摘要:

SUMMARYWe have studied GH secretory dynamics in 38 (25 F, 13 M) children referred for investigation and treatment of tall stature (Height SD score (SDS)<1·8). Five children had elevated basal GH levels (mean 20·4 mU/l) and a further four had abnormal GH responses to exogenous TRH. Two other children had paradoxical GH responses to oral glucose loading. Although one of these was receiving high dose testosterone to limit final height. All these children were pubertal and did not show concordance between peak GH concentration observed after insulin‐induced hypoglycaemia and during stage IV sleep. Twenty‐four hour GH profiles revealed increased GH pulse amplitude and area under the pulse during puberty. Morning GH secretion was also regularly observed and it is possible that the paradoxical responses seen by us and reported by others reflect this increased physiological secretion. Pituitary radiology revealed morphological abnormalities suggestive of microadenomata in 17 patients but these were all in late puberty and these changes may be related more to the effects of sex hormones than to somatotroph pathology. ‘Abnormal’ endocrinology and radiology are seen in tall children in puberty and must be interpreted wit

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01686.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYAntipyrine (AP) metabolism was studied in four adult patients with congenital adrenal hyperplasia (CAH) due to classical 21‐hydroxylase deficiency and in four (adult) patients with CAH due to non‐classical 21‐hydroxylase deficiency. This investigation was prompted by the known biochemical and functional similarities between drug‐ and steroid‐metabolizing enzymes. We hypothesized that a common genetic mechanism may regulate the expression and activity of both the adrenal and hepatic cytochrome P450 enzymes. AP half‐lives (T1/2, mean ± SD) were 10·7 ± 2·1 h in classical CAH patients, 10·1 ± 0·4 h in the non‐classical CAH patients and 10·9 ± 2·2 h in the control group, suggesting that there was no significant difference in AP metabolism among the three groups. Similarly, no significant differences were found in the AP apparent volume of distribution (aVd) and metabolic clearance rate (MCR) among the three groups. These results indicate that despite the deficiency of adrenal cytochrome P450 in patients with 21‐hydroxylase deficiency CAH, these individuals have normal hepatic drug metabolizing activity for th

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01687.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYTo evaluate the effect of changes in plasma catecholamines on the pituitary‐adrenal response to ovine corticotrophin releasing factor (CRF) in normal man, the response to CRF alone (10 subjects) was compared with responses after infusions of adrenaline (6 subjects), noradrenaline (6 subjects) and after oral administration of the α2agonist clonidine (10 subjects). Compared to control levels, plasma adrenaline and noradrenaline concentrations were increased three‐ and four‐fold respectively by exogenous infusions, whereas plasma noradrenaline was significantly lowered by clonidine. Despite these changes in plasma catecholamine levels, the responses of plasma ACTH, cortisol and aldosterone to CRF did not differ significantly from control (CRF alone) in any of the three studies. Neither clonidine pretreatment nor catecholamine infusions altered basal levels of plasma ACTH, cortisol or aldosterone and no effect of CRF or catecholamine manipulations on plasma arginine vasopressin concentration was observed. These results show that modulation of peripheral plasma catecholamine levels within physiological limits does not affect CRF‐stimulated release of ACTH or the adrenal response in no

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01688.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYIn order to determine the effects of protracted nursing in American women, blood was collected hourly for 24 h and nursing periods recorded in 20 mothers, 10 amenorrhoeic, 3 3/4 to 17 1/4 months postpartum (PP), and 10 menstruating, 5 1/4 to 46 months PP. These data were compared to the daytime nursing behaviour and 1000–1100 h PRL of women among Kung hunter‐gatherers of Botswana, a non‐contraceptive using population with a birth space interval of<3 years. Intense nursing behaviour maintained amenorrhoea and hyperprolactinaemia for 1 to nearly 2 years PP in both American and Kung mothers. Among Americans, 80 min of nursing per day, in conjunction with a minimum of six nursing episodes, was highly predictive of remaining amenorrhoeic up to 18 months PP. Amenorrhoea was always accompanied by hyperprolactinaemia, but delay in the onset of menses was related more to nursing behaviour than to a particular 24 h PRL level. The 1000–1100 h sample is equivalent to and about half of the 24 h mean in high and low intensity nursers, respectively. The Kung women were similar to the high intensity nursing American women in 1000–1100 h PRL, percent amenorrhoeic, and the number of minutes of daytim

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01689.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYSerum TSH was determined with a sensitive radioimmunometric method (TSH IRMA) in 57 patients on suppression therapy with T4 after operation for differentiated thyroid carcinoma. When using a conventional RIA technique basal TSH was not detectable and remained so even after stimulation with TRH. With the TSH IRMA method 46 patients had a basal TSH below the detection limit (0·02 mU/l) (81 %) and in seven patients the values were between 0·02 and 0·05 mU/l (12%). In 23 of these patients there was a small increment of 0·01–0·15 mU/l. In two patients the basal TSH was 0·08 and 0·09 mU/l, and the increment after TRH was less than 0·7 mU/l. In two other patients with basal values close to 0·2 mU/l the increment after TRH was more than 1·0 mU/l. An undetectable basal TSH value did not thus predict an absent response to TRH. The responses were, however, in all but two cases, so small that they could be regarded as clinically insignificant. Therefore, the authors conclude that a basal TSH of 0·1 mU/l, as measured with a TSH IRMA method with a detection limit of 0·05, is a sufficient indication of TSH suppression in carcinoma patients on T4 therapy and that further testing with the TRH‐stimulation test

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01690.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYTransient hypogonadotrophic hypogonadism commonly occurs after major medical insults. Because data on testosterone precursors are sparse and because little is known about the aetiology of these changes, we studied the interactions of traumatic brain injury with gonadal steroidogenesis and with sympathetic nervous system activation. Patients were divided into two groups based upon the severity of neurological dysfunction using the Glasgow Coma Score (GCS); Group 1>8, Group 2 ≥ 8. Group 1 was further divided into those patients treated (Group 1b) and those not treated with dexamethasone (Group 1a). Plasma levels of testosterone, androstenedione, 17‐hydroxyprogesterone, DHEA sulphate, cortisol, LH, FSH, and the catecholamines noradrenaline (NE), adrenaline (EPI) and dopamine were measured in 31 acutely brain injured men, aged 18–95, shortly after their accident and 4 days later. In all patients, NE and EPI were elevated on admission (NE: 841 ± 105 (SEM) pg/ml; EPI: 191 ± 32 pg/ml and there were highly significant inverse correlations between admission NE (r=−0·52,P>0·003) and EPI (r=0·44,P>0·02) levels and day 4 testosterone concentrations. Testosterone fell 53% (P>0·001) in 13 Group la men, but only 25% (P=NS) in the less severely injured. Similar reductions occurred in cortisol and the steroid precursors. However, only testosterone, 17‐hydroxyprogesterone, and DHEA sulphate levels were significantly lower than normal on day 4. LH and FSH levels were also significantly reduced from elevated admission levels. In the eight men treated with dexamethasone (8–40 mg/ml) (Group 1b), the decrease in testosterone, LH and FSH concentrations were similar to those present in Group 1a. Thus, severe traumatic brain injury leads to hypogonadotrophic hypogonadism which affects testosterone and its precursors. The magnitude of the hormonal dysfunction is dependent upon the severity of the neurological insult. Finally, the decrease in testosterone is significantly correlated with admission catecholamine levels, which may suggest a role for the sympathetic nervous system (SNS) in mediating th

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01691.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThe ability of sera from patients with thyroid disease to block TSH stimulation of cyclic AMP release from isolated porcine thyroid cells has been assessed and the blocking activity characterized. TSH receptor binding activity was also measured. No blocking or receptor binding activity was detectable in patients with primary myxoedema (n= 23), Hashimoto's disease (n= 11), multinodular goitre (n= 6), or rheumatoid arthritis (n= 10). However, analysis of sera from 23 patients (out of an initial screen of 110 patients) with treated Graves' disease which did not stimulate cyclic AMP production in the bioassay showed that two of these sera contained powerful blocking and receptor binding activity. Both these patients had been treated with131I, Analysis of the two sera by gel filtration on Sephadex G‐200 indicated that blocking and TSH receptor binding activity were associated only with the IgG fraction. Digestion of the IgG with pepsin followed by reduction showed that both (Fab)2and Fab fragments contained high levels of blocking and binding activity. Antibody divalency was not necessary therefore for TSH antagonist activity. However, our studies suggest that autoantibodies of this type with TSH antagonist activity do not occur frequently in patients from the Cardiff region with primary myxoedema, Hashimoto's or treated Graves' diseas

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01692.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYNine boys with anorchia and 9 individuals with diminished testicular function were followed between ages 10 and 18 with serial determinations of urine gonadotrophins and serum testosterone. Ten hCG stimulation tests were performed in eight of these patients. Adult levels of LH (>500 mIU/h) and low measurements of serum testosterone (>54 ng/dl) confirmed the anorchic state. Boys with diminished testicular reserve exhibited urinary gonadotrophin changes similar to peripubertal anorchic patients but testosterone levels increased progressively with age (90–715 ng/dl). FSH attained adult castrate levels (>1700 mIU/h) by age 13 in these boys and served to distinguish them from normal controls. The longitudinal assessment of basal hormone levels can separate anorchia from diminished testicular reserve in boys of pubertal age and testing with hCG is not required for evaluatio

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01693.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYTo re‐evaluate the clinical utility of the prolonged management of hyperthyroidism with sodium tyropanoate (TP), an oral cholecystographic agent, we studied the changes in the scoring of thyrotoxic signs and symptoms (thyrotoxic index; TI), serum concentrations and binding of thyroid hormone, and circulating TSH receptor antibodies (TRAb) in two groups of patients with Graves' disease; seven patients (TP group) received TP (1·5 g daily) alone for 14 weeks, and six patients (TP+MMI group) received methimazole (MMI; 30 mg daily) in addition to TP for 8 weeks and MMI alone thereafter. In the TP group, the TI reduced significantly, but it failed to reach a euthyroid level in all except one. Serum total T4 (TT4), free T4 (FT4), and T3 uptake (T3U) values declined by the third week of treatment, but an ‘escape’ occurred thereafter. Serum rT3 and T4 binding globulin (TBG) levels were increased. The TRAb titres were increased slightly but significantly. Serum T3 levels fell within a week but remained higher than normal during the treatment.In the TP+MMI group, all patients achieved a normal TI by the end of the treatment. Serum TT4, FT4 and T3U fell more significantly than those in the TP group, indicating no escape from the effect of TP. The serum TRAb decreased significantly. Serum T3 levels showed a greater reduction than those in the TP group, and remained decreased even after withdrawal of TP. In a further 9 patients receiving TP alone for 4–14 weeks (7·3±5·0 weeks on the average), TP was withdrawn and replaced by MMI. A rebound of TI and serum T3 occurred within a week. These data suggest that, in the chronic treatment of hyperthyroidism, doses of combined TP and thionamide drug may have the advantage over those of TP alone both for achieving a more significant improvement of thyrotoxicosis and for precluding the recurrence of hyperthyroidism after cessation of

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01694.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYSerum concentrations of total and free T4 (TT4 and FT4), total and free T3 (TT3 and FT3), rT3, T4 binding globulin (TBG), T3 uptake (T3U) and TSH were measured in 12 patients with severe hypothyroidism before and during the introduction of replacement therapy with oral T4. The dose of T4 was increased by increments of 50 μg at intervals of 4 weeks to a total of 200 μg daily. There was a linear correlation between the concentrations of FT3 and FT4 (FT3 = 1·35 + 0·23FT4, r = 0·916,P>0·001). The correlation between TT3 and TT4 was more complex: the data were best fitted by the expression TT3 = 0·195 TT4, (r=0·936,P>0·001). The relatively greater rise in TT3 initially may reflect a greater binding of T3 by TBG when the concentration of T4 is low. TBG concentration fell after 50 and 100 μg of T4 but did not change at the higher doses. There was a simple linear relation between TT4 and rT3 (rT3 = ‐ 0·022 + 0·0027TT4,r= 0·921,P>0·001). The expected inverse relation between TSH concentration and the thyroid hormones was seen, the three closest correlations being between the logarithm of the TSH concentration and FT3, the ratio T4/TBG and FT4 (r= 0·927, −0·917 and −0·900 respectively). These correlations were significantly better (P>0·05) than the correlations with untransformed TSH values. Suppression of TSH occurred while FT3 tended to remain within normal limits, but FT4 was often raised. During incremental treatment with T4 there was no disproportionate increase in rT3 as TT4 and FT4 rose, nor was there evidence of a changing relation between the concentrations of FT3 and FT4 over the range of concentrations encountered. The findings suggest that the deioidination of T4 does not change with

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb01695.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY