摘要:

For many years now the German Society for Clinical Chemistry has organized interlaboratory surveys by order of the Federal Medical Association. Human growth hormone (GH) is one of 20 endocrine parameters included in a set of two control specimens and offered to survey participants at least 4 times a year. Since no reference method exists for GH, the ‘true value’ remains unknown. Thus, evaluating survey results is limited to a presentation of how far one participant’s results agree with those of other participants using the same or different methods. Medians and percentiles are calculated for all participants and, when possible, for subgroups using the same kit. Over the last years, 60–80 laboratories have participated in each GH survey with 12–16 different kits. The participants’ results have shown considerable scatter with differences in GH levels of several hundred percent. The largest discrepancies have occurred with specimens of low GH concentrations, those especially interesting for pediatricians. An evaluation of subgroups using the same kit has shown a relatively good group agreement but large method-dependent differences between these groups. As regards the median, the results of different kits varied by as much as 250%. Accordingly, different reference values have to be applied to different GH kits. For the last 3 years not only have several companies changed their methods, but also one third of the laboratories participating in the survey have switched to other GH kits. This leads us to wonder if all the clinicians served by these laboratories are being informed of this and of any resulting discrepancies in their GH

ISSN:1663-2818    

DOI:10.1159/000182178

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Human growth hormone (GH) consists of a number of molecular variants which derive from 2 genes, several alternative mRNA splicing mechanisms, and post-translational modifications such as deamidation, acylation, glycosylation, and oligomerization. After secretion, GH binds to two (or possibly more) circulating GH-binding proteins, one of which is a truncated GH receptor. The resulting mixture of GH moieties in plasma is enormously complex, consisting of over 100 molecular states. The various GH forms undergo differential clearance, receptor binding, and complexing with binding proteins, each exhibiting distinct kinetics. The net effect on bioactivity is correspondingly complex, and measurements by immunoassay or receptor assays are complicated by the lack of a homogeneous analyte. GH is best seen as a family of proteins, many of which fulfill as yet unknown functions in biology.

ISSN:1663-2818    

DOI:10.1159/000182179

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

To construct an immunochemical assay of human growth hormone (hGH) is difficult due to the complicated nature of the hormone. Several forms coexist in the circulation with a 22,000 molecular weight form dominating. Related hormones with up to 93% homology are also present. hGH with its 191 amino acids presents more than 10 epitopes. Furthermore, the existence of two binding proteins adds to the complexity of the assay. Despite intensive efforts involving establishment of international standards, analytical consensus has not yet been reached. It is concluded that more specific immunoassays should be established.

ISSN:1663-2818    

DOI:10.1159/000182181

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The availability of high quality reagents and new methodology have contributed to overall improvements in the performance of immunoassays of human growth hormone in recent years. Discrepancies between superficially similar methods do occur as a result of the heterogeneous nature of the hormone itself. However, there is also evidence of incorrect standardisation in widely used, commercially available assays. Careful interpretation of growth hormone assays is still required, therefore, especially when results from different laboratories are being compared.

ISSN:1663-2818    

DOI:10.1159/000182182

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

In most of the children with short stature, no organic basis can be found, which has led to the suggestion that some cases of growth failure may be due to an immunoreactive but bioinactive growth hormone (GH). In order to compare GH immunoreactivity and bioactivity (measured as receptor binding ability), a radioreceptor assay allowing the measurement of GH levels in human serum was developed using cultured human lymphocytes and 125I-labeled human GH purified by high-performance liquid chromatography. Serum samples were obtained after pharmacological stimulation with either insulin, glucagon or GRF from 19 healthy control subjects and 114 patients with various growth disturbances, aged 2.3–24.8 years. In general, there was a good correlation between the GH levels measured by the two methods, the RRA-GH levels being lower than the RIA-GH levels at all times irrespective of the stimulation test. In all the groups studied, most of the individual RRA/RIA ratios were within normal limits. It is concluded that the presence of an abnormal (bioinactive) GH molecule is extremely rare in patients with short statur

ISSN:1663-2818    

DOI:10.1159/000182183

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Hypopituitarism is associated with reduced lean body mass and increased body fat, while in acromegaly the converse is true. Fasting plasma glucose is increased in acromegaly but fasting plasma insulin and C-peptide are increased in both groups. There is a positive association between fat mass and fasting serum insulin in hypopituitarism, suggesting insulin resistance. Hypoglycaemia unresponsiveness, rather than insulin sensitivity, is the feature of growth hormone deficiency. Basal metabolic rate (expressed per kg body weight) is increased in acromegaly and decreased in hypopituitarism but when expressed ‘per kg lean body mass’, is increased in both groups. There is a close correlation between fat mass and fasting free fatty acid and glycerol levels in obese but not normal weight patients with hypopituitarism; slim patients appear to metabolise and oxidise their fat stores more effectively than those who remain obese. Thus indirect evidence suggests that growth hormone has an important role in maintaining normal body composition and energy sto

ISSN:1663-2818    

DOI:10.1159/000182184

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Growth hormone (GH) counteracts in general the effects of insulin on glucose and lipid metabolism, but shares protein anabolic properties with insulin. Under physiological circumstances GH does not affect total glucose turnover directly. There is however evidence that GH acutely decreases glucose oxidation (secondary to an increase in lipid oxidation) and suppresses muscle uptake of glucose, suggesting that GH redistributes glucose fluxes into a non-oxidative pathway, which could be a build up of glycogen depots through gluconeogenesis. Since GH secretion is inhibited in the fed state these actions are mainly important in the postprandial or fasting state. Under pathological conditions of GH excess (e.g. acromegaly, poorly controlled tp. 1 diabetes or high dose GH treatment) the diabetogenic actions of GH become apparent. In these patients increased endogenous glucose production, decreased muscle glucose uptake and rising blood glucose levels are observed. In patients with intact β-cell function these changes are counterbalanced by hyperinsulinemia – such hyperinsulinemia may in the long term induce increased cardiovascular morbidity and mortality (‘Reavens syndrome X’). When stimulated with insulin these patients exhibit insulin resistance at the liver, in adipose tissue and in muscle. Few elaborate studies on the effects of GH on glucose metabolism in GH deficient patients have been conducted. These patients are hypersensitive to the actions of insulin on glucose metabolism and there is some evidence that when GH initially is given to such patients in the GH deprived state, paradox insulin-like effects of GH may be observed. Whether this may relate to increased activity of insulin-like growth factors is uns

ISSN:1663-2818    

DOI:10.1159/000182185

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

It has been known for more than 30 years that growth hormone has a lipolytic properties and growth hormone excess (acromegaly) and growth hormone deficiency have been reported to be associated with abnormalities in serum lipoprotein concentrations. Due to the lipolytic effect of growth hormone, its administration in man has been reported to increase plasma nonesterified fatty acid (NEFA) concentrations. Ketone body production increases during acute growth hormone excess as a result of increased NEFA concentrations; similarly, the increase in serum triglycerides may be explained by an increase in substrate (NEFA) supply to the liver for VLDL production. The effect may be enhanced by a simultaneous decrease of serum lipoprotein lipase activity. The cholesterol-lowering effect of growth hormone administration has not been investigated in detail, specifically, the effect of growth hormone on LDL kinetics is unknown. Growth hormone-excess and growth hormone deficiency have been reported to be associated with increased risk for atherosclerosis; an association with serum lipoprotein changes is likely but evidence for a causal link is yet lacking.

ISSN:1663-2818    

DOI:10.1159/000182186

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Adults with growth hormone (GH) deficiency have decreased lean body mass which can be normalized by GH treatment. The anabolic action of GH involves redistribution of nitrogen from ureogenesis to the extrahepatic anabolic process together with stimulation of amino acid uptake and protein synthesis.

ISSN:1663-2818    

DOI:10.1159/000182187

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Administration of human growth hormone (GH) is associated with clinically significant sodium retention. There is evidence that the antinatriuretic properties of GH are mediated by activation of the renin-angiotensin system, as well as a direct action on the kidney. The antinatriuretic properties of GH may be of pathophysiological significance in acromegaly, where increased body sodium and plasma volume occur, and may contribute to the development of hypertension in this condition.

ISSN:1663-2818    

DOI:10.1159/000182188

出版商:S. Karger AG    

年代:1991

数据来源: Karger