ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02502.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02503.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEWe have developed and validated a two‐site immunoassay for the measurement of dimeric inhibin in plasma and subsequently measured dimeric inhibin levels in plasma through the normal female menstrual cycle.DESIGNRecombinant inhibin added to plasma samples was quantitatively recovered in both follicular and luteal phase, and serial dilutions of samples were tested for parallelism to similar dilutions of recombinant 32kDa inhibin. Daily samples were assayed from four women through a menstrual cycle.PATIENTS(a) Four groups of six women who (i) were in the follicular phase of a normal menstrual cycle, (ii) were in the luteal phase of a normal menstrual cycle, (iii) were post‐menopausal and (iV) who had received hMG to induce superovulation. (b) Four healthy female volunteers aged 25–33.RESULTSPost‐menopausal women had less than 2ng/l of inhibin whereas six women treated with hMG had dimeric inhibin concentrations up to 1125ng/l.During the early follicular phase, at the time of onset of menstruation, extremely low levels of dimeric inhibin were found (3‐4ng/l (CI 2.2‐5.0)) while in the late follicular phase, there was a marked increase in dimeric inhibin concentration. The concentration of dimeric inhibin was maximal (65.6 ng/l (CI 53.1‐81,1)) in the mid‐luteal phase. The overall pattern of dimeric inhibin concentration during the menstrual cycle was similar to that observed with previous inhibin assays although the magnitude of change was considerably greater.CONCLUSIONThe human ovary, In particular the corpus luteum, secretes significant amounts of dimeric and therefore biologically

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02504.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEIn men and male monkeys, a short‐term fast has been reported to have a major effect on the reproductive axis. In this study we investigated the effects of a short‐term fast (72 hours) on female reproductive hormone secretion and menstrual function.DESIGNThe study consisted of an admission day (control), three successive fasting days (fast 1, 2 and 3) and a refeeding day (post fast).PATIENTSEight normal cycling women, ages 21–35, within 10% of ideal body weight, were fasted for 72 hours during the follicular phase of their menstrual cycle.MEASUREMENTSOn the admission day, the last day of the fast and the day of refeeding, blood samples were collected at 10‐minute intervals from 0800 to 2000 h for determination of the LH pulse pattern. Daily determinations of immuno LH, FSH, oestradiol (E) and progesterone (P) were performed throughout the menstrual cycle in which the fast occurred.RESULTSThroughout the fasting days, the consistently low serum levels of glucose and insulin confirmed that all the subjects were fasting. However, in spite of profound metabolic changes and a significant loss of weight, the short‐term fast did not have discernible effects upon the reproductive hormones studied. Basal mean LH concentrations did not show any significant variation throughout the study period. The mean ± SEM number of LH pulses was 134 ± 1.5/12h on the control day, 12.4 ± 1.2/12h (NS) on the third day of fasting and 11 0 ± 1.5/12 h (NS) the day of refeeding. Each woman maintained a physiological pattern of LH, FSH, E and P throughout the menstrual cycle including the LH surge; ultrasound evidence of normal growth of a dominant follicle; and cycle length consistent with previous cycles.CONCLUSIONSOur results indicate that in spite of profound metabolic changes, a 72‐hour fast during the follicular phase does not affect the menstrual cycle of normal cycling women. It appears that the female reproductive axis during this phase of the cycle Is more resistant to an acute caloric deprivation than that of men

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02505.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVETesticular differentiation can occur in the absence of the Y chromosome giving XX sex‐reversed males. Although Y chromosomal sequences can be detected in the majority of male subjects with a 46,XX karyotype, several studies have shown that approximately 10% of patients lack Y material including theSRYgene. The aim of this study was to see if the classification of XX sex‐reversed individuals into three groups, Y‐DNA‐positive phenotypically normal XX males, Y‐DNA‐negative XX males with genital ambiguities and Y‐DNA‐negative true hermaphrodites can be applied to our cases.DESIGNEndocrinological and genetic studies were conducted in 20 XX sex‐reversed patients.PATIENTSTwenty patients with various phenotypes were studied. They were between 20 days and 35 years old. Ten presented ambiguous external genitalia (Prader's stages II to IV). After laparotomy or gonadal biopsy, the diagnosis was 46, XX true hermaphroditism in five, and XX male in 15.MEASUREMENTSBlood samples were obtained from all patients for hormonal and molecular studies. Basal levels of testosterone, oestradiol and pituitary gonadotrophins were measured by RIA, In addition, two stimulation tests were performed: gonadotrophin stimulation with GnRH and testicular stimulation with hCG. Several Y‐specific DNA sequences of the short arm of the Y chromosome were analysed by Southern blot and polymerase chain reaction methods.RESULTSIn this study, three categories of XX sex‐reversed individuals were observed: phenotypically normal males with or without gynaecomastia, males with genital ambiguities, and true hermaphrodites. Endocrinological data were similar in XX males and in true hermaphrodites. Testosterone levels exhibited normal (n= 9) or decreased (n= 11) values. The hCG response was low. FSH and LH were elevated in 13 patients. Molecular analysis in ten patients showed varying amounts of Y material including the Y boundary and SRY. Ten patients with various phenotypes lacked Y chromosomal DNA. There was no relation between Leydig cell function (as indicated by testosterone levels before or after hCG stimulation) and the presence of Y chromosome material.CONCLUSIONAlthough the presence of Y‐specific DNA generally results in a more masculinized phenotype, exceptions do occur. In the Y‐DNA‐negative group, complete or incomplete masculinization in the absence ofSRYsuggests a mutation of one or more downstream non

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02506.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEAND DESIGN No data are available on effects of long‐term exposure to oestrogen on bioactivity of gonadotrophins in men. We studied the effects of a 6‐month oestrogen therapy on serum FSH and LH bioactivity (B), immunoreactivity (I) and isohormone distribution, and on serum l‐inhibin levels, in patients with prostatic carcinoma.PATIENTSEleven men with advanced prostatic cancer were studied, each receiving 160 mg of polyoestradiol phosphate (Estradurin) once a month intramuscularly for 6 months.MEASUREMENTSSerum samples were collected before, and after 2 and 6 months of oestrogen treatment. Serum B‐and l‐FSH levels were measured by immature rat granulosa cell bioassay and immunofluorometric (IFMA, Delfia) assay, respectively, and those of B‐ and I‐LH by mouse interstitial cell bioassay and IFMA, respectively. Serum oestradiol (E2) concentrations were measured by IFMA assay, and serum testosterone (T) and inhibin levels by radioimmunoassay. Isoelectric focusing was used for fractionation of the FSH and LH isoforms.RESULTSThe pretreatment levels of B‐FSH and I‐FSH were 84.7 ± 21.6 and 11.4 ± 3.2 IU/I (mean ± SEM), respectively, and the B/I ratio of FSH was 8.3 ± 1.0. The pretreatment levels of B‐LH and I‐LH were 23.5 ± 3.2 and 10.1 ± 2.3 IU/I, respectively, and the B/I ratio was 3.0 ± 0.4. After 6 months of oestrogen therapy, B‐FSH and I‐FSH decreased to 37.5±8.1 (P<0.05)and 1.3 ± 0.3 IU/I(P<0.01), respectively, but the B/I ratio of FSH increased to 28.5 ±4.2 (P<0.05). B‐ and I‐LH levels decreased in 6 months to 7.4 ± 0.9 and 2.3 ± 0.5 IU/I (P<0.01), respectively, but no change was found in the B/I ratio of LH. Serum T levels decreased from 19.0 ± 2.6 to 2.7± 0.9 nmol/l (P<0.01) during the 6‐month treatment, and the respective E2levels increased from 0.2± 0.01 to 4.4±0.5 nmol/l (P<0.01). Serum l‐inhibin levels were analysed from eight patients. The levels at 0,2 and 6 months were 0 81 ± 0.09,0.50 ± 0.03 and 0.54 ± 0.01 μ/l, respectively. Gonadotrophins in the pretreatment and 6‐month samples of four patients were analysed by Isoelectric focusing. In FSH of all subjects, and in LH of three subjects, a shift from acidic to more basic isoforms occurred after oestrogen therapy. This is in keeping with the increase of the B/l ratio of FSH. With LH, the isoform shift occurred between fractions with similar B/I ratios, and hence there was no shift in the overall B/I ratio.CONCLUSIONSOestrogen therapy of men suppressed bioactive and immunoreactive levels of gonadotrophins. The B/I ratio of FSH increased, and this increase was associated with a shift in the isohormone profile to more basic forms. In contrast, no change occurred in the B/I ratio of LH, even though changes in the isohormone profile were observed. Hence, not all changes in the isohormone distribution of gonadotrophins

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02507.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryBACKGROUNDAbnormalities of the serum thyroid hormone binding proteins are not uncommon but, when properly asessed, they do not present diagnostic difficulties. In contrast, the presence of two inherited defects of thyroid hormone transport, of the type presented in the family described here, may cause a major problem in diagnosis and has not been described previously.METHODSAll conventional thyroid function tests were carried out. In addition, thyroid hormone binding to serum proteins was assessed by agarose gel electrophoresis, and thyroxine binding globulin by immunoassays and by immunodiffusion. The affinity of TBG for thyroxine and its maximal binding capacity were assessed by Scatchard analysis.RESULTSTests carried out on 22 members of the family revealed familial dysalbuminaemic hyperthyroxinaemia in 10 family subjects. All five living siblings of the propositus had familial dysalbuminaemic hyperthyroxinaemia and two tested transmitted this trait to their children and grandchildren. This was not the case with the propositus. Partial thyroxine binding globulin deficiency only, inherited presumably from the propositus' mother, was found in two family members. Both thyroxine binding globulin deficiency and familial dysalbuminaemic hyperthyroxinaemia were detected in the propositus and in his male nephew, masking the typical laboratory abnormalities associated with each of these defects.CONCLUSIONSCoexistence of two inherited defects of thyroid hormone transport proteins produce atypical thyroid function test abnormalities, which can be misinterpreted as thyroid hormone dysfunction.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02508.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVELithium is known to cause goitre and hypothyroidism, and has been associated less commonly with hyperthyroidism. We report a series of 14 patients with lithium associated thyrotoxicosis (LiAT), and have used epidemiological data to assess the association between long‐term lithium treatment and the development of thyrotoxicosis.DESIGNInformation for this retrospective study was obtained from records of patients attending the thyroid clinic between 1973 and 1991. Statistical analysis of the association between long‐term lithium treatment and incidence of thyrotoxicosis was made using local thyrotoxicosis incidence figures and lithium prescription data. MEASUREMENTS Investigations included99mTc pertechnetate thyroid scans, and blood analyses to measure serum T4, serum T3, free T4 index, and thyroid microsomal and thyroglobulin antibody litres.RESULTSDuring the 18‐year period there were 14 patients with LiAT. This number of cases of thyrotoxicosis occurring in patients on lithium was more than three times greater than that predicted from local thyrotoxicosis incidence rates (P<0.05). Scintiscans were obtained for 13 patients: 8 had toxic diffuse goitre, 2 toxic multinodular goitre, 1 toxic uninodular goitre, and 2 had a lack of visualization consistent with ‘painless thyroiditis'. Nine patients received a course of carbimazole and 6 of these remain in remission. Six patients have received131I therapy. Eight patients have become hypothyroid at follow‐up (5 post131I, 1 following a course of carbimazole, and the 2 with ‘painless thyroiditis').CONCLUSIONSStatistical analysis has shown that long‐term lithium therapy is associated with an increased risk of thyrotoxicosis. LiAT is a heterogeneous condition with differing underlying thyroid pathologies and the mechanisms remain uncertain. The management of LiAT should initially be with antithyroid medication, and131I therapy should be given only to patients who do not obtain long

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02509.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryBACKGROUNDPost‐partum thyroid disease occurs in 50% of anti‐thyroid peroxidase (TPO) antibody positive women (detected at 16 weeks' gestation) and is characterized by a transient episode of hyper, hypo or hyper‐hypo thyroidism. In approximately 20% of these women the hypothyroidism is permanent. However, the extent of long‐term thyroid dysfunction, possibly mediated by immune attack, in those anti‐TPO Ab + ve women who have had only transient or no thyroid dysfunction during the postpartum period is not clear.OBJECTIVEWe have therefore studied the frequency of iodide organification defects by iodide perchlorate discharge testing, and of thyroid morphological abnormalities by ultrasound scanning in euthyroid women following their episode of post‐partum thyroiditis (PPT).DESIGNThe study group comprised 17 women with previous PPT (PPT +ve) and 12 women who had positive anti‐TPO antibodies during pregnancy but who did not develop PPT (PPT‐ve). Women were studied 15‐47 months following their episode of PPT.RESULTSIodide perchlorate discharge tests were positive (more than 10% discharge) in 7 (41 %) PPT + ve and 5 (42%) PPT‐ve subjects (P = NS). Morphological abnormalities on thyroid ultrasound were detected in 7 of 14 (50%) PPT + ve and 7 of 9 (77%) PPT‐ve subjects (P = NS). There was a strong association between abnormalities of iodide organification and morphology: of 11 subjects with positive iodide perchlorate discharge tests, 10 had abnormal (positive) ultrasound scans; of 12 subjects with negative iodide perchlorate discharge tests 8 had negative ultrasound scans (P= 0.013, Fisher's exact test).CONCLUSIONSLong‐term subtle defects of thyroid function and morphology are common in women with anti‐TPO antibodies in pregnancy, whether or not they develop postpartum thyroiditis. The clinical significance of these findings is unclear but a continuing thyroid patholog

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02510.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEPatients with adrenal crisis are at risk of severe hypotension not responding to administration of catecholamines. As glucocorticoids may be a prerequisite for intact β‐adrenoceptor function, impaired adrenoceptor activity may explain the hypotension and reduced cardiac performance in adrenal insufficiency. The aim of our study was, therefore, to further elucidate the permissive action of glucocorticoids on adrenergic function and cardiac performance.DESIGNProspective randomized controlled study.PATIENTSNine patients with adrenal insufficiency were investigated before and 48 hours after glucocorticoid withdrawal. Mineralocorticoid therapy remained unchanged during the study period.MEASUREMENTSLymphocyte β2‐adrenoceptor density, intracellular c‐AMP response to isoprenaline, platelet α2‐receptor density, plasma catecholamines, serum Cortisol, plasma ACTH, echocardiography.RESULTSGlucocorticoid depletion was demonstrated by a fall in serum Cortisol from mean ± SEM 441 ± 62 to 45 ± 18 nmoI/I. Glucocorticoid withdrawal decreased lymphocyte β2‐receptor density from 798±111 to 498 ± 54 binding sites/cell (P<0.05) and the intracellular c‐AMP response to isoprenaline from 15.0 ± 4.2 to 8.2 ± 1.7 pmol/106cells (P<0.05). Echocardiography showed impaired diastolic relaxation after glucocorticoid withdrawal with prolongation of the rapid filling period (80.3 ± 12.5vs138.3 ± 11.8 ms,P<0.05). Plasma catecholamines, platelet α2‐receptor density and systolic left ventricular function were not affected by glucocorticoid deficiency.CONCLUSIONSThis study demonstrates the importance of normal glucocorticoid levels for β2‐adrenoceptor function and helps to explain the decreased responsiveness to catecholamines and the impaired cardiac

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02511.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY