摘要:

SUMMARYIn order to evaluate the effect of alpha‐1 adrenoreceptor regulation of ACTH release during insulin‐induced hypoglycaemia, we studied the response to hypoglycaemia with and without prazosin premedication in eight normal men. Prazosin pretreatment did not affect basal or peak plasma ACTH, Cortisol or GH during hypoglycaemic stress. However basal plasma levels of noradrenaline were increased (P<0.02) as were responses of AVP, angiotensin II (P<0.05) and noradrenaline (P<0.05) to hypoglycaemia after prazosin. Though it is possible that these augmented responses masked an inhibitory effect of prazosin, we were unable to demonstrate a major role for alpha‐1 adrenergic receptors in mediating the ACTH response to hypoglycaemic stress in norma

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb03632.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYShort‐term fasting in humans is associated with diminished Δ TSH to TRH. The purposes of the present study were to reassess basal TSH levels and TRH responsiveness during fasting utilizing a sensitive radioimmunoassay (RIA: sensitivity 0.3 μU/ml; normal range 0.66‐2.98 μU/ml) and to determine if normal feedback regulation is maintained during the fasting state. Eight control subjects (C) and six iodide‐treated (I) subjects (262 mg/d) were studied in the fed state and on day 10 of fasting. T3, T4, and TSH were measured by RIA, and free T4 and free T3 by equilibrium dialysis. Basal serum TSH levels in the control group were 2.0 ± 0.3 μU/ml (mean ± SEM) in the fed state and increased to 14.7 ± 3.5 μU/ml 20 min after TRH administration. The fasting basal TSH level of 1.6 ± 0.3 μU/ml was significantly decreased (P<0.01) compared to control, as was the level of 8.8 ± 2.3 μU/ml (P<0.01) obtained 20 min after TRH. In the iodide‐treated group the basal TSH level was 1.4 ± 0.2 μU/ml during feeding which increased (P<0.025) to 2.9 ± 0.7 μU/ml during fasting; the TSH value 20 min after TRH was 12.6 ± 2.5 μU/ml while feeding and 17.3 ± 2.9 μU/ml while fasting. Free and total T3 decreased during fasting in both groups. Total T4 was unchanged between the fed and fasted periods in the two groups. That free T4 (pmol/l) rose significantly during fasting (28.7 ± 1.3 vs 33.8 ± 1.3,P<0.01) in the control group but was unaltered in the iodide‐treated group (23.8 ± 1.3 vs 26.2 ± 2.5) suggests an aetiological role for free T4 in blunting TSH responsiveness. The abolition by iodide of the fasting‐related changes in TSH further suggests that normal pituitary feedback regu

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb03633.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYSeven women with secondary hypogonadism who had been previously unresponsive to two 5‐d courses of clomiphene citrate, were treated with clomiphene citrate 100 mg daily for 10 d. LH and FSH concentrations were measured in serum collected at 15‐min intervals for 5 h before and on the 10th day of treatment and oestradiol was measured in the first two samples on each day. Four women responded with an increase in the amplitude of LH pulses and in mean LH values and in three there was a marked increase in serum oestradiol concentrations. Three women who showed no gonadotropin response were subsequently unresponsive to pulsatile LHRH therapy. These preliminary data are consistent with the hypothesis that hypothalamic hypogonadotrophism may result from hypersensitivity of the hypothalamus to oestrogen negative feedback and that the hypothalamic potential for secretion of LHRH is unimpaired. Prolonged treatment with clomiphene may provide a simple test of hypothalamic function in women with normal pituitary funct

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb03634.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYTo determine whether calcium fluxes and angiotensin II influence osmoregulation of vasopressin (AVP) secretion, the effects of the calcium antagonist nifedipine and of the converting enzyme inhibitor enalapril on the AVP response to an osmotic load were compared to those of a placebo in seven normal female subjects. Plasma and urinary AVP were measured before and during a 3‐h infusion of 2.5% hypertonic saline. Nifedipine (10 mg orally 2 h before and 10 mg at the start of the infusion) increased heart rate but did not change blood pressure. The changes in free water clearance and in urinary AVP induced by hypertonic saline under nifedipine were greater than in the control test, but the slope and the intercept of the regression line of plasma AVP upon plasma osmolality were not significantly different. Enalapril (10 mg 3 h before the infusion) did not change heart rate or blood pressure. Free water clearance and urinary AVP did not differ from the control test, but the slope of the regression line was less steep. These slight modifications of the response to an osmotic load suggest that calcium fluxes and angiotensin II only exert a limited influence on AVP osmoregulation in normal female

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb03635.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYWe have used a method based on a perchlorate discharge test to estimate the duration of antithyroid effect of two doses of methimazole (MMI). Six patients with diffuse toxic goitre took 5 mg MMI twice daily and six took 20 mg twice daily over the study period of 12 weeks. Biochemical control of hyperthyroidism was achieved in all patients and thyroid hormone supplementation was required by all of the patients in the higher dose group to avoid hypothyroidism. Discharge of radioiodine from the thyroid by perchlorate diminished in both groups with time after MMI. After 5 mg MMI, perchlorate discharge as a percentage of the 30‐min uptake (mean ± SD), was 81.7 ± 3.3% at 2.2 h, 69.3 ± 18.9% at 5.9 h, 22.6–23.4% at 13.4 h and 2.7–6.7% at 25.1 h. After 20 mg MMI, the discharge was 92.5 ± 1.9% at 2.2 h, 84.3 ± 8.8% at 6.3 h, 64.8 ± 24.1 % at 13.3 h and 26.9–29.4% at 25.1 h. Only four patients (one in the lower dose group) showed a detectable discharge at 25 h and one of the patients treated with the lower dose showed no discharge at 13 h. These estimates of the effect of MMI on thyroidal iodide organification are not in keeping with published thyroidal MMI concentrations which do not show a fall between 3–6 h and 17–20 h after carbimazole. The explanation for this disparity is not clear but may be based on a redistribution of thioureylenes within the thyroid with time after dosage. The present data suggest that once daily is not the optimum dosage interval for MMI with respect to its effect on the organif

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb03636.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYWe have developed a sensitive two‐site immunoradiometric assay (IRMA) for intact ACTH and its precursors, pro‐opiomelanocortin and 22 kDa peptide in unextracted human plasma. The assay uses two monoclonal antibodies. Antibody 1A12, specific for ACTH 10–18, is radiolabelled and antibody 2A3 specific for the C‐terminal region (ACTH 24–39), is coupled to Sephacryl S300 for the solid‐phase. Samples are incubated for 18 h with labelled antibody followed by 2 h with solid‐phase antibody. Separation employs the sucrose layering technique. Using human pituitary ACTH 1–39 (code 74/555) in diluent containing 10% horse serum to standardize the assay, the sensitivity (upper 99% confidence limit of zero standard) is 3.5 ± 0.8 ng/l (n= 7). The mean coefficient of variation is 5.9% within‐assay and 6.7% between‐assay and is less than 10% between 22 and>5000 ng/l. Mean recovery of ACTH 1–39 added to dexamethasone‐suppressed human plasma is 109% and endogenous ACTH behaves indistinguishably from standard ACTH on dilution. In normal subjects, mean plasma ACTH levels are 30 ng/l at 0730 h, and 15 ng/1 at 1630 h at rest. ACTH concentrations are between 60 and 330 ng/l, 8–10.5 h after metyrapone (2 g orally at 2300 h), between 140 and 320 ng/1, 30–60 min after insulin‐induced hypoglycaemia, and<4 ng/1, 8 h after dexamethasone (1.5 mg orally at 2300 h). In a range of pathological conditions ACTH concentrations accurately reflect the disorders of the pituitary‐adrenal axis. Endogenous ACTH immunoactivity is stablein vitroat 22°C for at least 1 h in whole blood and at least 4 h in plasma. It is concluded that this two‐site IRMA for ACTH in unextracted plasma offers a r

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb03637.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYThe insulin hypoglycaemia test has been widely used for assessing the hypothalamic‐pituitary‐adrenocortical function. The outcome of this test has been compared to that of the 30 min ACTH test in 200 consecutive patients with proven or suspected hypothalamic‐pituitary disorder. A significant correlation (R= 0.83,P<0.001) between the results of the two tests was found. In patients in whom blood glucose levels fell to 2.2 mmol/l (40 mg/dl) or below, the ratio between the peak plasma Cortisol concentration during hypoglycaemia and plasma Cortisol concentration 30 min after ACTH was 1.002. In patients in whom blood glucose concentration declined to 2.3–30 mmol/l (41–54 mg/dl) the ratio was significantly lower (0.828). In eight patients discordant results between the two tests were found. In two patients the ACTH test was normal despite impaired response to insulin. They were studied shortly after acute symptoms of a pituitary adenoma necrosis. Two patients had subnormal responses to insulin despite the fact that pituitary‐adrenal function appeared to be intact. In both cases relative insufficiency of the hypoglycaemic stimulus was the likely cause of the discrepancy. In the remaining four patients results of one test was marginally below, and that of the other test marginally above the lower limit of normal. It is concluded that the 30 min ACTH test is reliable for assessing integrated hypothalamic‐pituitary‐adrenal function (except shortly after acute AC

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb03638.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYWe have studied the role of central alpha‐1 adrenoceptor mechanisms which stimulate Cortisol secretion throughout the 24 h period in man. Six normal subjects were given 24 h i.v. infusions of the alpha‐1 adrenoceptor agonist methoxamine, the alpha‐1 antagonist thymoxamine, and saline under double‐blind conditions. The only cardiovascular effects of these adrenergic manipulations was a slight bradycardia accompanying the methoxamine infusion. The methoxamine infusion was accompanied by higher concentrations of Cortisol than the saline infusion during waking hours and the food related secretory surges were exaggerated, while the converse held with thymoxamine. In contrast, the nocturnal surge of Cortisol secretion was unaffected by these adrenergic manipulations. These findings suggest that an alpha‐1 adrenoceptor mechanism contributes to the maintenance of Cortisol secretion during waking hours, but not

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb03639.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYThe response of ACTH and Cortisol to corticotrophin‐releasing hormone (CRH) after pretreatment with various doses of dexamethasone was investigated in five healthy subjects. The five subjects participated in six experiments. In each experiment 200 μg ovine CRH was administered as an i.v. bolus injection at 0900 h after pretreatment with respectively: (A) 1 mg dexamethasone orally at 2300 h in the evening before CRH injection, (B) 2 mg dexamethasone orally at 2300 h in the evening before CRH injection, (C) 4 mg dexamethasone orally at 2300 h in the evening before CRH injection, (D) 2 mg dexamethasone orally at 2300 h in the evening before CRH injection, followed by 2 mg dexamethasone orally 1 h before CRH, (E) no dexamethasone and (F) 1 mg dexamethasone orally 1 h before CRH injection. In spite of overnight suppression with a single dose of dexamethasone CRH elicited Cortisol rises in all individuals (experiments A‐C). Dexamethasone pretreatment in experiment D abolished the CRH‐induced stimulation of the pituitary‐adrenal axis. There was a significant and negative correlation between the basal dexamethasone levels (i.e. the dexamethasone levels immediately before CRH administration) in the experiments A‐D and the areas under the individual ACTH (R=−0.62;P<0.01 by Spearman's rank correlation test) and Cortisol (R=−0.81;P<0.001 by Spearman's test) curves, i.e. the lower the basal dexamethasone levels, the greater the rise in ACTH and Cortisol levels after CRH administration. Pretreatment with a single dose of 1 mg dexamethasone 1 h before CRH injection (experiment F) led to a significant inhibition of the CRH‐induced ACTH and Cortisol response, despite unsuppressed pre‐CRH ACTH and Cortisol levels. We conclude that CRH is able to overrule the inhibition of the pituitary‐adrenal axis by overnight suppression with pharmacological doses of dexamethasone. The strongly negative correlation between the basal dexamethasone levels and the CRH‐induced pituitary‐adrenal responses suggests that circulating glucocorticoid levels modulate the response of

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb03640.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYHigh plasma concentrations of neuropeptide Y (NPY) were found in a patient with bilateral adrenal phaeochromocytomas and medullary thyroid carcinoma associated with MEN IIa (32 pmol/l, normal<3.5 pmol/l). Both adrenal tumours contained and secreted NPY. Manipulation at operation produced a remarkable increase in plasma NPY concentrations (peak =1631 pmol/l) coinciding with increases in plasma levels of catecholamines and arterial pressure. NPY was also shown to be present in thyroid tumour tissue: the concentration of NPY in tumour was 50‐fold higher (0.9 nmol/g vs 0.004 nmol/g) than in adjacent normal thyroid tissue. It is possible that NPY from some phaeochromocytomas may contribute to hypertension during surger

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb03641.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY