The Journal of pediatric endocrinology最新文献

We report a case of mixed gonadal dysgenesis with 45 X/46 XY karyotype and aortic coarctation. An eight month-old patient was admitted to our endocrinology department for evaluation of ambiguous genitalia. On physical examination, a wide neck with a low posterior hairline, bifid scrotum, small phallus, testis in the right labioscrotal fold, single orifice and typical findings of aortic coarctation were present. The chromosome karyotype of the patient was 45 X/46 XY. On the laparotomy there was an infantile uterus, fallopian tubes, and a streak gonad on the left. The follow-up of the patient included sex assignment, genital reconstruction and cardiovascular treatment.

A seven year-old girl who presented with vaginal bleeding and a right ovarian cyst was diagnosed as having acquired primary hypothyroidism. She had menstruation in spite of a delayed bone age, absence of pubertal growth spurt and lack of adrenarche. Elevated levels (age-matched) of gonadotropins, normal levels of estradiol, and hyperprolactinemia were documented. The clinical and laboratory findings were reversed by thyroxin treatment. The clinical presentation in this case, and other similar descriptions in the literature, support the mechanism of pseudo-precocious puberty in untreated hypothyroidism.

As a significant number of children with growth hormone deficiency have been shown to be able to respond to GHRH with a rise in serum growth hormone (GH) levels, GHRH has been used to treat such children with varying success. GHRH has been given subcutaneously (SC) in GH deficient children to improve growth in dose frequencies of daily, twice daily, three-hourly overnight or three-hourly throughout the day. The dosages of GHRH used have been wide ranging, varying from 4 micrograms/kg/day to 50 micrograms/kg/day. Continuous infusion of GHRH has been shown to augment GH secretion in normal adults and GH deficient children without evidence of desensitization of the somatotrophs. Continuous SC infusion of GHRH has been shown to promote growth in short slowly growing children. Poor growth response to GHRH has been reported by some authors using daily SC injection while others reported significant growth acceleration in 42-87% of GH deficient children treated using different GHRH regimens. Although GH treatment in GH-deficient children results in more consistent growth acceleration, comparable growth response can be seen in some children treated with GHRH. The optimal mode of GHRH therapy remains to be determined, but it would appear that the growth response is dependent on the dose used and possibly on the frequency of administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth retardation is a common feature in children with end-stage renal failure (ESRF). Medical management of renal insufficiency rarely normalizes growth and optimistic reports on the effect of rhGH treatment on growth velocity may presage more extensive use of rhGH in pediatric nephrology. Ample evidence has shown beneficial effects of GH replacement therapy in both childhood and adolescent hypopituitarism. However, the remarkably few side effects of treatment reported in these conditions cannot necessarily be extrapolated to children with ESRF. Uremia is associated with a wide range of metabolic and hormonal derangements including decreased glucose tolerance. This is mainly due to impaired insulin-stimulated glucose disposal in peripheral tissues and insufficient insulin-induced suppression of hepatic glucose production. Insulin-stimulated glucose uptake in skeletal muscle in ESRF is reduced by 30-50% as compared to that in healthy subjects, and a reduction may be detected even in subjects with a more moderate reduction in renal function (GFR around 25 ml/min). Dialysis therapy improves the disturbed insulin action significantly. The cause of the insulin resistance in ESRF is multifactorial. Impaired physical fitness, accumulation of uremic toxins, raised levels of GH and glucagon, metabolic acidosis, dyslipidemia and the medication applied may all contribute. If exogenous GH administration is added to the already marked uremic insulin resistance, insulin action may be severely disturbed and the secondary hyperinsulinism further magnified. However, frank diabetes mellitus does not develop unless the beta cells fail to meet the enhanced demands. This will probably occur only in patients with a beta-cell genotype pivotal for the phenotypic expression of non-insulin dependent diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone (GH) influences not only skeletal growth and maturation but also bone turnover and mineral deposition. The effect on bone mineral status of 2 different regimens of rhGH therapy was evaluated in 22 children with idiopathic GH deficiency (GHD) - age 5-8 yrs; bone age 3-5 yrs. Ten of them (group 1) were treated 3 times a week with rhGH, administered subcutaneously, for a total weekly dose of 0.5 IU/kg and 12 (group 2) with the same weekly dose 6 times per week. Insulin-like growth factor 1 (IGF-1) and osteocalcin (OC) levels increased in both groups after therapy but they were higher in group 2. In basal conditions bone mineral content (BMC) and BMC/bone width ratio (determined by dual image-assisted photon absorptiometry) were significantly lower in patients than in controls and significantly increased after 6 months of rhGH therapy only in patients of group 2. rhGH administered 3 times a week increased IGF-1 and OC levels, indicating that turnover and remodeling processes of the bone had started, but the same dose had to be given every day to lead to calcium deposition in the bones. Probably a continuous supply of rhGH better optimizes the body utilization of the hormone, as indicated by better height velocity and bone density in patients of group 2. The response to an acute load of 1,25(OH)2D3 (1.5 micrograms/day for 4 days), both before and after a month of rhGH therapy (weekly dose of 0.5 IU/kg 6 times were week), was evaluated in 16 children with GHD - age 6-9 yrs.(ABSTRACT TRUNCATED AT 250 WORDS)

The number of survivors of childhood leukemia treated with growth hormone for growth retardation is increasing. The debate about the direct or indirect relationship of GH and insulin-like growth factor I (IGF-I) to the occurrence or recurrence of malignancy, especially in the case of GH therapy in patients with leukemia, is still unresolved. We, therefore, studied the effect of GH and IGF-I on bone marrow of patients with acute leukemia (ALL and AML) in diagnosis and recurrence and in chronic leukemia patients (CML) in remission. GH increased blast colony numbers by a mean of 68% and 77% at GH concentrations of 250 and 300 ng/ml, respectively. IGF-I increased blast colony numbers in ALL patients by 50, 93 and 105%, and in AML patients by 33, 58 and 65%, at IGF-I concentrations of 0.05, 0.25 and 0.5 ng/ml, respectively. In 3 CML patients in remission a granulocyte-macrophage colony forming assay did not reveal stimulation of peripheral blood blast colony formation by GH or IGF-I. Our in vitro data (as previously reported) suggest that GH and IGF-I may promote blast cell proliferation, and the supplemental administration of these peptides in leukemia patients in remission must be carefully monitored for early relapse. Additional studies on bone marrow cells of leukemic patients in remission are needed in order to examine the effects of GH and IGF-I on these cells.

Decreased osteoblastic activity seems to be of major importance in the pathogenesis of postmenopausal and senile osteoporosis and several lines of evidence suggest that GH may become useful in treatment of osteoporosis. GH stimulates osteoblastic proliferation and differentiation in vitro and increases production of Insulin-like Growth Factor-I and II (IGF-I and IGF-II) which both have profound stimulatory effects on osteoblasts and are important local regulators of bone remodeling. GH affects several other osteotropic hormones in vivo and increases bone turnover while the effect on bone mass is less pronounced and depends on the skeletal compartment. The few published clinical studies on the use of GH in treatment of osteoporosis have been inconclusive and well controlled studies of adequate size are greatly needed. Future research should focus on intermittent use of GH in combination with other hormones stimulating IGF production or antiresorptive agents.