摘要:

Functional, metabolic and molecular studies using purified beta cells (β-cells) have contributed to our understanding how insulin synthesis and release are regulated by glucose. Individual rat islet β-cells are heterogeneous in their threshold sensitivity to glucose, so that the physiological graded glucose-induced response of the pancreatic β-cell population can be explained – at least in part – by dose-dependent recruitment of cells. β-Cell threshold sensitivity to glucose is correlated to glucokinase gene expression rather than glucose transport, reinforcing the concept that glucokinase is directly involved in β-cell glucose sensing. This idea is further supported by observing major species differences in islet GLUT2 expression, whereas islet cell glucokinase expression and function are strongly conserved. Studies on pure rat β-cells have also shown that cyclic AMP acts – in addition to its well-known potentialtor function of glucose-induced insulin release – as a competence factor which is absolutely required for normal β-cell responsiveness to glucose. Intraislet glucagon appears to be a paracrine regulator of cyclic AMP production in vitro, but this signalling pathway can be an artifact of the islet isolation procedure. In rat β-cells, expression and functional activity can be demonstrated of receptors recognising glucagon, glucagon-like peptide 1 and glucose-dependent insulinotropic peptide. Whether this diversity in signalling reflects another form of β-cell heterogeneity, functional complementation or biological redundancy, remains to

ISSN:1663-2818    

DOI:10.1159/000185004

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We studied the hypothalamic-pituitary-thyroid function in two groups of healthy elderly subjects: group A (n = 23, age range 65-80 years), and group B (n = 11 age range 81-92 years), and in 32 controls, aged 20-60. A TRH test for TSH and prolactin was performed in all subjects, while the TSH circadian modulation was evaluated in elderly subjects only. Group B showed significantly lower fT3 and TSH, and higher fT4 levels with respect to controls (fT3: 4.4 ± 0.2 vs. 5.2 ± 0.2 pmol/l, p < 0.05; fT4: 13.1 ± 0.9 vs. 11.4 ± 0.4 pmol/l, p < 0.05; TSH: 1.07 ± 0.21 vs. 1.46 ± 0.13 mIU/1, p < 0.05). Morning TSH showed an inverse correlation with age (r = -0.42; p < 0.02) among the 34 elderly subjects, but not among controls. Evidence for TSH circadian modulation was found only in group A (nighttime TSH: 1.60 ± 0.17, vs. daytime: 1.25 ± 0.13 mIU/1, p < 0.001). The TRH-stimulated TSH peak was reduced among all elderly subjects with respect to controls (A: 6.26 ± 0.64 mIU/1, p = 0.01; B: 5.02 ± 0.58 mIU/1, p < 0.01). The maximal PRL response was also blunted (A: 25.7 ± 2.6 μg/l, B: 27.7 ± 5.2 μg/l, p < 0.0005). In conclusion, a resetting of the pituitary threshold of the TSH feedback suppression, along with complex alterations in peripheral thyroid hormone levels, may progressively develop in older people, becoming apparent only with extreme senescence. Moreover, the TSH nocturnal surge may be lost with increasing age, thus providing evidence also for hypothalami

ISSN:1663-2818    

DOI:10.1159/000185005

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We examined the association between slipped capital femoral epiphysis (SCFE) and growth hormone (GH) treatment in 16,514 children who had not been treated with GH prior to their enrollment in the National Cooperative Growth Study. Fifteen children had SCFE prior to receiving GH therapy, 26 developed SCFE during GH treatment, and one had SCFE on one side prior to GH treatment and developed it on the contralateral side while receiving GH. Children with GH deficiency were significantly more likely to develop SCFE while on GH treatment than were children with idiopathic short stature (p = 0.006). There was no difference between GH-deficient girls and boys in the risk of developing SCFE during GH treatment. There were 3 cases of SCFE in girls with Turner syndrome before GH treatment and 3 during. Typically, children who developed SCFE while on GH were older, heavier, and grew more slowly during the first year of GH than those who did not. Children with GH deficiency, Turner syndrome, and other known causes of short stature are more likely to develop SCFE before or during GH treatment than children with idiopathic short stature.

ISSN:1663-2818    

DOI:10.1159/000185006

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We report 4 cases of preclinical Cushing’s syndrome (PCS) that were discovered incidentally by computed tomography (CT) as adrenal incidentalomas. Routine endocrine examinations revealed a suppressed plasma ACTH level. A final diagnosis was made by means of precise endocrine assessments and adrenal scintigraphy with radiolabelled iodocholesterol. Although endocrine data varied, the positive accumulation of radioisotope in the adrenal tumor, with nonvisualization of the contralateral side, was observed in all cases. Endocrine studies and analyses of steroid contents in tumors by HPLC suggested that subtypes or heterogenous forms of this disease entity may exist. One type shows small tumors with relatively elevated cortisol production, and a disturbed diurnal rhythm and suppression of plasma cortisol with dexamethasone (DXM). The other type showed large tumors with weak-to-average cortisol production, and the diurnal rhythm of cortisol was preserve

ISSN:1663-2818    

DOI:10.1159/000185007

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Defective aldosterone receptor binding is present in pseudohypoaldosteronism, and sporadic as well as familial cases have been reported. In familial pseudohypoaldosteronism, autosomal dominant as well as autosomal recessive inheritance has been described. The autosomal dominant form is characterized by a relative mild course of the disease and asymptomatic carriers of the defect in these families, whereas the autosomal recessive form is characterized by severe salt-losing symptoms; not uncommonly these families are consanguineous. To date no genetic mutation has been identified in the aldosterone receptor gene of affected patients. Studies to evaluate the biochemical defect and to characterize the inheritance pattern are of major interest for clinical as well as research purposes. Thus we studied the response of the renin-angiotensin-aldosterone system to sodium depletion using a single dose of furosemide. In 5 patients from five nonconsanguineous families and in all available family members the renin and aldosterone levels as well as serum sodium was measured before and after an oral dose of furosemide. The aldosterone receptor binding of peripheral mononuclear leukocytes was determined at the beginning of the study. In three families asymptomatic carriers of the defect could be identified in the baseline state by elevated levels of basal aldosterone and high renin concentration. The levels of renin and aldosterone did not differ between the symptomatic and asymptomatic individuals in these families. Interestingly the aldosterone receptor binding in the asymptomatic carriers of these families was normal. In the other two families, however, the basal hormonal data were normal in all relatives suggesting at first sporadic cases. During sodium depletion with furosemide, renin as well as aldosterone levels rose significantly in 1 parent and a sibling, respectively. In contrast to the first three families the aldosterone receptor binding in these family members was low. We propose to reclassify these family members as asymptomatic carriers and the patients as familial cases. Whether these cases are genetically identical to the ‘classical autosomal dominant cases’ remains to be seen. It seems that the pathogenesis of pseudohypoaldosteronism is even more heterogeneous than previously thought and factors other than aldosterone receptor binding are crucial and need further identificat

ISSN:1663-2818    

DOI:10.1159/000185008

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The normal values of insulin-like growth factor I (IGF-I), IGF-binding proteins 1 and 3 (IGFBP-1 and IGFBP-3), and the high-affinity growth hormone binding protein (GHBP) are not well established in large series of healthy full-term newborns. We report the normative data for IGF-I, IGFBP-1, IGFBP-3, and GHBP in 271 normal Spanish full-term newborns, born between 37 and 42 weeks of gestation, and compare these results with the same parameters studied in 39 premature infants. Furthermore, we report the relationship between results found in the normal full-term newborns and those of 252 healthy prepubertal (Tanner stage I) Spanish children. Serum GHBP, IGF-I, and IGFBP-3 levels are very low in the premature infant and show a significant increase in full-term newborns and during childhood (p < 0.001; analysis of variance). In contrast, the serum IGFBP-1 levels are very high in premature newborns, fall in full-term newborns, and continue to decline during childhood (p < 0.001; analysis of variance). A positive correlation between GHBP, IGF-I, and IGFBP-3 versus gestational age was observed. In contrast, we found a negative correlation between IGFBP-1 and gestational age. There is a direct relationship between the ponderal index and IGF-I and IGFBP-3. When the group of premature newborns was divided into infants born before or after 32 weeks of gestation, we found higher levels of IGF-I and IGFBP-3 (p < 0.01 and p < 0.05, respectively, by Student’s t test) in the group with the higher gestational age; however, the IGFBP-1 level was lower in this group (p < 0.001 by Student’s t test), with no differences seen in serum GHBP concentrations. The presence of IGFBPs in the premature infant suggests that they are important modulators of IGF-I action during fetal growth and developm

ISSN:1663-2818    

DOI:10.1159/000185009

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Radioiodinated metaiodobenzylguanidine (MIBG) scintigraphy is known for its high specificity in detecting pheochromocytoma and other tumors of neural crest origin. We describe herein the first case of a definite adrenocortical adenoma that demonstrated false-positive uptake on MIBG scintigraphy. In addition, we reviewed all 13 reported cases showing false-positive uptake, and suggest that careful evaluation is needed before diagnosing a ‘silent’ or ‘asymptomatic’ pheochrom

ISSN:1663-2818    

DOI:10.1159/000185010

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000185011

出版商:S. Karger AG    

年代:1996

数据来源: Karger