摘要:

OBJECTIVE We have recently demonstrated multiple aberrations in the GH–IGF axis in the sera of children with untreated insulin‐dependent diabetes mellitus (IDDM) which were restored after insulin replacement. However, the net result of these alterations in the IGF system on the concentrations of free/biologically available IGF‐I in the serum have not been examined directly in diabetic children. In the present study, the effect of diabetes and subsequent insulin replacement on the circulating free IGF‐I concentrations are assessed.DESIGN Fasting venous serum samples were obtained longitudinally, before and at various times after the initiation of insulin treatment in untreated diabetic subjects.SUBJECTS Ten prepubertal, aged (mean ± SEM) 6.3±1.0 years, and six adolescent, aged 12.7±1.1 years, subjects with newly diagnosed and untreated IDDM, and age and pubertal status‐matched control children and adolescents were recruited.METHODS The serum samples were collected before initiating insulin treatment and 12–24h, 1 week, and 1 month thereafter in subjects with IDDM. Insulin doses ranged from 0.5 to 1.2 U/kg/day.MEASUREMENTS Free IGF‐I concentration was assayed by a recently developed two‐site immunoradiometric assay. Total IGF‐I was measured by radioimmunoassay after acid–ethanol extraction of binding proteins. Differences in free and total IGF‐I concentrations in IDDM subjects before and during insulin treatment were analysed by repeated measures analysis of variance followed by pairwise multiple comparisons test. In seven subjects with IDDM, where serum IGFBP‐1 and IGFBP‐3 concentrations, and IGFBP‐3 protease activity had also been measured in a previous study, the relationship between these variables and circulating free IGF‐I concentrations were examined by linear regression analysis.RESULTS Free IGF‐I concentrations in prepubertal subjects with IDDM were 0.9±0.2, 1.5±0.3, 1.6±0.3 and 2.5±0.4μg/l before, 1 day, 1 week and 1 month after insulin treatment, respectively. Free IGF‐I concentrations of control prepubertal children were 2.6±0.5μg/l. Pubertal subjects had higher free IGF‐I concentrations than prepubertal subjects but demonstrated a similar type of pattern; before insulin 2.3±1.1, 1 day 3.8±1.3, 1 week 3.7±0.6, 1 month 6.5±1.5vspubertal controls 7.7±2.0μg/l. Total IGF‐I concentrations were also reduced in untreated diabetic subjects and showed a slower pattern of normalization than free IGF‐I concentrations. Free IGF‐I concentrations correlated positively with total IGF‐I and negatively with IGFBP‐1 concentrations. There was no significant correlation between free IGF‐I and either serum IGFBP‐3 concentrations or IGFBP‐3 protease activity.CONCLUSION Alterations in the IGF system during untreated IDDM lead to a reduction in circulating free IGF‐I concentrations which is restored progressively during insulin treatment. An increase in free IGF‐I precedes that of total IGF‐I suggesting that the former is a more sensitive indicator of the metabolic status. An inverse correlation between free IGF‐I and IGFBP‐1 supports the h

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.7760786.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE While the effects of age on the growth hormone/insulin‐like growth factor (IGF) axis are well documented, the influence of ethnic background is unknown. The differences in IGF and IGF binding proteins (IGFBPs) were investigated in two ethnic groups.DESIGN A cross‐sectional study of an age‐selected cohort of healthy, normoglycaemic, non‐obese Caucasian (C) and Asian (A) subjects.PATIENTS Fifty‐three (27 C, 26 A) subjects with a mean age (±SD) of 20.6±0.8 years were studied.MEASUREMENTS Fasting measurements of glucose, insulin, IGF‐I, IGF‐II, IGFBP‐1 and IGFBP‐3. Western ligand blotting and immunoblotting with IGFBP‐2 and IGFBP‐3 of serum samples.RESULTS There were no significant differences in IGF‐I levels between Caucasian and Asian subjects (C 218±55vsA 229±40μg/l;P=0.44). IGF‐II (C 707±110vsA 583±75μg/l;P<0.0001) and IGFBP‐3 (C 5.9±1.2vsA 5.12±1.17 mg/l;P=0.01) levels were significantly higher in Caucasian subjects. Immunoblotting of ligand blots revealed no protease activity on either IGFBP‐3 or IGFBP‐2 to account for these ethnic differences.CONCLUSIONS Ethnic differences in IGFBP‐3 and associated IGF‐II levels may affect the inter‐relationships of IGFs and their binding proteins and need to be c

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00815.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim of the present study was to evaluate the short‐term metabolic effects of GH following i.v. and s.c. delivery.DESIGN AND MEASUREMENTS In a cross‐over design 10 GH‐deficient patients were randomized to receive GH (0.03 μg (0.1 mU)/kg/min) as a continuous i.v. or s.c. infusion for 39 hours on two different occasions. Preceding each study GH therapy was discontinued for 5 days. Serum profiles of GH, IGF‐I, IGF‐II, IGF binding protein 3 (IGFBP‐3), insulin, glucose and non‐esterified fatty acids (NEFA) were recorded during the studies. Serum GH was measured by a polyclonal radio‐immunoassay (RIA) and by a double monoclonal immunofluorimetric assay (DELFIA).RESULTS Higher mean integrated values (AUC) of serum GH (mU/l) were obtained with i.v. GH delivery [47.4±5.1 (i.v.), 33.3±3.0 (s.c.),P<0.05]. The two GH assays showed qualitatively similar results, but higher mean GH concentrations were measured by RIA following both s.c. (P<0.001) and i.v. infusion (P<0.001). Serum IGF‐I levels displayed different patterns following i.v. and s.c. GH infusion (P<0.05 by ANOVA) and mean IGF‐I levels (μg/l) were lower following s.c. GH infusion [159.5±21.8 (s.c.), 185.2±27.7 (i.v.),P=0.002]. Serum IGF‐II levels were unaffected by short‐term GH treatment and by the route of GH administration. Serum IGFBP‐3 levels increased in response to GH administration (P<0.001), irrespective of route (P=0.76). The IGF‐I/IGFBP‐3 molar ratio increased significantly following GH administration (P<0.001), and a higher ratio was obtained following i.v. infusion (P<0.005). Subcutaneous GH infusion resulted in significantly lower mean levels of serum NEFA (P<0.02), whereas similar mean levels of serum insulin (P=0.54), blood glucose (P=0.24), energy expenditure (P=0.13), and respiratory exchange ratio (P=0.09) were observed on the two occasions.CONCLUSIONS A reduced bioavailability of s.c. as compared with i.v. administered GH has been recorded with two independent GH assays, and this was also accompanied by a significant,

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00814.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Protein hypercatabolism and preservation of fat depots are hallmarks of critical illness, which is associated with blunted pulsatile GH secretion and low circulating IGF‐I, TSH, T4 and T3. Repetitive TRH administration is known to reactivate the pituitary‐thyroid axis and to evoke paradoxical GH release in critical illness. We further explored the hypothalamic‐pituitary function in critical illness by examining the effects of GH‐releasing hormone (GHRH) and/or GH‐releasing peptide‐2 (GHRP‐2) and TRH administration.PATIENTS AND DESIGN Critically ill adults (n=40; mean age 55 years) received two i.v. boluses with a 6‐hour interval (0900 and 1500 h) within a cross‐over design. Patients were randomized to receive consecutively placebo and GHRP‐2 (n=10), GHRH and GHRP‐2 (n=10), GHRP‐2 and GHRH+GHRP‐2 (n=10), GHRH+GHRP‐2 and GHRH+GHRP‐2+TRH (n=10). The GHRH and GHRP‐2 doses were 1μg/kg and the TRH dose was 200μg. Blood samples were obtained before and 20, 40, 60 and 120 minutes after each injection.MEASUREMENTS Serum concentrations of GH, T4, T3, rT3, thyroid hormone binding globulin (TBG), IGF‐I, insulin and cortisol were measured by RIA; PRL and TSH concentrations were determined by IRMA.RESULTS Critically ill patients presented a striking GH response to GHRP‐2 (mean±SEM peak GH 51±9 μg/l in older patients and 102±2μg/l in younger patients;P=0.005vsplacebo). The mean GH response to GHRP‐2 was more than fourfold higher than to GHRH (P=0.007). In turn, the mean GH response to GHRH+GHRP‐2 was 2.5‐fold higher than to GHRP‐2 alone (P=0.01), indicating synergism. Adding TRH to the GHRH+GHRP‐2 combination slightly blunted this mean response by 18% (P=0.01).GHRP‐2 had no effect on serum TSH concentrations whereas both GHRH and GHRH+GHRP‐2 evoked an increase in peak TSH levels of 53 and 32% respectively. The addition of TRH further increased this TSH response< ninefold (P=0.005), elicited a 60% rise in serum T3 (P=0.01) and an 18% increase in T4 (P=0.005) levels, without altering rT3 or TBG levels. GHRH and/or GHRP‐2 induced a small increase in serum PRL levels. The addition of TRH magnified the PRL response 2.4‐fold (P=0.007). GHRP‐2 increased basal serum cortisol levels (531±29nmol/l) by 35% (P=0.02); GHRH provoked no additional response, but adding TRH further increased the cortisol response by 20% (P=0.05).CONCLUSIONS The specific character of hypothalamic‐pituitary function in critical illness is herewith extended to the responsiveness to GHRH and/or GHRP‐2 and TRH. The observation of striking bursts of GH secretion elicited by GHRP‐2 and particularly by GHRH+GHRP‐2 in patients with low spontaneous GH peaks opens the

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00805.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

A 17‐year‐old girl presented with primary amenorrhoea and failure to develop secondary sexual characteristics, although her height was above the 90th centile. Endocrine investigations revealed hypogonadotrophic hypogonadism (basal LH and FSH levels<0.5 U/l; FSH rose to 2.0 U/l and LH to 1.0 U/l after GnRH). ACTH, GH, TSH and PRL secretion were normal. A magnetic resonance scan revealed no abnormality in the pituitary, pituitary stalk or hypothalamus but demonstrated a partly cystic enhancing lesion in the pineal region. Melatonin production (assessed as urinary 6‐sulphatoxymelatonin: aMT6s) at baseline was markedly increased: 459–530 ng/kg/24 h compared with aged‐matched controls: 136±69 (P=0.01). However, melatonin production retained a largely normal rhythm with increased production during the night. Treatment with ethinyloestradiol 100 μg daily had no apparent effect on the production of melatonin. Treatment with atenolol, 100 mg daily at 1600 h, was associated with suppression of nocturnal melatonin secretion but a brisk rebound in the morning and a considerably delayed peak excretion time (10.2 h) compared with controls (3.9 h). It is likely the pineal lesion, which may be hyperplasia or possibly even tumour, was responsible for the increased melatonin secretion. These data support the hypothesis that melatonin may have a causal role in

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.729549.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Involvement of the thyroid gland by Langerhans' cell histiocytosis is quite rare. We describe the case of a 58‐year‐old man referred for treatment of a progressively enlarging goitre. The trachea was severely stenotic and adjacent structures such as the left carotid vein and the thyroid cartilage were also involved. Central diabetes insipidus and severe combined immunodeficiency were associated. Although fine needle aspiration biopsy of the thyroid was initially interpreted as papillary carcinoma, anaplastic thyroid cancer was suspected. Treatment with prednisolone, doxorubicin and irradiation controlled the tracheal compression. A diagnosis of thyroid Langerhans' cell histiocytosis was finally made on the basis of the presence of Birbeck granules and CD1a and CD4 antigen in the thyroid tumour cells. Furthermore, positive staining for CD68 and lysozyme suggested that the tumour cells may have had the character of phagocytic cells in addition to their dendritic cell nature. This is the first case of thyroid involvement by malignant histicytosis of Langerhans' cell type with unusual phagocytic mark

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8020819.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

We report a case of amiodarone‐induced thyrotoxicosis of protracted duration, unresponsive to conventional thionamide therapy, with therapy limited by severe adverse drug reactions. Other treatment modalities included high dose corticosteroids, plasmapheresis, lithium and perchlorate. Temporary amelioration was achieved following plasmapheresis; however, this and other measures were unsuccessful in controlling the thyrotoxicosis, which deteriorated to thyroid storm. Histopathologically, a degenerative, inflammatory thyroiditis was evident.We discuss the limitations of conventional drug therapy and the lack of a sustained response to plasmapheresis. The failure of high dose steroids to alter the course of illness and to completely suppress the thyroidal inflammatory process is highlighted. A potential role for renal and hepatic impairment in the observed protracted course of amiodarone‐induced thyrotoxicosis is sugges

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00566.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00818.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.d01-1586.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY