ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02383.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02384.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02385.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We examined the effects of different doses of GH on insulin‐like growth factor I (IGF‐I), IGF binding protein 3 (IGFBP‐3), body composition, energy expenditure, and various metabolites in GH deficient adults, in order to approach a metabolically appropriate GH dosage in young GH deficient adults.DESIGN Ten GH deficient patients (age 21–43) were studied after 4 weeks without GH followed by three consecutive 4‐week periods, where the patients received in a fixed order GH 1,2 and 4 IU/m2s.c. per day. At the end of each period the patients were hospitalized for a 24‐hour examination.RESULTS Mean 24‐hour levels of GH (mIU/l) were 2.7±0.3 (0 GH), 7 2±0.9 (1), 10.8±1.5 (2) and 18.9±2.7 (4 IU/m2) (mean ±SEM) (P<0.01). Likewise, IGF‐I levels increased dose dependently from 61 ± 21 to 206 ± 65, 260 ± 70 and 468 ± 171 /μg/l (P<0 05); serum IGF‐I in an age and sex matched control group was 248 ± 25 /μg/l. Corresponding serum IGFBP‐3 levels also increased from 1860 ±239 to 3261 ±379, 3762 ±434 and 4384 ±652 /μg/l (P = 001) respectively. Significant increases in diurnal serum insulin levels after 4 IU/m2were recorded, whereas plasma glucose levels remained unchanged. Lipid intermediates increased dose independently during GH administration. GH caused a significant increase in resting energy expenditure, whereas the respiratory exchange ratio was unaltered. Fat mass was increased without GH therapy and decreased during the study. Four patients made complaints during 4 IU/m2GH administration, probably related to GH induced fluid retention.CONCLUSION Based primarily on IGF‐I and IGFBP‐3 levels our data suggest that a GH replacement dose in young GH deficient adults in the order of 1–2 IU/m2per day is adequate. This is a relatively low dose as compared to

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02386.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE In view of the fact that GH‐deficient adults present with pronounced osteopaenia and can be considered at risk for osteoporotic fractures, we wanted to investigate the effects of biosynthetic GH replacement therapy (0.25 IU/kg/week) on biochemical indices of bone turnover and on bone mineral content (BMC) in a group of GH‐deficient adult males.DESIGN We performed a 6‐month randomized, double‐blind, placebo‐controlled study, followed by 12–24 months of GH treatment in all patients.PATIENTS Twenty adult males with GH deficiency of childhood onset were studied.MEASUREMENTS We measured serum IGF‐I, serum phosphate, biochemical indices of bone turnover (serum alkaline phosphatase activity, serum osteocalcin, serum carboxyterminal propeptide of type‐I procollagen, fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios) and bone mineral content, measured at the forearm and the lumbar spine by single and dual‐photon absorptiometry respectively.RESULTS After 3 and 6 months of GH administration, the serum levels of alkaline phosphatase, osteocalcin and carboxyterminal propeptide of type‐I procollagen, and the fasting urinary hydroxyproline/creatinine ratio were significantly increased compared to placebo‐treated patients (P<0.01 toP<0.001). During the open study phase, the values for these indices of bone turnover remained elevated above pretreatment levels (P<0 01 toP<0 001 at 12 months), a downward trend becoming apparent after about one year of GH treatment. BMC values showed an initial decline after 3 months of GH treatment (most likely due to an expansion of the remodelling space), followed by a significant and progressive increase above pretreatment values, reaching 7–8% for total BMC at the lumbar spine (L2‐L4) and 9–9% for total BMC at the forearm, after 30 months of GH administration.CONCLUSIONS The data of our study show that administration of substitutive doses of growth hormone to GH‐deficient adult males activates bone turnover for a period of at least one year and suggests that this may have a beneficial effect o

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02387.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We studied the relationship between plasma level of insulin‐like growth hormone I (IGF‐I), changes in lean body mass and in adipose mass, and adverse side‐effects during human growth hormone (hGH) treatment of elderly men who had low IGF‐I levels.DESIGN The first six months was a period of baseline observation. The subjects were then randomized into two groups so that during months 7–18, men in group I received hGH, and men in group II served as untreated controls.SUBJECTS Eighty‐three overtly healthy elderly men, who were selected because their plasma IGF‐I level was less than 0.35 units/ml. The men were randomly assigned in a ratio of three to one into group I (n= 62) or into group II (n= 21).MEASUREMENTS Plasma IGF‐I level was measured monthly. Lean body mass and adipose mass were measured every six months.RESULTS Fifteen men left the study during the baseline period because of personal reasons or intercurrent medical events. In those who received drug (group I), there were a number of adverse reactions which could have been related to the hGH therapy: carpal tunnel syndrome 10, gynaecomastia 4, and hyperglycaemia 3. In total there were 27 dropouts from group I and two dropouts from group II after the six‐month point, for a variety of medical and non‐medical reasons, the majority probably not related to hGH therapy.During the hGH treatment of group I, plasma IGF‐I increased from the range 0.10–0.35 units/ml into the range 0.5–2.2 units/ml. Among the 18 men who completed 12 months of hGH treatment without experiencing one of the three above‐noted presumed hGH side‐effects, mean and peak plasma IGF‐I during treatment were significantly lower than among the 13 men who experienced carpal tunnel syndrome or gynaecomastia (one subject had both) while on hGH. With one exception, neither carpal tunnel syndrome nor gynaecomastia occurred in any individual with a mean IGF‐I level less than 10 units/ml during hGH treatment.Twelve months of hGH treatment (group I) caused an increase in lean body mass to 106% of the initial baseline (month one of the protocol), and a reduction in adipose mass to 84% of the baseline. Meanwhile, the lean body mass of the untreated men in group II declined to 97% of the initial baseline. The body composition responses after 12 months of treatment in group I were larger in the men whose mean intra‐treatment IGF‐I level was 0.5–1.0 units/ ml, than in the men whose mean intra‐treatment IGF‐I level was 1.0–1.5 units/ml.CONCLUSIONS These observations show that when elderly men with low circulating IGF‐I concentrations are treated continuously with hGH, elevation of plasma IGF‐I above 10 units/ml is associated with a substantial frequency of carpal tunnel syndrome or gynaecomastia. It may be that the effects of the hormone in expanding lean body mass and reducing adipose mass can be achieved, and the side‐effects avoided, by maintaining

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02388.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We assessed the relationship between serum IGFBP‐3 levels with IGF‐I and quantitative GH secretory status in poorly growing children.DESIGN We studied the relationship between 24‐hour integrated concentration of GH, peak GH to paired sequential stimulation tests, IGF‐I and the IGFBP‐3 serum levels. PATIENTS One hundred and two children (82 males, 20 females, age 11.7±2.7 years) with short stature (height 2.6±0.7 SDS) were studied.MEASUREMENTS Quantitative GH secretory status was assessed by the 24‐hour integrated GH and by response to arginine and insulin stimulation. GH, IGFBP‐3 and IGF‐I were measured by radioimmunoassay. To adjust for age and gender, IGFBP‐3 levels were converted to SD score. RESULTS IGFBP‐3 SDS was strongly correlated with IGF‐I SDS (r= 0 64,P<0.0001), and weakly with peak GH (r= 0.28,P<0 0004), but not with the integrated GH concentration (r= 0 07,P<0 46). IGFBP‐3 SDS increased with pubertal maturation (P<0 0001). There was no difference in mean IGFBP‐3 SDS in subgroupings of the patients based on the results of their quantitative GH tests. CONCLUSION In short children, IGFBP‐3 levels increase with puberty, are strongly correlated with IGF‐I levels, weakly correlated with peak response to GH stimulation tests, but not correlated with integrated GH. Consequently, diagnostic classifications of patients based on quantitative measurements of

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02389.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We examined basal inositol phospholipid turnover and the response to the kinin, kallidin, in human pituitary adenomas and determined whether or not there was an association between these parameters and interleukin (IL‐6) secretion status by the tumours.DESIGN Pituitary adenoma tissue was dispersed and cells were cultured in monolayer for 96 hours. The medium was then removed and assayed for IL‐6 and anterior pituitary hormones. The cells were labelled with3H‐myoinositol for 24 hours and then incubated under basal conditions with kallidin and, in some cases, with TRH and GnRH for 60 minutes. Total inositol phosphate accumulation and pituitary hormone secretion were assessed.PATIENTS Tissue was collected from 29 consecutive patients being treated surgically for pituitary adenomas.MEASUREMENTS Total3H‐inositol phosphates, growth hormone, prolactin, LH, FSH, TSH and immunoreactive IL‐6.RESULTS Two groups of pituitary adenomas were identified, one with high and one with low basal inositol phospholipid turnover. Kallidin stimulated inositol phosphate accumulation in seven of the 29 adenomas studied. The kallidin‐responsive adenomas were associated with high basal phosphoinositide turnover. All seven kallidin‐responsive adenomas secreted IL‐6. The adenomas studied with high basal inositol phosphate production were also responsive to TRH and in two tumours to GnRH. Kallidin stimulated GH release in one GH‐secreting adenoma but had no effect on hormone secretion from any other tumour.CONCLUSION Two groups of pituitary adenomas have been identified with high and low basal inositol phosphoinositide turnover. Phosphoinositide metabolism is readily stimulated by kallidin and TRH in adenomas with high but not low turnover. Kinin‐responsive adenomas secreted IL‐6 but IL‐6 secretor status does not preclude that they w

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02390.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE The aim was to determine the target range into which mean daily serum Cortisol should be lowered in patients on medical therapy for Cushing's syndrome, using isotopically estimated Cortisol production rates as'gold standard.DESIGN Patients with Cushing's syndrome on medical treatment were given 12 ng of tritiated Cortisol intravenously and a 24‐hour urine collection was made in a single day. On the same day, serum Cortisol was measured at 0900,1200,1500,1800, 2100, and at 2400 h in in‐patients. In addition, serum Cortisol was measured at the same times as above in a group of healthy volunteers.SUBJECTS Twenty‐two patients on medical therapy for Cushing's syndrome were studied on a total of 29 occasions. In addition, serum Cortisol profiles were obtained in 12 healthy volunteers.RESULTS The median serum Cortisol in patients with Cushing's syndrome was 400 (range 66–839) nmol/l, and in the healthy volunteers 178 (range 137–299) nmol/l. The median isotopic Cortisol production rate in the patients with Cushing's syndrome was 84 μmol/24 h, range 10–343 (normal range 22–83) μmol/24 h. In the patients with Cushing's syndrome, the correlation of mean serum Cortisol to Cortisol production rate was +0.77 (P<0.001). Normal rates were found when mean serum Cortisol levels were between 150 and 300 nmol/l.CONCLUSIONS The aim of drug therapy for Cushing's syndrome should be to lower the mean serum Cortisol through the day into the range

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02391.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We wished to discriminate between the opioid peptideβ‐endorphin (β‐EP) and its non‐opioid precursorβ‐lipotrophin (β‐LPH) in normal subjects and patients with ACTH‐related disorders.DESIGN We produced monoclonal antibodies toβ‐EP andβ‐LPH for the development of two‐site immunoradiometric assays (IRMAs) which specifically quantitateβ‐EP andβ‐LPH.PATIENTS Samples were obtained from patients with a range of ACTH‐related disorders and compared with 18 normal subjects. Peptide levels were also compared in six patients with Cushing's syndrome undergoing bilateral inferior petrosal sinus sampling with corticotrophin releasing hormone administration.MEASUREMENTS In theβ‐EP IRMA, antibody 6B2, specific forβ‐EP 18–27, is radiolabeled and antibody 2E10, recognizingβ‐EP 1–5, is coupled to Sephacryl S‐300 as solid phase. The IRMA is specific forβ‐EP (β‐LPH cross‐reacts<0.02%), has a detection limit of 14 ± 0 7 pmol/l (n = 7) and has a within‐assay coefficient of variation of<10% between 4.9 and 1200 pmol/l. In the β‐LPH IRMA, antibody 6B2, which recognizes an epitope common toβ‐LPH andβ‐EP, is radiolabeled and paired with solid‐phase antibody 5C11 which recognizesβ‐LPH 39–56. The binding site of this antibody ensures thatβ‐EP cannot be measured in theβ‐LPH assay. The detection limit is 0.8 ± 0.1 pmol/l (n= 9) and the within‐assay coefficient of variation is<10% at concentrations 1.7–870 pmol/l.RESULTS In normal subjects,β‐EP andβ‐LPH levels were<1.4–1.7 pmol/l (<5–6 ng/l) and 2.5–6.7 pmol/l (29–77 ng/l) at 0930 h and<1.4–1.7 pmol/l (<5–6 ng/l) and 1.9–4.5 pmol/l (22–49 ng/l) at 1600 h, respectively. In patients with ACTH‐related pathologies concentrations ofβ‐EP andβ‐LPH paralleled those of ACTH. The ratio ofβ‐LPH:β‐EP in plasma varied between 3.2:1 and 38:1 in these patients demonstrating thatβ‐LPH is the major circulating peptide derived from the C‐terminal of pro‐opiomelanocortin in man. However, in two patients undergoing bilateral inferior petrosal sampling with corticotophin releasing hormone for diagnosis of Cushing's diseaseβ‐EP concentrations increased rapidly during the first 5 minutes of the test, resulting in a sharp decrease in theβ‐LPH:β‐EP ratio. These results suggest thatβ‐EP is preferentially released in response to acute corticotrophin releasing hormone stimulation.CONCLUSI

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02392.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY