摘要:

SUMMARYA radioimmunoassay using a proinsulin‐specific antiserum that does not react preferentially with the split forms of proinsulin has been used to compare the response of circulating proinsulin to low (25 g) and high (75 g) oral glucose loads in healthy subjects and in patients with liver cirrhosis. The patients were divided into two groups: Group A (n= 7) with normal glucose tolerance and Group B with diabetic (n= 5) and impaired (n=1) glucose tolerance. There was no apparent correlation between glucose tolerance and the results of quantitative liver function tests. In the fasted state, the concentrations of serum proinsulin did not differ significantly in patients of Group A (0·022 ± 0·002 nmol/1) or Group B (0±026 · 0±004 nmol/1) from those in healthy subjects (0·021 ± 0·002 nmol/l). After 75 g glucose, the rise in serum proinsulin to a maximum concentration of 0·082 ± 0·012 nmol/1 in patients of Group A and to 0·070 ± 0·019 nmol/1 in Group B was not significantly different at any time point up to 180 min from the rise in healthy subjects (to 0·063 ± 0·005 nmol/1). After 25 g glucose, the response of serum proinsulin in Group B patients (maximum concentration 0·035 ± 0·003 nmol/1) was not significantly different from that in healthy subjects (maximum concentration 0·032 ± 0·003 nmol/1) but a slightly enhanced release was observed in the Group A patients (maximum concentration 0·049 ± 0·003 nmol/1) that was significantly greater (P>0·05) at 60 min post‐glucose. In contrast, the concentrations of serum immunoreactive insulin and immunoreactive C‐peptide in all patients with cirrhosis were significantly elevated compared with healthy subjects both in the fasted state and at several time points following high and low oral glucose. In the fasted state, the serum proinsulin/C‐peptide molar ratio, an index of the relative state of secretion of proinsulin and insulin, was significantly lower (P>0·05) in both groups of cirrhotic patients than in healthy subjects. After high and low glucose, this ratio fell in all patients and in the healthy subjects. We conclude that cirrhosis of the liver is associated with a hypersecretion of insulin but hyperproinsulinaemia does not contribute appreciably to the elevated concentration of immunoreactive i

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01701.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThe aim of this study was to determine whether patients with homozygous familial hypercholesterolaemia (FH) have impaired adrenal cortical function. Plasma levels of cortisol, dehydroepiandrosterone (DHA), pregnenolone sulphate (PS) and DHA sulphate (DHAS) were measured during an 8 h ACTH infusion in six controls and two patients with homozygous FH. The basal PS levels of both patients and the basal DHA level of one were abnormally low for age and pubertal stage. During ACTH infusion we observed in both patients: (1) a mild impairment of control response after sustained stimulation (P>0·002); (2) a clear impairment of PS response (values less than 2 SD of those in controls); (3) a clear impairment of DHA response (values less than 2 SD) until 4 h in the boy who was at pubertal stage 4 and whose response could be compared to controls; no increase at all in the affected girl (pubertal stage 2) at a stage where normal subjects respond with significant increase. These results suggest that patients with FH lack cholesterol for corticosteroid biosynthesis under maximal ACTH stimulation and that mild chronic ACTH stimulation due to a deficit in the cholesterol supply to adrenal cells might increase the conversion of Δ5to Δ4‐steroids. They provide further evidence to support the primordial role of low density lipoprotein (LDL)‐cholesterol in adrenal steroidogenesisi

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01702.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYAlopecia is a frequent feature in hereditary resistance to (1,25(OH)2D). We sought insight into this feature by analysing data from affected members of 30 kindreds. We assessed indices of mineral metabolism in one group with normal hair compared with a group with alopecia. Hereditary resistance to 1,25(OH)2D was diagnosed at an earlier age in alopecic patients (0·9 vs 3·3 years,P>0·05); this reflected late presentation of metabolic bone disease in some cases with normal hair and could not be attributed to early diagnosis resulting from the striking feature of alopecia. For untreated subjects, serum concentrations of calcium and 1,25(OH)2D were similar in both groups of patients. During calciferol therapy, however, the cases with alopecia showed lower serum calcium (1·9 vs 2·4 mmol/1,P>0·005), but higher serum 1,25(OH)2D (2900 v 340 pg/ml,P>0·005). Hair status did not predict the type of defect identified with cultured skin fibroblasts but did correlate with responsiveness of 25(OH)D 24‐hydroxylase to 1,25(OH)2D3in those cells. Cells from seven of eight kindreds with alopecia showed no 24‐hydroxylase response to high doses of 1,25(OH)2D3while cells from five of six kindreds with normal hair showed a 24‐hydroxylase response to high doses of 1,25(OH)2D3. We conclude that in cases with hereditary resistance to 1,25(OH)2D alopecia reflects the more severe grades of this resistance based upon earlier age at time of diagnosis, lower potential for calcaemic response to calciferols, and lower potential for 24‐hydroxylase response to 1,25(OH)2D3by cultured sk

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01703.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYLeucocyte ouabain‐sensitive22Na+efflux was studied in 35 normal and 12 obese subjects. This efflux rate constant was raised in the obese (2·72 ± SEM 0·13 vs 2·31 ± 0·08 h‐1,P>0·006), indicating a higher activity of the sodium pumpin vivo.There was a significant correlation between this efflux rate constant and fasting insulin level in both the whole population and in the normals alone (rs= 0·36,P>0·007, andrs= 0·40,P>0·009 respectively). A hyperinsulinaemiceuglycaemic clamp was performed on seven normal volunteers. After 2 h, there was a significant stimulation of the leucocyte efflux rate constant (from 2·86 ± 0·17 to 3·33 ± 0·18 h‐1,P>0.01). In‐vitro incubation of leucocytes with insulin produced a maximal stimulation of the Na+‐K+‐ATPase activity of about 35% at 2 h with half‐maximal stimulation achieved at 46 mU/1. Insulin (100 mU/1) also stimulated the leucocyte ouabain‐sensitive22Na+efflux rate constantin vitroby about 11 % with or without 1 h of preincubation with the insulin. These findings may explain the hypokalaemic and sodium retaining effects of insulin in man; they may also partially explain the raised Na+

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01704.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYOvarian hyperstimulation was induced in 17 normally cycling women undergoing in‐vitro fertilization (IVF) and embryo transfer with clomiphene (9 cycles), clomiphene followed by pulsatile hMG (12 cycles) or clomiphene followed by pulsatile FSH (11 cycles). Hyperstimulation was greater with the combined treatments than with clomiphene alone. In all 32 cycles an endogenous LH surge occurred. The peak values and the duration of the LH surge showed significant negative correlations with the plasma oestradiol levels, the number of the follicles and the total follicular fluid volume aspirated at laparoscopy. We suggest that during superovulation induction for IVF, the endogenous LH surge is attenuated by factors which are related to the degree of ovarian hyperstimulatio

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01705.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYIn a re‐evaluation of the use of dopamine as a prognostic factor in phaeochromocytoma, a series of 34 patients was imaged with iodine‐131‐meta‐iodobenzyl‐guanidine, a radiopharmaceutical specifically localized in chromaffin tumours. Fourteen patients were found to have malignant disease. Increased dopamine excretion was found in 9 (64%) of these patients, including all four with primary intra‐adrenal tumours, and this was associated with a poor prognosis. Of the five patients in the malignant group with normal dopamine excretion on referral, the disease extent was minimal and in four the primary tumour had been resected. Twenty patients appeared to have benign phaeochromocytoma from the imaging results. Of these, 16 were intra‐adrenal and four were extra‐adrenal. In 19 the dopamine excretion was within the control range but in one it was marginally increased. From these observations it would seem that dopamine excretion may be a useful prognostic factor when combined with imaging to determine the extent

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01706.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThirty‐nine patients with idiopathic cranial diabetes insipidus (DI) and 81 secondary to hypothalamic lesions were investigated for the presence both of associated autoimmune diseases and autoantibodies. Eleven (28%) of the idiopathic but none of the secondary DI cases had an overt autoimmune disease. A further two patients with idiopathic DI had associated organ‐specific autoantibodies. Autoantibodies to vasopressin (AVP)‐secreting hypothalamic cells were detected in 12 patients with idiopathic DI (31 %). Seven out of 13 cases of DI secondary to histiocytosis X (HX) were also positive (54%), whereas only two (3%) of the other 68 sera from patients with secondary DI reacted with AVP cells. Of the 13 patients with DI associated with frank organ‐specific autoimmune diseases or autoantibodies alone, eight (62%) were positive for AVP‐cell antibodies. The finding of associated autoimmune diseases in a patient with idiopathic DI is therefore suggestive of an autoimmune origin of DI, and this can be supported by the detection in the serum of AVP cell antibodies. In cases of HX, the new finding of the presence of AVP‐cell antibodies reflects hypothalamic infiltration by HX cells, and suggests that these DR+‘Langer‐hans‐like’ cells play more than a passive role in the

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01707.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThe met‐enkephalin analogue, DAMME, suppresses the pituitary‐adrenal axis in normal subjects; it is not clear whether this occurs at the level of the pituitary or above. We therefore administered synthetic ovine corticotrophin releasing factor (CRF‐41) 100μgi.v. to a group of normal male subjects, with or without pretreatment with DAMME 250μgi.v., and monitored the response of plasma ACTH and serum cortisol. CRF‐41 caused a marked stimulation of ACTH and cortisol release, but this was significantly attenuated by pretreatment with DAMME. It is therefore concluded that DAMME either directly inhibits the corticotroph at the level of the pituitary, or that it suppresses release of an additional factor which normally potentiates the action of CRF‐41 on th

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01708.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThe effect of dopamine (1 μg/kg /min by i.v. infusion) on corticosteroid levels was studied in five patients with cortisol excess caused by increased ACTH secretion. In four of the five subjects dopamine, when compared with placebo infusion, caused plasma concentrations of 11‐deoxycorticosterone to rise without affecting levels of cortisol, corticosterone or aldosterone. In a parallel in‐vitro study using incubations of bovine adrenal zona glomerulosa cells, dopamine (10‐9mol/1–10‐5mol/l) had no effect on basal or ACTH stimulated secretion of aldosterone, cortisol or 11‐deoxycorticosterone. However, dopamine (10‐5mol/l) partially inhibited angiotensin II (10‐7mol/l) stimulated secretion of aldosterone (4.36 ng/106cells/h ± 0·28 vs 2·90 ± 0·20, P>0·05) but did not alter 11‐deoxycorticosterone secretion in the same incubations. These data suggest that the effect of dopamine on 11–deoxycorticosterone secretionin vivomay not be due to its direct action on the adrenal to inhibit corticosteroidogenesis. An alternative explanation is that dopamine may alter extra‐adrenal synthesis of 11‐deoxycorticosterone, possibly by increasing substrate availability to tissues capable

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01709.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYIt has been reported recently that patients with hyperprolactinaemia may develop hypothyroidism as a consequence of the increased inhibition of TSH release by dopamine which occurs in the majority of such patients. In this study we have evaluated thyroid function in a large number of hyperprolactinaemic patients in order to delineate more precisely the relationship between thyroid status, free thyroid hormone levels and the control of TSH release by dopamine. Biochemical euthyroidism was present in the majority of the hyperprolactinaemic patients. Our data indicate that the increased dopaminergic inhibition of TSH release does not lead to hypothyroidism. Instead, the slightly elevated basal TSH levels and TSH responses to TRH (within the normal range) may reflect the operation of a compensatory mechanism to maintain euthyroidism in the face of the increased inhibition of TSH release by hypothalamic dopamine.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01710.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY