We investigated hypothalamic-pituitary function in two patients with CHARGE association to evaluate the cause of growth retardation and genital hypoplasia in this disorder. Case 1 was an 8 5/12-year-old boy. GH response to stimuli and spontaneous secretion during the first 3 hours of nocturnal sleep were normal. Gonadotropin response to GnRH and testosterone response to hCG were low, indicating hypogonadotropic hypogonadism. Case 2 was a 5 4/12-year old girl. GH responses to all provocative tests except GRF were low, indicating GH deficiency. She was treated with GH, which was remarkably effective in promoting her growth.
We concluded that hypothalamic-pituitary dysfunction was, at least in part, the cause of growth retardation and hypogonadism in CHARGE association.

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The prevalence of the syndrome of ACTH-ADH discharge in Japan was studied by means of a questionnaire to all members of the Japanese Society for Pediatric Endocrinology. Ninety-one patients were reported by 107 members, and clinical details of 46 cases were obtained. The age of the patients was widely distributed, from one to 15 yrs (median, eight yrs), while the age of onset was usually between zero and four yrs, indicating a long duration of the symptoms. Eight patients had various congenital diseases. As for the three cardinal symptoms of vomiting, hypertension and psychotic depression, five cases (10.8%) did not have hypertension. Association of autonomic symptoms was common (85%). Laboratory data showed a consistent rise in ACTH and ADH at the initial phase of the attack, whereas hyponatremia did not occur in 30% of patients. Elevation of plasma norepinephrine and a concomitant decrease of dopamine were also constantly found. Eleven (26.8%) of 41 cases had an abnormal EEG, showing high voltage slow bursts. A wide variety of drugs was used for treatment, but the most effective were anticonvulsants, especially phenytoin, while antagonists of catecholamine were only transiently effective. These data indicate that (1) the syndrome of ACTH-ADH discharge is a fairly common disorder in Japan, (2) it is a quite different syndrome from cyclic vomiting in childhood, (3) the symptoms last for a long time, in some cases beyond adolescence, and (4) the most effective drugs are anticonvulsants. It is suggested that this syndrome may be due to periodic epileptic discharge in the hypothalamus involving paraventricular CRH- and ADH- neurons and the emetic center in the medulla.

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The kabuki make-up syndrome is characterized by peculiar facies, skeletal anomalies, abnormal dermatoglyphics, mental retardation and postnatal growth failure. Until 1988, 62 cases had been reported and 50 (81%) of them had short stature. However, the cause of short stature has not been elucidated, while one case had growth hormone (GH) deficiency. We report another case of growth hormone deficiency associated with abonormal brain magnetic resonance (MR) imaging findings which were characterized by a non-visualized pituitary stalk, atrophic anterior pituitary gland and ectopic posterior lobe. However, this case had no notable perinatal history but had a cleft palate. Therefore, the GH deficiency in this case might have been caused by hypothalamo-pituitary dysgenesis, i. e. a part of a series of midline anomalies.

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We report a three-year-old male patient with juvenile rheumatoid arthritis (JRA) who developed the syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH was proved to be due to osmoreceptor resetting and the cause of the SIADH may have been pleural effusion accompanied by JRA.

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Recent studies have demonstrated that deoxycorticosterone sulfate can be formed at extra-adrenal sites, but its actual origin and role are not yet clear. The present study was undertaken to elucidate the origin of deoxycorticosterone sulfate and the usefulness of this steroid for the diagnosis of 11β-hydroxylase deficiency in the early neonatal period. We measured serum deoxycorticosterone sulfate levels during glucocorticoid therapy in an infant with 11β-hydroxylase deficiency. Before therapy, the serum deoxycorticosterone sulfate concentration at 6 days of life was higher than normal. Following glucocorticoid therapy, the serum deoxycorticosterone sulfate concentration showed a marked and dose-dependent suppression, as did the serum deoxycorticosterone and 11-deoxycortisol levels. These findings suggest that serum deoxycorticosterone sulfate can be used as another specific indicator for the diagnosis of 11β-hydroxylase deficiency in neonates, and that the adrenal glands may play an important role in neonatal deoxycorticosterone sulfate production under the control of ACTH.

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Fifteen children with 45, X and Y-containing chromosome mosaicism were studied. Fourteen had unilateral or bilateral streak gonads. The remaining one patient had bilateral intra-abdominal testes. Development of genital ducts was studied by laparotomy.
Group 1: One patient showed bilateral intra-abdominal testes accompanied by an epididymis, a was deferens, and a fallopian tube. Group 2: Eight patients showed an unilateral scrotal testis and a contralateral streak gonad. On the streak gonad side, an epididymis or was deferens or both were found in five, a uterus was found in seven and a fallopian tube was found in all eight patients. Group 3: Four patients showed a unilateral intra-abdominal testis and a contralateral streak gonad. On the streak gonad side, a was deferens was found in two patients and a fallopian tube and a uterus were found in all four patients. On the testis side, an epididymis and a was deferens were found in all four patients, although a fallopian tube was found in only one patient. Group 4: Two patients showed bilateral streak gonads associated with a fallopian tube and a uterus. A rudimentary epididymis and was deferens accompanied one out of four streak gonads of these two patients. Twelve patients of Group 2 and Group 3 were compatible with a diagnosis of mixed gonadal dysgenesis (MGD). Wolffian duct remnants accompanied seven (58%) out of 12 streak gonads in 12 patients with MGD, and eight (50%) out of 16 streak gonads in 14 patients of Group 2, Group 3, and Group 4.
These findings indicated that the streak gonads in children with 45, X and Y-containing chromosome mosaicism frequently had functioning Leydig cells at least at the time of differentiation of the genital ducts, although none had properly functioning Sertoli cells at that time.

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We report a patient with short stature with normal GH provocative tests and low physiological 24 hour GH concentration. After starting GH treatment, growth velocity increased similarly to that seen in patients with a severe type of growth hormone deficiency. This is the first precise case report of a patient with typical neurosecretory dysfunction without any other complications.

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We report standard growth curves in Japanese Prader-Willi syndrome (PWS) for height. Growth patterns for height are quite different between PWS and normal controls, showing the mean height in PWS ranging at -2SD of normal control data until pubertal age and dropping off far below -2SD of normal control after puberty. These data indicate that the pathogenesis of the short stature of PWS originates from both chromosomal abnormalities and hypogonadism. In addition to these factors we suspect that bone dysplasia seen in patients with this syndrome is also one of the factors in the short stature of PWS.

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A 13 years and eight months old girl with severe short stature (-7.8 SD) and obesity (+52%) was diagnosed as having congenital hypothyroidism resulting from a sublingual thyroid gland. Two weeks after the start of administration of 1-thyroxine (50μg/day) the patient became active. 1-Thyroxine was increased to 75μg/day, but two weeks later wheezing appeared and typical asthmatic attacks were observed. The association of asthma and hyperthyroidism has been known for more than 60 years and there have been several reports on the relation between bronchial asthma and thyroid status. To the best of our knowledge, this is the first report of a patient who developed, for the first time in her life, asthmatic attacks following treatment of congenital hypothyroidism. Although the combination of these two disorders seems to be extremely rare, supplements of thyroid hormone in patients with congenital hypothyroidism who are diagnosed after the neonatal period should be given with caution.

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The effect of leuprolide acetate in depot suspension (TAP-144-SR), a synthetic analog of luteinizing hormone-relasing hormone, was studied in 34 patients with central precocious puberty. The doses were adjusted according to changes in hormone levels or clinical manifestations. The treatment was terminated or prematurely discontinued within 96 weeks in seven patients but was continued for more than 96 weeks in 27 patients.
Mean basal and peak gonadotropin levels in response to LH-RH test decreased to the normal range from the fourth week of treatment and were maintained at prepubertal levels till 96 weeks. Mean concentrations of plasma testosterone and estradiol were mostly maintained at low levels during the treatment with TAP-144-SR.
At 96 weeks of treatment, breast development had progressed in three, regressed in 10 and remained at the same stage in the other patients. The growth velocity was significantly suppressed from the pretreatment rate of 9.83 ±5.70 cm/year to 5.81 ± 2.80cm/year at 48 weeks of treatment (32 patients) and further to 4.87 ± 2.20 cm/year at 96 weeks (27 patients). The ratio δ bone age/ δchronological age for all the patients was 0.83 ± 0.78 at 48 weeks of treatment and 0.69 ± 0.47 at 96 weeks. The progression of bone age was suppressed by the treatment, especially in those patients with an initial bone age of 12 years or older.
Of the adverse effects that appeared, those presumably related directly to TAP-144-SR were only genital bleeding in the stimulatory phase following the initial dose, and redness and induration at the site of injection. The once-monthly injection is a regimen well tolerated by children, and when its reliability and efficacy are considered, TAP-144-SR will be the drug of first choice in the treatment of precocious puberty.

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Urinary GH levels in the first voided urine in the morning were measured in schoolchildren aged 7 y (331 boys and 322 girls) and 10 y (355 boys and 354 girls). Each group had a normal height/weight distribution with average values very similar to those of the Japanese cross-sectional growth standard. Urinary GH levels were inversely correlated with obesity index. Obese children (obesity index ≥20%) had lower urinary GH levels in spite of their greater height and normal growth velocity, and were excluded in further analysis. The average values of urinary GH and growth velocity were similarly less in 10 year-old boys than in other groups. In comparison among sub-groups divided according to bone age, urinary GH level showed a significant decrease at bone age 11.0 y in boys, and in girls it was slightly lower at bone age 9-10 y with the following peak at bone age 11.5 y coinciding with that of growth velocity.
These data show that the physiological decrease of GH secretion leads to the deceleration of growth which is observed as the dip of growth rate immediately before the pubertal growth spurt.

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