The Journal of pediatric endocrinology最新文献

Several patients with pituitary dwarfism and a variable degree of hypothyroidism have been shown to have mutations in their Pit-1 gene. Pit-1 activates transcription of the growth hormone and prolactin genes and is necessary for the control of the beta-TSH gene transcription. The various mutations have different effects on the DNA binding and transactivating properties of Pit-1. Multiple pituitary hormone deficiency due to Pit-1 mutations is inherited either dominantly or recessively depending on the DNA binding properties of the mutant protein. The comparison of pheno- and genotype in patients with multiple pituitary hormone deficiency provides some insight into the function of the Pit-1 protein.

Whilst the molecular basis for GH action remains unclear, increasingly our understanding of the critical role(s) played by the GHR and GHBP is being aided by studies on the structural forms of the GHR and GHBP, the specific mechanisms for GHBP generation, their specific cellular distribution and localization, and the nature and consequences of their independent physiological regulation. What is emerging as a result is a multi-functional model for GH action in which the GHBP, in addition to the cell membrane GHR, would appear to have an important role as an endocrine, autocrine/paracrine and possibly intracrine factor.

Until recently, the limited supplies of pituitary derived growth hormone (GH) enabled us to treat only those patients who were classical GH deficient. With the unlimited supplies of recombinant GH available, there is no limitation to the number of patients we can treat. It becomes necessary, however, to select those patients who will most benefit from GH therapy. Our preliminary results demonstrate that the short-term growth response to growth hormone is not an all-or-none phenomenon. The lower the growth velocity and the growth hormone reserve, the better the growth response to therapy. On the other hand we do not recommend institution of GH therapy for children with a normal growth rate and a normal GH spontaneous secretion. In children with classical GH deficiency (GHD) and in children with a subnormal spontaneous secretion of GH (NSD) adult height prediction decreases when GH therapy is started at an age older than 12. We have found that GHD and NSD boys differ in their growth pattern. Pubertal maturation and bone age maturation progress more rapidly in NSD patients. Therefore special caution is needed in NSD patients older than 12 years. The older the patient and the longer the treatment period, the faster the pubertal process can advance. Further studies are needed before recommendations for therapy in non-classical GHD patients can be made. Until patients involved in clinical trials reach final height, recommendations for new indications cannot be made.

Pharmacological tests are essential for the diagnosis of growth hormone (GH) insufficiency. Obesity is a pathological state associated with blunted GH response to all the classical stimuli tested. In the present study, three new pharmacological stimuli for GH reserve were evaluated in three groups of subjects: Normal, GH-insufficient and normal growing obese children. Dexamethasone provokes a clear GH-response in normal children, whereas the response in the other 2 groups of patients is significantly diminished. Galanin-induced GH-secretion is significantly higher in normal than in obese children. GHRP-6 causes a potent GH release in normal children, higher than in GH-insufficiency or obesity. The overlap shown between GH-insufficient patients and normal children reduces the usefulness of the tests. Similar to the classical stimuli, the response to these new tests is also decreased in obesity.

Recent data show that in humans IGF-1 has insulin-like anabolic and growth promoting effects. However, the plasma levels at which IGF-1 exerts these effects differ. IGF-1 plasma levels similar to those in normal children and adults have a growth promoting effect, but higher levels are necessary for IGF-1 to exert insulin-like anabolic effects, and hypoglycemia is a potential risk. Longitudinal bone growth results from the proliferation and differentiation of chondrocytes in epiphyseal cartilage. We present our data from cultured human epiphyseal chondrocytes, which suggest that epiphyseal cartilage may be a target tissue for IGF-1 action during human fetal and postnatal development.

Magnetic resonance images of the pituitary-hypothalamic area in patients with GH secretory disorders, divided into two groups (hypersecretory and hyposecretory), were studied. In the first group there were 42 patients with pituitary adenoma; size, signal characteristics, direction of growth, and type of enhancement were analyzed and compared with similar studies in 40 age and sex matched control patients with non-GH secreting pituitary adenomas. No significant differences were found except for a higher frequency of chiasm involvement and a more pronounced contrast enhancement in the control group. The hyposecretory group was composed of 101 patients with congenital idiopathic growth hormone deficiency (CIGHD). MR revealed morphological abnormalities consisting of hypoplastic anterior pituitary and ectopic posterior pituitary (PPE) in 59 patients, without evidence of a complete pituitary stalk; in 42 patients the posterior pituitary was in normal position and the pituitary stalk visible. The group with PPE showed a greater frequency of multiple pituitary hormone deficiency (51% vs 12%), breech delivery (30% vs 7%) and associated congenital brain anomalies (12% vs 7%). These data suggest that CIGHD could be the result of a congenital midline brain anomaly in a significant proportion of patients.

Normal growth in childhood requires, amongst other factors, an emotionally supportive environment. Psychosocial deprivation results in poor growth, and also growth disorders themselves can cause psychosocial problems /1/.