摘要:

OBJECTIVE The impact of the menopause on androgen production is poorly understood. We have investigated the impact of the menopause, as well as other factors such as age, body mass index (BMI) and cigarette smoking, on ovarian and adrenal androgen levels in women aged 40–60 years.DESIGN Cross‐sectional study of blood hormones sampled weekly over one month in volunteer 40–60‐year‐old women.SUBJECTS One hundred and forty‐one women, aged between 40 and 60, recruited from community sources (non‐clinical), not using hormone replacement or steroidal contraceptives, and with a current sexual partner. Fifty were categorized as premenopausal (ovulating), 37 as perimenopausal and 54 as post‐menopausal.MEASUREMENTS The following variables were assessed; menopausal status (based on menstrual history and pattern and plasma progesterone), age, BMI, smoking, oestradiol (E2), oestrone (E1), LH, FSH, total testosterone (TT), androstenedione (A), SHBG, free androgen index (FAI), dihydroepiandrosterone (DHEA), dihydroepiandrosterone sulphate (DHEAS) and cortisol.RESULTS are based on multiple regression analysis. TT was positively related to A, BMI and LH. A was negatively related to age and FSH, and positively to DHEA, DHEAS and premenopausal status. SHBG was negatively related to BMI and positively to E1and non‐smoking. DHEA and DHEAS were negatively related to age and were higher in smokers. Both E1and E2were related to menopausal status and to FSH. Surprisingly, E2was negatively related to BMI.CONCLUSIONS A variety of factors influence androgen production in this age group. Whereas it is difficult to predict the effect of menopause on androgen levels, LH stimulation of post‐menopausal interstitial cells, modulated by a variety of factors including nutrition, and smo

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00846.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Adult patients with Turner's syndrome are rarely followed up at specialist clinics after discharge from paediatric care but do have a predisposition to several long‐term medical problems. We have assessed the undiagnosed morbidity that exists among adult women with Turner's syndrome.PATIENTS A group of 32 women (age range 17–52 years; mean 25 years) attending a specialist out‐patient clinic.MEASUREMENTS Blood samples were obtained at the initial visit for lipid assessment, thyroid function, gonadal status and routine biochemical profile. Bone mineral density (BMD) was measured in 31 of the women.RESULTS Thirty‐one women were receiving some form of oestrogen replacement. Two were receiving T4 therapy. In 50%, total cholesterol was greater than 5.2 mmol/l (range 3.4–9.3 mmol/l, mean 5.8 mmol/l) and 28% had an abnormality of thyroid function tests. Two women were newly diagnosed as hypothyroid, 6 had compensated hypothyroidism and one was under‐replaced with T4. Lumbar spine BMD was below 100% of age matched reference range in 84% and below 75% in 26% of patients. Femoral neck BMD was below 100% of age matched reference range in 90% and below 75% in 10% of patients.CONCLUSIONS There is a high incidence of undiagnosed lipid, thyroid and bone mineral density abnormalities in the adult population with Turner's syndrome. Doctors caring for these women need to be aware of and look for the potential problems. Appropriate long‐term treatment should be commenced to help prevent the development of lipid, skeletal and thyroid abnormalities which may cause these patients

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00849.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE GH increases oestradiol secretion and promotes oocyte development in women with polycystic ovary syndrome (PCOS). However, there are no data on ovarian androgen production after GH treatment. We have therefore assessed the effect of sequential treatment with a long‐acting somatostatin analogue (octreotide) alone and octreotide/GH simultaneously on ovarian steroid levels in PCOS and non‐PCOS normal women.PATIENTS Twenty‐six PCOS and 12 non‐PCOS women, aged 18–35 years, were studied. Ten of the PCOS and six of the non‐PCOS women received sequential treatment with octreotide alone and followed by octreotide + GH together, while another eight PCOS and six non‐PCOS women received saline instead of octreotide–octreotide + GH. The remaining eight PCOS women received GH alone.DESIGN The octreotide–octreotide +GH and saline studies lasted 12 days, the GH alone 7 days. Octreotide (100 μg, s.c., t.d.s.) was given from the 2nd to the 10th and octreotide + GH (4 IU, s.c. at 2300h) from the 7th to the 10th day of the study. The GH alone treatment was given from the 2nd to the 5th day. On the 1st day, two tests were performed: (1) an oral glucose tolerance test (OGTT, 75 g, orally) at 0830h and (2) a buserelin (long‐acting GnRH agonist) test (100 μg, s.c.) at the end of the OGTT. Both tests were repeated on the 6th and 11th days in the octreotide–octreotide + GH or on the 6th day only in the GH alone study.MEASUREMENTS Blood glucose, insulin (IRI), C‐ peptide and IGF‐I (at time 0 only) were measured before glucose administration and at 30‐minute intervals for 3 hours and LH, FSH, Δ4‐androstenedione (Δ4A), testosterone (TT), free testosterone (FT) and oestradiol (E2) before buserelin and at 1,2,6,10,14 and 18 hours.RESULTS Octreotide alone significantly reduced the basal IGF‐I, stimulated LH and both basal and stimulated IRI, Δ4A, TT, FT and E2levels in all PCOS women tested. Both octreotide+GH and GH alone increased significantly the basal IGF‐I and both basal and stimulated IRI and E2levels in all PCOS women, while the basal and stimulated LH, Δ4A, TT and FT levels were completely unaffected. In contrast, octreotide–octreotide + GH treatment did not modify either basal or stimulated gonadotrophin or ovarian steroid levels in non‐PCOS women. No changes in either basal or stimulated hormone levels were observed in those PCOS women who received saline. Although both basal and stimulated levels of all ovarian androgens were significantly reduced by octreotide– octreotide + GH treatment in PCOS women, they still remained significantly higher than in the non‐PCOS women.CONCLUSIONS The data show that (1) octreotide is a potent inhibitor of ovarian steroid secretion, (2) GH increases oestradiol secretion, possibly by stimulating ovarian aromatase activity, and (3) the combined treatment with octreotide and GH significantly improves ovarian function in women with PCOS and may thus have

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00854.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Two isoforms of 11β‐hydroxysteroid dehydrogenase (11β‐HSD) catalyse the interconversion of cortisol to hormonally inactive cortisone; defects in the 11β‐HSD2 isoform result in hypertension. The kidney, expressing high levels of 11β‐HSD2, is the principal source of cortisone in man. We have validated the measurement of urinary free cortisone (UFE) excretion in normals and in patients with disorders of the pituitary‐adrenal axis in an attempt to more accurately measure the activity of 11β‐HSD2in vivo.SUBJECTS Forty‐one normal adults, 12 normal children<12 years of age, 15 patients with Cushing’s syndrome, 12 with hypopituitarism on replacement hydrocortisone, 12 with the syndrome of apparent mineralocorticoid excess (AME) and 7 volunteers consuming liquorice.MEASUREMENTS A complete 24‐hour urine collection was analysed by gas chromatography/mass spectrometry for ‘A‐ring’ reduced cortisol and cortisone metabolites, i.e. tetrahydrocortisols (THF and allo‐THF) and tetrahydrocortisone (THE). In addition, urinary free cortisol (UFF) and urinary free cortisone were quantified using deuterium‐labelled internal standards.RESULTS In normal adults and children, UFE excretion exceeded that of UFF (UFF 30.4 ± 2.4 μg/24h (mean ± SE), UFE 54.6 ±4.1 μg/24h, adults) (for conversion to nmol/24h multiply E by 2.78 and F by 2.76 respectively). Thus the normal UFF/UFE ratio was 0.54 ± 0.05 in contrast to the (THF+allo‐THF)/THE ratio of 1.21 ± 0.06. UFE excretion was normal in hypopituitary patients on replacement hydrocortisone. Although UFE was elevated in all forms of Cushing’s syndrome, the UFF/UFE ratio was grossly elevated in patients with the ectopic ACTH syndrome (14.0 ± 6.7,n=6). UFE was below the lower limit of the assay (<1 μg/24h) in most patients with the so‐called type 1 variant of AME and significantly reduced in 4 patients described as having the type 2 variant of AME (10.5 ± 3.5 μg/h,P<0.05) and in 7 volunteers consuming liquorice (26.8 ± 10.0 μg/24h,P<0.01). In ectopic ACTH syndrome, AME, and liquorice ingestion the UFF/UFE ratio was more deranged than the (THF+ allo‐THF)/THE ratio.CONCLUSION In normals the discrepant THF + allo‐THF/THE and UFF/UFE ratio suggests that much more of the UFE is derived from the kidney. Reduction in UFE excretion is seen following liquorice ingestion and in both variants of AME, though it is more profound in AME1. The high UFF/UFE ratio in the mineralocorticoid excess state seen in the ectopic ACTH syndrome is compatible with substrate‐saturation of renal 11β‐HSD2. The measurement of UFE and the UFF/UFE ratio is a significant advance in the analysis of human 11β‐HSD activityin vivo; in particular,

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00853.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00867.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Although insulin has been shown to stimulate ovarian steroidogenesis and hyperinsulinaemia has been implicated in the raised androgen levels found in diseases associated with significant insulin resistance, ovarian function has not been studied so far in women with NIDDM. We have assessed ovarian function in women with NIDDM at the early (hyperinsulinaemic) and late (relative insulinopaenic) stages of evolution of the disease after strong stimulation with buserelin, a long‐acting GnRH analogue. Significant differences in ovarian function would be expected, depending on the stage of evolution of NIDDM.DESIGN Following an overnight fast, a standard OGTT (75 g, orally) was performed (0830 h) in all diabetic and control women. Blood samples were obtained for blood glucose, insulin and C‐peptide measurements before and at 30‐minute intervals for 2 hours. On the termination of the OGTT, a buserelin test (100 μg, s.c.) was performed (1030 h) and blood samples were obtained for FSH, LH, Δ4‐androstenedione, total testosterone, free testosterone and oestradiol measurements before and then at 4‐hour intervals for 20 hours.SUBJECTS Thirty‐one women with NIDDM (13 hyperinsulinaemic and 18 with relative insulinopaenia), 12 obese and 11 normally menstruating non‐obese, non‐diabetic women, aged 29–39 years, were studied.RESULTS The integrated response (AUC) of oestradiol to buserelin was found to be normal in hyperinsulinaemic NIDDM and obese non‐diabetic women in the face of an increased free testosterone response, while in relatively insulinopaenic NIDDM women the oestradiol response was significantly reduced in the face of a normal free testosterone response.CONCLUSIONS The results suggest that in women with NIDDM the ovaries have a reduced ability to convert androgen to oestrogen, probably due to a reduction of ovarian aromatase activity. As oestrogens protect against atherogenesis, it is speculated that the relative inability of the ovaries to produce oestradiol in NIDDM women with relative insulinopaenia might be involved in the development of the macroangiopath

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00795.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Hyperinsulinaemic women with the polycystic ovary syndrome (PCOS) may be at increased risk of vascular disease later in life, mediated by blood pressure or lipid abnormalities or by elevated plasma levels of plasminogen activator inhibitor‐1 (PAI‐1) activity. PAI‐1 may also be involved in ovarian follicle development and ovarian connective tissue remodelling. We measured plasma PAI‐1 activity and 24‐hour ambulatory blood pressure records in women with and without PCOS.DESIGN Cross‐sectional study of three groups.PATIENTS Twenty‐four non‐obese women with a classic ovarian ultrasound appearance of PCO and extreme menstrual disturbance (Group 1), 26 matched controls with a normal menstrual cycle and an ultrasound appearance of PCO (Group 2) and 10 matched controls with a normal menstrual cycle and normal ovarian ultrasound (Group 3).MEASUREMENTS Twenty‐four hour ambulatory blood pressure recordings (Spacelabs 90207), ovarian ultrasonography, fasting plasma insulin and glucose, plasma PAI‐1 activity, HDL and total cholesterol, triglycerides, gonadotrophins and testosterone. Family history of premature vascular disease.RESULTS Median fasting plasma insulin was significantly higher in Group 1 (45 .8 pmol/l, range 12.9–161.9) than in Group 2 (28.1 pmol/l; range 13.6–91;P <0.05) or Group 3 (26.0 pmol/l; range 13.5–63.3;P <0.05). There were no differences between groups in 24‐hour, daytime or night‐time ambulatory blood pressure measurements, and no relation between plasma insulin and any blood pressure variable.  Mean plasma PAI‐1 activity was higher in Group 1 (10.0 ±7.1 AU/l) than in Group 2 (6.0 ±4.6 AU/lP < 0.05) or Group 3 (5.1 ± 3.5 AU/l;P =0.06). There was a significant independent direct relation between fasting plasma insulin and PAI‐activity (r = 0.41,R2 = 0.154;F1,59 = 11.38;P = 0.001). Groups did not differ in parental history of premature vascular disease, or in mean HDL or fasting triglyceride levels.CONCLUSIONS The only measurable vascular risk factor associated with hyperinsulinaemia and menstrual disturbance in non‐obese women with PCOS is an elevated plasma PAI‐1 activity. These women did not differ from controls in ambulatory blood pressure profiles, lipid measurements or in a parental history of premature vascular disease. PAI‐1 and plasminogen are involved in ovarian follicle maturation and the present finding s

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00863.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Thyroid autoimmunity is frequently associated with insulin‐dependent diabetes mellitus (IDDM). The genetic factors which contribute to thyroid autoimmunity and IDDM have been described but vary between different races. We have therefore investigated the effect of class II HLA genes at both loci and the HLA haplotypes on the presence of autoimmunity in patients with IDDM in Taiwan.SUBJECTS AND MEASUREMENTS Eighty‐three patients with IDDM and 105 unrelated normal controls were recruited for the measurement of thyroid autoantibodies and for genotyping of HLA DRB1, DQA1 and DQB1 by polymerase chain reaction‐based DNA typing techniques.RESULTS Among 83 patients with IDDM, 23 (27.7%) were positive for antithyroid autoantibodies. Compared to those without thyroid autoimmunity, there was a female preponderance for IDDM with thyroid autoimmunity (female: male, 3:20vs29:31). Among the DR specificities, DR6 was associated with a weak protective effect against thyroid autoimmunity in IDDM patients. Upon detailed analysis of class II HLA haplotypes, the DRB1*0301/DQA1*0501/DQB1*0201 haplotype was found to be associated with an increased risk of IDDM regardless of thyroid autoimmunity, while DRB1*0405/DQA1*0301/DQB1*0401 was significantly increased only in the IDDM patients with thyroid autoimmunity. IDDM individuals with the HLA DRB1*0405/DQA1*0301/DQB1*0302 haplotype were not at risk of thyroid autoimmunity.CONCLUSIONS Our data indicated that there was a generalized genetic factor within or associated with the DRB1*0301/DQA1*0501/DQB1*0201 haplotype, and a more restricted effect with the DRB1*0405/DQA1*0301/DQB1*0401 haplotype which led to thyroid autoimmunity in patients with insulin‐dependent di

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00857.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

We report a 17‐year‐old girl with short stature, external ophthalmoplegia, atypical retinal pigmentary degeneration, sensorineural hearing loss, and cardiac conduction defect (Kearns–Sayre syndrome). A large‐scale deletion (6741 base pairs) in mitochondrial DNA was found in her muscle specimen. She also had insulin‐dependent diabetes mellitus (IDDM). On admission, her plasma glucose level was elevated at 31.0mmol/l with mild ketoacidosis, and haemoglobinA1c elevated at 16.5%. After improvement of diabetic ketoacidosis, she was placed on insulin 24–30 units/day despite her small body weight of 25 kg. There was reduced excretion of urinary C‐peptide at 3.97 nmol/day. In addition, she had idiopathic hypoparathyroidism with a serum calcium level of 2.15 mmol/l, phosphate 1.7 mmol/l, and intact PTH below 10 ng/l. Human leucocyte associated antigen typing showed A24, A26; B54, B61; CW1, CW3; DR8, DR14; DQ1 and DQ3, suggesting that the presence of HLA‐A24 and CW3 antigen contributed to the association of IDDM and hypoparathyroidism, similar to Japanese patients with polyglandular autoimmune syndrome, complicated by hypoparathyroidism and IDDM. We suggest that a genetic linkage, as well as mitochondrial dysfunction, may be responsible for the association of the two disease states. This is an extremely rare case of Kearns–Sayre syndrome, presenting in association with IDDM and id

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00856.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Oestrogen producing adrenocortical tumours are extremely rare. We report a 65‐year‐old woman who presented with abnormal vaginal bleeding, with no significant abnormalities in her uterus or ovaries, who was found to have a right adrenal mass by radiological examination. Excessive secretion of oestrogens from the tumour was demonstrated by adrenal venous sampling. Basal levels of corticosteroids were within normal limits. Adrenalectomy was performed and pathological examination revealed an adrenocortical adenoma measuring 5.5 cm in its greatest dimension, in which both clear and compact tumour cells were observed. Oestrogen levels normalized following the removal of the adrenal mass. Tissue concentrations of oestrone and oestradiol in the tumour were 6.9 (69.5 pmol/g wet tissue weight) and 34.6 (93.6 pmol/g wet tissue weight)‐fold greater respectively than those of adjacent non‐neoplastic adrenal cortex. Aromatase activity in the tumour tissue determined by the3H‐water method was 118.6 pmol/h/mg protein, equivalent to that of a full‐term human placenta. Immunohistochemical analysis of aromatase demonstrated immunoreactivity in the tumour cells, especially in compact cells, but not in adjacent non‐neoplastic adrenal cells. This is the first reported case of an oestrogen producing adrenocortical adenoma in which aromatase in the tumour

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00833.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY