bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low serum concentrations of insulin‐like growth factor I are associated with femoral bone loss in a population‐based sample of postmenopausal women
Authors: Seck Thomas , Scheidt‐Nave Christa , Leidig‐Bruckner Gudrun , Ziegler Reinhard , Pfeilschifter Johannes 
Published: March 2003

OBJECTIVE Cross‐sectional studies suggest that the decline in insulin‐like growth factor‐I (IGF‐1) levels with age may contribute to age‐associated bone loss. However, prospective data on the relation between circulating IGF‐I and bone loss in old age have not yet been reported.DESIGN A longitudinal study (follow‐up time 3·3 years) of the change of bone mineral density (BMD) at the lumbar spine and femoral neck in relation to serum IGF‐I.PATIENTS A population‐based sample of 173 elderly men and 107 postmenopausal women without medical conditions or medication known to significantly affect BMD or serum IGF‐I levels.MEASUREMENTS BMD at the lumbar spine and femoral neck at baseline and after a mean follow‐up‐time of 3·3 years, serum‐IGF‐I, insulin‐like growth factor binding protein 3 (IGFBP‐3), sex hormone‐binding globulin (SHBG) and biologically available testosterone (BAT).RESULTS In women, there was a graded negative relationship between quartiles of serum IGF‐I and bone loss at the proximal femur (P = 0·04), which persisted after adjustment for potential covariables of bone loss and serum IGF‐I. In subgroup analysis the association between serum IGF‐I and change in BMD was only apparent in women more than 10 years past menopause (r = + 0,38, P = 0·01). No association between serum IGF‐I levels and changes in BMD was observed in men. IGF‐I levels were not associated with changes in spinal BMD.CONCLUSIONS Our data suggest that low circulating levels of IGF‐I in elderly women are associated with greater femoral bone loss, and support previous findings of gender differences in the relation between serum IGF‐I and BMD in older age.
Thyroid function in survivors of childhood acute lymphoblastic leukaemia: the significance of prophylactic cranial irradiation
Authors: Lando Ane , Holm Kirsten , Nysom Karsten , Rasmussen Åse Krogh , Feldt‐Rasmussen Ulla , Petersen Jørgen Holm , Müller Jørn 
Published: March 2003

OBJECTIVE Focus on long‐term side‐effects after cancer therapy in childhood has become of the utmost importance. The hypothalamic‐pituitary thyroid (HPT) axis is exposed to irradiation when some children are treated for acute lymphoblastic leukaemia (ALL) with prophylactic cranial irradiation (CIR). Whether this treatment causes hypofunction of the HPT axis remains controversal.DESIGN We measured plasma levels of total T3 (T3), total T4 (T4) and TSH before stimulation with TRH and plasma levels of TSH, 30 and 150 minutes after stimulation with TRH in 95 patients in first continuous remission of childhood ALL.PATIENTS Patients diagnosed with ALL before the age of 15 years between 1970 and 1991 and who were in first continuous remission and off treatment for at least one year were studied. The children were aged between 0·5 and 14·8 years (median: 3·9) at diagnosis of ALL. Thyroid function was assessed between 1·2 and 18·3 years (median: 7·6) after completion of therapy.MEASUREMENTS We measured T4 levels before, and compared TSH levels before and after, stimulation with TRH in patients who were treated with prophylactic CIR (15–24 Gy) (n = 38) (CIR group) with patients who were treated with chemotherapy only (n = 57) (non‐CIR group).RESULTS We found that T3 and T4 levels were normal in all individuals (excluding the women who were on oral contraceptives). The median time from end of treatment to time at follow‐up was 9·1 years in the non‐CIR group vs. 4·2 years in the CIR group (P < 0·001), and the effect on follow‐up time was significant (P = 0·04). It was estimated that just after irradiation, the TSH levels before and 30 and 150 minutes after TRH stimulation was 49% lower in the CIR group; however, after 4·0 years, TSH levels were not significantly different between the two groups. Although within normal limits, the T4 levels were significantly higher in the CIR group compared to the non‐CIR group (P = 0·003). It was estimated that, just after the end of treatment, T4 was 19·9% higher in the CIR group. However, in the CIR group, the T4 level decreased significantly over time with −1·5% per year (P = 0·025), while the difference in the non‐CIR group was not significant. There was no correlation between T4 and TSH levels and sex, age at diagnosis, age at the end of treatment or age at follow‐up.CONCLUSIONS We conclude that, in our cohort of survivors of childhood ALL, prophylactic cranial irradiation of the central nervous system did not have an adverse effect on hypothalamo‐pituitary‐thyroid function within a median follow‐up time of 8 years.
Computer assisted learning is an effective way of teaching endocrinology
Authors: Holt Richard I. G. , Miklaszewicz Pawel , Cranston Iain C. , Russell‐Jones David , John Rees P. , Sönksen Peter H. 
Published: March 2003

OBJECTIVES Computers are a part of everyday life and offer an exciting way of learning. The aim of our study was to determine the effectiveness of teaching undergraduate endocrinology using a Computer Assisted Learning (CAL) programme.DESIGN AND SUBJECTS One hundred and eighty‐five first year clinical medical students were randomly assigned either to attend a series of conventional lectures (n = 77) or to have the same material available through a CAL programme.MEASUREMENTS A multiple choice question examination was performed before and after the course. Lecture attendance and individual usage of the computer system were recorded. Students were asked to fill in an evaluation form at the end of the study.RESULTS There was no significant difference in the first examination scores between the groups. Both groups improved their scores after the course. Students spent longer performing CAL than attending lectures. Those who scored lowest in the first examination spent the most time on the CAL course. Those who spent the most time on the CAL course showed the largest improvement in examination score. Thirty‐six out of the 42 students, who completed an evaluation of the CAL programme, rated it better than the standard lectures.CONCLUSIONS Computer assisted learning is an effective way of increasing knowledge in teaching undergraduate endocrinology. The course was easy to run and was valued more highly than conventional lectures. The module is now running routinely in the year 3 clinical firms at St Thomas' and has resulted in an increase in knowledge in the end of firm assessment.
Long‐term follow‐up of contralateral lobe in patients hemithyroidectomized for solitary follicular adenoma
Authors: Niepomniszcze Hugo , Garcia Alejandro , Faure Eduardo , Castellanos Alejandro , Del Carmen Zalazar Maria , Bur Grato , Elsner Boris 
Published: March 2003

OBJECTIVES Since there are no available conclusive studies on the long‐term evolution of remnant thyroid tissue after hemithyroidectomy in patients who undergo surgery for solitary follicular adenomas, we searched for such cases in our records to elucidate this issue.DESIGN Search criteria were as follows: (i) presence of a single palpable thyroid nodule with the remainder of the gland normal on palpation; (ii) clinically euthyroid status at the time of surgery; (iii) histological diagnosis of nodule as follicular adenoma; (iv) a hemithyroidectomy operation, sparing the contralateral lobe; (v) normal macroscopic aspect of the contralateral lobe at the time of surgery; and (vi) at least 4 years of postoperative follow‐up.PATIENTS Only 47 female cases were found to meet above criteria, with a mean age of 45·9 years (range: 23–79) at the time of surgery and a mean follow‐up of 7·2 years (range: 4–32). Besides evaluating the presence or absence of antithyroid antibodies and the extranodular histology of tissue removed during surgery, a preoperative TRH test also allowed patients to be classified into two groups: normal extranodular thyroid (NET) (n = 32) and abnormal extranodular thyroid (AET) (n = 15).RESULTS Eleven of the 15 patients with AET had thyroid autoimmunity, with or without overt histological thyroiditis, and the remaining four had subclinical hypothyroidism with negative antithyroid antibody titres. In the entire study population, only 28 patients received treatment with L‐T4 immediately after surgery, none of whom had any alterations in the contralateral lobe. However, six of the nineteen patients not treated with T4 (31·6%) developed overt abnormalities in the contralateral lobe, including the only three with AET who had not received L‐T4 treatment. The remaining three were two patients with NET, who showed postoperative TSH hyper‐responsiveness to TRH (peak TSH > 25 mU/l), and one who developed a new follicular adenoma 32 years later. To date, none of the patients with NET, who had a normal TRH test after surgery, have developed any kind of alterations in the contralateral lobe, even those who received no L‐T4 prophylactic treatment.CONCLUSIONS The findings of this study suggest that: (i) there is a higher risk of follicular adenomas developing in a gland affected by thyroid autoimmunity than in a previously normal gland; (ii) L‐T4 therapy may prevent the formation of new nodules or the development of goitre in the contralateral lobe; and (iii) in the absence of prophylactic treatment after surgery, the contralateral lobe of subjects with thyroid autoimmunity and/or previous subclinical hypothyroidism develops morphological abnormalities.
Clinical features in women with polycystic ovaries: relationships to insulin sensitivity, insulin gene VNTR and birth weight
Authors: Michelmore Katherine , Ong Ken , Mason Sam , Bennett Simon , Perry Leslie , Vessey Martin , Balen Adam , Dunger David 
Published: March 2003

OBJECTIVE Polycystic ovaries are a common ultrasound finding, yet few of these women have many clinical features of polycystic ovary syndrome. Clinical presentation may relate to degree of insulin resistance, common polymorphism at the insulin gene VNTR, and birth weight. We therefore examined the relationship between insulin sensitivity, insulin gene VNTR genotype, birth weight and presence of polycystic ovaries/features of polycystic ovary syndrome in a normal population study.DESIGN AND PATIENTS In 224 young women recruited as normal volunteers, ovarian morphology was determined by transabdominal ultrasound and features of polycystic ovary syndrome were identified on clinical and biochemical examination. Insulin sensitivity was estimated from fasting glucose and insulin levels using the homeostasis model. Insulin gene VNTR genotypes were determined in women and their parents.MEASUREMENTS AND RESULTS Thirty‐three per cent (74/224) had polycystic ovaries on ultrasound. These women had higher birth weights (P = 0·004), higher insulin sensitivity (P = 0·02) and higher leptin levels for body mass index (P = 0·04) than women with normal ovaries. However among women with polycystic ovaries, increasing severity of clinical phenotype (based on number of features of: menstrual irregularity, acne, hirsuitism, serum testosterone > 3 mmol/l and LH > 10 IU/l) was associated with decreasing insulin sensitivity (P < 0·0001) and related to paternally transmitted insulin gene VNTR class III alleles (P = 0·03).CONCLUSION Women with polycystic ovaries on ultrasound have increased insulin sensitivity and possible leptin resistance, which could predispose to future weight gain. However, in these women the appearance of clinical features of polycystic ovary syndrome is related to insulin resistance and insulin gene VNTR class III alleles.
Relationships between the TaqI polymorphism of the dopamine D2 receptor and blood pressure in hyperglycaemic and normoglycaemic Chinese subjects
Authors: Thomas G. Neil , Critchley Julian A. J. H. , Tomlinson Brian , Cockram Clive S. , Chan Juliana C. N. 
Published: March 2003

BACKGROUND We have previously reported an association of the A2 allele of the dopamine D2 receptor (DRD2) TaqI polymorphism with increased blood pressure in normoglycaemic Chinese subjects, but conversely possibly with decreased indices of obesity. Hypertension is also a common feature of patients with type 2 diabetes, with up to 50% being hypertensive.OBJECTIVE To compare the relationship between the DRD2 TaqI polymorphism, blood pressure and obesity in Chinese patients with and without fasting hyperglycaemia.METHOD The DRD2 TaqI polymorphism was determined by PCR‐RFLP in 519 normoglycaemic and 471 hyperglycaemic Chinese subjects, of whom 53·2 and 48·8% were hypertensive, respectively.RESULTS In the normoglycaemic subjects there was a significant increase in mean arterial pressure (P = 0·041) with increasing proportions of the A2 allele, 95 ± 16, 96 ± 17 and 100 ± 17 mmHg for the A1A1, A1A2 and A2A2 genotypes, respectively. However, the relationship was not observed in the subjects with fasting hyperglycaemia either in the total group or in the subgroup who were not receiving blood pressure‐lowering medication (n = 383, 97 ± 15, 98 ± 14 and 97 ± 15 mmHg, respectively). When the whole group was divided into those subjects obese by either body mass index or waist‐to‐hip ratio (n = 484) and those subjects not obese by both these criteria (n = 506), the A1 allele (49·2 vs. 43·8%, P = 0·02) and A1 allele containing genotypes (P = 0·03) were more frequent in the obese subjects. Similar relationships were seen in the normoglycaemic and hyperglycaemic groups separately, although these did not reach significance.CONCLUSIONS In the normoglycaemic subjects, the A2 allele was associated with increased blood pressure and possibly lower indices of obesity, but in the hyperglycaemic subjects only the possible association with obesity was noted.
Reduced capillary permeability and capillary density in the skin of GH‐deficient adults: improvement after 12 months GH replacement
Authors: Oomen P. H. N. , Beentjes J. A. M. , Bosma E. , Smit A. J. , Reitsma W. D. , Dullaart R. P. F. 
Published: March 2003

Summaryobjective Several lines of evidence suggest that the GH–IGF‐1 axis affects capillary permeability and angiogenesis. We evaluated skin capillary permeability and capillary density in GH‐deficient adults, before and after GH replacement therapy.patients Seven normotensive, nondiabetic GH‐deficient adults (two women) were matched with 14 control subjects.measurements Large‐window videodensitometry with sodium fluorescein was performed in all subjects. Capillary permeability was expressed as the average relative light intensity over the first 7 min after the appearance of fluorescein in the skin capillaries; Iav(7). Skin capillary density was determined by counting the visualized capillaries and was expressed as n/mm2. The GH‐deficient patients were restudied after 12 months of GH replacement therapy (2 U/day).results Both capillary permeability and capillary density were lower in untreated GH‐deficient patients than in control subjects (median, interquartile range): Iav(7) in GH‐deficient patients 47·1 (45·1–52·2)%vs. 57·5 (50·5–64·8)% in controls, P < 0·05; capillary density in GH‐deficient patients 18 (12–24)/mm2 vs. 32 (26–36)/mm2 in controls, P < 0·05. GH treatment normalized plasma IGF‐1 from 4·3 (1·0–13·4) to 22·2 (19·8–48·2) nmol/l (P < 0·05). Furthermore, both capillary permeability [Iav(7) 53·1 (48·8–58·4)%, P < 0·05] and capillary density [26 (17–34)/mm2, P < 0·05] increased to a level that was not different from that in control subjects.conclusions The present study demonstrates that the growth hormone deficiency syndrome is associated with microvascular alterations, which are responsive to growth hormone replacement therapy.
The effects of hormone replacement therapy on endothelial function in women with Turner’s syndrome
Authors: Chan N. Norman , Vallance Patrick , Colhoun Helen M. , MacAllister Raymond J. , Hingorani Aroon D. , Conway Gerard S. 
Published: March 2003

Summaryobjectives To examine the effect of hormone replacement therapy (HRT) on endothelial function of forearm resistance vessels in women with Turner’s syndrome.design Subjects were studied on three occasions: on their usual HRT (study 1), then after 6 weeks off HRT (study 2) and finally after a further 6 weeks on HRT (study 3).patients Seven young women with Turner’s syndrome were studied.measurements Forearm blood flow in response to intrabrachial infusion of bradykinin, 10, 30, 100 pmol/min (endothelium‐dependent vasodilator), glyceryl trinitrate, 4, 8, 16 nmol/min (GTN; endothelium‐independent vasodilator), noradrenaline, 60, 120, 240 pmol/min (NA, α‐adrenergic receptor agonist) and NG‐monomethyl‐l‐arginine, 1, 2, 4 µmol/min (L‐NMMA; NO synthase inhibitor) was assessed by bilateral venous plethysmography.results The vasodilator response to bradykinin, expressed as the within‐subject mean difference in area under the dose–response curve between study 2 and study 1, was significantly diminished (−744·2 ± 287·2, P = 0·04) but improved 6 weeks after HRT recommencement. However, there was no significant change in response to GTN (between study 2 and study 1, 189·5 ± 247·8, P = 0·47). The vasoconstrictor response to L‐NMMA was also diminished in study 2 when compared to study 1 (−100·4 ± 35·4, P = 0·039) and was restored after HRT was recommenced (between study 3 and study 2, 117·5 ± 69·3, P = 0·17) whereas there was no significant difference in response to NA between study 2 and study 1 (76·7 ± 50·6, P = 0·18) or study 3 and study 2 (−70·8 ± 71·1, P = 0·38).conclusions HRT improves endothelial function in women with Turner’s syndrome.
Screening for macroprolactinaemia and pituitary imaging studies
Authors: Hauache Omar M. , Rocha Antonio J. , Maia Antonio C. M. , Maciel Rui M. B. , Vieira José Gilberto H. 
Published: March 2003

Summaryobjective Hyperprolactinaemia is caused by high levels of monomeric, dimeric or macro forms of prolactin in circulation, the monomeric form being predominant in patients with prolactinomas. Macroprolactinaemia, however, is common and is associated with asymptomatic cases. In this study, we reviewed our records regarding clinical and imaging investigations in patients who were found to have hyperprolactinaemia predominantly due to the presence of macroprolactin and compared them with the findings observed in patients whose prolactin molecular size consisted predominantly of the monomeric form.patients and methods We conducted a retrospective study of 113 consecutive patients (nine men and 104 women, aged 19–67 years, median age 39 years) with hyperprolactinaemia who were screened for the presence of macroprolactin by polyethylene glycol precipitation and/or chromatography and submitted to pituitary magnetic resonance imaging (MRI) and/or computerized tomography (CT).results Fifty‐two of 113 patients (46%) had hyperprolactinaemia due to macroprolactin, whereas the remaining 61 patients (54%) had their hyperprolactinaemia confirmed by the predominance of the monomeric form. Both groups shared similar mean prolactin levels (79·9 ± 63·6 µg/l, median of 62·0 µg/l, and 97·9 ± 155·4 µg/l, median of 61·0 µg/l, respectively). Of the patients with macroprolactinaemia, 46% had no symptoms of hyperprolactinaemia, whereas only 10% of the patients who screened negative for macroprolactin were asymptomatic. There was an association between macroprolactinaemia and negative pituitary imaging findings: normal pituitary images were found in 78·9% of patients who had macroprolactinaemia and in 25% of patients with monomeric hyperprolactinaemia. In addition, none of the patients with macroprolactinoma (seven cases) had macroprolactinaemia.conclusions The presence of macroprolactinaemia does not exclude the possibility of a pituitary adenoma and consequently may not prevent pituitary imaging studies. However, our data demonstrate that all asymptomatic patients who screened positive for macroprolactin had normal pituitary imaging studies. Patient samples showing hyperprolactinaemia should be first tested for macroprolactin, before the patient is submitted to imaging studies. We suggest that imaging studies should be ordered in patients with macroprolactinaemia when indicated by clinically relevant features. As a result, unnecessary anxiety and costly medical procedures may be prevented.
The metabolic effects of short‐term administration of physiological versus high doses of GH therapy in GH deficient adults
Authors: Yuen K. , Cook D. , Ong K. , Chatelain P. , Fryklund L. , Gluckman P. , Ranke M. B. , Rosenfeld R. , Dunger D. 
Published: March 2003

Summaryobjective GH treatment has demonstrated favourable effects on most features of GH deficiency in hypopituitary adults. However, most studies employed supraphysiological GH doses, resulting in deterioration in insulin sensitivity (SI). The short‐term metabolic effects of physiological doses of GH therapy in GH deficient (GHD) adults are largely unknown. We therefore compared the effects of short‐term administration of two ‘physiological’ (‘lowest’ dose: 0·0017 mg/kg/day; ‘low’ dose: 0·0033 mg/kg/day) with two ‘supraphy‐siological’ (‘high’ dose: 0·010 mg/kg/day; ‘highest’ dose: 0·025 mg/kg/day) GH doses on SI, β‐cell function, IGF‐1 and IGFBPs −1 and −3 in a group of GHD adults.patients and methods Thirteen GHD adults were recruited (seven men, aged 23–63 years). For each of the four doses, six patients (three men) were allocated randomly to undergo a 7‐day treatment phase. Fasting blood samples were collected daily (days 1–8), and SI and β‐cell function were calculated using the homeostasis model assessment (HOMA).results All four GH doses increased IGF‐1, IGFBP‐3 and IGF‐1/IGFBP‐3 ratio, and decreased IGFBP‐1 from day 3 onwards (P < 0·05). The highest dose increased fasting glucose (P < 0·001), insulin (P < 0·001) and β‐cell function (P < 0·001), but decreased SI (P < 0·001). The high and low doses did not modify fasting glucose and insulin, SI or β‐cell function, whereas the lowest dose enhanced β‐cell function (P < 0·05). The overall increase in the GH dose increased IGF‐1, IGFBP‐3, fasting glucose and insulin (P < 0·001), demonstrated a positive correlation with the final change in fasting glucose (r = 0·5, P < 0·05) and insulin (r = 0·8, P < 0·001) and a negative correlation with final SI (r = −0·5, P < 0·05).conclusions Our results suggest that short‐term administration of the highest GH dose induced insulin resistance, whereas the lowest dose (0·0017 mg/kg/day) could represent the optimal starting dose in GHD adults due to its beneficial effects on β‐cell function without compromising SI. It is, however, yet to be determined whether the positive effects of the lowest GH dose on β‐cell function can be demonstrated over a longer period of time.