypothyroidism, depending on maternal thyroid function, activity of maternal TSH receptor antibody (TRAb) and maternal antithyroid agents due to transplacental passage. We observed a premature neonate born to a mother with three-year-untreated Graves' disease, who developed transient central hypothyroidism in the immediate postnatal period. Placental transfer of thyroxine and TRAb from the thyrotoxic mother may cause fetal peripheral thyrotoxicosis resulting in suppression of the fetal pituitary-thyroid axis.

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We prospectively investigated the effects of growth hormone (GH) replacement therapy on glucose tolerance and insulin resistance. An oral glucose tolerance test (OGTT) was conducted on 36 prepubertal children with GH deficiency (20 boys and 16 girls, 4.9~12.8 yr old) at 0, 0.5, 1, 1.5, 2 and 3 yr after the start of the therapy. As the parameter of glucose tolerance, the sum of 0, 30, 60, 120, and 180 min plasma glucose (ΣPG) (mg/dl), immunoreactive insulin (ΣIRI) (μU/ml), and C-peptide immunoreactivity (ΣCPR) (ng/ml), were used. The homeostasis model assessment ratio (HOMA-R), an index of insulin resistance, and β-cell function, assessed by the Matthews' formula, was also calculated. ΣPG exhibited a significant increase at 1.5 yr after the start of the therapy. ΣIRI and ΣCPR had increased significantly at 1 yr and thereafter. The blood glucose curve exhibited normal glucose tolerance (NGT) in 33/36, impaired glucose tolerance (IGT) in 3/36, and a diabetic pattern (DM) in 0/36 at the beginning of the therapy. The percentage of subjects exhibiting the IGT increased over time and a DM pattern appeared in some patients. The HOMA-R exhibited a significant increase at 1.5 yr. β-cell function showed a significant increases at 1 and 1.5 yr. In summary, increases in insulin resistance and in insulin secretion, and a tendency to an increased blood glucose level were observed after GH therapy. These results showed that careful observation should be conducted about the possibility of developing glucose intolerance during long-term GH therapy.

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