摘要:

SUMMARYWe have followed nine adult patients with congenital adrenal hyperplasia (CAH) for between 7‐77 months on dexamethasone (DXM) 0.5 mg mane and 0.25 mg nocte, reducing to 0.5 mg mane. Twenty‐four hour profiles of ACTH, 17‐hydroxyprogesterone (17OHP), and androstenedione were performed; the areas under the curves (AUC) and the heights of the morning peaks were used to assess biochemical control. Comparisons were made between treatment before DXM (pre‐DXM), 0.75 mg for 2 weeks (DXM‐ST), 0.75 mg for at least 3 months (DXM‐LT), and 0.5 mg for at least 3 months (DXM‐0.5). None of the three males suffered any significant side‐effects. All women had menstrual disturbance but in three ovulation was induced. One female developed Cushing's syndrome and two developed hirsutism which resolved on stopping DXM. Overall there was no significant difference between DXM‐ST and DXM‐LT (mean AUCs for ACTH: DXM‐ST 660, DXM‐LT 383, for 170HP: DXM‐ST 1177, DXM‐LT 587, for androstenedione DXM‐ST 232, DXM‐LT 121). Reduction of the dose from 0‐75 mg to 0‐5 mg led to significant deterioration in control (Mean AUCs for ACTH DXM‐0 5,1123 (P<0‐02), for 170HP DXM‐0‐5, 2068 (P<0‐002), for androstenedione DXM‐05, 213 (P<0‐5). We conclude that DXM is a satisfactory regi

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb02945.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYΔ5 and Δ4 steroid levels were studied in the plasma and cyst fluid of women with gross cystic breast disease (GCBD). In luteal phase a significant increase in plasma levels (mean + SEM) of DHA (11.2 ± 2.4 ng/ml), DHAS (1.45 ± 0.6fig/ml) and Cortisol 277 ± 15.7 ng/ml) was found; in follicular phase the mean levels were 4.09 ± 0.47 ng/ml for DHA, 0.65 ± 0.08μg/ml for DHAS and 190 ± 46.3μg/mlfor Cortisol. The DHA/DHAS and cortisol/androstenedione ratios were significantly higher in the plasma and lower in the cyst fluid of GCBD patients, than in the plasma of controls; the androstenedione/DHA ratio was higher in the cyst fluid than in the plasma of controls. The hormonal situation of the GCBD patients thus differed from that of the controls both in the plasma and cyst fluid, particularly as regards the Δ

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb02946.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYSleep history and pituitary function were studied and sleep polygraphy performed in 11 acromegalic patients before and after pituitary surgery. Excessive daytime sleepiness or habitual snoring or both together, as well as an elevated fasting level of serum GH occurred in all the patients. In five men but in none of the women an abnormal number of episodes of sleep apnoea were observed. Pituitary adenomectomy improved the apnoea frequency in one patient, whereas in the others the abnormality was still present 1 year later. After operation the fasting level of serum GH became normal in eight patients, two of them with persisting sleep apnoea. The sleep apnoea syndrome is common and clinically important in acromegaly. Its early diagnosis using polygraphic monitoring is emphasized, as it is a treatable disorder.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb02947.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYTreatment of tuberculosis with rifampicin in patients with pre‐existing adrenal failure has been reported to induce adrenal crisis due to alteration of Cortisol metabolism by induction of hepatic mixed liver oxygenase enzymes. To determine whether mineralocorticoid metabolism is altered by rifampicin treatment, we established the pharmacokinetics of immunoreactive aldosterone. The metabolic clearance rate (MCR) and plasma half‐life of this material were measured before and after 6 days of rifampicin treatment (600 mg/day) in seven patients with Addison's disease due to tuberculosis. Antipyrine clearance and urinary 6‐β‐hydroxycortisol excretion was determined to demonstrate induction of the cytochromeP450 dependent enzymes. Infusion of aldosterone at a constant rate of 0‐17 mg/h over 4‐5 h produced steady state concentrations after 2 h, with no difference before and after rifampicin treatment (mean ± SD, 1649 ± 144vs1586 ± 80 pg/ml, respectively). The disappearance curve of IR‐aldosterone from plasma was biexponential. No change could be observed in the plasma half‐lives (α‐phase 29 ± 1.9 minvs30 ± 1.5 min, β‐phase 129 ± 3.2 minra126 ± 4.3min), the MCR (1‐47 ± 0.1 1/h/kgvs1.46 ± 0.1 1/h/kgvs), and the volume of distribution (9.9 ± 1.9vs10.2 ± 0.3 1). The antipyrine half‐life decreased significantly from 12.2 ± 2.6 h to 7.6 ± 0.9 h (P± 0.05) with a rise in antipyrine clearance from 0.38 ± 0.07 to 0.80 ± 0‐23 ml/min/kg (Plt;0.05) and no change in the volume of distribution. Urinary excretion of 6‐β‐hydroxycortisol increased from 711 ± 130 μg/24 h before to 1670 ± 387/μg/24 h (P<0‐05) after 6 days of rifampicin treat

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb02948.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYThe concentration of immunoreactive inhibin in serum was measured in three pregnant women with premature ovarian failure involved in a donor oocyte in‐vitro fertilization programme. Inhibin was not detectable in peripheral serum prior to conception but rose within 2‐4 weeks of embryo transfer, whereafter levels rose gradually during pregnancy (20 weeks 2.28 U/ml (1.42‐3.67),P<0.01; geometric mean ± 67% confidence interval) and were similar to those observed in 24 normal pregnant women. hCG rose in parallel with inhibin during early gestation, but declined after 3 months. FSH levels were elevated before conception and were suppressed during pregnancy. In conclusion (i) immunoreactive inhibin is detectable from early gestation in women with no endogenous ovarian function indicating that the maternal ovary does not contribute significantly to inhibin secretion during pregnancy; (ii) the trophoblast is the likely source of inhibin during pregnancy; (iii) the regulation of hCG and inhibin secretion differs throughout gestation; and (iv) inhibin may have a role in FSH regulation during pregnancy and/or a local role within the feto‐pl

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb02949.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYThere is evidence indicating that the cholinergic system positively modulates GH release probably by inhibiting somatostatinergic tone. In the present study, the effects of cholinergic enhancement by pyridostigmine, (PD), a cholin‐esterases inhibitor, on GH release in normal adults(n=14) (NA) and in both normal (n = 5) (NC) and short children(n =19) (SC) with familial short stature(n =7)or constitutional growth delay(n=12) were studied. In SC the insulin hypoglycaemia (IH)‐induced GH increase was also studied. In both NC and SC 60 mg orally PD induced a significant GH increase with mean peak at 90 min (mean ± SEM 11.0 ± 2.2 ng/ml in NC and 11.2 ± 2.3 ng/ml in SC). The GH areas under response curve (AUC) were 379.3 ± 76.6 and 327.8 ±43.2 ng/ml/h in NC and SC respectively. In NA 120 mg orally PD induced a significant GH increase with mean peak at 120 min (5.1 ± 11 ng/ml) which was significantly lower(P<0.05) than that observed in both NC and SC. This statistical difference was strengthened by evaluating AUC (NA: 205.6 ± 33.7 ng/ml/h,P<0.05vsNC and SC). The correlation of drug dosage with body area ruled out that this difference could be related to the different PD dose in adults and children. In SC, IH induced a GH increase significantly lower than that observed after PD (GH peak 7.8 ± 0.6vs16.4 ± 1.9 ng/ml P<0.001). Our data show that cholinergic enhancement by PD induces a higher GH increase in both normal and short children than that observed in adults. This could be related to a variation of somatostatinergic tone. The higher PD‐induced GH response compared to the IH‐induced one indicates that PD test may be considered a more potent GH provocative stimulus than insul

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb02950.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYThe effects of human growth hormone‐releasing factor (hGRF) and somatostatin on growth hormone (GH) and prolactin (PRL) secretion in perifusion of dispersed cells of human GH‐secreting adenomas, obtained from seven acromegalic patients with hyperprolactinaemia, were examined. Six adenomas stained for both GH and PRL on immunohistochemical examination, and one contained only GH. GH release was consistently stimulated in a dose‐dependent manner by hGRF (0.01, 0.1 and 1.0 nM) in all seven adenomas studied. PRL release was undetectable in two adenomas. In the other five, hGRF stimulated PRL release and the response was dose related. Furthermore, the PRL response was significantly correlated with the GH response to hGRF. When cells were perifused with somatostatin (1 nM), GH and PRL secretion induced by hGRF was completely antagonized. We also evaluated the effect of hGRF pretreatment on the subsequent GH response to hGRF in two adenomas. hGRF pretreatment (1 nM) for 210 min reduced the GH response to a subsequent hGRF challenge (100 nM) in one tumour but not in the other. In conclusion, the PRL response is similar to the GH response in mixed GH and PRL‐secreting adenomas after exposure to GH release‐stimulating and inhibiting hormones. After prolonged exposure to hGRF, some adenomas remain responsive to further stimulation with hGRF, whereas othe

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb02951.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYEighteen men (mean age 27, range 18‐30 years) treated for Hodgkin's disease with 6‐8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age‐matched men (n= 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 ± SD 6‐9vs2.0 ± 1.5 IU/1,P<0‐0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10‐3 + 3‐9 IU/1) than in controls (3‐9+1‐9 IU/1,P<00001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n= 17, mean age 27, range 17‐43 years) and in a further age‐matched control group (n= 17). Bioactive and immunoreactive LH levels were significantly increased (P<0‐005 andP<0‐001, respectively) in the patient group. However, the biological: immunological (B:I) LH ratios were found to be similar in the patients (2.7 ± 0.6, mean ± SD) and controls (2.8 ± 0.7). There was a significant correlation between immunoreactive LH and FSH concentrations in the patient group (r = 0‐65,P<001), but not in the controls. In conclusion Leydig cell function, as judged by the steroidogenic responses to HCG stimulation, is normal in patients with chemotherapy‐induced spermatogenic damage. The biological activity of LH is not changed, but there is a

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb02952.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYWe examined basal and bTSH‐stimulated human thyreoglobulin (hTg) secretion by autologous normal and abnormal (benign and malignant) human thyroid cell monolayers. Basal and bTSH‐stimulated hTg secretion was highly variable and ranged from 50‐700 ng/ml/105cells over a 6 day period. All normal and benign ‘non‐functioning’ adenoma cells demonstrated a dose and time related stimulation of hTg secretion in response to bTSH. Comparison of hTG secretion by autologous normal and abnormal cells showed that in six of eight pairs, the normal thyroid cells had a greater output of hTg than the benign adenoma cells in contrast to our previous studies using non‐autologous cells. Malignant thyroid cell hTg production was less predictable than that obtained with normal and benign thyroid cells varying from absent to normal responses to bTSH. Characterization studies of the secreted hTg showed no difference between normal, benign and malignant thyroid cell hTg with reference to molecular weight. However, hTg secretedin vitrowas non‐iodinated and had a marked reduction (up to 200‐fold) in immunoreactivity assessed by both polyclonal and monoclonal antibodies to hTg when compared to hTg standard prepared from intact thyroid tissue (which had 4.58μg iodine/mg). This reduction in hTg immunoreactivity was greatest for hTg secreted by malignant thyroid cells. These data demonstrate the wide variability in the hTg secretory capacity of human thyroid cell monolayers and indicate, when compared to autologous normal cells, that abnormal human thyroid epithelial cells may be relatively deficient in their ability to secrete hTgin vitro.There were also qualitative differences in the immunoreactivity, and iodine content, of in‐vitro secreted hTg. These observations suggest that there may be much greater heterogeneity in hTg secretedin vitrothan previously realized, perhaps secondary to differences in iodine content and/or deg

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb02953.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYThis study was designed to evaluate the long‐term effect (6 months) of the luteinizing hormone‐releasing hormone (LH‐RH) agonist buserelin on pituitary and ovarian function in a group of 14 patients presenting with the polycystic ovarian (PCO) syndrome. Buserelin was given subcutaneously 200 μg three times daily for the first 7 days followed by 500μg once daily. Blood samples were taken weekly for the first month and then every month for radioimmunoassay of LH, FSH and sex steroids. While LH levels were stimulated during the first 2 weeks and then declined towards baseline, serum FSH levels were reduced after only 1 week (P<0.05). Serum oestradiol levels were maximally suppressed to the menopausal range after 1 month and testosterone levels were also significantly inhibited (P<0.05) after 2 weeks of therapy. Dehydroepiandrosterone (DHEA) sulphate did not show any significant change while 17‐hydroxyprogesterone was suppressed after the first month of buserelin administration (P<0.01). The apparent divergent response of the gonadotrophins and the reduction of ovarian steroids in spite of a lack of suppression of LH levels can be explained by the marked inhibition of the bioactivity of LH assessed by dispersed mouse Leydig cells assay. The clinical evaluation of hirsutism did not detect any change during the 6 month period. No patient had any menstrual bleeding or spotting after the sixth week of buserelin. The monthly incidence of hot flushes varied between 50 to 66%. This study shows that LH‐RH agonist administration can selectively inhibit ovarian function and could be an interesting approach to evaluate the respective contribution of the ovary and adrenal on the pathophysiology of the polycystic ovar

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb02954.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY