Considerable evidence has been accumulated showing that most cases of insulindependent diabetes mellitus (IDDM) are a consequence of progressive beta cell destruction during a lengthy asymptomatic period. While genetic susceptibility appears to be a prerequisite for the development of the disease, concordance for IDDM between identical twins only approaches 50%, suggesting that environmental factors must also be involved in the expression of the disease.
Several immunological abnormalities precede the onset of IDDM. Circulating islet cell autoantibodies and cell-mediated immune responses have been detected during the prediabetic period. Beta cell autoantigens, such as glutamic acid decarboxylase, 38 kD autoantigens, 52 kD autoantigens, heat shock proteins and insulin molecules have been considered to be involved in the initiation or process of beta cell-specific autoimmunity. Both CD4+ and CD8+ T cell subsets are thought to be implicated in the destruction of pancreatic beta cells. Autoreactive CD4+ T cells may be able to effect beta cell damage by non-specific inflammatory mechanisms, such as releasing beta cell cytotoxic cytokines, while CD8+ cytotoxic T cells may be involved in the destruction of pancreatic beta cells as final effectors assisted by CD4+ T cells.

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We describe an unusual presentation of virilizing adrenal adenoma in a prepubertal girl. The patient's adrenal mass had been detected incidentally at one year of age, but no clinical signs were evident until the appearance of pubic hair at 7 years of age. Plasma testosterone concentration was elevated (166ng/dl), but further endocrinological examination revealed prominent elevation of δ5-pregnene steroids including 17-hydroxypregnenolone, dehydroepiandrosterone and dehydroepiandrosterone-sulfate. Finally, a diagnosis of adrenocortical adenoma was made after surgical resection. This adrenal tumor, clinically non-functional early, was considered to be “late functioning”.

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We report a 17-year-old female patient who developed a severe agranulocytosis at 12 months of treatment with methimazole (MMI) for hyperthyroidism. White blood cell (WBC) count was 1200/μL with 48/μL of granulocytes at the onset of a high fever and sore throat due to necrotizing laryngitis and ulcerative pharyngitis. Granulocyte colony-stimulating factor (G-CSF) was administered intravenously on a daily basis at a dosage of 50μg/M² of body surface for 9 days. The count of WBC and granulocytes revealed a rapid increase followed by an improvement in the clinical symptoms. As a decrease of granulocytes was seen after ceasing G-CSF, additional G-CSF therapy was carried out for 11 days. Total thyroidectomy was performed on the 5th day of the second G-CSF therapy. The patient has been doing well and is euthyroid after replacement therapy with thyroxine. In this case, G-CSF was found to be a potent agent for the management of MMI-induced agranulocytosis.

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To investigate the role of growth hormone (GH) and its downstream axis in normal growth and growth disorders, we measured serum GH-binding protein (GHBP) levels in normal children and children with short stature by ligand-mediated immunofunctional assay (LIFA). Samples were obtained from 512 healthy children with normal stature, 146 5-day-old healthy neonates, and 153 short children with normal GH secretion (normal short children). Serum GHBP showed significant correlation with percent overweight (r=0.71, P<0.01) in normal children. Diurnal variations in serum GHBP were scarcely observed. Serum GHBP levels were low in neonates, rose acutely within 6 months, and gradually increased toward pubertal age in normal children (r=0.2, P<0.01, assessed among subjects over 1 year old). Neither significant sex differences nor rapid peaked changes during puberty were observed. In normal short children, GHBP levels were lower than in normal controls.
These data suggest resistance to GH or low efficacy of GH utilization could be one of the etiologies of growth disorder in normal short children.

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There are few reports about reactivation of gonadal function and progress through puberty after withdrawal of therapy with LHRH-A in patients with central precocious puberty (CPP). Eight patients (5 females and 3 males) with CPP were treated with LHRH-A (D-Ser⁶-LHRH) with a dose of 10μg/kg by single or twice daily subcutaneous injections for periods ranging from 3 to 5.3 years. We have studied 30-day consecutive patterns of first morning voided urinary gonadotropin and ovarian hormone excretion in these patients during and after withdrawal of therapy with LHRH-A. During the treatment, the mean and maximum concentrations of urinary LH and FSH in 7 patients studied were low. After withdrawal of therapy, a rapid resumption of puberty was observed in 3 patients, who also had a hypothalamic hamartoma. In the remaining 5 patients with idiopathic CPP, the testes increased rapidly in size in one boy; but among 4 girls, only 1 had regular menstruation and the other 3 had irregular or no menstruation. The urinary patterns of these hormones did not return quickly to a pubertal pattern after withdrawal of treatment in these girls. This may be partly related to the long-term use of LHRH-A, but seems to be partly caused by psychological factors. These patients treated with long-term LHRH-A will head follow-up and evaluation of the reproductive function.

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We measured the bone mineral content of the wrist and spine using single and dual photon absorptiometry (SPA and DPA) in 165 normal boys and girls to quantitate the contribution of normal pubertal development to the attainment of adult bone mass. We constructed bone density ranges for spine and wrist bone density for each pubertal stage in girls (breast) and boys (pubic hair). Wrist bone density measurements (±SD) for girls and boys, pubertal stages 1 and 5, were 0.41±0.06 and 0.62±0.05gm/cm² (girls) and 0.46±0.08 and 0.70±0.08gm/cm² (boys), respectively. Spine bone density measurements (±SD) for girls and boys, pubertal stages 1 and 5, were 0.78±0.09 and 1.18±0.13gm/cm² (girls) and 0.81±0.10 and 1.22±0.23gm/cm² (boys), respectively. Thus, bone mineral content of the wrist and spine increased during pubertal development (between stage 1 and 5) by approximately 50% for boys and girls. The wrist bone density of boys was significantly greater than that of girls (p<0.03). Bone mineral content of the spine was similar for boys and girls throughout pubertal development. The bone mineral content of the wrist and spine in girls and boys correlated significantly with chronologic age, bone age, body mass index, height age, height, weight, serum IGF-I, and testosterone (boys), (all p<0.0001). We conclude that bone density of the wrist but not the spine is increased in boys versus girls, that bone mineral content increases by approximately 50% between Tanner stage 1 and 5 for both sexes, and that bone mineral content at both sites correlates with advances in pubertal development.

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