bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relations between sex hormones, sex hormone binding globulin, insulin‐like growth factor‐I and insulin‐like growth factor binding protein‐I in post‐menopausal breast cancer patients
Authors: Lønning Per E. , Helle Svein‐Inge , Johannessen Dag C. , Adlercreutz Herman , Lien Ernst A. , Tally Michael , Ekse Dagfinn , Fotsis Theodore , Anker Gun B. , Hall Kerstin 
Published: March 2008

SummaryOBJECTIVE Oestrogens, androgens and anti‐endocrine drugs such as tamoxifen and aminoglutethimide influence plasma Insulin‐like growth factor‐I (IGF‐I). IGF‐I, in turn, has been found to stimulate the peripheral aromatase in vitro. The aim of this study was to examine relations between sex hormones, IGF‐I and insulin‐like growth factor binding protein‐1 (IGFBP‐1) In post‐menopausal women with breast cancer.DESIGN To measure plasma sex steroids, sex hormone binding globulin (SHBG), IGF‐I, IGFBP‐1, Insulin and urinary oestrogen metabolites In post‐menopausal women with breast cancer not receiving any endocrine therapy.PATIENTS Thirty‐two patients had fasting blood samples obtained between 0800 and 1000h. A sub‐group of 10 patients had 24‐hour urine oestrogen metabolites determined.MEASUREMENTS Plasma steroids and proteins were measured by radioImmunoassays. Urinary oestrogens were measured by GC‐MS.RESULTS SHBG correlated negatively with plasma androstenedione (P < 0·001), insulin (P < 0·001), IGF‐I, height and plasma oestrone sulphate (P < 0·025 for all), but positively with plasma IGFBP‐1 (P < 0·025). IGFBP‐1 correlated negatively with IGF‐I (P < 0·001) and the testosterone/SHBG ratio (P < 0·05). Neither IGF‐I nor IGFBP‐1 correlated with any of the plasma or urinary sex hormones or with the oestrone/androstenedione and oestradiol/testosterone ratios.Multivariate analysis revealed plasma SHBG to correlate positively with IGFBP‐1 (P= 0·029) and negatively with Insulin (P= 0·031). Plasma IGFBP‐1 correlated negatively with IGF‐I (P < 0·0001) but not with insulin.CONCLUSION Our results do not suggest any influence of plasma sex steroids in physiological concentrations on IGF‐I or IGFBP‐1 in post‐menopausal breast cancer patients, nor do they indicate IGF‐I at physiological concentrations Influences the ratios between plasma oestrogens and their androgen precursors.
Measurement of TSH receptor blocking immunoglobulins using 3H‐adenine incorporation into FRTL‐5 and JPO9 cells: use in a child with neonatal hypothyroidism
Authors: Michelangell Vaido P. , Poon Cathy W. , Arnus Emllia E. , Frauman Albert G. , Connelly John , Colman Peter G. 
Published: March 2008

SummaryOBJECTIVE The aim of this study was to develop an assay for the measurement of thyroid blocking antibodies (TBAb), based on the ability of patient serum to inhibit TSH stimulated 3H‐cAMP production following incubation of FRTL‐5 or JPOS cells with 3H‐adenine. The assay was then used to evaluate a child born with neonatal hypothyroidism.DESIGN The levels of TBAb, TSAb (thyroid stimulating antibodies), TBII (TSH binding Inhibitory antibodies), and the thyroid antibodies anti‐thyroid peroxidase and thymoglobulin antibodies were measured in both mother and child over a 6‐month post‐natal period.PATIENT The assay for TBAb was used to evaluate a child born with neonatal hypothyroidism whose mother had a history of hypothyroidism due to Haehimoto's thyrolditis. A 99mTc pertechnetate scan showed no evidence of functioning thyroid tissue. At 20 months of age an ultrasound verified a normally positioned thyroid.RESULTS Initially, high levels of TBII and antithyroid antibodies were present in the serum of both mother and child. In both, the levels of TSAb were undetectable but there were significant levels of TBAb. The levels of TBAb decreased to control levels in the child within 2 months of birth but remained elevated in the mother's serum.CONCLUSIONS This case of neonatal hypothyroidism associated with the passage of thyroid blocking antibodies demonstrates the utility of this new assay in the differential diagnosis of neonatal hypothyroidism.
Effect of chronic daily oral administration of 17βoestradiol and norethisterone on the isoforms of serum gonadotrophins in post‐menopausal women
Authors: Wide Leif , Naessén Tord , Phillips David J. 
Published: March 2008

SummaryOBJECTIVE Chronic treatment with 17βoestradlol (E2Implants has been found to counteract the formation of more acidic isoforms of the gonadotrophins in post‐menopausal women. Oral medication with an oestrogen in combination with a progestagen is a common hormone replacement therapy (HRT) in post‐menopausal women. The present study investigated the effect of such a therapy on the concentration and charge of the gonadotrophin isoforms in serum.DESIGN Serum samples were obtained from 20 post‐menopausal women, mean age 60 years (range 50–72 years), treated with continuous dally oral medication of 2 mg E2 combined with 1 mg norethisterone acetate (NETA). FSH, LH and E2 in the serum was measured with fluoroimmunoassays. The median charge and charge heterogeneity of the FSH and LH isoforms were determined for each serum by electrophoresis in 0·1% agarose suspension. Sera from 20 post‐menopausal women without a history of HRT served as controls. The results were compared with those from previous studies on post‐menopausal women treated with E2 Implants and on women with normal menstrual cycles.RESULTS The E2 level in the oral‐E2+ NETA treated women was 198‐610 pmol/l, within the range expected during the mid‐luteal phase of the normal menstrual cycle and similar to that of the group of women with an E2 Implant. The mean LH level was similar to that of the luteal phase of the cycle and significantly lower than that of the controls (P < 0·001), the E2 Implant group (P < 0·001) and at the follicular phase of the cycle (P < 0·01). The mean FSH level was slmllar to that of the folllcular phase and the E2 implant group but lower than that of the controls (P < 0·001) and higher than at the luteal phase of the cycle (P < 0·01). The mean values for median charge of both FSH and LH were less acidic than those of the controls (P < 0·001) but more acidic than those for the E2 Implant group (P < 0·01; P < 0·001) and for different phases of the menstrual cycle (P < 0·05; P < 0·001). The mean degree of charge heterogeneity of FSH was larger (P < 0·01), while that of LH was smaller (P < 0·01), than for the controls. The mean concentrations of SHBG in the oral E2+ NETA group, the E2 implant group and the controls were similar.CONCLUSION Chronic oral therapy with 2mg 17β oestradiol combined with 1 mg norethisterone in post‐menopausal women efficiently decreased the serum gonadotrophin levels but only partly counteracted the formation of the more acidic isoforms of FSH and LH after menopause. The differences in the charge for both FSH and LH between the E2 Implant and the oral E2+ NETA treated groups may be due to the differences in route of administration of E1 or to the effect of norethisterone or both.
The acute effects of oral ethanol on the hypothalamic‐pituitary‐adrenal axis in normal human subjects
Authors: Inder W. J. , Joyce P. R. , Wells J. E. , Evans M. J. , Ellis M. J. , Mattioll L. , Donald R. A. 
Published: March 2008

SummaryOBJECTIVE To evaluate the acute effects of oral ethanol on the hypothalamic‐pituitary‐adrenal axis in normal human subjects and, in particular, to examine the effect of background alcohol intake and gastrointestinal side‐effects on this response.DESIGN Plasma ethanol, cortisol, ACTH, corticotrophin‐releasing hormone (CRH) and AVP were measured half‐hourly for 4 hours following 1·1 ml/kg of 95% ethanol or placebo in a cross‐over study. At least one week elapsed between each procedure.SUBJECTS Twelve healthy non‐alcoholic volunteers with a wide range of background alcohol Intakes.MEASUREMENTS Peptide hormones were measured by radioimmunoassay, cortisol by ELSA and blood ethanol by headspace gas chromatography. Results are expressed as mean ± SEM.RESULTS Blood ethanol levels peaked at one hour post ethanol ingestion. Three subjects developed significant gastrointestinal (GI) side‐effects, with two vomiting and one experiencing moderate to severe nausea. There was no difference between peak blood ethanol levels in the groups with and without GI side‐effects (34·5 ± 2·4 mmol/l vs 34·3 ± 1·7 mmol/l respectively). ACTH and cortisol rose in those subjects who experienced GI side‐effects (P < 0·0001 for each). The remaining subjects had a tendency for ACTH and cortisol to be higher on the placebo day. The group with GI side‐effects following ethanol administration had a significant rise in AVP (P < 0·02) that was synchronous with ACTH and cortisol. No consistent alcohol related changes were seen in peripheral CRH levels, although there was a significant increase over time on both active and placebo days (P < 0·0001). In the group with no GI side‐effects, AVP did not significantly fail in the first half hour following ethanol, while a significant fall did occur following placebo (P < 0·05). Plasma renin activity was, however, increased by ethanol (P < 0·05). The background alcohol intake of the group with GI side‐effects was significantly lower than the group without (18 ± 7 vs 235 ± 51 g/week, P < 0·05), but no hormonal response was seen in two subjects with a relatively low alcohol intake (< 100g/week) who did not experience GI side‐effects.CONCLUSION intoxicating levels of ethanol per se do not result in activation of the hypothalamic‐pituitary‐adrenal axis in humans. However, gastrointestinal side‐effects induced by the ethanol do result in such activation, which appears to be mediated by AVP as the dominant ACTH secretagogue. One of the factors which influences the blood ethanol level at which GI side‐effects occur appears to be background alcohol Intake.
Effect of glucocorticoid replacement therapy on glucose tolerance and intermediary metabolites in hypopituitary adults
Authors: Al‐Shoumer Kamal A. S. , Beshyah Salem A. , Niththyananthan Ratnam , Johnston Desmond G. 
Published: March 2008

SummaryBACKGROUND AND OBJECTIVES Excess Impaired glucose tolerance and diabetes mellitus have been reported in hypopituitary adults on conventional replacement therapy Including glucocorticoids. We investigated the effect of the glucocorticoid component on glucose tolerance and intermediary metabolites in hypopituitary adults.DESIGN A 3‐hour 75‐g oral glucose tolerance test (OGTT) was performed on two study days, at least one week apart. On one study day, the glucocorticoid replacement morning dose was taken 60 minutes before the OGTT, and on the other it was left until after the OGTT. All other pituitary replacement therapies were kept unchanged on the two study days.PATIENTS Eight hypopituitary adults (3 males and 5 females; aged 46–76 years) on conventional replacement therapy were studied. Their duration of hypopituitarism was mean (range) 15 (5–31) years. Their mean body mass index (BMI) was 28·4 (24·1–35·1) kg/m2. Their total daily cortisol dose was 26 (15–30) mg.MEASUREMENTS Plasma glucose, insulin, non‐esterified fatty acids (NEFA), glycerol and 3‐hydroxybutyrate were measured at 30‐minute intervals and plasma cortisol levels were measured hourly. RESULTS Fasting glucose and insulin concentrations were similar on the glucocorticoid day (GD) and the non‐glucocorticoid day (NGD) (glucose (mean ± SD) 4·9 ± 0·9 vs 4·4 ± 0·5 mmol/l, insulin (median (range) 5 (1‐17) vs 2 (1‐15) mU/l, respectively). Post‐glucose glycaemia was higher on the GD than on the NGD with a significantly higher glucose area under the curve (AUC) (45·0 ± 82 vs 38·9 ± 11·7 mmol/l h, P < 0·05). Post‐glucose insulinaemia was also higher on the GD than on the NGD with significantly higher insulin AUC (270 (47‐909) vs 207 (46‐687)mU/l h, P < 0·02). Impaired glucose tolerance was found in three patients on the GD, one of whom continued to have impaired glucose tolerance on the NGD. The areas under the curves of NEFA, glycerol and 3‐hydroxybutyrate were not significantly different on the two days. On the NGD, plasma cortisol levels were undetectable (<50nmol/l) in all patients and on the GD the median (range) peak was 500 (330–740) nmol/l dropping to 125 (60‐330) nmol/l at 180 minutes. The difference in glucose AUC between the two days correlated with the maximal plasma cortisol levels (Spearman's p= 0·83, P < 0·01).CONCLUSIONS Glucocorticoid replacement therapy taken pre‐prandially In hypopituitary adults induces mild elevations In circulating glucose and insulin levels even with acceptable plasma cortisol concentrations. Optimal regimens for glucocorticoid replacement require more study.
Effects of gonadal androgens and oestrogens on adrenal androgen levels
Authors: Polderman Kees H. , Gooren Louis J. G. , van der Veen Eduard A. 
Published: March 2008

SummaryOBJECTIVE The physiological role of adrenal androgens In humans remains unclear. Furthermore, there are few data on the relation between sex steroids and adrenal androgen production. We have assessed the effects of sex steroid hormone administration on adrenal androgen levels, by studying a large group of transsexual patients. DESIGN A non‐randomized intervention.SETTING A university teaching hospital.PATIENTS Thirty‐one male‐to‐female and 22 female‐to‐male transsexual patients.MEASUREMENTS Plasma levels of adrenal androgens were measured in a group of male‐to‐female and female‐to‐male transsexual patients both before and during cross‐gender hormone treatment. This treatment involves administration of testosterone esters to women and of ethlnyloestradiol and cyproterone acetate to men. RESULTS High dose sex steroid administration had marked effects on adrenal androgens levels, which decreased by 27–48% in males treated with ethinyloestradiol and increased by 23–70% in females treated with testosterone.CONCLUSION We conclude that administration of high doses of testosterone and oestradiol exert opposing effects on adrenal androgen production.
A comparison of the naloxone test with ovine CRH and insulin hypoglycaemia in the evaluation of the hypothalamic‐pituitary‐adrenal axis in normal man
Authors: Inder W. J. , Ellis M. J. , Evans M. J. , Donald R. A. 
Published: March 2008

SummaryOBJECTIVE It has been suggested that naloxone might be useful in clinical testing of the hypothaiamic‐pituitary‐adrenal (HPA) axis. We have therefore evaluated this non‐selective oploid receptor antagonist, as a test of HPA axis function, and compared the results to ovine cortlcotro‐phin‐releasing hormone (oCRH) and the Insulin tolerance test (ITT).DESIGN Following i.v. administration at the zero of naloxone 20mg (n= 12) on day 1, and either oCRH 1 μg/kg (n= 6) or soluble insulin 0.15 U/kg (n= 6) on day 2, venous blood was sampled at times ‐20, 0, 15, 30, 45,60,90 and 120 minutes for cortisol, ACTH and AVP. Peripheral CRH was also measured following naloxone and insulin hypoglycaemia.SUBJECTS Twelve normal males (age 20–57 years) with no history of hypothalamic‐pituitary‐adrenal axis disease.MEASUREMENTS Peptide hormones in plasma samples were measured by radioimmunoassay and cortisol by ELISA. Results are expressed as mean ± SEM.RESULTS Following naloxone, there was a highly significant overall rise in ACTH (P < 0.0005) and cortisol (P < 0.0001), but 1 out of the 12 subjects failed to respond. This subject had a normal ACTH and cortisol response to oCRH, indicating normal pituitary‐adrenal function. Peripheral levels of CRH also increased significantly following naloxone (P < 0.002), while AVP did not alter significantly (P= 0.38). Maximal levels of CRH were seen following the ACTH peak however, at a time when ACTH was returning to baseline.All six subjects who received oCRH had an increase in ACTH and cortisol, and the ACTH response to oCRH was greater than that to naloxone (P < 0–05). One subject who developed nausea and hypotension following oCRH had a large rise In AVP and very high levels of ACTH and cortisol.Following Insulin each subject had symptomatic hypoglycaemla and significant rises in cortisol (P < 0.0001), ACTH (P < 0.0001), AVP (P < 0.0005) and CRH (P < 0.01) were seen. Both cortisol and ACTH responses to ITT were significantly greater than those to naloxone (P < 0.05 for each).CONCLUSION The HPA axis response to naloxone Is smaller In magnitude overall compared to oCRH or insulin hypoglycaemia and Is variable in normal subjects. This variability probably reflects changes In central opiold tone rather than alterations in pituitary responsiveness to CRH. It Is unlikely that the naloxone test will replace currently used clinical tests of HPA axis function, particularly in the setting of possible ACTH deficiency, because some subjects with a normal HPA axis appear not to respond to naloxone. As the mechanism involved in the ACTH response to naloxone has not yet been defined with certainty, the naloxone test should not be regarded simply as a test of endogenous CRH release.
Dehydroepiandrosterone sulphate in critical illness: effect of dopamine
Authors: Van den Berghe Greet , de Zegher Francis , Wouters Pieter , Schetz Miet , Verwaest Charles , Ferdinande Patrick , Lauwers Peter 
Published: March 2008

SummaryOBJECTIVE As part of a study on the effect of dopamine therapy on pituitary dependent hormone secretion in critical illness, we documented the impact of this inotropic and vasoactive catecholamine on the serum concentrations of dehydroepiandrosterone sulphate (DHEAS). Concomitantly, serum levels of PRL and cortisol were determined.PATIENTS AND DESIGN In a prospective, randomized, controlled, open‐labelled clinical study, 20 critically ill, adult polytrauma patients receiving dopamine treatment (5 μg/kg/ml i.v. for a median 109 hours (range 21–296 hours), were studied to evaluate the effect of dopamine withdrawal on serum concentrations of DHEAS, PRL and cortisol. The median age of the studied patients was 37 years (range 18–83 years)MEASUREMENTS Serum DHEAS and cortisol concentrations were measured by RIA and PRL by IRMA. The assessed serum samples were obtained at 0300h on each of two consecutive study nights.RESULTS Withdrawal of dopamine infusion was found to elicit a median 25% Increase of serum DHEAS concentrations within 24 hours whereas no significant change in DHEAS levels was observed when dopamine infusion was continued throughout both study nights (P= 0.01 continued vs interrupted dopamine). Prolactin levels were undetectable as long as dopamine was infused, and increased to a median of 317 IU/I after 24 hours of dopamine withdrawal (P = 0.0007). Elevated serum cortisol levels remained comparable with continued and interrupted dopamine infusion.CONCLUSIONS Dopamine infusion appears to suppress serum DHEAS concentrations in critically ill patients without affecting their elevated serum cortisol levels, suggesting a differential regulation of DHEAS and cortisol metabolism in critical illness. The lowering effect of dopamine on DHEAS levels could be linked to the concomitant suppression of circulating PRL. The simultaneous suppression of circulating PRL and DHEAS by dopamine infusion may be an iatrogenic factor maintaining or aggravating the anergic state of prolonged severe illness.
High prevalence and little change in TSH receptor blocking antibody titres with thyroxine and antithyroid drug therapy in patients with non‐goitrous autoimmune thyroiditis
Authors: Cho Bo Youn , Kim Won Bae , Chung Jae Hoon , Yi Ka‐Hee , Shong Young Kee , Lee Hong Kyu , Koh Chang‐Soon 
Published: March 2008

SummaryOBJECTIVE We have reevaluated the prevalence and pathogenetic importance of TSH receptor blocking antibodies (TRBAb) in autoimmune hypothyroidism, and investigated the changes in TRBAb activities during thyroxine and antithyroid drug treatment.DESIGN Serum TSH binding inhibitor immunoglobulin (TBII) and thyroid stimulation blocking antibody (TSBAb) were measured serially in all patients with non‐goitrous autoimmune thyroiditis (AT) and measured monthly during methimazole treatment in 6 patients.PATIENTS Ninety patients with non‐goitrous AT and 95 patients with goitrous AT were entered consecutively into this study. All patients with non‐goitrous AT were treated with thyroxine and followed at intervals of 6 months for 2 years initially and then yearly intervals. The duration of follow‐up was 1–8 years. Six patients from the TRBAb‐positive non‐goitrous AT group who were treated with thyroxine were randomly selected and given additional treatments with methimazole (40 mg per day) for 6 months.MEASUREMENTS Serum TBII was measured by 8 radioreceptor assay, TSBAb by using FRTL‐5 cells, and antithyroid peroxidase and antithyroglobulin antibodies by radioimmunoassay.RESULTS The prevalences of TBII and TSBAb in non‐goitrous AT were 47–8 and 58.9%, respectively, which were significantly higher than those in goitrous AT (6.3% for TBII, 10.5% for TSBAb). All but one patient showed persistent TBII and TSBAb activities during the thyroxine treatment for up to 8 years. A high dose of methimazole (40 mg per day) did not affect the titres of TBII and TSBAb in 5 out of 6 patients with non‐goitrous AT tested. However, antithyroid peroxidase and antithyroglobulin antibodies activities were significantly decreased during the methimazole treatment.CONCLUSION The high prevalence of TSH receptor blocking antibodies (TRBAb) suggests that TRBAb may play a major role in the development of hypothyroidism and thyroid atrophy in the vast majority of patients with non‐goitrous autoimmune thyroiditis. Most TRBAb activities are stable for at least 8 years and are not affected by thyroxine and antithyroid drug treatment.
IGFBP‐3 is a poor parameter for assessment of clinical activity in acromegaly
Authors: de Herder W. W. , van der Lely A. J. , Janssen J. A. M. J. L. , Uitterlinden P. , Hofland L. J. , Lamberts S. W. J. 
Published: March 2008

SummaryOBJECTIVE Elevated serum IGF‐I and IGF binding protein‐3 (IGFBP‐3) levels have been found in patients with active acromegaly. We have studied the relative diagnostic merits of measurements of IGFBP‐3 compared with IGF‐I as a parameter of disease activity in these patients.DESIGNIPATIENTS Thirty untreated patients with acromegaly were compared with 30 healthy adults.MEASUREMENTS Twenty‐four‐hour sampling for serum GH in patients with acromegaly, serum IGF‐I and IGFBP‐3.RESULTS Mean IGF‐l levels were 220 nmol/l (range 6.5–38.4) in the healthy adults and 118.7 nmol/l (range 67.7–206.0) in patients with acromegaly. Mean IGFBP‐3 levels were 3.5 mg/l (range 2.1–4.8) in controls and 5.4 mg/l (range 4.2–6.6) in patients with acromegaly. Mean IGF‐I/IGFBP‐3 ratios were 6.5 nmol/mg (range 1.9–14.5) in the healthy adults and 220 nmol/mg (range 14.3–32.7) in patients with acromegaly. There was a considerable overlap for IGFBP‐3 levels but not for IGF‐I levels, between normals and acromegalics. The IGF‐I/IGFBP‐3 ratio also showed overlap between normals and acromegalics. There was a significant correlation between the mean 24‐hour GH and IGFBP‐3 levels (P= 0.036) and between the IGF‐I and IGFBP‐3 levels (P < 0.002) in acromegaly. In patients with acromegaly, the IGFBP‐3 levels showed a decrement, but the IGF‐I/IGFBP‐3 ratio did not change significantly with age. CONCLUSIONS IGFBP‐3 has no additional discriminatory value over IGF‐I measurements for the assessment of clinical activity in acromegaly. in acromegaly, IGFBP‐3 decreases with increasing age. in acromegaly, IGFBP‐3 levels significantly correlate with mean 24‐hour GH levels and IGF‐I levels.