bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of the selective oestrogen receptor modulator—raloxifene—on calcium and PTH secretory dynamics in women with osteoporosis
Authors: Oleksik A. , Duong T. , Popp‐Snijders C. , Pliester N. , Asma G. , Lips P. 
Published: March 2003

OBJECTIVES A possible mechanism for the maintenance of bone mass by oestrogens and the selective oestrogen receptor modulator (SERM)—raloxifene—is an interaction with calciotropic hormones. We studied the effects of raloxifene on calcium‐PTH homeostasis.PATIENTS AND MEASUREMENTS Calcium and EDTA infusions were performed in 32 post‐menopausal women with osteoporosis (BMD T score < − 2·5). This cross‐sectional study was performed in the third year of the MORE (Multiple Outcomes of Raloxifene Evaluation) trial, a double‐blind, placebo‐controlled study. After an overnight fast, calcium glubionate (5 mg/kg BW*h), and after 2·5 h of test‐free interval, Na3EDTA (40 mg/kg BW*h) were given intravenously. The duration of infusions was based on individual plasma total calcium before the calcium infusion (t = 0), the target calcium (2·60 and 1·95 mmol/l, respectively), and desired mean calcium change (0·010 mmol/L*min). Blood samples were taken at 0 and every 5 minutes of both infusions. Plasma PTH levels were fitted into an inversed sigmoidal relation with plasma calcium. The effect of raloxifene on calcium‐PTH homeostasis was tested in linear regression models adjusted for age and BMI. Nine patients used placebo, 13 raloxifene 60 mg/day and 10 raloxifene 120 mg/day.RESULTS Raloxifene use was associated with lower plasma albumin (40·7 ± 1·8 vs. 38·0 ± 2·0 and 38·5 ± 2·3 g/l, for placebo, raloxifene 60 mg/day and raloxifene 120 mg/day, respectively, P = 0·01), lower plasma total calcium at t = 0 (2·28 vs. 2·24 and 2·21; ± 0·07 mmol/L; P = 0·03), lower plasma total calcium at 50% of maximal PTH secretion (PTH set‐point: 2·23 ± 0·06 vs. 2·18 ± 0·07 and 2·16 ± 0·08 mmol/l, P = 0·06), and lower plasma non‐suppressible PTH (0·84 ± 0·19 vs. 0·75 ± 0·10 and 0·73 ± 0·05 pmol/l, P = 0·02). After correction for plasma albumin, the differences for plasma calcium at t = 0 and at PTH set‐point were no longer significant. In contrast, the difference in PTH suppression during calcium load was not explained either by differences in plasma albumin or calcium.CONCLUSION Raloxifene did not have any detectable effect on the PTH set‐point. An effect on non‐suppressible PTH secretion cannot be excluded.
Bone metabolism and body composition in Japanese patients with active acromegaly
Authors: Kaji Hiroshi , Sugimoto Toshitsugu , Nakaoka Daiki , Okimura Yasuhiko , Kaji Hidesuke , Abe Hiromi , Chihara Kazuo 
Published: March 2003

OBJECTIVE Skeletal involvement is a common clinical feature in acromegalic patients. Although several recent reports are available concerning bone mineral density (BMD) in acromegaly, the controversy still exists as to whether BMD of acromegalic patients is increased or not. The present study was performed to examine biochemical bone metabolic indices and BMD as well as body composition in 26 Japanese patients with active acromegaly and 26 control subjects matched for age, sex, race and height in a cross‐sectional study.MEASUREMENTS BMD of the lumbar spine and femoral neck, as well as body composition, was measured by dual‐energy X‐ray absorptiometry. Mid‐radial BMD was measured by single‐photon absorptiometry. We also determined serum levels of IGF‐I, IGFBP‐3 and osteocalcin (OC) as well as urinary levels of deoxy‐pyridinoline (D‐Pyr) and CrossLaps.RESULTS Percent lean body mass was increased and percent fat mass was decreased in the acromegalic patients compared to control subjects. Serum levels of OC, as well as urinary levels of D‐Pyr and CrossLaps, were significantly higher in acromegalic patients compared to control subjects (9·8 ± 1·2 vs. 5·7 ± 0·77 for OC; 11·8 ± 1·66 vs. 5·0 ± 0·49 for D‐Pyr; 437·6 ± 68·4 vs. 156·5 ± 39·6 for CrossLaps). Z scores of BMD at mid‐radius as well as lumbar spine and femoral neck were significantly higher in acromegalic patients compared to control subjects (1·086 ± 0·311 vs.−0·060 ± 0·274 for mid‐radius; 1·022 ± 0·280 vs. 0·319 ± 0·165 for lumbar spine; 1·292 ± 0·347 vs. 0·232 ± 0·264 for femoral neck).CONCLUSIONS The present study revealed that a decrease in percent fat mass and an increase in percent lean body mass were observed in Japanese patients with active acromegaly. Bone mineral density at all sites and bone metabolic markers were also increased in acromegaly. The present findings provide additional evidence that the GH/IGF‐I axis might play an important role in the maintenance of bone mass as well as the regulation of body composition in Japanese adults.
Hyperthyroidism is associated with lengthening of ventricular repolarization
Authors: Colzani R. M. , Emdin M. , Conforti F. , Passino C. , Scarlattini M. , Iervasi G. 
Published: March 2003

OBJECTIVELengthened ventricular repolarization, as assessed by the QT interval on electrocardiogram (ECG), can predispose to an increased risk of cardiac dysrhythmias; no data are available on QT corrected for heart rate (QTc) in hyperthyroidismin vivo.DESIGNQT and RR intervals from 24 h ambulatory ECG Holter recording were measured in patients with hyperthyroidism and again following pharmacological achievement of stable euthyroidism for at least 2 months.PATIENTSWe enrolled a total of 16 hyperthyroid patients with Graves' disease, six males and 10 females (mean age 47 ± 4 years, mean ± SEM); 13 healthy age‐ and sex‐matched subjects were utilized as a control group.MEASUREMENTSThe QT analysis was carried out by a computerized algorithm (QTc was corrected by the heart rate by Bazett's formula). Serum total T4, total T3, free T4, free T3 and TSH concentrations were measured by a fully automated immunoenzymometric assay; plasma norepinephrine by automatized high‐pressure liquid chromatography, potassium and chloride by a potentiometric method, magnesium and calcium by a colourimetric method.RESULTSThe 24‐h average QTc in the hyperthyroid patients was significantly prolonged compared to controls (458 ± 7vs.431 ± 6 ms,P = 0·01) and it returned to normal after treatment of thyrotoxicosis (432 ± 6 ms,P < 0·05vs.time H, NSvs.controls). QTc positively correlated with FT3 (r = 0·63,P < 0·001) and with FT4 (r = 0·481,P < 0·02). Conversely, QTc did not correlate with plasma basal norepinephrine levels, nor with electrolytes.CONCLUSIONSHyperthyroidism is associated with prolonged QTc that normalizes once the patient becomes euthyroid. The strong positive correlation between FT3 and QTc supports the hypothesis of an important role of thyroid hormone on modulation of QTc lengthening.
The nature of human chorionic gonadotrophin glycoforms in gestational thyrotoxicosis
Authors: Talbot J. A. , Lambert A. , Anobile C. J. , McLoughlin J. D. , Price A. , Weetman A. P. , Robertson W. R. 
Published: March 2003

OBJECTIVE We examined the charge heterogeneity and carbohydrate complexity of hCG in healthy pregnant Asian subjects and Asian women with gestational thyrotoxicosis to assess whether particular glycoforms of hCG are associated with the thyrotoxicosis of pregnancy.DESIGN Blood was taken at 8–16 weeks of gestation from five pregnant Asian women with clinical symptoms of gestational thyrotoxicosis and biochemical indicators of hyperthyroidism and from six age‐matched healthy pregnant women. hCG charge heterogeneity and carbohydrate complexity were assessed by fast protein liquid chromatography chromatofocusing and concanavalin A affinity chromatography, respectively. The degree of terminal sialylation of the different glycoforms was measured by ricin affinity chromatography, which detects exposed galactose residues following desialylation.RESULTS Free T3, free T4 and hCG levels were elevated and TSH suppressed in the thyrotoxic subjects compared to controls (P < 0·007). Overall, the glycoform distribution of the hCG in the blood from the control and thyrotoxic groups was similar, with a median pI of 4·34 (median and range: 3·78–4·68) and pI 4·23 (3·98–4·38). Free T4 (P < 0·028) and free T3 (P < 0·03) levels were positively correlated to both the absolute hCG concentration and the percentage of hCG forms between pI 3·36–4·0. The distribution of simple (73–88·6%), intermediate (9·7–26·4%) and complex (0·1–7·3%) branching oligosaccharide forms was similar in both groups, as was the percent hCG which bound to ricin (< 3·2%).CONCLUSION We conclude that excessive thyroid stimulation in the thyrotoxic patients is associated both with the absolute concentration of hCG and the relative proportion of acidic glycoforms between pI 3·36 and 4·0.
Mothers with congenital adrenal hyperplasia and their children: outcome of pregnancy, birth and childhood
Authors: Krone Nils , Wachter Isolde , Stefanidou Marianna , Roscher Adelbert A. , Schwarz Hans Peter 
Published: March 2003

OBJECTIVES Fertility rates in women with congenital adrenal hyperplasia (CAH) are reported to be poor, but few data are available. We assessed rates and course of pregnancy, mode of delivery and long‐term outcome of offspring from women with CAH.DESIGN A large cohort of women with CAH due to 21‐hydroxylase deficiency had initially been diagnosed and followed at one centre. Those women who had given birth were contacted. Information was gathered from hospital records, direct patient contact, structured questionnaire and the Documentation of Pregnancy and Preventive Care Booklets.RESULTS Between 1978 and 1998, 18 women with CAH (one salt wasting, 12 simple virilizing, five nonclassical) had given birth to 31 children (18 females, 13 males). Delivery was by Caesarean section in 16 out of the 31 children. None of the female newborns was masculinized. Twenty‐nine children were born at term, five children were small for gestational age (SGA). Postnatal development was basically normal in all children; 18 are now older than 10 years, seven are between 5 and 10 years old, six are less than 5 years old.CONCLUSIONS Fertility is reduced in females with CAH, especially those with the severe or salt wasting phenotype. In those women with CAH who do conceive, course and outcome of pregnancy is mostly uneventful, although the rate of SGA offspring may be increased. Psychomotor and somatic long‐term development of the children was within normal limits.
Indirect evidence for decreased hypothalamic somatostatinergic tone in anorexia nervosa
Authors: Støving R. K. , Andersen M. , Flyvbjerg A. , Frystyk J. , Hangaard J. , Vinten J. , Koldkjær O. G. , Hagen C. 
Published: March 2003

Summaryobjective In animals, somatostatin (SRIH) and growth hormone (GH)‐releasing hormone (GHRH) increase feeding via a common neural mechanism. Furthermore, SRIH counteracts the suppressive action of corticotrophin‐releasing hormone (CRH) on food intake. Hypothetically, SRIH could be involved in the central feeding mechanism in anorexia nervosa (AN). Peripheral administration of pyridostigmine (PD) minimizes the release of hypothalamic SRIH.design To study the influence of hypothalamic somatostatinergic inhibition on the exaggerated somatotroph responsiveness to GHRH in patients with severe AN, two GHRH stimulation tests were performed in random order following pretreatment with placebo or PD 2 mg/kg body weight in 13 patients and in 10 age‐matched healthy controls. The test procedure was repeated in the patients after weight gain.results In controls, PD potentiated the GHRH‐stimulated GH rise but this effect was absent in AN patients. The relative potentiating effect of PD was inversely correlated to cortisol excretion levels and positively correlated to leptin serum levels. After weight gain the relative PD effect increased twofold.conclusion The pyridostigmine–GHRH responsive pattern points indirectly to greater SRIH withdrawal and greater GHRH release in anorexia nervosa. Moreover, hypothalamic SRIH activity seems to be inversely related to cortisol levels, indirectly supporting the hypothesis that SRIH and CRH neuronal activity are inversely related in anorexia nervosa. Leptin, which is believed to act on hypothalamic feeding mechanisms, seems to be positively related to SRIH activity. Finally, the present data demonstrate that the potentiating effect of pyridostigmine in anorexia nervosa is related to body mass index and increases upon weight gain, suggesting that the low somatostatinergic tone is not primary but is related to the weight loss.
Clinical significance of elevated level of serum antithyroglobulin antibody in patients with differentiated thyroid cancer after thyroid ablation
Authors: Chung J.‐K. , Park Y. J. , Kim T. Y. , So Y. , Kim S.‐K. , Park D. J. , Lee D. S. , Lee M. C. , Cho B. Y. 
Published: March 2003

Summaryobjective This study was designed to investigate whether an elevated serum antithyroglobulin antibody (TgAb) reflects cancer recurrence in thyroglobulin (Tg)‐undetectable patients with differentiated thyroid carcinoma (DTC) after thyroid ablation.design We measured serum TgAb level and evaluated the disease status in 226 DTC patients who had undergone remnant ablation and showed an undetectable Tg result as assessed by immunoradiometric assay.measurements Radioligand assay of TgAb was performed. Recurrence was assessed by 131I scan, 18F‐fluorodeoxyglucose positron emission tomography, sonography, computed tomography, or by surgical operation.results Fifty‐one patients (22·6%) of the Tg‐undetectable patients showed positive TgAb, and 25 (49·0%) of these were confirmed with recurrence. The recurrence rate of TgAb‐positive patients was higher than that of TgAb‐negative patients (3·4%; P < 0·0001). During follow‐up, 73·1% of the disease‐free patients showed spontaneously decreased TgAb levels. A total of 71·4% of patients with recurrent cancer, who showed responses to surgical operation or radio‐iodine treatment, also showed a decreased TgAb level.conclusions Persistently elevated TgAb levels appear to serve as a useful marker for recurrent or persistent DTC in patients with undetectable serum Tg results. Thus, the routine measurement of TgAb in such patient populations may be indicated.
Spontaneous growth hormone secretory characteristics in children with partial growth hormone insensitivity
Authors: Bjarnason Ragnar , Banerjee Kausik , Rose Steven J. , Rosberg Sten , Metherell Louise , Clark Adrian J. L. , Albertsson‐Wikland Kerstin , Savage Martin O. 
Published: March 2003

Summaryobjective To investigate the characteristics of spontaneous GH secretion in four male children with short stature due to partial GH insensitivity. Their molecular defect consists of inclusion of a mutant intronic pseudoexon in the region of the GH receptor involved in homodimerization.subjects The subjects were two pairs of brothers who were first cousins, aged 10·4–14·2 years, heights −3·3 to −5·6 SDS, from a consanguineous Pakistani family. Basal serum IGF‐I levels were extremely low (20–29 mg/l; NR > 50), with absent or minimal response to human recombinant GH (hGH) stimulation. Serum IGFBP‐3 SDS levels were also low (−2·9 to −8·9). GH binding protein (GHBP) levels were normal (28·1–51·7%).methods Spontaneous GH secretion was studied by intermittent (20 min) venous sampling from 2000 to 0800 h. The secretion profiles were analysed using the Pulsar programme and compared to data from a reference population of 76 prepubertal Swedish children [median age 10·7 years, median height −1·1 SDS (−2·0 to 1·4)] according to Swedish growth standards.results Median (range) Pulsar‐derived values in the four patients and controls were, respectively: GHmax (mU/l) 276·6 (178·7–325·8) and 27·2 (13·1–94·9), mean GH (mU/l) 64·5 (41·9–77·8) and 5·8 (3·2–20·6), baseline (mU/l) 12·3 (11·7–20·1) and 1·1 (0·2–6·1), AUCb (mU/l × 24 h) 1210 (684–1555) and 112·5 (60·6–316·4), i.e. all parameters of GH secretion in the four patients were markedly elevated compared with the control population.conclusions Spontaneous GH secretion is elevated in partial GH insensitivity. This investigation could be of diagnostic value in children with short stature.
Transdermal oestradiol replacement therapy enhances platelet constitutive nitric oxide synthase activity in postmenopausal women with type 2 diabetes mellitus
Authors: Martina Valentino , Bruno Guido Albino , Origlia Carla , Gaia Daniela , Trucco Fulvia , Pescarmona Gianpiero 
Published: March 2003

Summaryobjective To determine whether treatment with transdermal oestrogen replacement therapy (TERT) in postmenopausal women with type 2 diabetes mellitus was able to increase the activity of constitutive nitric oxide synthase (cNOS) in platelets.research design and methods Eighteen postmenopausal women with type 2 diabetes mellitus (group A) were studied in basal conditions (A1) and on the 10th day of the third month of a sequential opposed TERT (A2) evaluating platelet cNOS activity measured by the conversion of radiolabelled l‐arginine to l‐citrulline. As a control group (B) 25 normal postmenopausal women underwent the same treatment (B1 and B2 before and during treatment, respectively).results Basal values of platelet cNOS activity were superimposable (0·6 ± 0·1 vs. 0·7 ± 0·1 fmol/min/109 plts, NS). During TERT, platelet cNOS activity rose in A and B (0·6 ± 0·1 vs. 1·8 ± 0·1 fmol/min/109 plts, P < 0·05 and 0·7 ± 0·1 vs. 2·4 ± 0·2, P < 0·001, A1 vs. A2 and B1 vs. B2, respectively). However, platelet cNOS activity of A2 did not reach the values of B2 (1·8 ± 0·1 vs. 2·4 ± 0·2 fmol/min/109 plts, P < 0·05; A2 vs. B2, respectively).conclusions Sequential opposed transdermal oestrogen replacement therapy was able to increase platelet cNOS activity in postmenopausal women with type 2 diabetes mellitus, suggesting that its use might be positive in preventing cardiovascular pathologies.
Underexpression of Gcm2, a master regulatory gene of parathyroid gland development, in adenomas of primary hyperparathyroidism
Authors: Correa Pamela , Åkerström Göran , Westin Gunnar 
Published: March 2003

Summaryobjective Glial cells missing (Gcm) was first identified as a binary switch between neuronal and glial determination in Drosophila. Two homologues of DrosophilaGcm have been identified in mice and humans, namely Gcm1 and Gcm2. Mouse Gcm2 is restricted to parathyroid tissues and Gcm2 was recently identified as a master regulatory gene of parathyroid gland development as Gcm2 knockout mice lack parathyroid glands.design/patients To identify Gcm2 transcripts in human non‐neural tissues and to examine whether Gcm2 is involved in parathyroid gland tumorigenesis we analysed Gcm2 transcript levels in several non‐neural tissues by reverse transcriptase polymerase chain reaction (RT‐PCR) and performed real‐time quantitative RT‐PCR analysis on five normal glands, 15 parathyroid adenomas of primary hyperparathyroidism (HPT) and nine hyperplastic glands of secondary HPT.results We found high Gcm2 mRNA expression in human parathyroid glands in comparison with other non‐neural tissues and underexpression in parathyroid adenomas but not in lesions of HPT secondary to uraemia.conclusion Because adenomas demonstrate lower Gcm2 expression than normal glands we suggest that reduced expression of Gcm2 contributes to parathyroid gland tumorigenesis. We speculate that a proper expression level of the Gcm2 transcription factor could be important for maintaining a fully differentiated state of the parathyroid cell.
Preparation for radioactive iodine administration in differentiated thyroid cancer patients
Authors: Liel Yair 
Published: March 2003

Summaryobjective Because in recent years the practice of TSH suppression has changed, and thyroxine doses have been reduced significantly in the treatment of patients with low‐risk differentiated thyroid cancer, the goal of this study was to determine the time needed to attain a target TSH level (of 30 mIU/l) following levothyroxine withdrawal in patients treated with thyroxine according to current guidelines, in anticipation of radioactive iodine (RAI) administration.design Observational study.patients Thirteen consecutive patients with differentiated thyroid cancer on suppressive doses of levothyroxine planned for RAI administration. Five of the patients received cholestyramine in an attempt to facilitate TSH recovery.measurements Serum TSH, free‐T3 and free‐T4, at 3–4‐day intervals.results In 13 patients on suppressive doses of thyroxine, on 15 separate occasions, baseline TSH levels were between 0·01 and 0·4 mIU/l. The mean interval required to reach the target TSH concentration of at least 30 mIU/l was 17 days (95% CI 15–19; range 11–28 days). Cholestyramine had no effect on the rate of TSH recovery. Once TSH concentration became detectable, it increased exponentially; and once it reached the upper limit of normal, it rarely took more than 10 days to attain target level.conclusions Attaining target TSH level before radioactive iodine administration requires a considerably shorter time than is currently recommended. Reducing preparation time might improve patients’ acceptance of the procedure.
Thyroid peroxidase and thyroglobulin autoantibodies in a large survey of populations with mild and moderate iodine deficiency
Authors: Pedersen Inge Bülow , Knudsen Nils , Jørgensen Torben , Perrild Hans , Ovesen Lars , Laurberg Peter 
Published: March 2003

Summarybackground and aims Autoimmune thyroiditis is one of the most common autoimmune disorders. Autoantibodies against the thyroid gland, with thyroid peroxidase antibody (TPO‐Ab) and thyroglobulin antibody (Tg‐Ab) as the most common autoantibodies, can often be demonstrated in serum in population surveys. In the present study we evaluated if TPO‐Ab and Tg‐Ab tend to develop in parallel or whether one or the other may be more prevalent in subsets of the population.methods In a cross‐sectional comparative study, performed in two areas of Denmark with mild and moderate iodine deficiency, 4649 randomly selected subjects in age groups between 18 and 65 years were examined. Blood tests were analysed for TPO‐Ab and Tg‐Ab using assays based on the radioimmunoassay (RIA) technique. The participants answered questionnaires, were clinically examined and had urine samples collected.results The overall prevalence rate of thyroid autoantibodies (TPO‐Ab and/or Tg‐Ab) was 18·8%. The prevalence rates of TPO‐Ab and Tg‐Ab were similar (13·1 vs. 13·0%). Both antibodies were more frequent in females than in males, and in females the prevalence rates increased with age. In the age group 60–65 years thyroid antibodies were more frequently measured in sera from moderate than from mild iodine‐deficient area (P = 0·02), whereas no differences were seen in younger subjects. In 38·8% of participants with thyroid autoantibodies in serum, both antibodies were present. In sera with both TPO‐Ab and Tg‐Ab present the concentrations of the antibodies were generally higher than in sera with only one type of antibody present.conclusion The prevalence rates of TPO‐Ab and Tg‐Ab were similar in this large population survey. The results suggest that TPO‐Ab and Tg‐Ab predominantly develop due to a general alteration in the immune system, whereas specific antigenic mechanisms are probably of less importance. However, further studies are needed to clarify the mechanisms involved in the development of thyroid autoantibodies.