bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with insulin lispro changes the insulin profile but does not affect the plasma concentrations of IGF‐I and IGFBP‐1 in type 1 diabetes
Authors: Hedman C.A. , Orre‐Pettersson A.‐C. , Lindström T. , Arnqvist H.J. 
Published: March 2003

OBJECTIVE IGF‐I levels in patients with type 1 diabetes without endogenous insulin production are low. Our aim was to examine whether the plasma insulin profile obtained by treatment with the insulin analogue lispro has a different effect on plasma concentrations of IGF‐I and IGFBP‐1 than that seen during treatment with conventional human insulin (regular insulin).DESIGN AND PATIENTS Twelve patients with type 1 diabetes, age 47·8 ± 2·4 years (mean ± SEM), body mass index 26·5 ± 1·0 kg/m2, diabetes duration 30·5 ± 3·2 years participated in this open label randomized cross‐over study. IGF‐I and IGFBP‐1 levels were measured at the end of 6 weeks treatment with each insulin being administered by a continuous subcutaneous insulin infusion. IGF‐I was measured fasting while IGFBP‐1, free insulin and blood glucose were measured fasting and repeatedly after a morning meal preceded by an insulin bolus dose.RESULTS Lispro gave a marked insulin peak of 135 ± 20 pmol/l 50 minutes after injection. After an initial rapid rise, human regular insulin reached a plateau of approximately 50 pmol/l. The plasma free insulin area under the curve (AUC) from 0710 h to 0910 h was more than twice as large on lispro as on regular insulin (P = 0·01). Plasma IGF‐I concentration was 78·8 ± 10·9 µg/l on lispro and 82·3 ± 10·5 µg/l on human regular insulin (not significant). AUC for IGFBP‐1 did not show a significant difference even when divided from 0710 h to 0910 h and from 0930 h to 1430 h. Blood glucose AUC after administration of the bolus was significantly lower during treatment with lispro (P = 0·006) but glycosylated haemoglobin (HbA1c) was 6·4 ± 0·2% on both therapies.CONCLUSIONS Our results indicate that the effect of lispro on IGF‐I and IGFBP‐1 in patients with type 1 diabetes does not differ from that of human regular insulin.
Currently used growth‐promoting treatment of children results in normal bone mass and density. A prospective trial of discontinuing growth hormone treatment in adolescents‡
Authors: Fors Hans , Bjarnason Ragnar , Wirén Lena , Albertsson‐Wikland Kerstin , Bosaeus Ingvar , Bengtsson Bengt‐Åke , Johannsson Gudmundur 
Published: March 2003

BACKGROUND AND AIMS The need for continued GH replacement in patients with childhood‐onset GH deficiency (GHD) into adulthood has been recognized. The consequences of discontinuing GH treatment on bone mineralization in adolescent patients with GHD and short stature were examined over a period of 2 years.PATIENTS Forty adolescents (aged 16–21 years) treated with GH for more than 3 years and 16 closely matched healthy controls were studied. After a baseline visit, GH treatment was discontinued. The patients were then re‐examined with the same protocol after 1 and 2 years. Twenty‐one patients had continuing severe GHD into adulthood, while 19 patients were regarded as having sufficient endogenous GH secretion (GHS).RESULTS At baseline, there were no differences between the groups in total bone mineral content (BMC) or bone mineral density (BMD). After 2 years without GH treatment, BMC increased similarly in the GHD and GHS groups. BMC of the lumbar spine (L2–L4) increased only in the GHD group. Lumbar spine BMD increased in the GHD and the GHS groups. No changes were observed in the femoral neck region. Biochemical measurements showed that carboxy‐terminal cross‐linked telopeptide of type I collagen (ICTP) and bone specific alkaline phosphates (ALP) were higher in the GHD and GHS groups at baseline compared with controls. Osteocalcin, carboxy‐terminal propeptide of type I procollagen (PICP), ICTP and ALP decreased during the 2 years off treatment in both the GHD and GHS groups. PICP was also lower after 2 years in the GHD group compared with both the GHS group and controls.CONCLUSIONS After discontinuation of GH therapy in adolescents at or near final height, there was a continued increase in BMC and BMD both for adolescents with growth hormone deficiency and for those classified as growth hormone sufficient. These groups did not differ from controls at baseline or after 2 years. In the growth hormone deficiency group, biochemical markers for bone formation decreased to levels below those in the growth hormone sufficient and healthy control groups. Although the number of patients and controls in this study were small, the results indicate that the present treatment of Swedish GH‐deficient children to final height results in normal BMD.
Elevation of soluble E‐selectin levels following gestational diabetes is restricted to women with persistent abnormalities of glucose regulation
Authors: Lawrence Natasha J. , Kousta Eleni , Penny Anna , Millauer Barbara , Robinson Stephen , Johnston Desmond G. , McCarthy Mark I. 
Published: March 2003

Summaryobjective Increased levels of the soluble adhesion molecule sE‐selectin have been reported in normoglycaemic women with previous gestational diabetes but not in other groups at increased risk of future type 2 diabetes. To explore the basis for these discrepant findings, we studied the relationship between sE‐selectin and glucose regulation in a large group of women with previous gestational diabetes.design Comparison of sE‐selectin levels between a study cohort ascertained on the basis of recent gestational diabetes and suitable control subjects.patients One hundred and forty women with recent gestational diabetes (104 European, 20 South Asian and 16 Afro‐Caribbean) and 125 normoglycaemic control women (90 European, 19 South Asian and 16 Afro‐Caribbean).measurements sE‐selectin, fasting lipids, insulin and current glucose regulation status.results There was no overall difference in sE‐selectin levels between women with a history of gestational diabetes and control women among the 3 ethnic groups. European post‐GDM women with abnormal glucose regulation postpartum (n = 30) had higher sE‐selectin than control women (67 (54–91) ng/ml vs. 57 (43–75) ng/ml, P= 0·049). There was no difference in sE‐selectin between normoglycaemic European women with a history of gestational diabetes (n = 74) and control women, even though the former displayed metabolic abnormalities predictive of diabetes. In those European post‐GDM women with normal glucose regulation postpartum, sE‐selectin levels were negatively correlated with time since delivery (r = –0·25, P= 0·04), suggesting that the previously described elevation of sE‐selectin following GDM pregnancies slowly resolves postpartum. There was no correlation between sE‐selectin levels and features of insulin resistance.conclusions In contrast to previous findings, this larger study does not support a role for sE‐selectin as a marker, independent of prevailing glucose levels, of early metabolic abnormalities or future diabetes risk in women with previous gestational diabetes.
Galanin in human pituitary adenomas: frequency and clinical significance
Authors: Leung Betty , Lismaa Tiina P. , Leung Kin‐Chuen , Hort Yvonne J. , Turner Jennifer , Sheehy John P. , Ho Ken K. Y. 
Published: March 2003

Summaryobjectives Galanin (GAL) is a neuropeptide widely expressed in the central and peripheral nervous system and in neuroendocrine tissue, including the adenohypophysis where, in humans, it is expressed in corticotrophs and in ACTH‐producing adenomas. Previous analyses of human tissue have used antiserum against porcine GAL for detection of GAL immunoreactivity (GAL‐IR) and no pathophysiological correlates have been reported. Given significant differences between the sequence of porcine and human GAL peptides, the aim of this study was to use antiserum raised against synthetic human GAL to investigate GAL‐IR in non tumorous pituitaries and in pituitary adenomas, and to correlate GAL‐IR with the clinical and hormonal characteristics of patients with Cushing’s disease.patients Six nontumorous pituitaries were obtained from autopsy and 151 pituitary adenomas, comprising 62 functioning (16 corticotroph, 26 somatotroph, 19 lactotroph and one thyrotroph) and 89 nonfunctioning adenomas, were obtained by surgery.results All non tumorous pituitary glands showed GAL‐IR in corticotrophs, in basophil cells within the neurohypophysis and in nerve fibres of the neurohypophysis. GAL‐IR was found in a subset (10 of 16) of patients with ACTH‐secreting tumours causing Cushing’s syndrome. GAL‐IR was rarely expressed in somatotroph adenomas and prolactinomas, but was expressed in approximately one‐third of nonfunctioning tumours. GAL‐IR was found in almost 90% of nonfunctioning tumours that were positive for ACTH. There were no significant differences in sex ratio, age at presentation or 24‐h urinary free cortisol secretion in the subset of patients with Cushing’s disease positive (n = 10) or negative (n = 6) for GAL‐IR. However, Cushing’s patients positive for GAL‐IR tended to have smaller tumours and achieved a higher cure rate than those without (100 vs. 50%, P = 0·017).conclusions Galanin is present in normal and tumorous human pituitaries. In addition, GAL colocalizes exclusively in corticotrophs of normal pituitaries and is coexpressed almost exclusively in corticotrophs from functioning and nonfunctioning tumours. The finding that corticotroph adenomas can function irrespective of the presence of GAL suggests that GAL may not play a pathophysiological role in Cushing’s disease. However, the better surgical outcome observed in patients with Cushing’s disease who had tumours positive for GAL‐IR suggests that the expression of GAL confers a less aggressive tumour phenotype.
Use of GnRH agonist and human chorionic gonadotrophin tests for differentiating constitutional delayed puberty from gonadotrophin deficiency in boys
Authors: Kauschansky Arieh , Dickerman Zvi , Phillip Moshe , Weintrob Naomi , Strich David 
Published: March 2003

Summaryobjectives The differentiation of constitutional delayed puberty (CDP) from gonadotrophin deficiency (GD) in boys at referral poses a difficult challenge. The effectiveness of the GnRH agonist (GnRH‐a) test in distinguishing between the two conditions was evaluated and compared with findings of the GnRH and hCG stimulation tests.patients, methods and design The study sample included 32 prepubertal boys aged 14 years or older. Thirteen entered spontaneous puberty within 1 year of referral (group A) and 19 remained prepubertal (group B). All underwent the GnRH test (Relefact, Hoechst AG, 0·1 mg/m2 i.v. in one bolus), GnRH‐a test (Decapeptyl, Ferring GmbH, 0·1 mg/m2 s.c.) and hCG stimulation (Chorigon, Teva, 1500 units i.m. on three alternate days) at 1‐week intervals. All tests were performed at referral at 0800 h. Blood samples were collected before testing and at 30 and 60 min (GnRH test) or 4 h (GnRH‐a) for LH and FSH determination, and before testing and at 4 h (GnRH‐a) or on the seventh day (hCG) after stimulation for serum testosterone measurement.results The LH response to GnRH‐a and the testosterone response to hCG stimulation were significantly higher in group A (LH, mean ± SD 20·4 ± 7·5 mIU/ml, range 10·8–32·6; testosterone, mean ± SD 18·0 ± 5·9 nmol/l, range 9·4–26, P < 0·0001) than in group B (LH, mean ± SD 2·3 ± 2·0 mIU/ml, range 0·7–6·9; testosterone, mean ± SD 1·0 ± 0·7 nmol/l, range 0·7–3·2), with no overlap between the groups. The cut‐off for the LH response to GnRH‐a was 8·0 mIU/ml, and for the testosterone response to hCG, 8 nmol/l. There were also significant differences between the groups in mean basal serum LH and FSH (LH, 1·1 ± 0·5 vs. 0·6 ± 0·2 mIU/ml, P < 0·05; FSH, 2·2 ± 2·0 vs. 0·4 ± 0·3 mIU/ml, P < 0·02) and their response to GnRH (LH, 11·4 ± 4·4 vs. 2·7 ± 1·1 mIU/ml, P < 0·0001; FSH, 5·1 ± 3·4 vs. 2·5 ± 2·4 mIU/ml, P < 0·0001), and mean serum testosterone level at 4 h after GnRH‐a administration (1·9 ± 1·0 vs. 0·9 ± 0·4 nmol/l, P = 0·002), but all showed a great overlap in range. Mean age, testicular volume and basal serum testosterone levels were similar in the two groups at referral. One year later, the testicular volume of group A (5·0–12·0 ml) was significantly larger than that of group B (1·0–3·0 ml, P < 0·0001), which remained unchanged on re‐examination 3·0 ± 0·5 years later.conclusions The GnRH‐agonist test and the repeated‐injection hCG test are reliable diagnostic tools for differentiating CDP from GD in boys.
Long‐term effects of androgen deprivation therapy in prostate cancer patients
Authors: Basaria Shehzad , Lieb John , Tang Alice M. , DeWeese Theodore , Carducci Michael , Eisenberger Mario , Dobs Adrian S. 
Published: March 2003

Summarybackground Prostate cancer (PCa) is one of the most common cancers in men and has an increasing incidence. In 1999, 37 000 men died from PCa in the USA. Androgen deprivation therapy (ADT) with GnRH agonists is frequently employed in the treatment of recurrent and metastatic PCa by inducing medical castration, rendering these men hypogonadal. Because hypogonadism in men is associated with a wide range of complications, we attempted to determine the effects of long‐term ADT in men with PCa.methods We conducted a cross‐sectional study at a tertiary care centre to determine the effect of ADT on lean body mass (LBM), muscle strength, bone mineral density (BMD), sexual function, and quality of life (QOL) in men with PCa. Three groups of men were enrolled: (1) 20 men with PCa who were undergoing medical castration with GnRH agonists for at least 12 months prior to the onset of the study (ADT group); (2) 18 age‐matched men with nonmetastatic PCa who were post prostatectomy and/or radiotherapy but had not yet undergone ADT (non‐ADT group); and (3) 20 age‐matched normal men who were healthy and ambulatory (control group).results Men on ADT had castrate levels of serum total testosterone (P < 0·0001), free testosterone (P < 0·0001) and oestradiol (P < 0·0001), which were significantly lower than in the other groups. Total body (P = 0·03) and lumbar spine (P < 0·0001) BMD was significantly lower in patients on ADT compared to other groups and was associated with higher levels of urinary N‐telopeptide (P = 0·02). The ADT group had higher fat mass compared to the other groups (P = 0·0001) and significantly reduced upper body strength (P = 0·001) when compared to non‐ADT patients. The ADT group had lower overall scores on Watt's Sexual Function Questionnaire compared to other groups (P = 0·0001), in particular a decrease in desire, arousal and frequency of spontaneous early morning erections. The ADT group also had lower overall QOL scores, resulting in significant limitation of physical function (P = 0·001), role limitation (P = 0·02) and perception of physical health (P = 0·004).conclusions This study suggests that osteoporosis, unfavourable body composition, sexual dysfunction and reduced quality of life are seen in patients receiving androgen deprivation therapy for at least 12 months. Longitudinal studies in this patient population will shed further light on the timing of the development and the extent of these complications. Meanwhile, this information will assist both physicians and patients with prostate cancer to make informed decisions regarding androgen deprivation therapy.
Growth hormone deficiency and vascular risk
Authors: McCallum Roland W. , Petrie John R. , Dominiczak Anna F. , Connell John M. C. 
Published: March 2003

SummaryThe importance of growth hormone deficiency (GHD) in adult life has become more apparent over the last decade. As well as a distinct clinical syndrome there is a significant excess risk of cardiovascular disease. Although it is difficult to ascertain what part is played by the original pituitary disorder and the concomitant replacement hormonal therapies, there is clear evidence that GHD is associated with known cardiovascular risk factors such as body shape, lipid profile, insulin resistance, blood pressure, vessel wall morphology and haemostatic factors. Novel means of assessing vascular risk such as pulse wave velocity and flow‐mediated dilatation can also estimate the risk without invasive procedures. The role of possible mediators of endothelial function such as nitric oxide and free radicals is being investigated further. Replacement of GH in GH‐deficient patients leads to many effects on the above indices, some but not all of which are associated with reduced vascular risk. Long‐term follow‐up studies of morbidity and mortality are required for an accurate assessment of the beneficial effects of therapy.
Evaluation of the optimum dose of growth hormone (GH) for restoring bone mass in adult‐onset GH deficiency: results from two 12‐month randomized studies
Authors: Abrahamsen B. , Hangaard J. , Horn H. C. , Hansen T. B. , Gregersen G. , Hansen‐Nord M. , Vahl N. , Junker P. , Andersen M. , Hagen C. 
Published: March 2003

Summaryobjective To establish the optimum GH dose for restoring bone mineral density (BMD) in adult‐onset GH deficiency (GHDA).design Two separate randomized, controlled clinical trials.patients Fifty‐eight adults aged 45·1 (20–64) years with severe GHDA were followed in two 12‐month studies. In the first study, patients were randomized to placebo or GH 1·7 IU/m2/day and in the second study GH 0·5 IU/m2/day or 1·0 IU/m2/day.measurements BMD of the spine, hip, forearm and whole body was measured at 0 and 12 months. Alkaline phosphatase (AP) and collagen markers serum C‐terminal propeptide of type I collagen (PICP), type I collagen telopeptide (ICTP) and N‐terminal propeptide of type III collagen (PIIINP) were measured at baseline and every 3 months.results Biochemical markers of skeletal and soft tissue collagen increased significantly and remained elevated throughout the study period. BMD changes depended on site, dose and gender. In placebo‐treated patients, spinal BMD declined by 2·5%. At the low and medium doses, BMD increased by 2·4 and 3·1%, respectively, while a nonsignificant 0·2% decrease was seen with high dose. Forearm BMD decreased by 4·9% (P < 0·05) with high‐dose treatment but remained unchanged at lower doses. Males showed larger gains in BMD, but the dose–response relationship was similar in males and females.conclusion A GH dose of 0·5–1·0 IU/m2/day (4–9 µg/kg/day) stimulated bone remodelling and increased BMD over 12 months in patients with severe GHDA, irrespective of gender. A higher dose (1·7 IU/m2/day ≅ 15 µg/kg/day) was associated with initial declines in forearm and whole‐body BMD.
Neonatal thyrotoxicosis and maternal infertility in thyroid hormone resistance due to a mutation in the TRβ gene (M313T)
Authors: Blair J. C. , Mohan U. , Larcher V. F. , Rajanayagam O. , Burrin J. M. , Perry L. A. , Grossman A. B. , Chatterjee V. K. K. , Savage M. O. 
Published: March 2003

SummaryWe report two unusual cases of resistance to thyroid hormone (RTH) in one family. The first case, a male infant, had clinical features of thyrotoxicosis in the neonatal period. In the fourth week of life weight gain was poor despite a daily intake of standard infant formula almost double the infant's estimated requirements. At this time serum free T4 (fT4) was 60·7 pmol/l (Normal range [NR] 11–25 pmol/l) and TSH was inappropriately normal at 1·8 mU/l (NR 0·3–4·0 mU/l). The infant responded clinically and biochemically to propylthiouracil (PTU) at a dose of 10 mg/kg/day. Following 27 days of treatment serum fT4 was 22·6 pmol/l and TSH had risen to 24·9 mU/l. As the infant was thriving treatment was discontinued. The infant, now aged 6 months old, remains clinically euthyroid and developmentally normal off treatment.The infant's mother, from whom he had inherited a mutation of the thyroid receptor β (TRβ) gene (M313T), presented earlier with secondary infertility and clinical features of thyrotoxicosis. Treatment with PTU restored her fertility and she spontaneously conceived. In the subsequent pregnancy, clinical and biochemical features of RTH improved, and she gave birth to a small but healthy female infant. In the next pregnancy, resulting in the birth of the affected male infant, clinical and biochemical features of RTH worsened, and high doses of PTU were required to maintain a clinically euthyroid state.To our knowledge, these are the first case reports of RTH associated with added features of a hypermetabolic state in infancy and secondary infertility.
Individualized growth hormone substitution with normalized IGF‐I levels does not stimulate the renin–angiotensin–aldosterone system
Authors: Ekman Bertil , Öhman Peter K. , Arnqvist Hans J. , Lindström Torbjörn , Nyström Fredrik H. 
Published: March 2003

Summaryobjective To study the effects of individualized recombinant GH substitution, aiming at normal circulating IGF‐I levels, in GH‐deficient adults on blood pressure, the renin–angiotensin–aldosterone system (RAAS), natriuretic peptides and urine free cortisol.study design Open study with control group. The patients were titrated in dose steps of 0·17 mg GH/day every 6–8 weeks until an IGF‐I level around the mean + 1 SD was attained (Tmax). After another month the dose was reduced by 0·17 mg (minimum dose 0·17 mg/day) to produce IGF‐I levels at or slightly below the age‐related mean (Tend), and this maintenance dose was held constant for 6 months.subjects Eighteen patients (11 males and seven females) with GH deficiency participated. For comparison we also prospectively evaluated 17 matched control subjects.measurements Blood pressure and heart rate, circulating levels of IGF‐I, plasma renin activity (PRA), immunoreactive active renin (IRR), angiotensin II, aldosterone, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and 24‐h urine aldosterone and urine free cortisol levels.results Blood pressure was unchanged by GH substitution but heart rate increased significantly (P < 0·03). PRA was elevated on the highest GH dose (Tmax) compared to baseline (P < 0·01), but returned to baseline and levels of controls at Tend. Four patients developed transient oedema and tended to have higher PRA levels than the rest of the subjects (P = 0·09). The circulating levels of IRR, angiotensin II, aldosterone, BNP and 24‐h urine aldosterone and urine free cortisol levels were unchanged by GH substitution, and did not differ from the levels in the control subjects. Baseline ANP levels in the patients were lower than in the controls (P < 0·01), but increased after GH substitution (P < 0·01) to levels found in with the controls.conclusions We found no major changes of the variables in the circulating renin–angiotensin–aldosterone system and a normalization of atrial natriuretic peptide when an individualized dose of GH was titrated to near‐normal IGF‐I levels.