bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prevalence of polycystic ovaries in women with a history of gestational diabetes
Authors: Kousta Eleni , Cela Ester , Lawrence Natasha , Penny Anna , Millauer Barbara , White Davinia , Wilson Helen , Robinson Stephen , Johnston Desmond , McCarthy Mark , Franks Stephen 
Published: March 2003

OBJECTIVEWomen with a history of gestational diabetes mellitus (GDM) and women with polycystic ovary syndrome (PCOS) both demonstrate abnormalities in insulin action and secretion, and both are at increased risk of developing type 2 diabetes. To determine whether these similarities reflect a common pathophysiological basis, we examined the prevalence of ultrasound‐based polycystic ovarian morphology in a large multiethnic group of women with a history of GDM and a group of women who had normal glucose tolerance during pregnancy.PATIENTS AND DESIGNWe studied 91 women with previous GDM (48 European, 20 South Asian, 10 Afro‐Caribbean and 13 of other or mixed ethnicity) and 73 normoglycaemic control women (56 European, one South Asian, 14 Afro‐Caribbean and two of other or mixed ethnicity), a median (interquartile range) of 20 (11–36) and 29 (17–49) months postpartum, respectively. A detailed history was taken, and the prevalence of PCO morphology on ultrasound scan was assessed. Fasting lipids, insulin, glucose status, gonadotrophins and testosterone were measured. Estimates of β‐cell function (%B) and insulin sensitivity (%S) were derived using the HOMA algorithm.RESULTSWomen with previous GDM had higher fasting glucose (5.4 (4.8–6.0) vs. 4.7 (4.4–5.0) mmol/l, P < 0.0001) and features reminiscent of syndrome X: higher BMI (26.4 (22.8–31.4) vs. 23.8 (21.0–27.5) kg/m2, P = 0.002), waist/hip ratio (0.82 (0.79–0.88) vs. 0.77 (0.73–0.81), P < 0.0001), fasting insulin (165 (68–299) vs. 54 (24–156) pmol/l, P < 0.0001), triglycerides (1.1 (0.8–1.6) vs. 0.8 (0.6–1.1) mmol/l, P < 0.0001) and lower insulin sensitivity (%S) (27 (16–62) vs. 86 (34–139)%, P < 0.0001) compared to control women. The prevalence of PCO was higher in the previous GDM group than in the control subjects (47/91 (52%) vs. 20/73 (27%), χ2 = 9.86, P = 0.002 overall, odds ratio 2.7, P = 0.007 by logistic regression allowing for ethnicity). There was no difference in any metabolic parameter between the post‐GDM PCO group and the post‐GDM normal ovaries group, but irregular cycles were more prevalent in the PCO group (22/47 (47%) vs. 9/44 (21%), χ2 = 7.03, P = 0.008).CONCLUSIONSWe found a higher prevalence of polycystic ovarian morphology in women with a history of gestational diabetes. Among the women with previous gestational diabetes, irregular cycles were more prevalent in the PCO group than in the women with normal ovarian morphology, but no other differences in endocrine or metabolic parameters were detected. These findings confirm an association between PCO and gestational diabetes and suggest that women with gestational diabetes display metabolic abnormalities irrespective of ovarian morphology.
Beta cell function declines with age in glucose tolerant Caucasians
Authors: Chiu Ken C. , Lee Nancy P. , Cohan Pejman , Chuang Lee‐Ming 
Published: March 2003

OBJECTIVEAs type 2 diabetes results from an imbalance between insulin sensitivity and beta cell function, either or both may worsen with age. However, existing data are controversial on the effect of ageing on both insulin sensitivity and beta cell function.SUBJECTS AND DESIGNWe enrolled 149 healthy, glucose tolerant and normotensive Caucasians (age 35 ± 1 years, body mass index 26.07 ± 0.44 kg/m2, waist‐hip ratio 0.842 ± 0.009 cm/cm, mean ± standard error). A cross‐sectional study was designed to examine the impact of age on insulin sensitivity and beta cell function. Their beta cell function (percentage B [%B]) and insulin sensitivity (percentage S [%S]) were estimated using the homeostasis model assessment.RESULTSSimple regression analysis revealed that %B declined with age (P = 0.008) while no relation was found between %S and age (P = 0.769). A stepwise regression analysis revealed that body mass index and diastolic blood pressure explained 14.7% of variation in %S, while age, waist‐hip ratio, gender, and systolic blood pressure had no influence on %S. Age, body mass index and diastolic blood pressure together accounted for 21.7% of variation in %B, with age being an independent variable.CONCLUSIONSIn the present study, we showed that beta cell function declined with age at a rate of about 1% per year. In contrast, insulin sensitivity was not affected by ageing. Our observations suggest that the age‐related decline in glucose tolerance is primarily related to the loss of beta‐cell function.
Recovery of growth hormone secretion following cabergoline treatment of macroprolactinomas
Authors: George L. D. , Nicolau N. , Scanlon M. F. , Davies J. S. 
Published: March 2003

OBJECTIVECabergoline therapy normalizes prolactin levels and reduces the size of macroprolactinomas. However there are no data indicating whether cabergoline can normalize growth hormone secretion in patients who were growth hormone deficient at the time of diagnosis of a macroprolactinoma.SUBJECTS AND METHODSWe studied nine patients with biochemical and radiological evidence of a macroprolactinoma who were also growth hormone deficient (peak growth hormone response to insulin‐induced hypoglycaemia < 10 mU/l). Patients were assessed before and after cabergoline therapy to assess their growth hormone secretory status, IGF‐I levels, cortisol response and change in tumour size.RESULTSTreatment with cabergoline was associated with a significant reduction in prolactin concentration (74341 ± 31939 mU/l vs. 265.9 ± 86.3, P = 0.009). The mean change in peak growth hormone response to insulin‐induced hypoglycaemia was significantly greater following cabergoline therapy compared with pretreatment levels (33.5 ± 11.8 mU/l vs. 4.34 ± 1.21 mU/l, P = 0.022). However IGF‐I levels were not different after treatment when compared with baseline although a nonsignificant trend towards improvement was noted (24.2 ± 3.97 nmol/l vs. 18.4 ± 4.94 nmol/l, P = 0.058). The mean peak cortisol concentration was 407.7 ± 64.1 nmol/l before treatment with a nonsignificant rise to 477.4 ± 84.8 nmol/l, P = 0.813 after treatment. These changes were associated with a significant reduction in mean maximal tumour diameter (21.2 ± 2.9 mm vs. 29.1 ± 2.8 mm, P = 0.009). There was no significant difference in either prolactin concentration or tumour size pre‐ or post‐treatment between those who recovered growth hormone secretion and those that did not. Six of the nine (67%) patients recovered a normal growth hormone response (> 10 mU/l) after cabergoline therapy. Those that remained growth hormone deficient after treatment were all panhypopituitary at baseline while those that recovered showed only partial anterior hypopituitarism.CONCLUSIONThese data indicate that growth hormone secretion may recover following successful reduction of prolactin levels after cabergoline therapy for a mean of 22 months (range 6–28 months) in most but not all subjects with a macroprolactinoma. It is therefore advisable that individuals with a macroprolactinoma in whom growth hormone replacement therapy is being considered undergo repeat assessment of growth hormone secretion following medical treatment.
Age‐related changes of serum sex hormones, insulin‐like growth factor‐1 and sex‐hormone binding globulin levels in men: cross‐sectional data from a healthy male cohort
Authors: Leifke Eckhard , Gorenoi Vitali , Wichers Christian , Von Zur Mühlen Alexander , Von Büren Erico , Brabant Georg 
Published: March 2003

The age‐dependent decline of the gonadal and somatotopic axis has been causally linked to frailty in the elderly by their effects on muscle mass and bone mineral density. However, for healthy men data on serum oestrogens and androgens, as well as IGF‐1, as a common outcome measure covering the whole adult age range are scarce. We therefore studied healthy, nonobese male subjects between 20 and 80 years of age to asses their morning concentrations of total (T), free (FT), bioavailable testosterone (bT), oestradiol (E2), bioavailable oestradiol (bE2), oestrone (E1), sex‐hormone binding globulin (SHBG), and insulin‐like growth factor 1 (IGF‐1).Five hundred and seventy‐two male healthy volunteers with a BMI < 30 kg/m2 recruited from regular blood donors and senior sports clubs participated in the study. Serum samples were obtained during morning hours and T, FT, E2, E1, SHBG, albumin and IGF‐1 were measured by radio‐immunoassay systems. In addition, bT and bE2 were calculated. A potential relationship between sex hormones and IGF‐1 was tested by multiple regression analysis including age and BMI.Ageing was negatively related to serum levels of sex steroids and IGF‐1 (both P < 0·0001) with a mean decrease (youngest vs. oldest) of 51% for T, 64% for FT, 78% for bT, 32% for E2, 62% for bE2, 29% for E1 and 51% for IGF‐1 starting in early adulthood whereas SHBG increased after the 5th decade of life (anovaP < 0·001). The decline of sex hormones and IGF‐1 remained relatively unchanged after adjustment for BMI. Multiple regression analysis revealed an age‐and BMI– independent association between oestradiol and IGF‐1.In contrast to the female situation sex hormones in healthy, nonobese men decline continuously with age. This process has already started in the third decade, and is paralleled by a decline of IGF‐1 serum levels leading to a substantial proportion of elderly men with markedly lowered serum levels of bioavailable sex hormones and IGF‐1 compared to the young adult male range. With the recent demonstration of beneficial effects of androgen replacement therapy in healthy males on general well being, muscle mass and bone mineral density the present data may underline the importance of more detailed studies on the biological significance of hormonal changes in men with age.
The testosterone:androstenedione ratio in male undermasculinization
Authors: Faisal Ahmed S. , Iqbal Asma , Hughes Ieuan A. 
Published: March 2003

Recent reports suggest that low testosterone:androstenedione (T:A) ratio following hCG stimulation may be a useful method of diagnosing 17β‐hydroxysteroid dehydrogenase‐3 (17 βHSD3) deficiency. The aim of this study was to establish the range of T:A ratios in cases of undermasculinization with proven aetiologies other than 17 βHSD3.Register‐based study of cases of male undermasculinization reported to a central database by clinicians.Amongst the 421 cases of under‐masculinization, 114 cases had testosterone and androstenedione levels before and after hCG stimulation. Of the 114, there were 18 cases of abnormal testes, 17 cases of complete androgen insensitivity syndrome (CAIS), 68 cases of partial AIS (PAIS). Of the 17 cases of CAIS, 13 had evidence of androgen receptor (AR) dysfunction; in the PAIS cohort, 26 cases had evidence of AR dysfunction.Analysis of T:A ratios in the above cohorts and comparison of these ratios to those in a group of previously described cases of 17 βHSD3 deficiency with a mean ratio of 0·4 (SD: 0·2)The median age (range) for the CAIS, PAIS and abnormal testes cohort was 1·25 years (0·06–16·5), 0·7 years (0·02–40·3) and 0·5 years (0·04–6·5), respectively. In CAIS, the median T:A rose from 0·4 (0·1 to 8·0) to 4·5 (0·5–16·7); in PAIS, median T:A rose from 0·7 (0·1 to 15) to 3·9 (0·3–20·5); in cases with abnormal testes, median T:A rose from 0·4 (0·1 to 5·6) to 0·6 (0·1–3·6). The median post‐hCG T:A ratio was significantly lower in the abnormal testes cohort (P < 0·01). None of the cases of AIS with AR mutation had a low T:A ratio. Only four out of 84 cases diagnosed as AIS had a T:A ratio less than 0·8 (mean + 2SD in 17βHSD3 deficiency). In one of the four cases, the T:A ratio rose to 3·5 following a prolonged hCG stimulation test.Deficiency of 17βHSD3 should be considered in 46XY undermasculinization if the post‐hCG stimulation T:A ratio is less than 0·8. However, low T:A ratios may be encountered in conditions such as abnormal testes. Before embarking on mutational analysis, we would also recommend careful evaluation for testicular dysgenesis including a prolonged hCG stimulation test in cases with a low T:A ratio.
Determinants of sex hormone‐binding globulin in normal postmenopausal women
Authors: Wu Fiona , Ames Ruth , Evans Margaret C. , France John T. , Reid Ian R. 
Published: March 2003

OBJECTIVE To examine the factors influencing the levels of sex hormone‐binding globulin (SHBG) in normal postmenopausal women by assessing the relationship between SHBG and measured anthropometric, metabolic and hormonal variables.DESIGN Cross‐sectional, observational study.SUBJECTS and METHODS Seventy normal postmenopausal women aged 47–71 years (mean 58 years), participated in the study. Information was collected on medical, reproductive and smoking history, alcohol use, dietary intake and physical activity. Body composition measurements using dual‐energy absorptiometry, and analyses of biochemical and hormonal indices were performed.RESULTS Bivariate correlation coefficients indicated that SHBG was inversely related to body weight (r = − 0·44), fat mass (r = − 0·35), and abdominal obesity (r = − 0·42). It was also inversely related to the glucose and insulin levels during an oral glucose tolerance test (− 0·24 < r < − 0·40), serum oestradiol (r = − 0·26), and physical activity (r = − 0·24). Multiple regression analysis indicated that significant independent correlates of SHBG concentration were fat mass, physical activity, alcohol intake, serum oestradiol, and insulin‐like growth factor‐1, all having a negative impact on SHBG.CONCLUSIONS From these observed associations, it is concluded that maintenance of body weight, moderate alcohol consumption, and physical activity will tend to reduce SHBG concentrations in postmenopausal women, thereby increasing the levels of free oestradiol. This mechanism could mediate the beneficial effects of these factors in preventing the development of osteoporosis and cardiovascular disease.
Effect of vitamin K and/or D on undercarboxylated and intact osteocalcin in osteoporotic patients with vertebral or hip fractures
Authors: Takahashi Masaaki , Naitou Kenichi , Ohishi Tsuyoshi , Kushida Kazuhiro , Miura Masakazu 
Published: March 2003

OBJECTIVETo examine serum undercarboxylated osteocalcin (OC) with application of an ELISA in normal women and in osteoporotic patients with vertebral fractures or hip fractures, and to investigate the effects of vitamin K and/or D treatment on undercarboxylated OC and intact OC in vertebral fractures.PATIENTSThey were 43 premenopausal (PRE) and 48 postmenopausal healthy females (POST), 89 osteoporotic patients with vertebral fractures (VX) and, 24 patients with hip fracture (HX).MEASUREMENTSIntact OC was measured by an IRMA and undercarboxylated OC was measured by an ELISA.RESULTSIntact osteocalcin was significantly higher in POST and VX than in PRE, and was significantly lower in HX than in POST and VX. Undercarboxylated OC tended to be higher in POST, VX and HX than in PRE, but not significantly. The ratio of undercarboxylated OC to intact OC was significantly higher in HX than in POST and in VX. After 4 weeks treatment with K, D, and K + D to 56 VX, undercarboxylated OC decreased significantly in the groups with K and K + D. Intact OC tended to increase slightly in the groups given K, D, K + D, but not significantly so. Vitamin K and vitamin K + D markedly decreased the ratio of undercarboxylated/intact OC to approximately 80%. On the other hand, vitamin D did not decrease that ratio.CONCLUSIONSThere was a disproportion of undercarboxylated osteocalcin to intact osteocalcin between postmenopausal women and osteoporotic patients with vertebral fractures or hip fractures. Vitamin K did decrease undercarboxylated osteocalcin, vitamin D did not change undercarboxylated osteocalcin, and vitamin D did not enhance the effect of vitamin K on undercarboxylated osteocalcin.
Growth hormone and the heart
Authors: Colao Annamaria , Marzullo Paolo , Di Somma Carolina , Lombardi Gaetano 
Published: March 2003

Impaired cardiovascular function has recently been demonstrated to potentially reduce life expectancy both in GH deficiency and excess. Experimental and clinical studies have supported the evidence that GH and IGF‐I are implicated in cardiac development. In most patients with acromegaly a specific cardiomyopathy, characterized by myocardial hypertrophy with interstitial fibrosis, lympho‐mononuclear infiltration and areas of monocyte necrosis, results in biventricular concentric hypertrophy. In contrast, patients with childhood or adulthood‐onset GH deficiency (GHD) may suffer both from structural cardiac abnormalities, such as narrowing of cardiac walls, and functional impairment, that combine to reduce diastolic filling and impair left ventricular response to peak exercise. In addition, GHD patients may have an increase in vascular intima‐media thickness and a higher occurrence of atheromatous plaques, that can further aggravate the haemodynamic conditions and contribute to increased cardiovascular and cerebrovascular risk. However, several lines of evidence have suggested that the cardiovascular abnormalities can be partially reversed by suppressing GH and IGF‐I levels in acromegaly or after GH replacement therapy in GHD patients.Recently, much attention has been focussed on the ability of GH to increase cardiac mass suggesting its possible use in the treatment of chronic nonendocrine heart failure. In fact, GH administration can induce an improvement in haemodynamic and clinical status in some patients. Although these data need to be confirmed in more extensive studies, such promising results seem to open new perspectives for GH treatment in humans.
An influence of variation in the aldosterone synthase gene (CYP11B2) on corticosteroid responses to ACTH in normal human subjects
Authors: Davies Eleanor , Holloway Christine D. , Ingram Mary C. , Friel Elaine C. , Inglis Gordon C. , Swan Lorna , Hillis W. Stewart , Fraser Robert , Connell John M. C. 
Published: March 2003

OBJECTIVE Previous evidence suggests that the efficiency of 11β‐hydroxylase is at least partly heritable and also that it may be mildly impaired in essential hypertension. In both cases, assessment of activity was based on the response of 11‐deoxycorticosterone (DOC) and 11‐deoxycortisol to ACTH. The gene (CYP11B1) coding for this enzyme is highly homologous with and lies a relatively short distance downstream from the gene coding for aldosterone synthase (CYP11B2) on chromosome 8. Two polymorphisms of CYP11B2 have been described. The first involves a change of −344C to T in a putative steroidogenic factor‐1 (SF‐1) binding site and the other, the intron conversion, an exchange of intron 2 for that of CYP11B1. These polymorphisms are in linkage dysequilibrium. Their effects on 11β‐hydroxylation were studied.METHODS AND RESULTS Normal subjects (n = 135) were genotyped and those homozygous for either or both the polymorphisms were given ACTH (250 µg, i.v.). Plasma was sampled before and 30 minutes after administration. Basal concentrations of DOC, corticosterone, 11‐deoxycortisol and cortisol and responses of corticosterone and cortisol to ACTH were not affected by genotype. However, the responses of DOC (P = 0·002 and P = 0·001, respectively) and 11‐deoxycortisol (P = 0·025 and P = 0·002, respectively) were significantly greater in subjects homozygous for SF‐1 T and/or intron conversion than in those homozygous for SF‐1 C and/or normal intron.CONCLUSIONS These results indicate different 11β‐hydroxylase efficiencies. Thus, variation in CYP11B2 appears to affect the product of CYP11B1. The mechanism is unclear. The close proximity of the two genes may lead to competition for transcription factors or specific differences in intron 2 may affect transcription. Alternatively, the polymorphisms may be acting as markers for adjacent functional genetic variations.
Genetic analysis of the cytochrome P‐450c17α (CYP17) and aldosterone synthase (CYP11B2) in Japanese patients with 17α‐hydroxylase deficiency
Authors: Takeda Yoshiyu , Yoneda Takashi , Demura Masashi , Furukawa Kenji , Koshida Hideo , Miyamori Isamu , Mabuchi Hiroshi 
Published: March 2003

OBJECTIVE To determine the clinical and molecular genetic characterization of two Japanese patients with 17α‐hydroxylase deficiency, we analysed the 17α‐hydroxylase/17,20‐lyase gene (CYP17). Next, to clarify the mechanism of hypoaldosteronism in 17α‐hydroxylase deficiency, we analysed the expression of aldosterone synthase (CYP11B2) messenger RNA and sequenced CYP11B2 in these patients.PATIENTS Patient 1 (46 XY), phenotypically female, sought medical attention for hypertension, amenorrhea and infantile genitalia. Patient 2 (46 XX), phenotypically female, presented for hypertension and amenorrhea. Hormonal data in both patients showed decreased levels of sex steroids, cortisol, aldosterone and plasma renin activity and extreme elevation of deoxycortisol.DESIGN Direct sequencing of CYP17 and CYP11B2 was performed using genomic DNA from the patients. An expression studies of mutated forms of CYP17 was performed using COS‐1 cells. The expression of CYP11B2 messenger RNA in mononuclear leucocytes (MNLs) of these patients and normal subjects was measured using the competitive polymerase chain reaction method. The effect of renin secretion stimulation on the levels of CYP11B2 messenger RNA in MNLs of normal subjects was also studied.RESULTS We detected two novel genetic defects in 17α‐hydroxylase. Sequence analysis revealed one base pair deletion (T) at codon 243 in exon 4 in patient 1. CYP17 in patient 2 contained a point mutation (C to T) at position 415 in exon 8. Transfected cells of mutant from patient 1 had no 17α‐hydroxylase or 17,20‐lyase activity. The R415C mutant protein showed very weak activity of 17α‐hydroxylase or 17,20‐lyase activity. In the renin secretion stimulating test, the increase in CYP11B2 messenger RNA levels in MNLs was parallel with that of plasma aldosterone concentration. The expression of CYP11B2 mRNA in NMLs of these patients was lower compared to controls. No mutations in CYP11B2, including the 5′ flanking region, were found.CONCLUSIONS These results indicate that the novel mutations of the CYP17 gene found in these patients inactivate cytochrome P450c17 function, and that hypoaldosteronism in these patients may be partly explained by a decreased activity of aldosterone synthase, which is regulated at the transcriptional level.