bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in gonadotrophin response to gonadotrophin releasing hormone in normal women following bilateral ovariectomy
Authors: Alexandris E. , Milingos S. , Kollios G. , Seferiadis K. , Lolis D. , Messinis I. E.
Published: November 2003

OBJECTIVE

Pituitary responsiveness to GnRH varies throughout the normal menstrual cycle. We have investigated whether there are differences in the ovarian mechanisms which regulate gonadotrophin secretion between the follicular and the luteal phase of the cycle.

DESIGN

Normally ovulating women were studied during the first week following hysterectomy plus bilateral ovariectomy performed either in the mid‐ to late follicular phase (follicle size 16 mm) or in the early to midluteal phase (5 days post LH peak). The response of LH to a single dose of 10 μg GnRH was investigated 2 hours before the operation and every 12 hours after the operation until postoperative day 4 and every 24 hours until day 8.

PATIENTS

Fourteen normally cycling premenopausal women with normal FSH (<10 IU/l). Seven women were ovariectomized in the follicular and 7 in the luteal phase.

MEASUREMENTS

Pituitary response to GnRH was calculated as the net increase in FSH (▵FSH) and LH (▵LH) at 30 minutes above the basal value.

RESULTS

Basal levels of FSH and LH before the operation were significantly lower in the luteal than the follicular phase (P  <  0.05), while those of oestradiol (E2) were similar. Also, similar were ▵LH and ▵FSH values. Serum progesterone and immunoreactive inhibin (Ir‐inhibin) concentrations before the operation were higher in the luteal than the follicular phase (P  <  0.05). Following the operation, serum E2, progesterone and Ir‐inhibin values declined dramatically, while basal FSH and LH as well as ▵FSH values showed a gradual and significant increase. The percentage increase in FSH and LH values (mean  ±  SEM) on day 8 after the operation was similar in the follicular (453  ±  99% and 118  ±  35% respectively) and the luteal phase (480  ±  71% and 192  ±  45% respectively). In contrast to ▵FSH, ▵LH values after a temporal increase 12 hours from the operation, remained stable in the follicular phase and declined significantly in the luteal phase up to day 4.

CONCLUSIONS

Basal gonadotrophin secretion during the normal menstrual cycle is predominantly under a negative ovarian effect. It is suggested that in contrast to FSH, the secretion of LH in response to GnRH is controlled by different ovarian mechanisms during the two phases of the menstrual cycle.
Spontaneous recovery of chemotherapy‐induced primary ovarian failure: implications for management
Authors: Nasir Joohi , Walton Christopher , Lindow Stephen W. , Masson Ewan A.
Published: November 2003

A 14‐year‐old female patient presented with a swelling, which was excised, over the left forearm. Histology revealed a poorly differentiated rhabdomyosarcoma and she was treated with multiple chemotherapy for 2 years, including cyclophosphamide, cisplatin and vincristine. She developed secondary amenorrhoea shortly after commencing treatment which persisted on its completion. Biochemical investigations were consistent with ovarian failure, which was assumed to be chemotherapy‐induced and permanent. She was given hormone replacement with a conjugated equine oestrogen/norgestrel combination, resulting in regular withdrawal bleeding. At 22 years of age, she presented with amenorrhoea for 3 months. Investigations revealed FSH 2.7 IU/l, LH >50 IU/l and oestradiol >1320 pmol/l. A pregnancy test was positive and subsequent ultrasound scanning confirmed the presence of a foetus of 18 weeks gestation. The patient initially considered a termination as she had been unprepared for this event but later elected to continue the pregnancy which proceeded uneventfully and resulted in the birth of a normal infant. Ovarian function should be reassessed periodically in patients with chemotherapy‐induced gonadal damage and/or the oral contraceptive pill should be used as hormone replacement unless fertility is desired.
Glucocorticoid replacement therapy: are patients over treated and does it matter?
Authors: Peacey Steven R. , Guo Chun‐Yuan , Robinson Anthony M. , Price Alun , Giles Martin A. , Eastell Richard , Weetman Anthony P.
Published: November 2003

BACKGROUND AND OBJECTIVES Adequate assessment of patients on glucocorticoid replacement therapy is of great importance to avoid the consequences of under or over treatment, but no simple test is available for this. The aims of this study were (1) to assess adequacy of glucocorticoid replacement in hypoadrenal patients, (2) to correlate serum cortisol levels (cortisol day curve) with 24‐hour urine free cortisol excretion and (3) to assess the impact of glucocorticoid dose optimization on markers of bone formation and bone resorption.

DESIGN Cross‐sectional study of current replacement therapy and a prospective study of the effect of dose alteration on bone turnover markers.

PATIENTS Thirty‐two consecutive patients on replacement glucocorticoid therapy (12 Addison’s disease, 20 hypopituitarism) from a University teaching hospital out‐patient department.

MEASUREMENTS Serum and urinary cortisol, osteocalcin, N‐telopeptide of type I collagen (NTX) and bone mineral density.

RESULTS 28/32 (88%) patients required a change of therapy; 24/32 (75%) a total reduction in dose, 18/32 (56%) a change in replacement therapy regimen or drug and 14/32 (44%) both changes. The mean daily dose of hydrocortisone was reduced from 29.5 ± 1.2 to 20.8 ± 1.0 mg. A significant correlation was found between peak cortisol and 24‐hour urine free cortisol/creatinine (Spearman correlation r = 0.60, P < 0.0001; n = 51). Following hydrocortisone dose reduction, median osteocalcin increased from 16.7 μg/l (range 8.2–65.7) to 19.9 μg/l (8.2–56.3); P < 0.01, with no change in the NTX/creatinine ratio.

CONCLUSIONS A high proportion of patients on conventional corticosteroid replacement therapy are over treated or on inappropriate replacement regimens. To reduce the long term risk of osteoporosis, corticosteroid replacement therapy should be individually assessed and over replacement avoided.
Mutations of the 5α‐reductase Type 2 gene in eight Mexican patients from six different pedigrees with 5α‐reductase‐2 deficiency
Authors: Canto Patricia , Vilchis Felipe , Chávez Bertha , Mutchinick Osvaldo , Imperato‐McGinley Julianne , Pérez‐Palacios Gregorio , Ulloa‐Aguirre Alfredo , Pablo Méndez Juan
Published: November 2003

BACKGROUND AND OBJECTIVE Male pseudohermaphroditism due to 5α‐reductase deficiency was originally described in 1974. Recently, 5α‐reductase Type 2 gene defects have been found generally to be due to point mutations within the 5 exons of the 5α‐reductase‐2 gene. In this report, we describe the molecular study of patients with 5α‐reductase deficiency.

DESIGN Previously diagnosed patients with 5α‐reductase deficiency were sampled in order to perform molecular studies.

PATIENTS Eight 5α‐reductase deficient individuals from 6 unrelated families.

MEASUREMENTS Single‐strand conformational polymorphism and DNA sequencing were performed after polymerase chain reaction amplification of each of the 5 exons of the gene.

RESULTS Five different missense mutations were found. In 4 patients a cytosine to guanine substitution was observed at codon 212 in exon 4. Two siblings presented a cytosine to adenine substitution at codon 207 in exon 4. Another patient exhibited a guanine to adenine substitution at codon 34 in exon 1, whilst one individual presented 2 mutations: a guanine to adenine substitution at codon 115 in exon 2 and a guanine to adenine substitution at codon 203 in exon 4 (previously undescribed mutation).

CONCLUSIONS The presence of the same mutation in 4 patients from 3 families indicates the increased prevalence of this mutation in a particular ethnic group, suggesting a common ancestry for the gene defect in these patients. The existence of hot spots is supported by the mutations in codons 34 and 207 which have also been found in other ethnic groups. Interestingly, the patient who presented 2 different mutations, one of them previously undescribed, was reared as a male and exhibited a more masculine phenotype. Further studies in patients with this and other mutations will be needed to verify genotype–phenotype correlation.
Differential effect of finasteride on the tissue androgen concentrations in benign prostatic hyperplasia
Authors: Habib Fouad K. , Ross Margaret , Tate Rothwell , Chisholm Geoffrey D.
Published: November 2003

OBJECTIVE The 5α‐reductase inhibitor, finasteride, provides a logical medical treatment for benign prostatic hyperplasia (BPH). However, the effects of chronic finasteride treatment on prostatic androgen levels, 5α‐reductase activity and tissue prostatic specific antigen (PSA) have not been studied. We have examined prostate tissue androgen concentrations and 5α‐reductase activity of the gland in men with BPH treated with the drug for 3 months.

DESIGN AND PATIENTS Twenty‐eight patients with clinically diagnosed BPH, awaiting transurethral resection of the prostate, were entered in a double‐blind placebo controlled study. Nineteen patients were randomly allocated to treatment with finasteride (5 mg daily) and 9 received placebo for 3 months.

MEASUREMENTS Prostate specimens were collected immediately following surgery and analysed for testosterone, dihydrotestosterone (DHT), androstenedione, 5α‐reductase activity and PSA. Blood specimens obtained before the start and immediately following treatment were also tested for steroid hormone concentrations and PSA levels.

RESULTS There was no significant difference in the median levels of intraprostatic testosterone (P = 0.77), DHT(P= 0.46) and androstenedione (P = 0.09) between the finasteride and placebo groups. However, the 5α‐reductase activity of the placebo group (237.9 pmol DHT/g tissue/30 min) was approximately 10 times that of the finasteride group (21.5 pmol DHT/g tissue/30 min; P = 0.0008). Although we were unable to detect any differences in the PSA concentrations of the prostate glands, there was a significant difference (P = 0.0002) in the median percentage change of serum PSA concentrations for the two patient groups. Serum DHT levels were also depleted (P = 0.038) whilst serum testosterone was increased (P = 0.054) in the finasteride patients when compared to the placebo group. Furthermore our study demonstrated no correlation between the in vitro 5α‐reductase activity of the gland and tissue DHT concentrations.

CONCLUSIONS Whilst finasteride treatment induced a reduction in serum dihydrotestosterone and prostatic specific antigen levels with a concomittant increase in blood testosterone concentrations, the impact of the drug on tissue androgen concentrations varied considerably from one patient to another. The differential effect of the drug on tissue androgen concentrations suggests that in the human prostate there are possibly more than one isoform of 5α‐reductase responsible for the accumulation of DHT in the gland.
Acromegaly or chronic renal failure: a diagnostic dilemma
Authors: Wong Newton A.C.S. , Ahlquist James A.O. , Camacho‐Hübner Cecilia , Goodwin Christian J. , Dattani Mehul , Marshall Nicholas J. , Wass John A.H.
Published: November 2003

Uraemic patients may have markedly elevated serum GH concentrations yet, for hitherto unknown reasons, they do not develop acromegaly. We discuss the diagnostic dilemma presented by a 33‐year‐old Caucasian male with chronic renal failure (creatinine clearance 10 ml/min) secondary to polycystic kidney disease, elevated GH concentrations (fasting concentration of 22.6 rising to 77.9 mU/l 30 minutes after a 75‐g oral glucose load) as well as acromegalic features. Review of the patient's relatives and the findings of a normal serum IGF‐I concentration and a normal pituitary fossa on magnetic resonance imaging, suggest that the patient's acromegalic appearance is a familial trait and his abnormal GH dynamics a result of his renal failure rather than acromegaly. The patient's normal GH bioactivity and reduced GH binding protein concentration supports the current belief that chronic renal failure leads to an increase in peripheral tissue resistance to GH due to decreased GH receptor numbers. These changes, together with reduced IGF‐I bioactivity, may explain why patients with chronic renal failure do not develop acromegaly in the presence of abnormally elevated levels of GH.
Effect of insulin on serum levels of dehydroepiandrosterone metabolites in men
Authors: Lavallée Bernard , Provost Pierre R. , Kahwash Ziad , Nestler John E. , Bélanger Alain
Published: November 2003

OBJECTIVE Insulin was found to decrease the concentration of serum dehydroepiandrosterone (DHEA) and DHEA‐sulphate (DHEAS) and recent data suggest that an increase in the metabolic clearance rate of DHEA (MCRDHEA) may be involved. In this study, we have investigated the effects of insulin on DHEA metabolism in men.

PATIENTS A total of 10 men were enrolled into the study, and all subjects completed the study. Subjects were healthy, non‐obese, and 20–30 years old.

DESIGN DHEA was administered intravenously to subjects, alone or in combination with insulin. A hyperinsulinaemic‐euglycaemic clamp was initiated for subjects with the insulin infusion and euglycaemia was maintained by checking blood glucose and adjusting the rate of a 25% dextrose infusion as needed. Serum was collected before DHEA infusion, during DHEA infusion after attaining steady state (3.5–4h), and during DHEA plus insulin infusion (6–6.5h) (steady state) and then assayed for DHEA, DHEA metabolites, and DHEA acylation by LCAT.

RESULTS Results showed rapid transformation of DHEA into androst‐5‐ene‐3β,17β‐diol, DHEA fatty‐acid esters (DHEA‐FA), androstenedione and 5α‐androstan‐3α‐ol‐17‐one glucuronide (androsterone glucuronide) whereas DHEAS, testosterone, androstane‐3α,17β‐diol glucuronide and oestradiol serum levels were not affected. When insulin was simultaneously infused once steady‐state DHEA levels had been attained, we observed a decline only in DHEA, DHEA‐FA and DHEAS levels, with no effect on other steroids examined. Although serum DHEA esterification was not affected by DHEA, a stimulation by insulin was observed.

CONCLUSIONS These results suggest that insulin increases the DHEA metabolic clearance rate by stimulating its conversion to DHEA‐FA and by enhancing uptake of DHEA‐FA by peripheral tissues.
The development of transient hypothyroidism after iodine‐131 treatment in hyperthyroid patients with Graves' disease: prevalence, mechanism and prognosis
Authors: Aizawa Yoshihiko , Yoshida Katsumi , Kaise Nobuko , Fukazawa Hiroshi , Kiso Yoshinori , Sayama Noriyo , Hori Hironobu , Abe Keishi
Published: November 2003

OBJECTIVE Recovery of thyroid function in patients following hypothyroidism induced by 131I therapy for Graves' disease has been described, but only a few detailed clinical and biochemical studies of this phenomenon (transient hypothyroidism) have been published. The prevalence, mechanism, and final outcome of transient hypothyroidism in 260 patients with Graves’ disease treated with 131I was studied.

DESIGN A retrospective study.

PATIENTS Two hundred sixty patients with Graves' disease, treated with 131I between 1 and 15 years previously, were categorized into 4 groups according to their thyroid function during and 1 year after therapy (Group 1: permanent hypothyroidism, 28 patients; Group 2: transient hypothyroidism, 39 patients; Group 3: euthyroidism without transient hypothyroidism, 83 patients; Group 4: hyperthyroidism, 110 patients).

MEASUREMENTS We compared total T4, total T3, TSH, anti‐thyroglobulin (TGHA) and anti‐microsomal (MCHA) antibodies, the TSH‐binding inhibitory immunoglobulin (TBII) index, thyroid weight, dose of 131I, and 24‐hour 131I uptake as pretreatment variables. The mean time for permanent hypothyroidism to develop was estimated by the Kaplan–Meier product limit method. The TBII index and thyroid stimulating antibody (TSAb) activity were measured in seven patients from Group 1 and in nine patients from Group 2 at the time that they became hypothyroid.

RESULTS Hypothyroidism developing within 12 months of therapy was transient in 58% (39/67) of patients. No pretreatment variables were found to differ between patients with and without transient hypothyroidism. The mean estimated time between therapy and the development of permanent hypothyroidism was 96 months in Group 2; this time interval was significantly shorter than 126 months in Group 3 and 129 months in Group 4 (P<0.05, P<0.01, respectively). TSAb activity was > 500% in 78% (7/9) of patients from Group 2, which was significantly higher than that found (14%, 1/7) in Group 1.

CONCLUSIONS These results indicate that (1) more than half the patients who developed hypothyroidism within 6 months after 131I treatment for Graves' disease recovered spontaneously, (2) TSAb activity might play some role in the recovery of transient hypothyroidism, and (3) the development of transient hypothyroidism may influence long‐term thyroid function.
Octreotide scintigraphy and catecholamine response to an octreotide challenge in malignant phaeochromocytoma
Authors: Kopf D. , Bockisch A. , Steinert H. , Hahn K. , Beyer J. , Neumann H. P. H. , Hensen J. , Lehnert H.
Published: November 2003

OBJECTIVE Octreotide scintigraphy has been reported to visualize chromaffine tumours. This study in patients with malignant phaeochromocytoma was designed to assess octreotide in comparison with standard m‐iodobenzylguanidine (MIBG) scintigraphy and to study functional activity of somatostatin receptors. Finally, two cases of octreotide treatment are reported.

DESIGN Open, prospective clinical trial.

PATIENTS In 12 patients with histologically proven malignant phaeochromocytoma, 111In‐octreotide scintigraphy, 123I‐MIBG scintigraphy and computed tomography were performed. In ten patients plasma catecholamine response to a single dose of octreotide (200 μg i.v.) was monitored up to 5 hours after injection. Two patients were treated with octreotide over several months.

MEASUREMENTS Plasma catecholamines were measured by high performance liquid chromatography (HPLC). Scintigraphy was performed using a large field gamma camera and SPECT technique where appropriate.

RESULTS At least one metastatic lesion was visualized by octreotide scintigraphy in eight patients while the remaining four patients had negative findings. In total, 43 out of 54 known metastases (79.6%) were detected by MIBG, 24 (44.4%) by octreotide. Nevertheless, octreotide scintigraphy detected six metastases that were negative by MIBG. There was no correlation between the results of octreotide scintigraphy and catecholamine suppression after i.v. octreotide. In two patients on octreotide treatment, symptomatic improvement, but not mass reduction, could be documented.

CONCLUSIONS Octreotide scintigraphy behaves in part complementary to MIBG, thus increasing diagnostic sensitivity. Presence of somatostatin receptors, as demonstrated by octreotide scintigraphy, does not necessarily predict functional activity or therapeutic response.
Diurnal variation in serum insulin‐like growth factor (IGF)‐I and IGF binding protein‐3 concentrations during daily subcutaneous injections of recombinant human growth hormone in GH‐deficient adults
Authors: Oscarsson Jan , Johannsson Gudmundur , Johansson Jan‐Ove , Lundberg Per‐Arne , Lindstedt Go¨ran , Bengtsson Bengt‐Åke
Published: November 2003

OBJECTIVE Whereas there seems to be little, if any, circadian variation in circulating concentrations of IGF‐I and IGFBP‐3 in healthy subjects, there are conflicting reports on this issue in GH‐deficient patients treated with GH as a daily subcutaneous injection. We have therefore investigated the 24‐hour serum profiles of IGF‐I and IGFBP‐3 concentrations after one week and more than one year of GH treatment.

PATIENTS Eleven subjects, with adult onset GH deficiency mainly caused by pituitary adenomas were included in the study.

DESIGN AND MEASUREMENTS In an open study, six subjects (three women and three men; age (±SEM) 41.2±3.9 years) were investigated after one week of GH therapy and five subjects (three women and two men; age (±SEM) 61.4±3.3 years) were investigated after 13–40 months of GH therapy. The GH injections were given at 2000 h. The subjects were hospitalized for 24‐hour blood sampling at 1‐hour intervals and serum concentrations of GH, IGF‐I and IGFBP‐3 were determined.

RESULTS There was a significant diurnal variation in serum IGF‐I and IGFBP‐3 concentrations both in the subjects who had received GH for one week and in those who had received GH treatment for more than one year. The serum concentrations of IGF‐I and IGFBP‐3 were highest in the morning and lowest during night‐time and early morning. The molar IGF‐I/IGFBP‐3 ratio varied significantly with time in both groups of patients in a similar way as IGF‐I and IGFBP‐3 indicating a more pronounced variation in IGF‐I compared with IGFBP‐3 in response to the GH therapy.

CONCLUSION Significant diurnal variations in serum IGF‐I and IGFBP‐3 concentrations occur after one week and more than one year of GH treatment with daily subcutaneous injections. The results indicate that the free fraction of IGF‐I may exhibit a diurnal variation.
Intersex disorders: shedding light on male sexual differentiation beyond SRY
Authors: MacLean Helen E. , Warne Garry L. , Zajac Jeffrey D.
Published: November 2003

Male sexual differentiation involves a cascade of events initiated by the presence on the Y chromosome of the SRY gene, which causes the indifferent gonad to develop into a testis. Hormonal products of the testis, predominantly testosterone and Mu¨llerian inhibiting substance (MIS), then control the sexual differentiation of the developing foetus. SRY is a transcription factor; however, target genes for its action have yet to be identified, because the DNA recognition sequence for SRY is found in many genes. Therefore the study of intersex disorders is being used to identify other genes active in the pathway of sexual differentiation. Genes identified as being important in the differentiation of the indifferent gonad include WT1 (abnormal in Denys Drash syndrome) and SF‐1. The DSS locus may contain a gene that controls ovarian differentiation, and SOX9 (identified from campomelic dysplasia) is required for testis differentiation. In addition to playing a role in the development of the bipotential gonad, SF‐1 may also activate MIS gene expression in the testis, causing regression of Mu¨llerian structures. Luteinizing hormone and its receptor are required for Leydig cell differentiation, and the testosterone biosynthetic enzymes (P450scc, 3β‐hydroxysteroid dehydrogenase, P45017α and 17β‐hydroxysteroid dehydrogenase) are all necessary for masculinization of external genitalia. 5α‐Reductase is required for the production of dihydrotestosterone, and the androgen receptor mediates the action of both testosterone and dihydrotestosterone. The identification of abnormal genes in other disorders of sexual differentiation is likely to provide further information about the factors required for testicular development and function.
Elevated fibrinogen levels decrease following treatment of acromegaly
Authors: Landin‐Wilhelmsen Kerstin , Tengborn Lilian , Wilhelmsen Lars , Bengtsson Bengt‐Åke
Published: November 2003

OBJECTIVE Acromegaly is associated with increased morbidity and mortality from cardiovascular disease and from stroke in particular. Fibrinogen is an established risk factor for stroke and myocardial infarction and high levels of plasminogen activator inhibitor‐1 (PAl‐1) activity were predictive of a recurrent myocardial infarction. The aim of this study was to analyse fibrinogen and PAI‐1 activity in patients with acromegaly before and after treatment.

PATIENTS Twenty patients with acromegaly were compared with healthy controls matched for sex (12 men, 8 women), age (mean 53±7 years), body mass index (mean 26.5±2.5kg/m2) and smoking. Fibrinogen was also compared with a random population sample of men and women (n=392), aged 25–64 years, from the WHO's MONICA Project, Go¨teborg, Sweden.

RESULTS The acromegalic patients had a higher lean body mass of 65±11 vs 59±11 kg (P<0.05), lower body fat of 17±8 vs 25±10kg (P<0.01), higher plasma fibrinogen of 4.0±0.9 vs 2.4±0.5g/l (P<0.001) and plasma insulin of 15±14 vs 7±2mU/l (P<0.01), serum triglycerides of 1.5±0.5 vs 1.2±0.5mmol/l (P<0.05), as well as serum insulin‐like growth factor‐I (IGF‐I) levels of 742±271 vs 168±51μg/l (P<0.001) compared with the matched controls. PAI‐1 activity was similar, as was total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, fasting blood glucose and blood pressure for acromegalic patients compared with controls. All the acromegalic patients had higher fibrinogen levels (P<0.001) than the population mean. Plasma fibrinogen correlated positively with serum IGF‐I in acromegaly (r=0.55, P<0.05). Fibrinogen decreased to a mean value of 3.2±0.3 g/l on treatment.

CONCLUSION Acromegaly is associated with high fibrinogen levels which may be one explanation for the increased risk of cardiovascular events, and stroke in particular, in this disease. Fibrinogen levels decreased following treatment of acromegaly.
Involvement of nitric oxide in arginine, but not glucose, induced insulin secretion in normal men
Authors: Coiro V. , Volpi R. , Capretti L. , Speroni G. , Caffarri G. , Chiodera P.
Published: November 2003

OBJECTIVE At present, there are no reports in the literature of studies in humans concerning a possible role of nitric oxide (NO) in the regulation of pancreatic endocrine secretions, whereas studies in the rat provided discrepant results. The aim of this study was to clarify whether NO is involved in the control of insulin and/or glucagon secretion in basal conditions and/or in response to arginine or glucose administration in normal male subjects.

DESIGN We investigated whether an intravenous infusion of the NO synthase (NOS) inhibitor L‐NAME, at a dose previously demonstrated not to produce blood pressure alterations or untoward side‐effects, modifies insulin and/or glucagon secretory patterns.

SUBJECTS Fourteen healthy male volunteers aged 24–35 years, within 10–13% of their ideal body weight and without family history of diabetes mellitus or other endocrine diseases.

METHODS Seven normal men were treated intravenously with L‐arginine (30g in 50ml of normal saline over 30 minutes) or glucose (0.33g/kg body weight in a bolus) with or without the concomitant infusion of L‐NAME (90μg/kg in 50 ml of normal saline). L‐NAME was infused for 30 minutes before and during arginine infusion and over 30 minutes before and 30 minutes after glucose injection. Another group of 7 men was infused over 60 minutes with L‐NAME (90μg/kg in 50 ml of normal saline) alone or saline alone.

RESULTS Basal and L‐arginine or glucose induced glucagon secretions and basal and glucose stimulated insulin secretions were not altered by L‐NAME administration. In contrast, the drug produced a partial but significant decrease in the insulin response to L‐arginine. In fact, the mean peak insulin response to L‐arginine was 5.3 times (53±5mU/l (mean±SE)) higher than basal value (10±2) in the absence of L‐NAME, but only 3.33 times (40±4) higher than baseline (12±3) during the infusion of the NOS‐inhibitor.

CONCLUSION These data suggest that NO at least partially mediates the stimulatory action of L‐arginine on insulin secretion in normal human subjects.
Treatment of post‐menopausal osteoporosis with recombinant human growth hormone and salmon calcitonin: a placebo controlled study
Authors: Gonnelli Stefano , Cepollaro Chiara , Montomoli Marcello , Gennari Luigi , Montagnani Andrea , Palmieri Rossella , Gennari Carlo
Published: November 2003

OBJECTIVE The usefulness of GH in the treatment of post‐menopausal osteoporosis (PMO) is still debated. We have studied the effects of recombinant human GH (rhGH) given alone or in combination with salmon calcitonin (sCT) in the treatment of PMO.

PATIENTS Thirty women with established PMO (aged 61.1±4.4 years) were divided into 3 groups of 10 and randomly assigned to 3 treatment sequences: rhGH (12 IU/day) s.c. for 7 days, followed by sCT (50 IU/day) s.c. for 21 days and by 61 days without treatment (group 1); placebo for 7 days, followed by sCT for 21 days and by 61 days without treatment (group 2); rhGH for 7 days, followed by placebo for 21 days, and by 61 days without treatment (group 3). Each cycle was repeated 8 times (24 months).

MEASUREMENTS At days 0, 8, 29 and 90 of each cycle, serum IGF‐I, calcium, phosphate, osteocalcin, alkaline phosphatase and urinary excretion of calcium, hydroxyproline and pyridinoline cross‐links (Pyr) were measured. At months 0, 6, 12, 18 and 24, bone mineral density (BMD) was measured by dual‐photon absorptiometry (DPA), at lumbar spine (LS), femoral shaft (F) and distal radius (DR).

RESULTS A significant increase in serum osteocalcin and urinary calcium, hydroxyproline and Pyr was detected after each rhGH period. In group 1, BMD at lumbar spine increased by 2.5% at year 2; in contrast, significant (P<0.05) decreases in BMD‐LS values were found in patients treated with CT and placebo (group 2) and with GH and placebo (group 3). BMD‐F did not show any significant change in patients of group 2, but a significant (P<0.05) decrease was found in groups 1 and 3. BMD‐DR did not show any significant change with respect to baseline in any of the three groups. No significant difference between the three groups was found in bone mass at the three different regions.

CONCLUSIONS Our study demonstrates that treatment with rhGH increases bone turnover in post‐menopausal osteoporotic women. Combined treatment with rhGH and CT over a period of 24 months is able to maintain bone mass at lumbar spine and distal radius, but induces a decline at femoral shaft; therefore, it does not seem particularly useful in the therapy of post‐menopausal osteoporosis.
Incidentally discovered adrenal mass (incidentaloma): investigation and management of 208 patients
Authors: Kasperlik‐Załuska A. A. , Rosłonowska E. , Słowińska‐Srzednicka J. , Migdalska B. , Jeske W. , Makowska A. , Snochowska H.
Published: November 2003

OBJECTIVE Incidentally discovered adrenal masses are fairly common, although there are some controversies concerning the results of hormonal investigation (especially DHEAS values) and the methods of management. We summarize our experience in diagnosis, pathological findings and treatment of a large group of patients with incidentally found adrenal tumours.

DESIGN AND PATIENTS Our study included patients referred to the Department of Endocrinology of the Centre of Post‐graduate Medical Education (Warsaw, Poland) during the last 10 years because of an adrenal tumour incidentally found on ultrasound scan. In all cases this was confirmed by computed tomography. There were 208 patients (148 female and 60 male), 14–76 years old. Unilateral adrenal masses were found in 172 patients (right 106, left 66), while bilateral masses were demonstrated in 36 patients. The size of the tumours ranged between 0.8 and 21.0cm. The most common clinical abnormalities were hypertension (36 cases), obesity (23 cases), diabetes (8 cases), Addison's disease (6 cases).

MEASUREMENTS Endocrine tests evaluating pituitary‐adrenal function (urinary excretion of 17‐hydroxycorticosteroids, 17‐ ketosteroids and catecholamines, plasma concentrations of ACTH, cortisol, DHEAS, androstendione and testosterone, dexamethasone suppression test and corticotrophin‐releasing hormone stimulation test).

RESULTS Cortisol hypersecretion was noted in two patients with coexisting Cushing’s disease and high normal 17‐OHCS values with lack of dexamethasone suppressibility were found in six other patients with pre‐clinical Cushing's syndrome. More common were subtle hormonal abnormalities: low ACTH levels (in 33 out of 98 investigated patients), diminished dexamethasone suppressibility and lack of ACTH response in the CRH test (in two out of 12 patients). Urinary catecholamine excretion was elevated in nine patients. In the group of 85 patients treated by surgery the most frequent pathological findings were: adrenocortical adenoma (21), carcinoma (17), phaeochromocytoma (13), metastatic masses (12) and myelolipoma (10). The size of carcinomas ranged from 3.2 to 20.0 cm, while the size of non‐malignant tumours ranged from 1.5 to 21.0 cm.

CONCLUSIONS Every patient with an incidentally discovered adrenal mass has to be investigated to detect malignancy and subtle hormonal overproduction, to select the cases for surgical treatment. Most of the adrenocortical carcinomas were >7.0 cm in diameter. For prophylactic purposes, adrenal incidentalomas >4.0 cm should be treated by surgery, while the smaller ones could be followed‐up (with especial care for those between 3.0 and 4.0 cm).
The effect of the treatment of hypothyroidism and hyperthyroidism on plasma lipids and apolipoproteins AI, AII and E
Authors: O'Brien T. , Katz K. , Hodge D. , Nguyen T. T. , Kottke B. A. , Hay I. D.
Published: November 2003

OBJECTIVE Although lipid abnormalities are well described in hypothyroidism, effects on apolipoproteins are less well understood. The aim of this study was to examine the effects of thyroid dysfunction on plasma lipids and apolipoproteins.

DESIGN A prospective study of lipids and apolipoproteins before and after treatment of hypothyroidism and hyperthyroidism.

PATIENTS Eighteen patients with hypothyroidism and 5 patients with hyperthyroidism were included.

MEASUREMENTS Plasma cholesterol, triglycerides, HDL cholesterol, apo AI, apo AII, and apo E were measured before and after treatment of the thyroid abnormality.

RESULTS Total and HDL cholesterol, apo AI and apo E decreased with treatment of hypothyroidism, while triglycerides and apo AII levels were unchanged. The total/HDL cholesterol and LDL/HDL cholesterol ratios also decreased with treatment of hypothyroidism. In contrast, treatment of hyperthyroidism was associated with an increase in total and HDL cholesterol, and apo AI. Triglycerides, apo AII and Apo E were unchanged by treatment of hyperthyroidism. The total/HDL cholesterol and the LDL/HDL cholesterol ratios increased with treatment of hyperthyroidism.

CONCLUSIONS Hypothyroidism and hyperthyroidism have opposite effects on plasma lipids and apolipoproteins. In hypothyroidism, total and HDL cholesterol, total/HDL cholesterol ratio, apo AI and apo E are elevated. The increase in apo AI without a concomitant increase in apo AII suggests selective elevation of HDL2. In contrast, hyperthyroidism is associated with decreased total and HDL cholesterol, total/HDL cholesterol ratio, and apo AI levels. These effects are reversible with treatment of the underlying thyroid disorder.
Effect of low dose oxandrolone and testosterone treatment on the pituitary‐testicular and GH axes in boys with constitutional delay of growth and puberty
Authors: Crowne E. C. , Wallace W. H. B. , Moore C. , Mitchell R. , Robertson W. H. , Holly J. M. P. , Shalet S. M.
Published: November 2003

OBJECTIVE To investigate the effect of low dose oxandrolone and testosterone on the pituitary‐ testicular and GH‐IGF‐I axes.

DESIGN Prospective double‐blind placebo‐controlled trial.

PATIENTS Sixteen boys with constitutional delay of growth and puberty (CDGP) with testicular volumes 4–6 ml were randomized to 3 months treatment: Group 1 (n = 5), daily placebo: Group 2 (n = 5), 2.5 mg oxandrolone daily or Group 3 (n = 6), 50 mg testosterone monthly intramuscular injections with assessment (growth, pubertal development and overnight hormone profiles) at 0, 3, 6 and 12 months.

MAIN OUTCOME MEASURES  LH and GH profiles (15‐minute samples) were analysed by peak detection (Pulsar), Fourier transformation and autocorrelation. Testosterone levels were measured hourly and insulin, SHBG, IGF‐I, and IGFBP‐3 levels at 0800 h. Statistical analysis was by multivariate analysis of variance for repeated measures.

RESULTS  LH and testosterone parameters increased significantly with time in all 16 (LH AUC, P < 0.0001; peak amplitude, P = 0.02; number of peaks, P = 0.02; testosterone AUC, P = 0.02; morning testosterone, P = 0.002). In Group 2, however, LH and testosterone parameters decreased at 3 months followed by a rebound increase at 6 and 12 months. SHBG levels were markedly reduced at 3 months (P = 0.006) and a wider range of dominant GH frequencies was present although GH AUC was not increased until 6 months, with an increase in GH pulse frequency but not amplitude. IGF‐I levels were increased at both 3 and 12 months. In Group 3, pituitary‐testicular suppression was not apparent, but GH levels increased with an increase in GH amplitude at 3 and 12 months.

CONCLUSION Oxandrolone transiently suppressed the pituitary‐testicular axis and altered GH pulsatility. Testosterone increased GH via amplitude modulation.
Orthostatic tests after a 4‐day confinement or simulated weightlessness
Authors: Pavy‐Le Traon A. , Sigaudo D. , Vasseur P. , Fortrat J. O. , Güell A. , Hughson R. L. , Gharib C.
Published: November 2003

Besides microgravity, inactivity is likely to play a role in the cardiovascular deconditioning after space flights and weightlessness simulations. The aim of the study was to compare the effects of a 4‐day head‐down bed rest (HDBR) (−68) and a 4‐day confinement (C) on cardiovascular responses to orthostatic stress. Eight male subjects underwent head‐up tilt (HUT) (+60°) and lower‐body negative pressure (LBNP) (−20, −30, −40 and −50 mmHg) before (D−1) and at the end (R1) of each situation. Blood pressure, heart rate variability (HRV) and spontaneous baroreflex slope (SBS) were determined. The HDBR reduced orthostatic tolerance, as five subjects presented orthostatic hypotension during the HUT at R1, compared with two subjects at D−1. These same two subjects presented orthostatic hypotension after confinement. The main findings, after HDBR, included reductions in RR interval and total spectral power and a decrease in the parasympathetic indicator (PNS) in favour of a decrease in vagal tone; the increase in the sympathetic indicator (SNS) was not significant. After confinement, the RR interval was also significantly reduced and PNS decreased, but not significantly. RR interval and PNS were further reduced during HUT and LBNP, reflecting a withdrawal of parasympathetic activity. SBS was reduced after HDBR (P<0·05) and confinement (P=0·05), with a further reduction during HUT and LBNP without difference between D−1 and R1. This experiment showed that a 4‐day HDBR leads to impaired baroreflex function and changes in autonomic balance, which may contribute to orthostatic intolerance. Although less significant, similar patterns of changes in the autonomic nervous system were observed after confinement, suggesting an influence of the inactivity in cardiovascular deconditioning.
Renal functional reserve in pigs: renal haemodynamics, renal tubular function and salt and water homeostatic hormones during amino acid and dopamine stimulation
Authors: Poulsen E. U. , Frøkiaer J. , Jørgensen T. M. , Pedersen E. B. , Rehling M.
Published: November 2003

The purpose of the study was to evaluate renal functional reserve [RFR is the difference between glomerular filtration rate (GFR) at rest and maximal GFR after stimulation] in a controlled study in normal pigs. Our basic hypothesis was that a decreased RFR may be used as an early indicator of renal deterioration, i.e. a test to disclose significant obstruction as opposed to simple dilatation in hydronephrosis. During various forms of stimulation (amino acids, captopril and dopamine), we measured changes in GFR, renal plasma flow (RPF), tubular reabsorption of sodium and water, net uptake from plasma to the kidney of three salt and water homeostatic hormones (angiotensin II, aldosterone and atrial natriuretic peptide) and of glucagon, which is thought to play a key role as mediator of the GFR increase during amino acid infusion. We found the largest GFR increase during combined infusion of amino acids and dopamine (+13%), but compared with a non‐stimulated control group, the GFR increase was statistically non‐significant. RPF increased by 57% during stimulation with amino acids plus dopamine (P<0·001), while tubular reabsorption of sodium and water, and renal uptake of angiotensin II, aldosterone and atrial natriuretic peptide showed no significant differences between control and stimulation groups. The renal uptake of glucagon increased significantly during amino acid stimulation with no concomitant GFR increase. We conclude that in this experimental, non‐obstructed model, RFR is a very insensitive measure, which cannot be used to discriminate between obstruction and simple dilatation in hydronephrosis. Further, our study does not support the hypothesis that glucagon is involved in GFR changes after amino acids.
Muscular activity of the shoulder and neck region during sustained and intermittent exercise
Authors: Hermans V. , Spaepen A. J.
Published: November 2003

Sustained isometric contractions of the neck and shoulder muscles in laboratory conditions are often assumed to be representative of muscular load in occupational tasks. The present study aims to investigate whether differences can be found between these contractions and those in intermittent tasks. Ten subjects performed forward flexions of the right arm during three tests to the limit of endurance: (1) a sustained contraction; (2) an intermittent contraction with a cycle time of 10 s and a duty cycle of 0·7; and (3) the same intermittent contraction with the possibility of changing the shoulder angle during relaxation. Muscular activities of the upper trapezius, deltoid pars anterior and medialis and infraspinatus were registered using surface electromyography, and changes in the signal were quantified by root mean square (RMS) and mean power frequency (MPF) values. During the continuous test, highly significant changes in both parameters were found for the four muscles. Significant changes were found during both intermittent conditions, although to a lesser degree than in the continuous test. Significant differences between the regression coefficients of the sustained test and the two intermittent tests were found on all occasions: for RMS and MPF of the four muscles. Significant differences were also found regarding the intermittent tests. The test in which no variation in limb position was allowed during relaxation caused a more pronounced MPF decrease for the trapezius (P≤0·01), which was confirmed by the subjective scores of perceived exertion and a higher RMS increase (P≤0·01) for the middle part of the deltoid. The intermittent condition with changes in shoulder angle showed more MPF decrease for the deltoid, significant for the middle part (P≤0·05), not significant for the anterior part and a larger RMS increase for infraspinatus (P≤0·05). It can be concluded that the latter condition represents more the trapezius and deltoid activity as in occupational tasks.
Validation of the acetylene rebreathing method for measurement of cardiac output at rest and during high‐intensity exercise
Authors: Liu Y. , Menold E. , Dullenkopf A. , Reißnecker S. , Lormes W. , Lehmann M. , Steinacker J. M.
Published: November 2003

The use of the acetylene rebreathing method to estimate cardiac output (CO) during high‐intensity exercise, which may be influenced by recirculation of acetylene, has not been validated. This study was designed to validate the acetylene rebreathing method to measure CO during high‐intensity exercise using the direct Fick method. CO was measured at rest and during exercise at 25%, 50%, 75% and 90% of the nine subjects maximum oxygen uptake (VO2max) by the direct Fick and acetylene rebreathing method. CO measured by the acetylene rebreathing method correlated with work rate (r=0·90, P<0·01) and with oxygen uptake (r=0·94, P<0·01). The correlation coefficient of CO between both methods was r=0·91 (P<0·01). There was no significant difference in CO measured by each method at rest as well as at each work rate. The difference in CO between each method was greater at lower CO than at higher CO. At 90% of VO2max, the CO measured by acetylene rebreathing was nearly identical to that measured by the Fick method. It can be concluded that acetylene rebreathing for measurement of CO is valid not only at rest but also during exercise, especially during high‐intensity exercise.
Finger‐to‐brachial comparability of ‘modelflow’stroke volume improves after pulsewave reconstruction
Authors: Voogel A. J. , Bos W. J. W. , Van Goudoever J. , Van Montfrans G. A. , Wesseling K. H.
Published: November 2003

Modelflow is a methodthat determines stroke volume (SV) from central or peripheral continuous blood pressuresignals. Pulsewaves are changed along the arterial tree; distortion occurs as the mean pressurelevel gradually declines. These changes might jeopardize the determination of SV from a distalmeasurement site. Techniques have been assessed to reconstruct brachial artery pressures(BAPs) from non‐invasive finger blood pressure (FIN) waveforms. In this study, wedetermined the effect of different forms of brachial reconstruction techniques on thecomparability of modelflow SV from FIN and BAP. Supine resting FIN and BAP weremeasured simultaneously in 57 subjects, covering a wide range of blood pressures and degreesof vascular disease. SV from the two sites were compared before correction and aftercorrection for pulse‐wave distortion or pressure gradient. The latter was determined by aregression formula and by a return to flow (RTF) method, using the brachial cuff pressure atthe moment of reappearance of FIN during cuff deflation. SV from unfiltered FIN exceededBAP‐derived SV by 4·6 (SD 11) ml. This difference was positively related to thesubjects’ age. Correction for pulsewave distortion increased the average difference to13 (12) ml (P<0·05 to the unfiltered condition). Adjustment for thepressure gradient reduced the difference to −2·5 (7) ml (P<0·01). RTF had no additional effect. We concluded that the FIN‐to‐BAPcomparability can be increased by brachial reconstruction techniques, which correct for thepressure gradient. This can be adequately performed without additional measurements,allowing its application to measurements already taken.
Autonomic nervous function at rest in aerobically trained and untrained oldermen
Authors: Boutcher S. H. , Cotton Y. , Nurhayati Y. , Craig G. A. , McLaren P. F.
Published: November 2003

Therelationship between aerobictraining, vagal influence on the heart and ageing was examined by assessing aerobic fitness andresting heart rate variability in trained and untrained older men. Subjects were 11 trained cyclistsand runners (mean age=6±61·6 years) and 11 untrained, age‐matchedmen (mean age=66±1·2 years). Heart rate variability testing involvedsubjects lying supine for 25 min during which subjects’ breathing was paced andmonitored (7·5 breaths min−1). Heart rate variability was assessedthrough time series analysis (HRVts) of the interbeat interval. Results indicated thattrained older men (3·55±0·21 l min−1) hadsignificantly (P<0·05) greater VO2maxthan that of control subjects (2·35±0·15 l min−1).Also, trained older men (52±1·8 beats min−1) hadsignificantly (P<0·05) lower supine resting heart rate than that of controlsubjects (65±4·2 beats min−1). HRVts at highfrequencies was greater for trained men (5·98±0·22) than for untrainedmen (5·23±0·32). These data suggest that regular aerobic exercise inolder men is associated with greater levels of HRVts at rest.