bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel application of IGF‐I and IGFBP‐3 generation tests in the diagnosis of growth hormone axis disturbances in children with β‐thalassaemia
Authors: Chrysis Dionisios C. , Alexandrides Theodore K. , Koromantzou Era , Georgopoulos Neoklis , Vassilakos Pavlos , Kiess Wieland , Kratsch Jürgen , Beratis Nicholas G. , Spiliotis Bessie E. 
Published: March 2003

OBJECTIVEChildren with β‐thalassaemia major (β‐thal) frequently have growth retardation in the presence of low serum IGF‐I and a normal GH response to pharmacological stimulation suggesting that they have GH insensitivity (GHIS). This study was carried out to study the cause of their growth retardation.DESIGNWe studied IGF‐I and IGFBP‐3 generation after exogenous GH administration for four days, in 15 prepubertal controls (C) and 41 prepubertal β‐thal patients divided into three groups according to their growth status: (Group 1) 15 with normal growth (N‐thal) (Group 2) 16 with decelerated growth (D‐thal) and (Group 3) 10 with short stature (S‐thal), in order to determine whether GHIS is the cause of their growth retardation.MEASUREMENTSIGF‐I and IGFBP‐3 were measured daily, before and for 4 days after daily administration of 0·1 IU/kg hGH, in 3 groups of prepubertal β‐thal patients and normal controls.RESULTSN‐thal and C had similar basal serum IGF‐I (142 ± 52 and 196 ± 56 ng/ml, respectively) and IGFBP‐3 concentrations (2·07 ± 0·49 and 2·66 ± 0·41 mg/l, respectively) as well as a similar percent increase of IGF‐I (101 ± 23% and 104 ± 37%, respectively) and IGFBP‐3 (52 ± 36%, and 38 ± 14%, respectively) during the generation tests. S‐thal and D‐thal had significantly lower basal IGF‐I and IGFBP‐3 concentrations (85 ± 42 and 101 ± 36 ng/ml; and 1·60 ± 0·49 and 1·79 ± 0·52 mg/l, respectively) as compared to N‐thal and C (P < 0·001 and P < 0·005, respectively), and a significantly higher percent increase of IGF‐I and IGFBP‐3 during the generation tests (249 ± 43 and 161 ± 76%; and 121 ± 99 and 73 ± 35%, respectively) as compared to N‐thal and C (P < 0·0001 and P < 0·01, respectively). Twenty‐five percent of the growth retarded patients had classic GH deficiency (GHD) and percent increases of IGF‐I and IGFBP‐3 in the generation tests (164 ± 86% and 80 ± 49%, respectively) which were similar to those of the remaining growth‐retarded children.CONCLUSIONThe greater percent increases of IGF‐I and IGFBP‐3 in the generation tests of the growth retarded β‐thal patients, both with and without GHD, strongly suggest impaired GH secretion rather than GHIS as the cause of their growth retardation. We conclude that the IGF‐I and IGFBP‐3 generation tests are useful tools for the study not only of GHIS but also of GH secretory disorders in patients with β‐thal and short stature that can easily be performed in an outpatient setting as an initial test to identify the patients that may benefit from GH therapy.
Hydrocortisone replacement dosage influences intraocular pressure in patients with primary and secondary hypocortisolism
Authors: Li Voon Chong J. S. W. , Sen J. , Johnson Z. , Kyle G. , MacFarlane I. A. 
Published: March 2003

BACKGROUNDIt has been suggested that the variation of intraocular pressure (IOP) during the day follows the diurnal variation of serum cortisol. There is also a higher risk of ocular hypertension and glaucoma in patients taking excessive oral steroid treatment. We assessed whether different replacement doses of hydrocortisone (HC) influenced IOP.METHODSSeventeen patients (six Addison's disease, 11 hypopituitarism; seven males) aged 24–58 years mean 42·7 years and 20 control subjects (nine males) aged 20–59 years mean 38·7 years were studied. On the first visit, the 17 patients had been taking HC replacement doses, 20 mg morning and 10 mg afternoon. Serum cortisol and IOP in both eyes (Goldmann applanation tonometer) were measured at 0900, 1100, 1300, 1500, 1700 hours with HC 20 mg taken after the 0900 h assessment. The dose of HC was then reduced to 10 mg morning and 10 mg afternoon for 1 week and the measurements were repeated in 16 patients, with HC 10 mg taken at 0900 h.RESULTSIn the patients the peak serum cortisol occurred at 1100 h after the 0900 h HC dose. Cortisol levels were significantly higher at 1100, 1300, 1500 and 1700 h after taking 20 mg compared to 10 mg HC. The mean (SEM) IOP (mmHg) was significantly higher after 20 mg HC compared with 10 mg HC at 1300 h: 14·7(0·6) v 13·1(0·6) (P = 0·004) and at 1500 h: 14·4(0·6) v 13·1(0·5) (P = 0·04). The total mean (SEM) daily IOP score was significantly higher after 20 mg HC compared with 10 mg HC: 14·5(0·3) v 13·5(0·3) (P = 0·0002). The total mean (SEM) daily IOP score after the 20 mg HC dose compared with the control subjects was: 14·5(0·3) v 13·7(0·3) (P = 0·08).CONCLUSIONIntraocular pressures during the day are influenced by the morning hydrocortisone replacement dosage with significantly higher intraocular pressure levels in the early afternoon following 20 mg compared with 10 mg. A morning hydrocortisone dose of 10 mg leads to a more physiological intraocular pressure profile during the day. These data support the view that a daily replacement dose of 30 mg hydrocortisone may be excessive.
Serum antibodies to human pituitary membrane antigens in patients with autoimmune lymphocytic hypophysitis and infundibuloneurohypophysitis
Authors: Nishiki Masateru , Murakami Yoshio , Ozawa Yasunori , Kato Yuzuru 
Published: March 2003

Serum antipituitary antibodies were investigated by the immunoblotting method using human anterior pituitary membrane preparation as the antigen.Thirteen patients with autoimmune lymphocytic hypophysitis, two patients with infundibuloneurohypophysitis, four patients with isolated ACTH deficiency, 21 patients with diabetes mellitus (type 1 and type 2) and 38 healthy subjects were studied.Human pituitary membrane antigens were electrophoresed by sodium dodecylsulphate‐polyacrimide gel electrophoresis (SDS‐PAGE). The antigens were transferred to polyvinylidene difluoride membrane and reacted with the sera followed by incubation with biotinylated anti‐human IgG goat serum.Serum antibodies to 68, 49, 43 kD human pituitary membrane antigens were detected in five of 13, one of 12 patients with infundibuloneurohypophysitis and none of four patients with isolated ACTH deficiency. These antibodies were not detectable when human thyroid, liver or rat pituitary preparations were used as the antigen.These findings suggest that serum antibodies to 68, 49, 43 kD human anterior pituitary antigen are specific but not so frequently detected in autoimmune lymphocytic hypophysitis.
Increased levels of insulin‐like growth factor binding protein‐2 in sera and tumours from patients with colonic neoplasia with and without acromegaly
Authors: Miraki‐Moud F. , Jenkins P. J. , Fairclough P. D. , Jordan S. , Bustin S. A. , Jones A. M. , Lowe D. G. , Monson J. P. , Grossman A. B. , Besser G. M. , Camacho‐Hübner C. 
Published: March 2003

OBJECTIVE Patients with acromegaly are at increased risk of developing colorectal carcinoma and premalignant tubulovillous adenoma. The pathogenesis of these neoplasms could involve a stimulatory effect of serum growth factors on colonic epithelial cell proliferation. The aim of this study was to evaluate changes in (1) serum IGF‐I, IGF‐II, IGFBP‐3 and IGFBP‐2 and (2) changes in local expression of IGFBPs and p53 in colonic epithelium in patients with colonic neoplasia with and without acromegaly.DESIGN A cross‐sectional retrospective study was performed. Fasting serum samples were obtained at the time of colonoscopy for patients with acromegaly and at the time of surgery for patients with colonic neoplasia without acromegaly.MEASUREMENTS Serum IGF‐I, IGF‐II, IGFBP‐2 and IGFBP−3 were measured using specific immunoassays. Tissue expression of IGFBP‐2, IGFBP‐3 and p53 status were determined by immunohistochemistry.PATIENTS Group 1: 26 age‐ and sex‐matched control subjects (range 40–69 years); group 2: 18 patients with acromegaly without colonic neoplasia (range 39–68 years); group 3: 18 patients with acromegaly and colonic neoplasia (range 41–74 years, 11 = adenoma, seven = carcinoma); group 4: 19 patients with colonic neoplasia without endocrine disease (range 43–91 years, four = adenoma, 15 = carcinoma). Immunohistochemical staining of colonic biopsies was performed for IGFBP‐2, IGFBP‐3 and p53 in groups 3 and 4.RESULTS Mean serum IGF‐I and IGFBP‐3 levels were significantly elevated in group 2 (371 ± 131 µg/l and 6·5 ± 1·8 mg/l, respectively) and group 3 (379 ± 174 µg/l and 5·8 ± 1·6 mg/l, respectively), and significantly reduced in group 4 (103 ± 36 µg/l and 2·4 ± 1 mg/l) compared to controls (165 ± 40 µg/l and 4·7 ± 1 mg/l; P < 0·0001, P < 0·001, respectively). However, median serum IGFBP‐2 levels were significantly elevated in group 3 (P < 0·01) and group 4 (P < 0·0001). Immunostaining for IGFBP‐2 showed strong areas of immunoreactivity in the cytoplasm of malignant colonic epithelium compared to benign epithelium. IGFBP‐3 immunostaining showed strong areas of immunoreactivity in the cytoplasm and in the nucleus of malignant and benign colonic epithelium compared to the normal epithelium. Nuclear staining for p53 was observed in three patients from group 3 (two carcinoma, one adenoma) and four patients from group 4 (all carcinoma).CONCLUSION Our results describe changes in IGFBP‐2 expression in colonic neoplasia in patients with and without acromegaly, which suggest that this binding protein may regulate local bioavailability of IGF, which in turn could modulate colonic cell proliferation and/or differentiation.
Characterization of premature atherosclerosis of carotid arteries in acromegalic patients
Authors: Otsuki Michio , Kasayama Soji , Yamamoto Hiroyasu , Saito Hiroshi , Sumitani Satoru , Kouhara Haruhiko , Saitoh Youichi , Ohnishi Takanori , Arita Norio 
Published: March 2003

OBJECTIVEAcromegalic patients have increased mortality from vascular diseases. Although atherosclerotic risk factors such as hypertension, diabetes mellitus and dyslipoproteinaemia are highly associated with acromegaly, the prevalence of premature atherosclerosis in acromegalic patients and its relationship to these risk factors have not been reported.DESIGNWe measured mean intima‐media thickness (IMT) of the carotid arteries in 21 acromegalic patients without symptomatic atherosclerotic vascular disease, by ultrasound high‐resolution B‐mode imaging. In analysis 1, it was compared with the predicted mean IMT based on data from existing risk factors (age, male sex, dyslipoproteinaemia, hypertension, diabetes mellitus, smoking status) in 282 non‐acromegalic subjects. In analysis 2, the mean IMT in the 21 acromegalic patients was compared with that in 42 non‐acromegalic subjects matched for age, sex and the other atherosclerotic risk factors. We also analysed clinical characteristics between the acromegalic patients with and without the atherosclerosis.RESULTSMean IMT in 21 acromegalic patients was 0·92 ± 0·21 (mean ± SD) mm. It was significantly (P < 0·05) lower than the mean IMT (1·03 ± 0·12 mm) predicted from their existing risk factors (analysis 1). It was also less than that in 42 non‐acromegalic subjects matched for atherosclerotic risk factors (1·07 ± 0·37 mm;P < 0·05) (analysis 2). Among the acromegalic patients, 10 patients (48%) had increased mean IMT (≧ 1·1 mm) and/or plaque lesions whereas the other 11 had no such atherosclerotic changes. In the patients without the atherosclerotic changes, plasma insulin‐like growth factor‐I (IGF‐I) concentration was significantly (P < 0·01) higher, and the prevalence of hypertension was significantly (P < 0·05) lower than in those with the atherosclerotic changes.CONCLUSIONSThe extent of carotid atherosclerosis in the acromegalic patients was not higher than that in non‐acromegalic subjects, considering their atherosclerotic risk factors. Increased concentration of IGF‐I might be involved in the lack of susceptibility to atherosclerosis in some acromegalic patients.
Hormone replacement therapy and risk of falling in early postmenopausal women – a population‐based study
Authors: Randell Kaisa M. , Honkanen Risto J. , Komulainen Marja H. , Tuppurainen Marjo T. , Kröger Heikki , Saarikoski Seppo 
Published: March 2003

OBJECTIVE The purpose of this study was to examine the effect of hormone (oestrogen) replacement therapy (HRT) on the risk of falling among early postmenopausal women.METHODS We assessed the incidence of falls in HRT users compared to non‐users using population‐based data from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study. The study group consisted of 9792 postmenopausal women who responded to the OSTPRE baseline and follow‐up inquiries.RESULTS A total of 3049 women reported sustaining a fall during the previous 12 months. The association between current continuous use of HRT and overall risk of falling was non‐significant − 9% (P = 0·10). However, current continuous HRT use was associated with a decreased risk (− 30%) of non‐slip falls (N = 1129) (P = 0·0001) but not with the risk (+ 9%) of slip falls (N = 1757) (P = 0·23). In early postmenopausal women (time since menopause < 5 years) the protective effect of current continuous HRT was strengthened: the risk of non‐slip falls was 71% lower in HRT users than non‐users (P = 0·0035) if menopause had occurred within the past 2·5 years, and 43% lower (P = 0·0015) if time since menopause was 2·5–5 years.CONCLUSION Hormone replacement therapy may reduce the risk of non‐slip falls in early postmenopausal women.
Additive effect of alfacalcidol on bone mineral density of the lumbar spine in Taiwanese postmenopausal women treated with hormone replacement therapy and calcium supplementation: a randomized 2‐year study
Authors: Chen Ming , Chow Song‐Nan 
Published: March 2003

OBJECTIVETo evaluate the effect of 1α‐hydroxyvitamin D3on bone mineral density of the lumbar spine in postmenopausal women receiving hormone replacement therapy and calcium supplement.DESIGNA randomized, prospective 2‐year clinical trial.PATIENTS AND MEASUREMENTSA total of 240 postmenopausal women were enrolled with randomized assignment of 120 patients to each treatment group (the D + E group of 1α‐hydroxyvitamin D3+ sequential combined HRT + calcium supplement; the E group: sequential combined HRT + calcium supplement). None of the patients had received HRT for menopausal syndrome or osteoporosis before being enrolled in our study. Serum biochemical assays, electrolytes and calcitonin were performed at baseline and after 6 and 12 months of treatment. Bone mineral density (BMD) of L2–L4 was measured by dual energy X‐ray absorptiometry (DXA) at the initial assessment and after 12 and 24 months of treatment.RESULTSOne hundred and five patients (87·5%) in the D + E group and 92 patients (76·7%) in the E group completed the first 1‐year study. Ninety‐six patients (80%) in the D + E group and 80 patients (66·7%) in the E group completed the 2‐year trial. Renal function, liver function, electrolytes and calcitonin showed no significant changes during the first year of follow‐up. In the D + E group, the BMD of L2–4 increased 3·24 ± 0·32% from baseline after 1 year (P < 0·05) and 5·32 ± 0·23% after 2 years of treatment (P < 0·05). On the other hand, the changes of BMD in the E group were 1·12 ± 0·34% after 1 year (P < 0·05) and 2·42 ± 0·26% after 2 years of treatment (P < 0·05). The changes of BMD of L2–L4 of the D + E group were higher than the changes of the E group after both 1 and 2 years of treatment (P < 0·05).CONCLUSIONSOur study demonstrated that combination of 1α‐hydroxyvitamin D3with HRT is superior to HRT alone for the preservation of bone mineral density in postmenopausal women under calcium supplementation.
Prevalence of gestational thyrotoxicosis in Asian women evaluated in the 8th to 14th weeks of pregnancy: correlations with total and free beta human chorionic gonadotrophin
Authors: Yeo Chin Pin , Khoo Daphne Hsu Chin , Eng Peter Hsi Ko , Tan Hak Koon , Yo Sui Lan , Jacob Edward 
Published: March 2003

OBJECTIVES The prevalence of gestational transient thyrotoxicosis (GTT) in Europeans evaluated during the 8th to 14th weeks of pregnancy is 2–3%. However, there is evidence that GTT may be more common in some Asian populations. The aims of this study were to evaluate the prevalence of thyroid hormone abnormalities in Asian women in their 8th to 14th weeks of pregnancy using highly sensitive free T4 and TSH assays and to correlate these with total and free β‐hCG levels.DESIGN AND PATIENTS One hundred and eighty‐four consecutive unselected Asian (Singaporean) pregnant women seen at ante‐natal clinics for the first time and who were in their 8th to 14th weeks of pregnancy were tested.MEASUREMENTS Serum free T4, free T3, TSH, total β‐hCG and free β‐HCG levels were measured on the Vitros ECi system (Johnson & Johnson Ortho‐Clinical Diagnostics, Amersham, UK) which employs chemiluminescent immunochemical technology. This free T4 assay is free of biases related to serum binding capacity. The TSH assay used was a third generation assay. Thyrotrophin‐receptor antibody (TRAb) levels were measured using LUMItest TRAK (BRAHMS Diagnostica, Berlin, Germany).RESULTS Two subjects (1·1%) were found to have Graves' disease. Elevated free T4, free T3, total T3 and suppressed TSH were seen in 14·8%, 3·3%, 26·4% and 33·0% of the remaining 182 pregnant women, respectively. Total and free β‐hCG correlated negatively with TSH (r = −0·30, P < 0·0001 and r = −0·29, P < 0·0001, respectively), positively with fT4 (r = 0·283, P < 0·001 and r = 0·253, P < 0·001) and fT3 (r = 0·273, P < 0·001 and r = 0·204, P < 0·01). 11·0% of cases had gestational thyrotoxicosis (GT) defined as elevated free T4 (> 19·1 pmol/l), suppressed TSH (< 0·36 mIU/l) and TRAb levels within the reference interval (0–0·9 U/l). The prevalence of GT was significantly higher in patients tested at 8–11 weeks compared to those evaluated at 12–14 weeks (14·4% vs. 4·7%, P < 0·05). Total β‐hCG (P = 0·0002), free β‐hCG (P < 0·0001) and free T4 (P = 0·02) levels were higher and TSH levels (P = 0·01) lower in patients tested at 8–11 weeks. Significant positive correlations between both total and free β‐hCG with free T4 were seen at 8–11 weeks but not in patients tested at 12 weeks or later. TT3 levels were similar in the two groups.CONCLUSIONS Using sensitive assays, the prevalence of gestational thyrotoxicosis in Asian women was found to be 11·0% and was significantly higher in subjects at 8–11 weeks of gestation than at 12–14 weeks. The positive correlation between hCG and free T4 seen in patients tested at 8–11 weeks was absent in patients tested at later stages of the first trimester. Future studies investigating the entity of gestational thyrotoxicosis, at least in Asian patients, should focus on patients at earlier stages of gestation than currently practised.
A placebo‐controlled trial of long‐term oral combined continuous hormone replacement therapy in postmenopausal women: effects on arterial compliance and endothelial function
Authors: Teede Helena J. , Liang Yu‐Lu , Kotsopoulos Dimitra , Zoungas Sophia , Craven Robyn , McGrath Barry P. 
Published: March 2003

OBJECTIVE To study the effects of long‐term combined continuous oral hormone replacement therapy (HRT) on vascular function in healthy postmenopausal women.BACKGROUND The cardiovascular effects of HRT are controversial. Improvement in vascular function is a proposed mechanism of oestrogen action but there are no long‐term controlled human trials in this area. In this study, we examined the effects of HRT on lipid profiles and vascular function, encompassing both biomechanical arterial properties [systemic arterial compliance (SAC) and pulse wave velocity (PWV)] and endothelial function [flow‐mediated vasodilation (FMD)].METHODS In this 2‐year, double‐blind, placebo‐controlled study, 59 healthy postmenopausal women were randomized to oral combined continuous oestrogen and progesterone [Kliogest®, oestradiol (2 mg), norethisterone (1 mg)] or placebo, with end‐points measured at baseline, 6 weeks and after 6, 12 and 24 months of treatment.RESULTS Oral combined HRT reduced lipoprotein a [Lp(a)], although other lipid benefits were not observed. There were no significant changes in SAC, PWV or FMD with oral combined HRT, compared to placebo.CONCLUSION In this long‐term, randomized placebo‐controlled trial, oral continuous HRT with combined oestradiol and norethisterone in healthy postmenopausal women did not improve a spectrum of indices of arterial function compared to placebo. These results suggest that HRT might not be of cardiovascular benefit in postmenopausal women.
The CAG repeat polymorphism in the androgen receptor gene affects bone density and bone metabolism in healthy males
Authors: Zitzmann Michael , Brune Maik , Kornmann Britta , Gromoll Jörg , Junker Ralf , Nieschlag Eberhard 
Published: March 2003

OBJECTIVE Bone metabolism and bone density (BD) are influenced by sex hormones. Testosterone (T) action is exerted through the androgen receptor (AR). We investigated the potential impact of the CAG repeat (CAGR) polymorphism within the AR gene on BD and bone metabolism in healthy younger males.PATIENTS AND MEASUREMENTS The number of CAGRs in 110 healthy men aged 20–50 years was determined by sequence analysis. We assessed BD by the radiation‐free method of quantitative ultrasound (QUS) of the phalanges. Serum levels of bone‐specific alkaline phosphatase (BAP) and urine secretion of free deoxypyridinoline (DPD, corrected for creatinine), serum levels of sex hormones, body fat content and lifestyle factors were determined.RESULTS In stepwise multiple regression models controlling for age, body fat content and lifestyle factors, the number of CAGRs was an independent negative predictor of BD (partial r = − 0·286, P = 0·001), whereas it was positively associated with markers of bone turnover (for BAP: partial r = 0·32, P = 0·001; for DPD: partial r = 0·241, P = 0·013). Levels of free T and oestradiol showed an independent and positive association with BD; age contributed significantly to lower BD. Age and free T were negatively associated with markers of bone turnover, whereas oestradiol showed a positive correlation with BAP and DPD. anova in groups according to age and the CAGR length suggested an increased age‐dependent bone loss in subjects with a CAGR length of 22–31 compared with 14–21 CAGRs (overall P < 0·01).CONCLUSIONS A high number of CAG repeats within the androgen receptor gene attenuates testosterone effects on bone density and bone metabolism. This seems to be associated with accelerated age‐dependent bone loss.