bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ovarian function in women with non‐insulin dependent diabetes mellitus
Authors: Stamataki K. E. , Spina J. , Rangou D. B. , Chlouverakis C. S. , Piaditis G. P. 
Published: November 2003

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 macroangiopathy, which often complicates this disease.
Bioavailability and bioactivity of intravenous vs subcutaneous infusion of growth hormone in GH‐deficient patients
Authors: Laursen Torben , Møller Jens , Jørgensen Jens O. L. , Ørskov Hans , Christiansen Jens S. 
Published: November 2003

OBJECTIVE The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim of the present study was to evaluate the short‐term metabolic effects of GH following i.v. and s.c. delivery. DESIGN AND MEASUREMENTS In a cross‐over design 10 GH‐deficient patients were randomized to receive GH (0.03 μg (0.1 mU)/kg/min) as a continuous i.v. or s.c. infusion for 39 hours on two different occasions. Preceding each study GH therapy was discontinued for 5 days. Serum profiles of GH, IGF‐I, IGF‐II, IGF binding protein 3 (IGFBP‐3), insulin, glucose and non‐esterified fatty acids (NEFA) were recorded during the studies. Serum GH was measured by a polyclonal radio‐immunoassay (RIA) and by a double monoclonal immunofluorimetric assay (DELFIA). RESULTS Higher mean integrated values (AUC) of serum GH (mU/l) were obtained with i.v. GH delivery [47.4±5.1 (i.v.), 33.3±3.0 (s.c.), P<0.05]. The two GH assays showed qualitatively similar results, but higher mean GH concentrations were measured by RIA following both s.c. (P<0.001) and i.v. infusion (P<0.001). Serum IGF‐I levels displayed different patterns following i.v. and s.c. GH infusion (P<0.05 by ANOVA) and mean IGF‐I levels (μg/l) were lower following s.c. GH infusion [159.5±21.8 (s.c.), 185.2±27.7 (i.v.), P=0.002]. Serum IGF‐II levels were unaffected by short‐term GH treatment and by the route of GH administration. Serum IGFBP‐3 levels increased in response to GH administration (P<0.001), irrespective of route (P=0.76). The IGF‐I/IGFBP‐3 molar ratio increased significantly following GH administration (P<0.001), and a higher ratio was obtained following i.v. infusion (P<0.005). Subcutaneous GH infusion resulted in significantly lower mean levels of serum NEFA (P<0.02), whereas similar mean levels of serum insulin (P=0.54), blood glucose (P=0.24), energy expenditure (P=0.13), and respiratory exchange ratio (P=0.09) were observed on the two occasions. CONCLUSIONS A reduced bioavailability of s.c. as compared with i.v. administered GH has been recorded with two independent GH assays, and this was also accompanied by a significant, albeit modest, reduction in biological activity.
Ethnicity affects IGFBP‐3 and IGF‐II in normal healthy young adult subjects
Authors: Hopkins K. D. , Lehmann E. D. , Jones R. L. , Holly J. M. P. , Cwyfan‐Hughes S. C. , Turay R. C. , Teale J. D. , Gosling R. G. 
Published: November 2003

OBJECTIVE While the effects of age on the growth hormone/insulin‐like growth factor (IGF) axis are well documented, the influence of ethnic background is unknown. The differences in IGF and IGF binding proteins (IGFBPs) were investigated in two ethnic groups. DESIGN A cross‐sectional study of an age‐selected cohort of healthy, normoglycaemic, non‐obese Caucasian (C) and Asian (A) subjects. PATIENTS Fifty‐three (27 C, 26 A) subjects with a mean age (±SD) of 20.6±0.8 years were studied. MEASUREMENTS Fasting measurements of glucose, insulin, IGF‐I, IGF‐II, IGFBP‐1 and IGFBP‐3. Western ligand blotting and immunoblotting with IGFBP‐2 and IGFBP‐3 of serum samples. RESULTS There were no significant differences in IGF‐I levels between Caucasian and Asian subjects (C 218±55 vs A 229±40μg/l; P=0.44). IGF‐II (C 707±110 vs A 583±75μg/l; P<0.0001) and IGFBP‐3 (C 5.9±1.2 vs A 5.12±1.17 mg/l; P=0.01) levels were significantly higher in Caucasian subjects. Immunoblotting of ligand blots revealed no protease activity on either IGFBP‐3 or IGFBP‐2 to account for these ethnic differences. CONCLUSIONS Ethnic differences in IGFBP‐3 and associated IGF‐II levels may affect the inter‐relationships of IGFs and their binding proteins and need to be considered when interpreting IGF data on growth and metabolism.
Long‐term cardiovascular effects of growth hormone treatment in GH‐deficient adults Preliminary data in a small group of patients
Authors: Johannsson Gudmundur , Bengtsson Bengt‐Åke , Andersson Bert , Isgaard Jörgen , Caidahl Kenneth 
Published: November 2003

OBJECTIVE The long‐term cardiovascular effects of GH administration in adults are of major clinical importance, given the increasing use of such treatment. We have evaluated long‐term cardiovascular effects of recombinant human GH (rhGH) substitution in GH deficient men. DESIGN S.c. rhGH 0.5 U/kg/week or placebo was administered in a 6‐month double‐blind, cross‐over study, followed (after a year without substitution) by a 42‐month period of open GH substitution. PATIENTS We evaluated 7 GH‐deficient men serially and compared the results with 21 men matched in terms of age and height. MEASUREMENTS Investigations included exercise tests and Doppler‐echocardiography to determine exercise capacity and cardiovascular performance. RESULTS Heart rate and systolic blood pressure at rest increased with GH substitution to the level of the controls, as did diastolic blood pressure after an initial reduction. Age‐adjusted exercise capacity increased during the study and we found no evidence of ischaemic heart disease on exercise ECG. Stroke volume increased with GH substitution, thereby normalizing the initially reduced cardiac index. There was no significant change in left atrial or ventricular internal dimensions, systolic function as measured by fractional shortening, or diastolic function as measured by isovolumic relaxation time and left ventricular filling (A/E ratio). However, a lower atrial emptying index than that seen among controls might indicate some diastolic disturbance and there was a definite increase in left ventricular wall thickness compared with controls (to 25.1±1.5 vs 19.7±0.4 mm, P<0.001). CONCLUSIONS We found that GH substitution in GH‐deficient adults had a beneficial effect on physical performance and cardiac output. The concomitant increase in left ventricular mass index might be an effect of an excessive substitution dose.
Immunological and chemical types of reversible hypothyroidism; clinical characteristics and long‐term prognosis
Authors: Sato Kaori , Okamura Ken , Hirata Tsuneo , Yamasaki Kouji , Ikenoue Hiroshi , Kuroda Takeo , Mizokami Tetsuya , Inokuchi Kaeko , Fujishima Masatoshi 
Published: November 2003

OBJECTIVE Spontaneous improvement occurs in about one‐half of patients with primary hypothyroidism who reside in an iodine‐sufficient area of Japan, but the pathogenetic factors related to reversible hypothyroidism are still not fully understood. We therefore investigated the clinical features and prognosis of patients with reversible hypothyroidism with or without iodine excess and antithyroid antibodies. DESIGN Amelioration of hypothyroidism was diagnosed when the elevated serum TSH concentrations (serum TSH concentration ≥ 40 mU/l) decreased by 50% or more during an iodine restriction period of 2–15 weeks without replacement therapy. Reversible hypothyroidism occurred in a post‐partum group (n = 20) and a non‐post‐partum group (n = 91). The latter was then further classified into chemical (n = 28), immunological (n = 20), and mixed (n = 43) groups, according to the presence of iodine excess (serum non‐hormonal iodine level > 50 μg/l or a history of excess iodine ingestion), antithyroid autoantibody, or both, respectively. MEASUREMENTS Clinical characteristics and long‐term prognosis were compared among the four groups. The rate at which hypothyroidism recovered was expressed as the number of days required for a 50% decrease in the serum TSH concentration. The level of thyroid echogenicity was measured by 10‐MHz ultrasonography. RESULTS In the chemical group, the mean age, male : female ratio, and serum non‐hormonal iodine concentrations were all higher than those in the immunological group. The estimated rate at which hypothyroidism recovered was rapid (6.1 ± 3.1 (mean ± SD) days), the levels of thyroid echogenicity were near normal, and a histological examination (n = 7) revealed either colloid goitre or a normal thyroid in the chemical group. In the immunological and post‐partum groups, the recovery rate was slow (16.8 ± 9.6 days and 16.2 ± 5.8 days, respectively). The levels of thyroid echogenicity were markedly reduced but increased after the spontaneous recovery of the thyroid function in both groups. Aspiration cytology suggested lymphocytic infiltration in all patients examined in the immunological (n = 6) and post‐partum groups (n = 4). Relapse to overt hypothyroidism was observed more frequently in the immunological (38%) and mixed groups (35%) than in the chemical group (5%). CONCLUSION Thyroid damage was more severe, recovery slower and the rate of relapse higher in the immunological than in the chemical type of reversible hypothyroidism.
Hyperprolactinaemia and verapamil: prevalence and potential association with hypogonadism in men
Authors: Romeo June H. , Dombrowski Robert , Kwak Yun S. , Fuehrer Susan , Aron David C. 
Published: November 2003

OBJECTIVE Verapamil has been associated with hyperprolactinaemia, but there have been no population‐based studies. Our objective was to determine the prevalence and degree of hyperprolactinaemia associated with verapamil in the clinical setting. DESIGN Observation with cross‐sectional and longitudinal components in the setting of an urban teaching hospital and its satellite out‐patient clinics. PATIENTS Male out‐patients excluding those taking other drugs known to raise PRL, renal failure and known primary hypothyroidism (1265 eligible subjects). Control subjects were drawn from eligible out‐patients not taking verapamil. MEASUREMENTS Serum PRL levels, frequency of persistent hyperprolactinaemia and total testosterone levels. RESULTS Prolactin levels were obtained in 449 subjects on verapamil (35.5% response rate) and 166 controls. The proportions of individuals with hyperprolactinaemia (PRL > 460 mU/l) were 0.085 and 0.030 in the verapamil and control groups, respectively (P = 0.012, χ2‐test). The mean (±SD) serum PRL levels were 267 ± 205 and 203 ±118 mU/l in the verapamil and control groups, respectively (P < 0.001, independent t‐test). Of the 38 patients with previously determined elevated PRL levels, follow‐up data were obtained in 25 (65.8%); one was found to have a pituitary adenoma and was excluded from the analysis. Fifteen of the 24 were still on verapamil (Group 1) and 14 (93.3%) continued to be hyperprolactinaemic. In 9 patients verapamil had been discontinued (Group 2) and all had normal PRL levels. Continued verapamil use was associated with persistent hyperprolactinaemia (odds ratio > 120, P < 0.00001). The ± SD serum testosterone levels at follow‐up were significantly lower in Group 1 (6.16 ± 2.52 nmol/l) than in Group 2 (9.42 ± 3.92 nmol/l, P = 0.029, independent t‐test). CONCLUSIONS The prevalence of hyperprolactinaemia associated with verapamil use in this study of male out‐patients was .5% (95% Cl 5.9–11.1%). The persistence of hyperprolactinaemia when verapamil was continued (Group 1) and the return to normal PRL levels when verapamil was discontinued (Group 2) confirm verapamil’s causal role in the development of hyperprolactinaemia. While low testosterone levels were common in both groups, testosterone levels were lower in patients on verapamil. Our data suggest that screening for hyperprolactinaemia should be considered in male patients taking verapamil.
Effect of follicle stimulating hormone or human chorionic gonadotrophin treatment on the production of gonadotrophin surge attenuating factor (GnSAF) during the luteal phase of the human menstrual cycle
Authors: Messinis I. E. , Lolis D. , Zikopoulos K. , Milingos S. , Kollios G. , Seferiadis K. , Templeton A. A. 
Published: November 2003

OBJECTIVE Although there is much in‐vivo evidence for the existence of a gonadotrophin surge attenuating factor (GnSAF), its source and identity remain unknown. We have studied the control of GnSAF production by FSH and hCG during the luteal phase of the cycle.DESIGN Normally cycling women were investigated in three cycle. Starting on day 5 after the midcycle LH peak, the women received i.m. injections of placebo (1st cycle control), hCG at a dose of 750 IU per day (2nd cycle) and FSH at a dose of 225 IU per day (3rd cycle) for five consecutive days. The response of LH to a single i.v. dose of 10 μg GnRH (GnSAF bioactivity) was investigated several times during the experimental period.PATIENTS Six normally ovulating women with long‐standing unexplained infertility were studied. The women were used as their own controls during the cycle treated with placebo.MEASUREMENTS Pituitary response to GnRH was calculated as the net increase in LH at 30 minutes (ΔLH) above the basal value.RESULTS Serum concentrations of FSH and hCG increased significantly during the second and 3rd cycles respectively. Compared with the control cycles, ΔLH was significantly attenuated as early as 12 hours from the onset of FSH injections. In contrast, basal concentrations of oestradiol (E2) and immunoreactive inhibin started to increase 48 hours after the first injection of FSH, while progesterone values remained similar to those in the controls. During treatment with hCG, no attenuation was seen in ΔLH values, while those of E2, progesterone and inhibin showed a significant increase.CONCLUSIONS These results demonstrate that during the luteal phase of the human menstrual cycle, FSH, but not LH, stimulates the production of gonadotrophin surge attenuating factor. It is suggested that the source of gonadotrophin surge attenuating factor at that stage of the cycle is a cohort of small follicles rather than the corpus luteum.
A low dose ACTH test to assess the function of the hypothalamic–pituitary–adrenal axis
Authors: Rasmuson S. , Olsson T. , Hägg E. 
Published: November 2003

OBJECTIVE The insulin tolerance test (ITT) has long been used to assess the hypothalamic–pituitary–adrenal axis, but may be hazardous. The standard synthetic ACTH (Synacthen) test has been advocated as a substitute but is sometimes insensitive. In this study the ITT has been compared to a low dose ACTH stimulation test (1 μg) and the standard ACTH stimulation test (250 μg).SUBJECTS Twenty‐seven subjects were studied, 24 with verified or suspected hypothalamic–pituitary disorders and three on long‐term glucocorticoid therapy.DESIGN Insulin tolerance, low dose ACTH and standard ACTH tests were performed in all patients. The ITT was performed less than 48 hours after the ACTH tests. Synacthen was administered as an intravenous bolus.MEASUREMENTS Serum cortisol values were determined by radioimmunoassay. The peak cortisol value during ITT was compared to the cortisol levels during the ACTH tests.RESULTS There was a highly significant correlation between peak cortisol values during ITT and cortisol levels after 20–60 minutes in the low dose ACTH test (rs = 0.91–0.93; P< 0.0001) and after 30 and 60 minutes in the standard ACTH test (rs= 0.85 and 0.89 respectively; P< 0.0001). Four patients showed discrepancies between the three tests.CONCLUSIONS The 1‐μg ACTH test follows the ITT more closely and may be more sensitive than the standard ACTH test in detecting more subtle insufficiency of the hypothalamic–pituitary–adrenal axis. The standard ACTH test and the insulin tolerance test may thus be replaced by the 1‐μg ACTH test in screening for secondary cortisol insufficiency. We recommend that serum cortisol is measured before and 30 and 40 minutes after the ACTH injection.
Flow cytometric analysis does not reliably differentiate benign from malignant phaeochromocytoma
Authors: Heaney A. P. , O'Rourke D. , Arthur K. , Beatty O. L. , Russell C. F. J. , Sloan J. M. , Hamilton P. , Atkinson A. B. 
Published: November 2003

BACKGROUND AND OBJECTIVE The differentiation of benign from malignant phaeochromocytoma is difficult. We have examined whether the use of flow cytometric determination of nuclear DNA content would be useful as a predictor of malignant behaviour in patients with phaeochromocytoma as some previous studies had suggested that a diploid cytometric DNA pattern indicated benign disease.DESIGN AND PATIENTS  DNA flow cytometry was performed on phaeochromocytoma tissue from 36 patients (19 female, 17 male; mean age at presentation 39.5 years). The results were correlated with clinical outcome after prolonged follow‐up.MEASUREMENTS DNA histograms were constructed following nuclear suspension analysis.RESULTS Of 26 patients followed up for more than 5 years after initial removal of primary phaeochromocytoma, three have died from malignant recurrence. In these patients a diploid DNA cytometric pattern was observed in two and an aneuploid pattern in one. Twenty‐one patients are still alive. DNA cytometry showed a diploid pattern in the one patient who developed recurrent phaeochromocytoma 4 years after removal of a primary tumour.CONCLUSION In this study, three of nine patients with an apparently benign diploid cytometric pattern subsequently developed recurrent disease. Routine use of DNA flow cytometry did not reliably differentiate benign from malignant phaeochromocytoma. Prolonged clinical and biochemical follow‐up is still necessary for all patients with this condition.
FSH isoforms: bio and immuno‐activities in post‐menopausal and normal menstruating women
Authors: Creus Silvina , Pellizzari Eliana , Cigorraga Selva B. , Campo Stella 
Published: November 2003

OBJECTIVE The full expression of gonadotrophin biological activity depends on the gonadotrophin carbohydrate component. Our aim was to study serum FSH isoforms present in the follicular phase (FPS) and in the menopause (PMS) since the endocrine status may influence the structure of incorporated oligosaccharides.SUBJECTS Ten healthy post‐menopausal women (age range 53–68) not receiving any hormonal treatment and 10 healthy women (age range 20–28) in the follicular phase of their menstrual cycle were studied.MEASUREMENTS Bio and immuno FSH‐activities (Sertoli cell aromatase induction assay and RIA, respectively) were determined in separated isoforms after concanavalin A chromatography. Isolated isoforms were: UB, unbound; WB, weakly bound and FB, firmly bound to the lectin.RESULTS PMS showed two groups of immuno and bio‐active FSH isoforms: WB, bearing biantennary galactosylated type and FB, bearing high mannose or hybrid type oligosaccharides. Immuno and bio‐active FSH were not detected in the UB fractions. WB isoforms represented 82 ± 6% of the total bioactivity recovered in samples analysed individually; their B/I ratio was 0.85 ± 0.20. FB isoforms were 18 ± 6%; their B/I ratio was 3.27 ± 0.60. Whole serum B/I ratio was 1.20 ± 0.30. Similar results were obtained when pooled sera was analysed: WB: 77%, B/I: 0.82; FB: 23%, B/I: 3.75. Whole serum B/I in pooled samples was 1.10. FPS showed a different pattern. UB isoforms, bearing triantennary or bisecting oligosaccharides, were 41 ±3% of the total bioactivity recovered in samples analysed individually. Their B/I ratio was 0.61 ± 0.23. WB isoforms were 59 ± 3% and their B/I 0.76 ± 0.14. FB FSH isoforms were not detected. The whole serum B/I ratio was 0.60 ± 0.30. Similar results were obtained when pooled sera was analysed: WB 43%, B/I 0.42; FB 57%, B/I 0.62. Whole serum B/I in pooled samples was 0.70.CONCLUSIONS These results show that, in normal women, circulating FSH bioactivity is associated with isoforms with different oligosacharide structures according to hormonal status. FSH in the follicular phase has a higher degree of branching and a more complete carbohydrate chain than the FSH secreted during the menopause.
Genetic analysis of seven Mediterranean families with multiple endocrine neoplasia type 2A
Authors: Oriola Josep , Hernandez Cristina , Simo Rafael , Barceló Anna , Casamitjana Roser , Vilardell Enric , Rivera‐Fillat Francisca 
Published: November 2003

OBJECTIVE  Genetic analysis is now essential for the accurate screening of families with multiple endocrine neoplasia type 2 (MEN2). We present the genetic analyses by both haplotype and direct RET proto‐oncogene mutation analysis in seven Mediterranean MEN 2A families and have compared these results with biochemical screening tests and pathological examinations.DESIGN Total DNA was extracted from leucocytes. Linkage analysis was performed using five RFLP systems from three loci that flank the MEN2A locus (FNRB, RBP3, D10S15). RET proto‐oncogene analysis was carried out by automatic DNA sequencing and adequate digestion of PCR amplified products for exons 10 and 11. Screening for medullary thyroid carcinoma or C‐cell hyperplasia was performed by the pentagastrin provocation test. Adrenal medullary function was assessed by measurements of 24‐hour urinary excretion of catecholamines and their metabolites. Serum calcium and phosphate measurements were the initial screen for hyperparathyroidism. Serum PTH was determined only if hyperparathyroidism was suggested by the former determinations.PATIENT  Genetic study was performed in 59 individuals (39 at risk) from seven kindreds of Mediterranean origin with MEN 2A.RESULTS  Diagnosis by linkage analysis was not possible in 30% of individuals at risk, but RET proto‐oncogene analysis identified all these individuals. Mutations of the RET proto‐oncogene were detected in exon 10 (codon 618) in one MEN 2A kindred and in exon 11 (codon 634) in the others. The results of direct analysis were concordant with linkage studies in each case. Three individuals from different MEN 2A kindreds, who were subsequently shown not to be gene carriers, had false positive pentagastrin stimulation tests.CONCLUSION  Biochemical tests can be replaced by direct DNA mutation analysis as the first line screening test in order to identify gene carriers of MEN 2A.