bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of urinary testosterone and epitestosterone during pubertal development: a cross‐sectional study in 141 normal male subjects
Authors: Raynaud E. , Audran M. , Pagès J. Ch. , Fédou C. , Brun J. F. , Chanal J. L. , Orsetti A. 
Published: March 2008

SummaryOBJECTIVES Exogenous testosterone administration is classically detected by measuring the ratio of testosterone to epitestosterone in urine. Athletes are considered to be positive for drug abuse if the urinary testosterone to epitestosterone ratio is greater than 6. We aimed at investigating the urinary excretion of testosterone and epitestosterone during pubertal development.DESIGN We performed a cross‐sectional study of 141 normal male subjects between ages 8 and 26 years.PATIENTS We studied 141 subjects: 32 at stage 1 of Tanner, 27 at stage 2,30 at stage 3,25 at stage 4 and 27 at stage 5.MEASUREMENTS Subjects performed a 24‐hour urine collection. Urinary testosterone and epitestosterone were measured by gas chromatography‐mass spectrometry with selected ion monitoring.RESULTS Urinary testosterone was 20.5 ± 1.7 nmol/24h (mean ± SEM) at stage 1, 49±2.9 at stage 2, 98.8 ± 3.4 at stage 3,371.8 ± 21.8 at stage 4 and 403.4 ± 16.1 nmol/24h at stage 5. Urinary epitestosterone was 13.1 ± 1.5 nmol/24h at stage 1, 291 ± 3.3 at stage 2, 48.3 ± 3.7 at stage 3, 156.3 ± 14.8 at stage 4 and 221.1 ± 18.6 nmol/24h at stage 5. The urinary excretions of both steroids increased significantly during puberty and were highly correlated with chronological age (P<0.001). Comparison of the correlation slopes (P<0.001) showed that the urinary profiles of testosterone and epitestosterone are not parallel during pubertal development.Two subjects presented a testosterone to epitestosterone ratio above 6, corresponding to a low urinary concentration of epitestosterone, without pathological explanation.CONCLUSION Testosterone and epitestosterone do not present the same urinary profiles throughout puberty. Marked increases of the testosterone to epitestosterone ratio can be observed at this period and may interfere with doping tests.
Malignant prolactinoma with extracranial metastases: a report of three cases
Authors: Walker J. D. , Grossman A. , Anderson J. V. , Ur E. , Trainer P. J. , Benn J. , Lowy C. , Sönksen P. H. , Plowman P. N. , Lowe D. G. , Doniach I. , Wass J. A. H. , Besser G. M. 
Published: March 2008

SummaryOBJECTIVE Prolactin‐secreting tumours of the pituitary almost never metastasize extracranially. However, we have recently seen three such patients, whose presentation, clinical course and response to treatment are reviewed in order to determine whether they possess unique clinical features, and to assess optimum therapy.DESIGN AND PATIENTS Three patients with extracranial metastases from prolactinomas have been retrospectively reviewed.MEASUREMENTS Clinical courses, biochemical parameters and imaging modalities (CT, MR and radiolabeled somatostatin analogue scanning) and histopathology were assessed before and during different therapeutic regimens.RESULTS All three patients’presentations were initially unremarkable, but later each had persistent and relentlessly increasing serum prolactin concentrations and evidence of distant spread of their tumours. The first patient presented aged 32 and was treated with repeated transsphenoidal resections of the tumour, pituitary radiotherapy, high dose bromocriptine therapy, the somatostatin analogue octreotide and chemotherapy. Nine years after the original diagnosis a liver biopsy revealed carcinoma cells positively immunostaining for prolactin. At autopsy further microscopically similar metastases were seen in both lungs and the left hilar lymph nodes. The second patient presented aged 48 and was treated with external beam pituitary radiotherapy, bromocriptine, transsphenoidal hypophysectomy and chemotherapy. Fifteen years after the original diagnosis bone biopsy revealed carcinoma cells positively immunostaining for prolactin; the patient developed interstitial nephritis and died in renal failure. The third patient presented aged 48 with hypogonadism and bitemporal hemianopia due to a macroadenoma. This was removed transfrontally and followed by external beam radiotherapy. After recurrence, further surgery and radiotherapy were undertaken, but the tumour continued to grow and the patient died suddenly of a pulmonary embolus. At autopsy, tumour was found in thoracic lymph nodes and lung capillaries.CONCLUSIONS These three patients may be added to the previous two reported cases of malignant prolactinoma with extracranial spread. Several different therapies were tried but were of limited value in controlling the progression of the disease, although chemotherapy is an important modality to be considered. No particular factor or combination of factors at presentation differentiated these patients from more typical patients whose disease is much less aggressive.
Effect of growth hormone administration frequency on 24‐hour growth hormone profiles and levels of other growth related parameters in girls with Turner's syndrome*
Authors: van Teunenbroek A. , de Muinck Keizer‐Schrama S. M. P. F. , Stijnen T. , Mouton J. W. , Blum W. F. , Mercado M. , Baumannl G. , Drop S. L. S. ,   the Dutch Working Group on Growth Hormone
Published: March 2008

SummaryOBJECTIVE The optimal dose and frequency of GH administration in Turner's syndrome is unknown. There is some evidence that a schedule which mimics normal pulsatile GH secretion may be more effective than a single dally dose. We therefore wished to study the influence of the frequency of GH administration on 24‐hour GH profiles and levels of other growth‐related factors in Turner's syndrome.DESIGN Four weeks after initiation of 005 μg/kg/day ethinyl oestradiol, we compared twice daily (b.I.d.‐fractionated dose) with once daily (o.d.) s.c. injections of 6 IU GH/m2/day in a 2‐week cross‐over design with a 2‐week washout Interval. Each treatment period was concluded with 24‐hour GH profile tests. Pretreatment plasma/serum levels of GH, IGF‐I, binding proteins for GH (GHBP) and IGF‐I (IGFBP‐3) were used as a basis for comparison of the levels found after each regimen. A one‐compartment open model was used for estimation of pharmacokinetic parameters.SUBJECTS Ten previously untreated girls with Turner's syndrome aged 11 years.MEASUREMENTS Plasma levels of GHBP by standardized binding assay; GH, IGF‐I, and IGFBP‐3 serum/plasma levels by radioimmunoassay.RESULTS There were significantly higher maximum GH levels and a greater area under the curve with o.d. than with b.I.d. GH, while GH clearance was greater with b.I.d. The pharmacokinetic values with o.d. injections were in conformity with values for healthy and GH‐deficient children. Pretreatment GHBP levels tended to be high compared with values in healthy prepubertal children. These levels decreased with GH therapy, significantly so with b.I.d. GH only. There was a significant increase in levels of IGF‐I and IGFBP‐3, irrespective of regimen. The IGF‐I to IGFBP‐3 ratio, a possible indicator of the growth response, rose significantly and comparably with both regimens. There was no consistent diurnal variation with either regimen in GHBP, IGF‐I or IGFBP‐3 levels. Four‐hourly levels of GH, GHBP, IGF‐I and IGFBP‐3 were not correlated.CONCLUSIONS Although the 24‐hour profiles differed during once or twice daily administration of the same total growth hormone dose, the diurnal pattern and mean levels of factors involved in the biological effects of GH are comparable for both regimens.
Interindividual differences in the pituitary‐thyroid axis influence the interpretation of thyroid function tests
Authors: Meier C. A. , Maisey M. N. , Lowry A. , Müller J. , Smith M. A. 
Published: March 2008

SummaryOBJECTIVE We investigated interindividual differences in the shape, slope and setpoint of the pituitary‐thyroid axis (PTA) in normal persons. Based on these physiological data we propose a novel bivariate concept for the interpretation of thyroid function tests which is less biased by interindividual differences in the PTA than the currently used univariate approach.DESIGN In two separate trials (A and B), healthy volunteers were given small, increasing doses of T3 (7 5.45 μg/day orally) over 5 days. The regulation characteristics of the individual PTAs and the effects of age and gender were assessed by general linear regression models. In addition, serum samples were collected from normal persons to establish the proposed bivariate approach for the interpretation of thyroid function tests.SUBJECTS The regulatory characteristics of the PTA were determined in a total of 21 normal volunteers (eight females, 13 males; age 24‐49 years). Single blood samples were collected from 257 normal volunteers. The participants had no history of pituitary or thyroid disease.MEASUREMENTS Free and total thyroid hormone and TSH concentrations were determined in the serum. All samples from one person were analysed in the same assay in duplicate.RESULTS A log‐linear relationship between T3 and TSH was found to describe best the individual PTA (multiple r= 0.96). However, significant differences in the setpoint (P < 0.001) and to a lesser degree in the slope (P± 0.05) of the PTA were detected; this variability was not dependent on age or gender. Since these findings invalidate the assumptions on which the current univariate interpretation of thyroid function tests is based, we propose a novel model for the evaluation of thyroid function tests derived from the experimentally determined shape and average slope of the PTA.CONCLUSIONS The presence of significant age and gender‐independent interindividual variations in the set‐point of the pituitary‐thyroid axis raises conceptual problems with the current approach for interpreting thyroid function tests. An easy to use graphical bivariate representation of the normal ranges for thyroid function tests is presented and exemplified by the thyroid hormone and TSH measurements in a large reference population. This concept should improve the diagnostic accuracy in the borderline‐normal, and particularly subclinical hypothyroid region of these hormone measurements.
Ovarian electrocauterization causes LH‐regulated but not insulin‐regulated endocrine changes
Authors: Tiitinen Aila , Tenhunen Anssi , Seppälä Markku 
Published: March 2008

SummaryOBJECTIVE We studied the effects of ovarian electrocauterization on the serum levels of luteinizing hormone (LH), testosterone, insulin, sex hormone‐binding globulin (SHBG) and insulin‐like growth factor binding globulin‐1 (IGFBP‐1) in women with polycystic ovarian disease (PCOD).DESIGN Prospective.PATIENTS Ten women with PCOD admitted to a University Infertility Clinic.MEASUREMENTS Fasting blood samples for determination of hormone levels were taken during the follicular phase before and one month after laparoscopic ovarian electrocauterization.RESULTS One month after electrocauterization the serum mean ± SE LH levels had decreased from 14 4 ± 1 9 to 10 9 ± 1 1 U/l (P<0 05), while the serum insulin levels showed no significant change (10 3 ± 2 0 and 8 1 ±1 3 μ/l). The levels of IGFBP‐1 (33 9 ± 8 2 and 38 4 ± 13 7 μg/l) and SHBG (48 ± 10 4 and 43 ± 5 7 nmol/l) showed no significant changes. Testosterone decreased from 3 9 ± 2 6 to 2 9 ± 0 3 nmol/l (P<0 001) and androstenedione from 15 0 ± 1 2 to 12 0 ± 1 5 nmol/l (P= 0 05). After electrocautery seven out of ten PCOD patients ovulated either spontaneously (n= 3) or with clomiphene citrate (n= 4), and two of them conceived.CONCLUSIONS Ovarian electrocautery leads to resumption of ovulatory cycles in some but not all PCOD patients. This effect seems to be mediated by reduction of serum LH and androgen levels, while the insulin‐driven pathway via SHBG and IGFBP‐1 remains unaffected.
The relationship between cortisol production rate and serial serum Cortisol estimation in patients on medical therapy for Cushing's syndrome
Authors: Trainer P. J. , Eastment C. , Grossman A. B. , Wheeler M. J. , Perry L. , Besser G. M. 
Published: March 2008

SummaryOBJECTIVE The aim was to determine the target range into which mean daily serum Cortisol should be lowered in patients on medical therapy for Cushing's syndrome, using isotopically estimated Cortisol production rates as'gold standard.DESIGN Patients with Cushing's syndrome on medical treatment were given 12 ng of tritiated Cortisol intravenously and a 24‐hour urine collection was made in a single day. On the same day, serum Cortisol was measured at 0900,1200,1500,1800, 2100, and at 2400 h in in‐patients. In addition, serum Cortisol was measured at the same times as above in a group of healthy volunteers.SUBJECTS Twenty‐two patients on medical therapy for Cushing's syndrome were studied on a total of 29 occasions. In addition, serum Cortisol profiles were obtained in 12 healthy volunteers.RESULTS The median serum Cortisol in patients with Cushing's syndrome was 400 (range 66–839) nmol/l, and in the healthy volunteers 178 (range 137–299) nmol/l. The median isotopic Cortisol production rate in the patients with Cushing's syndrome was 84 μmol/24 h, range 10–343 (normal range 22–83) μmol/24 h. In the patients with Cushing's syndrome, the correlation of mean serum Cortisol to Cortisol production rate was +0.77 (P<0.001). Normal rates were found when mean serum Cortisol levels were between 150 and 300 nmol/l.CONCLUSIONS The aim of drug therapy for Cushing's syndrome should be to lower the mean serum Cortisol through the day into the range 150–300 nmol/l.
Response of plasma low density lipoprotein subfractions to oestrogen replacement therapy following surgical menopause
Authors: Griffin Bruce , Farish Elizabeth , Walsh David , Barnes Judith , Caslake Muriel , Shepherd James , Hart David 
Published: March 2008

SummaryOBJECTIVE Epidemiological studies suggest that postmenopausal oestrogen replacement reduces the incidence of cardiovascular disease. The purpose of this study was to establish the effects of oestrogen replacement therapy on subfractions of plasma low density lipoprotein in bilaterally oophorectomized women.DESIGN In a placebo controlled, double‐blind study, patients were randomized on a two to one basis to receive either oestradiol valerate (2 mg/day) or placebo respectively for a period of 16 weeks.PATIENTS Seventeen women aged 28–51 years who had all had hysterectomy and bilateral oophorectomy at least 2 months before recruitment were assigned to either the active (n= 12) or placebo (n= 5) group.MEASUREMENTS Plasma lipids, lipoproteins, apolipoproteins and LDL subfractions were determined immediately before and after the treatment period. LDL subfractions were isolated directly from plasma by density gradient ultracentrifugation within 24 hours. Non‐parametric statistical analysis was carried out within each group using Wilcoxon's signed rank test for matched pairs.RESULTS After 16 weeks of treatment, HDL cholesterol, apo A‐1 and HDL‐2 were increased in the group receiving oestrogen (HDL cholesterol +12%, P < 0.01; apo A‐I + 14%, P < 0.01; HDL‐2 + 24%P < 0.01). While there were no significant changes in serum cholesterol, LDL cholesterol or triglycerides, the proportion and concentration of the least dense LDL‐I subtraction was decreased significantly (‐27%, P < 0.05). The LDL subtraction of intermediate density (LDL‐II) was decreased in eight subjects, while small, dense LDL‐III was unaffected. Overall, these changes resulted in an apparent shift in the distribution of LDL subfractions towards small, dense LDL‐III, although there was no net increase in the latter.CONCLUSION In view of a similar and characteristic response of LDL subfractions to hypolipidaemic drugs that enhance the clearance of LDL via the LDL receptor, the present findings suggest that oestrogen promotes the preferential removal of LDL‐I and II by activating LDL receptors. As this effect is normally associated with a reduction in the circulating level of LDL, it should not be regarded as an unfavourable response to oestrogen replacement therapy.
Insulin‐like growth factor‐l blood levels in severely burned patients: effects of time post injury, age of patient and severity of burn
Authors: Abribat Thierry , Brazeau Paul , Davignon Isabelle , Garrel Dominique R. 
Published: March 2008

SummaryOBJECTIVES Insulin‐like growth factor‐l (IGF‐I) is a polypeptide growth factor that stimulates protein synthesis. The aims of this study were to determine (1) the effect of a severe burn on blood IGF‐I levels and (2) the variables controlling IGF‐I level variations during recovery of these hypermetabolic patients.PATIENTS Eleven patients, nine men and two women (age range 22–55 years) were studied for 25 days following a severe burn (18–75% of total body surface area, mean 36%). Nitrogen balances were recorded daily and total IGF‐I levels were measured every 3 days.MEASUREMENTS IGF‐I was extracted from serum using a validated formic acid‐acetone methodology, then measured by a double antibody radioimmunoassay. IGF‐I levels were compared to those of a reference healthy population.RESULTS Within 24 hours following injury, IGF‐I levels were low in all patients when compared to normal values for the same age range (mean ± SEM of all patients, 131 ± 26 μ g/I) They remained low for the first week (days 4 and 7, 109 ±16 μg/I), then increased to reach normal values at the end of the study period (days 10–16,144 ± 19 μg/l, P= 0 005 when compared to days 4–7; days 19–25, 206 ±30 μg/l, P= 0 008 when compared to days 10–16). IGF‐I levels were negatively correlated with age in the second phase of recovery only (days 10–16, r= ‐0–70, P<005; days 19–25, r= ‐0 75, P<0 01) and with severity of burn between days 19 and 25 (r= ‐0 62, P<0 05). The presence of bronchial burn injury tended to lower IGF‐I blood concentration (P= 0 08). Whereas IGF‐I concentrations increased in the later phase of recovery, nitrogen balances did not. As a result, there was no significant correlation between these parameters.CONCLUSIONS IGF‐I levels followed a biphasic pattern in severely burned patients. They dropped dramatically in response to the traumatic shock, then increased during recovery. The degree of increase was dependent on the age of the patient and on the severity of the burn, but was not associated with an improvement in the nitrogen balance.
Reversibility of thyroid dysfunction induced by recombinant alpha interferon in chronic hepatitis C
Authors: Baudin Eric , Marcellin Patrick , Pouteau Michèle , Colas‐Linhart Nicole , Le Floch Jean‐Pierre , Lemmonier Catherine , Benhamou Jean‐Pierre , Bok Bernard 
Published: March 2008

SummaryOBJECTIVE Thyroid dysfunction has been reported as a complication of interferon therapy. The aim of our study was to assess the risk factors and reversibility of thyroid disorders induced by interferon therapy.DESIGN Prospective study.PATIENTS A series of 68 patients with chronic hepatitis C completed a therapeutic trial of interferon alpha 2b (IFN), randomized for dose adaptation, lasting for 24 weeks.MEASUREMENTS TSH and autoantibodies against thyroid were looked for at (‐ 2) weeks and 24 weeks in all patients. Blood samples obtained at (‐2), 12, and 24 weeks were stored for additional hormonal studies in patients who developed thyroid dysfunction. Such patients with thyroid dysfunction were followed up for at least one year.RESULTS Only one out of 68 patients had abnormal TSH levels, and two had thyroid autoantibodies prior to interferon therapy. Eight patients (12%) developed thyroid dysfunction (five hypothyroidism and three hyperthyroidism) during treatment. In four patients (all of them with thyroid dysfunction, P< 0‐001) antimicrosomal, antithyro‐globulin, and/or anti‐TSH receptor antibodies appeared during interferon therapy. All patients recovered normal thyroid function within 15 years after interferon withdrawal.No pretreatment risk factor was identified. The patients with thyroid dysfunction did not significantly differ from the others as regards the dose of interferon they received or the rate of normalization of transaminases.CONCLUSION (i) A 12% incidence of thyroid dysfunction was observed under interferon therapy: (ii) secondary appearance under interferon therapy of elevated thyroid autoantibodies was a risk factor; (iii) the thyroid disorders induced by interferon were reversible.
Short and long‐term cardiovascular effects of growth hormone therapy in growth hormone deficient adults
Authors: Thuesen Leif , Jergensen Jens O. L. , Müller Jern R. , Kristensen Bent Ø. , Skakkebk Nieis E. , Vahi Nina , Christiansen Jens S. 
Published: March 2008

SummaryOBJECTIVE Since GH substitution therapy is now available for adult GH deficient patients, information on the cardiovascular effects of GH substitution has assumed major clinical interest. We have therefore assessed cardiovascular effects of short and long‐term growth hormone substitution therapy in these patients.PATIENTS AND MEASUREMENTS Doppler echocardiography was performed in 21 GH deficient patients after 4 months placebo and 4 months GH therapy, in a double blind cross‐over study. In an open design study, 13 patients were reinvestigated following 16 months and 9 patients following 38 months of GH therapy. Twenty‐one age and sex‐matched normal control subjects were also investigated.RESULTS Heart rate was increased in placebo treated patients as compared to controls. After 4 months of GH treatment, heart rate showed a further Increase (10%, P<0·01) and seemed to remain elevated after 16 months of OH therapy. Systolic and diastolic blood pressures were significantly lower in placebo treated patients than in controls, and did not change significantly after OH treatment. The left ventricular diastolic diameter was reduced in patients as compared to controls, but increased after 4 months GH therapy (P>0·05) and seemed to increase further during prolonged GH treatment. Cardiac index was at the same level in controls and in placebo‐treated patients, but increased by 20% following OH therapy and remained elevated after 16 and 38 months (P < 0·05) of GH substitution.CONCLUSION Following GH substitution in GH deficient adult patients, left ventricular diastolic dimensions increased and seemed to normalize, while heart rate and cardiac output were found to be increased to supra‐normal levels.