We studied the effect of gonadal suppression and growth hormone (GH) combined treatment on bone maturation in children with non-endocrine short stature (NESS). Subjects were male children with NESS whose heights at the start of pubertal development had been less than 130 cm. Ten treated and eight untreated children were selected. Treated children were classified into two groups: Group 1 consisted of those with a bone age younger than 10.5 years at the start of treatment, and Group 2 of those with a bone age older than 10. 5 years at the start of treatment.
In the untreated group, acceleration of bone maturation and decline of height SD score for bone age were not recognized even after secondary sex characteristics had appeared.
In Group 1, bone maturation had not decelerated, and there had been no improvement in height SD score for bone age during the 3-year treatment. In Group 2, the δBA/δCA ratio was already suppressed from the first year of treatment, and the mean height SD score for bone age significantly increased during the three years.
Although the effect of this combined treatment cannot be evaluated until final heights are achieved, these data suggest that gonadal suppression and GH-combined treatment is effective in increasing the final height and that the combined treatment should be started at a bone age later than 10.5 years in children with NESS.

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To identify patients with nonclassic steroid 21-hydroxylase deficiency, 137 Japanese women who visited our clinics because of infertility and/or hyperandrogenism were tested with adrenocorticotropin (ACTH) stimulation. In women with serum 17α-hydroxyprogesterone (17 OHP) values 60 min after ACTH administration higher than 5 ng/mL, ratios of 17-hydroxypregnanolone (5α) (17OH-PO) (5α) to the sum of tetrahydrocortisone (THE) and tetrahydrocortisol (THF) in 24-hour urine after ACTH-Z administration were determined. None of the women investigated showed any evidence of having the nonclassic form of this deficiency.

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We present here an 18-month-old 46, XX true hermaphrodite with hypospadias and bifid scrotum. The patient's gonadotropin levels before and after the LH-RH test were within the normal range. The serum testosterone level was <5.0 ng/dL and rose to 381 ng/dL after the human chorionic gonadotropin test. The serum estradiol level was <10 pg/mL and did not rise after the human menopausal gonadotropin test. Pelvic magnetic resonance imaging (MRI) revealed a vagina-like structure. Bilateral gonads were palpable in the scrotum, and histologically, they were ovotestes. We could find no sequence of sex-determining region Y (SRY) in the ovotestes, perineal skin, or leukocytes by polymerase chain reaction (PCR) methods. Other Y-specific DNA sequences were also not detected.
These findings suggest that some XX true hermaphroditism is caused by a very low proportion of Y-containing cells, which cannot be detected by PCR methods. Alternatively, a mutation of one of the down-stream genes of SRY could be involved in the pathogenesis.

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A newly developed enzyme-linked immunosorbent assay (ELISA) for dehydroepiandros terone sulfate (DHEAS) and the chronological alterations of serum DHEAS levels in normal children are reported. The ELISA for DHEAS was developed by means of dehydroepiandrosterone (DHEA) -3-succinate conjugated to horseradish peroxidase and anti-DHEA-succinate-bovine serum albumin (BSA) serum. DHEAS was used as a standard. The sensitivity of the assay was 12.5 pg/well and the IC₅₀ was about 400 pg/well. The intra- and inter- assay coefficients of variation were <8% and <10%, respectively. There was close correlation between the DHEAS measurements by this ELISA method and the conventional radioimmunoassay (RIA) method (r=0.98, n=52). Serum DHEAS levels were determined in 923 normal children (485 males and 438 females) aged from 5 days to 18 years. The serum DHEAS levels were relatively high in newborns and decreased during the first year of life. The serum DHEAS levels stayed low until the age of 6 years, then increased exponentially until the age of 18 years. The serum DHEAS levels in males were significantly higher than in females at the 5-day and 13- to 18-year age groups (P<0.05), suggesting some testicular contribution to serum DHEAS levels in male subjects. In conclusion, this ELISA method for DHEAS is simple, sensitive, precise, accurate, and comparable to the conventional RIA method, and should provide a useful tool for the investigation of the physiological and pathological roles of adrenarche.

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We document a Japanese girl who, without apparent growth hormone (GH) -1 gene deletion, had a clinical phenotype identical to that of isolated growth hormone deficiency type 1A (IGHD-1A). The restriction fragment length polymorphism (RFLP) linkage analysis of the patient and her family members indicates that her GH-1 gene is structurally intact, though the molecular basis of her GH deficiency remains to be determined. We suspect that several congenital disorders other than GH-1 gene mutations may be responsible for IGHD-1A phenotype.

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We estimated the benefits of a transdermally applicable 10% lidocaine gel mixture with absorption promoter (glycyrrhetinic acid monohemiphthalate disodium: GA MHPh 2Na) for the self-injection of human growth hormone (hGH) to reduce injection distress in eight children with growth hormone deficiency (GHD). Pain rating scales upon both needle puncture and fluid injection of hGH were significantly lower with the lidocaine gel application than with the placebo. The use of the lidocaine gel application in hGH therapy can alleviate the pain of injection and accompanying anxiety, thus obtaining better compliance of children who need daily injections of hGH.

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