bluuebunny/crossref_metadata_2025_split huggingface dataset:
Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients
Authors: Kreutzer J , Buslei R , Wallaschofski H , Hofmann B , Nimsky C , Fahlbusch R , Buchfelder M 
Published: January 2008

ObjectiveMedical therapy with dopamine agonists (DA) is the primary treatment of choice in most patients with prolactinomas. ‘Classical’ surgical indications are intolerance or lack of efficiency of DA therapy. Focusing on a possible shift of recent indications, we retrospectively analyzed our results of surgical treatment in prolactinomas.Patients and methodsBetween 1990 and 2005, we have operated on 212 consecutive patients with prolactinomas. Surgical indications were divided into ‘classical’ indications and ‘modern’ indications defined as cystic prolactinomas or patients with microprolactinomas who individually decided on a primary surgical treatment.ResultsInitial overall remission was accomplished in 53.2% including giant prolactinomas. However, in microadenomas, the remission rate was significantly higher with 91.3%. Overall remission at the latest follow-up was 42.7%, but 72.5% in intrasellar tumors, 80% in cystic prolactinomas, and 84.8% in microprolactinomas. The overall recurrence rate was 18.7%. Relapse of hyperprolactinemia in microprolactinomas was 7.1%. In our series, continually less patients were surgically treated for ‘classical’ indications. By contrast, the number of patients who individually decided on a primary surgical therapy has increased considerably.ConclusionRemission rates after surgical treatment of prolactinomas remain excellent, particularly in microadenoma and intrasellar macroadenomas, whereas morbidity of transsphenoidal surgery is low in the hands of experienced pituitary surgeons. Our remission rates not only confirm the already interdisciplinarily accepted surgical indications, but also emphasize the value of primary transsphenoidal surgery as a discussion-worthy alternative to dopaminergic therapy in young patients with microprolactinomas or cystic tumors.
Changes in heart rate variability and QT dispersion in patients with overt hypothyroidism
Authors: Galetta Fabio , Franzoni Ferdinando , Fallahi Poupak , Tocchini Leonardo , Braccini Lara , Santoro Gino , Antonelli Alessandro 
Published: January 2008

ObjectiveThe aim of the present study was to evaluate the effect of clinical hypothyroidism on cardiovascular autonomic function and ventricular repolarization.Design and methodsWe studied 31 patients (22 females and 9 males; mean age 53.6±11.8 years) with overt hypothyroidism (TSH=56.2±14.7 μU/ml, low free thyroxine (T4), free tri-iodothyronine (T3)) and 31 euthyroid controls, to investigate the dispersion of the QT interval in electrocardiogram (ECG) (an index of inhomogeneity of repolarization) and heart rate variability (HRV; a measure of cardiac autonomic modulation). The hypothyroid patients and controls underwent a full medical examination, standard 12-lead ECG, and 24-h ambulatory ECG monitoring. The hypothyroid patients were re-examined after 6 months of treatment with l-T4.ResultsPatients with hypothyroidism showed higher QT dispersion and lower HRV measures than controls (P<0.01 or P<0.001). In hypothyroid patients, standard deviation of all R–R intervals was inversely related (by simple regression) to serum (log)TSH levels (r=−0.47, P=0.008), while QT dispersion (r=0.50, P=0.004) and QTc dispersion (r=0.46, P=0.008) were directly related to (log)TSH. Parameters of HRV improved after 6 months of l-T4 treatment, with the correction of hypothyroidism, becoming comparable with those of the control subjects, whereas the QT and QTc dispersion results were found to be only partially restored, remaining higher than the controls.ConclusionsThe results of the study demonstrate that hypothyroidism is associated with a decreased sympatho-vagal modulation of the heart rate and with an increased inhomogeneity of ventricular recovery times. The assessment of HRV and QT dispersion in patients with overt hypothyroidism may represent a useful tool in monitoring the cardiovascular risks.
Changes in circulating level of IGF-I and IGF-binding protein-1 from the first to second trimester as predictors of preeclampsia
Authors: Vatten Lars J , Nilsen Tom I L , Juul Anders , Jeansson Stig , Jenum Pål A , Eskild Anne 
Published: January 2008

ObjectiveTo assess whether circulating IGF-I and IGF-binding protein-1 (IGFBP-1) in the first and second trimester are associated with subsequent risk of preterm and term preeclampsia.MethodsNested case–control study within a cohort of 29 948 pregnant women. Cases were women, who later developed preeclampsia, and controls were randomly selected women, who did not develop preeclampsia. IGF-I and IGFBP-1 were measured with ELISA in maternal blood samples that were collected in the first and second trimesters. We assessed associations of IGF-I and IGFBP-1 concentrations with later development of preterm (before the 37th week of gestation) and term preeclampsia.ResultsAn increase in IGF-I from the first to second trimester was associated with higher risk of preterm preeclampsia; the odds ratio (OR) for the highest compared with lowest quartile of increase was 4.9 (95% confidence interval, 1.1–21.8). Low concentrations of IGFBP-1, both in the first and in the second trimesters, were related to higher risk of term preeclampsia (OR 4.0, 95% confidence interval, 1.9–8.4) and moderately increased risk of preterm preeclampsia (OR 2.3, 95% confidence interval, 1.2–4.4).ConclusionThe higher risk of preterm preeclampsia related to IGF-I increase may reflect placental disease, whereas low concentrations of IGFBP-1 associated with term preeclampsia may reflect maternal metabolic aberrations, indicating different etiologies in preeclampsia.
The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation
Authors: Phan Ha T T , Jager Pieter L , van der Wal Jacqueline E , Sluiter Wim J , Plukker John T M , Dierckx Rudi A J O , Wolffenbuttel Bruce H R , Links Thera P 
Published: January 2008

ObjectiveThis retrospective study describes the role of serum thyroglobulin (Tg) in relation to tumor characteristics in the prediction of persistent/recurrent disease in patients with differentiated thyroid cancer (DTC) with negative Tg at the time of ablation.DesignBetween 1989 and 2006, 94 out of 346 (27%) patients with DTC had undetectable Tg at the time of131I ablation and were included in this evaluation. The group of 94 patients consisted of 15 males and 79 females in the age range of 16–89 years with a median follow-up of 8 years (range 1–17). All medical records and follow-up parameters of the 94 patients were evaluated for the occurrence of persistent/recurrent disease. In patients with persistent/recurrent disease hematoxylin-eosin-stained slides of the primary tumors and/or metastatic lesions were also reviewed for histological features including immunostains for Tg.ResultsDuring follow-up, 8 out of 94 (8.5%) patients showed persistent/recurrent disease: in the course of the disease two patients showed Tg positivity, three showed Tg antibody (TgAb) positivity, and the other three showed persistently undetectable Tg and TgAb. Patients who developed Tg and/or TgAb positivity during follow-up had a significantly shorter disease-free survival period when compared with patients with persistently undetectable Tg and TgAb (P<0.006). Histological features were not able to predict the recurrent status.ConclusionsFollow-up of Tg and TgAb in patients with initially negative Tg and TgAb is useful since a number of patients had shown detectable Tg or TgAb during follow-up indicative for persistent/recurrent disease. Tg and TgAb negativity at the time of ablation is not a predictive determinant for future recurrent status.
Genetic investigation of four meiotic genes in women with premature ovarian failure
Authors: Mandon-Pépin Béatrice , Touraine Philippe , Kuttenn Frédérique , Derbois Céline , Rouxel Agnes , Matsuda Fumihiko , Nicolas Alain , Cotinot Corinne , Fellous Marc 
Published: January 2008

ObjectiveThe goal of this study was to determine whether mutations of meiotic genes, such as disrupted meiotic cDNA (DMC1), MutS homolog (MSH4),MSH5, andS. cerevisiaehomolog (SPO11), were associated with premature ovarian failure (POF).DesignCase–control study.MethodsBlood sampling, karyotype, hormonal dosage, ultrasound, and ovarian biopsy were carried out on most patients. However, the main outcome measure was the sequencing of genomic DNA from peripheral blood samples of 41 women with POF and 36 fertile women (controls).ResultsA single heterozygous missense mutation, substitution of a cytosine residue with thymidine in exon 2 ofMSH5, was found in two Caucasian women in whom POF developed at 18 and 36 years of age. This mutation resulted in replacement of a non-polar amino acid (proline) with a polar amino acid (serine) at position 29 (P29S). Neither 36 control women nor 39 other patients with POF possessed this genetic perturbation. Another POF patient of African origin showed a homozygous nucleotide change in the tenth ofDMC1gene that led to an alteration of the amino acid composition of the protein (M200V).ConclusionsThe symptoms of infertility observed in theDMC1homozygote mutation carrier and in both patients with a heterozygous substitution in exon 2 of theMSH5gene provide indirect evidence of the role of genes involved in meiotic recombination in the regulation of ovarian function.MSH5andDMC1mutations may be one explanation for POF, albeit uncommon.
A purification step prior to commercial sensitive immunoassay is necessary to achieve clinical usefulness when quantifying serum 17β-estradiol in prepubertal children
Authors: Ankarberg-Lindgren Carina , Norjavaara Ensio 
Published: January 2008

ObjectiveTo test the clinical usefulness of sensitive commercial immunoassays for determination of low 17β-estradiol concentrations in children.MethodsThe lower limit of detection and clinical usefulness (functional sensitivity) of three commercial estradiol immunoassays were validated by use of 500 sera from prepubertal and pubertal children and 55 pooled sera. The three immunoassays consisted of two modified direct immunoassays; one RIA (Spectria Estradiol RIA) and one time-resolved fluoroimmunoassay (AutoDELFIA Estradiol), both with increased serum volume in relation to antibody concentration and extended incubation time. In the third method, serum was purified and concentrated using diethyl ether extraction prior to measurement by the modified Spectria Estradiol RIA.ResultsThe lower limits of detection and clinical usefulness were 9 and 30 pmol/l for the direct RIA, 11 and 50 pmol/l for the AutoDELFIA, and 4 and 6 pmol/l for serum determined by extraction RIA. When measuring the serum pool originating from girls at breast stages 1–2, the direct RIA and AutoDELFIA resulted in significantly higher 17β-estradiol concentrations when compared with the extraction RIA (+58 and +267%,P<0.001). We found a significant difference in 17β-estradiol concentrations between girls at breast stages 1 (median 6 pmol/l) and 2 (median 16 pmol/l), when quantified by the extraction RIA (P<0.0001) but no difference when quantified with the direct RIA (median values 12 and 14 pmol/l respectively).ConclusionFor determination of low serum 17β-estradiol concentrations in children, an extraction step prior to commercial immunoassay is needed to achieve clinically useful results.
Ghrelin and acyl ghrelin in preterm infants and maternal blood: relationship with endocrine and anthropometric measures
Authors: Lányi Éva , Várnagy Ákos , Kovács Kálmán A , Csermely Tamás , Szász Mária , Szabó István 
Published: January 2008

ObjectiveThe objective of the present study was to examine the association of acylated and total ghrelin levels at birth in preterm infants with anthropometric features and with related hormones in infants and their mothers.DesignProspective, descriptive study.MethodsIn total 23 pregnant women and their 26 preterm infants were involved in the study (3 twin pregnancies; gestational age, 25–35 weeks). Maternal and umbilical vein blood samples were taken after the delivery. Serum acylated and total ghrelin, leptin, cortisol, insulin, GH, and glucose were determined.ResultsThe mean level of acylated ghrelin concentration was higher in the maternal than in the cord blood (P<0.01) and there was a significant correlation between the fetal and maternal acylated ghrelin levels (P<0.01). The total ghrelin concentration was higher in neonates than in mothers (P<0.01), but there was no correlation between them. The multivariate regression analysis for fetal acylated and maternal total ghrelin as dependent variables shows that the fetal acylated ghrelin has two independent predictors, the maternal acylated ghrelin (P<0.01) and the fetal cortisol (P<0.05), whereas the maternal total ghrelin has only one independent predictor, the maternal glucose (P<0.05).ConclusionsThese data provide the first evidence that umbilical cord acylated ghrelin concentrations are lower than in maternal blood and support the hypothesis that the acylation process in the fetus is partly affected by cortisol and the placenta may play a role in this process.
TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study
Authors: Laurberg Peter , Wallin Göran , Tallstedt Leif , Abraham-Nordling Mirna , Lundell Göran , Tørring Ove 
Published: January 2008

IntroductionAutoimmunity against the TSH receptor is a key pathogenic element in Graves' disease. The autoimmune aberration may be modified by therapy of the hyperthyroidism.ObjectiveTo compare the effects of the common types of therapy for Graves' hyperthyroidism on TSH-receptor autoimmunity.MethodsPatients with newly diagnosed Graves' hyperthyroidism aged 20–55 years were randomized to medical therapy, thyroid surgery, or radioiodine therapy (radioiodine was only given to patients ≥35 years of age). l-thyroxine (l-T4) was added to therapy as appropriate to keep patients euthyroid. Anti-thyroid drugs were withdrawn after 18 months of therapy. TSH-receptor antibodies (TRAb) in serum were measured before and for 5 years after the initiation of therapy.ResultsMedical therapy (n=48) and surgery (n=47) were followed by a gradual decrease in TRAb in serum, with the disappearance of TRAb in 70–80% of the patients after 18 months. Radioiodine therapy (n=36) led to a 1-year long worsening of autoimmunity against the TSH receptor, and the number of patients entering remission of TSH-receptor autoimmunity with the disappearance of TRAb from serum during the following years was considerably lower than with the other types of therapy.ConclusionThe majority of patients with Graves' disease gradually enter remission of TSH-receptor autoimmunity during medical or after surgical therapy, with no difference between the types of therapy. Remission of TSH-receptor autoimmunity after radioiodine therapy is less common.
Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol
Authors: Dullaart Robin P F , Groen Albert K , Dallinga-Thie Geesje M , de Vries Rindert , Sluiter Wim J , van Tol Arie 
Published: January 2008

ObjectiveWe tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport pathway, is maintained despite low high-density lipoprotein (HDL) cholesterol.DesignIn 76 subjects with and 94 subjects without MetS based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, we determined plasma (apo)lipoproteins, pre-β-HDL formation, phospholipid transfer protein (PLTP) activity, cholesterol esterification (EST), cholesteryl ester transfer (CET), adiponectin, and the ability of plasma from each subject to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single donor.ResultsApo E, PLTP activity, EST, and CET were higher (P=0.04 to <0.001), whereas adiponectin was lower in MetS subjects (P<0.01). Pre-β-HDL and pre-β-HDL formation were not different between subjects with and without MetS. Cellular cholesterol efflux to plasma from MetS subjects was slightly higher versus plasma from subjects without MetS (8.8±1.0 vs 8.5±0.9%,P=0.05), but the difference was not significant after age, sex, and diabetes adjustment. Cellular cholesterol efflux was positively related to pre-β-HDL formation, EST, PLTP activity, and apo E (P<0.05 for all by multiple linear regression analysis), without an independent association with MetS and diabetes status.ConclusionsThe ability of plasma from MetS subjects to promote fibroblast cholesterol efflux is not defective, although HDL cholesterol is decreased. Higher cholesterol esterification, PLTP activity, and apo E levels may contribute to the maintenance of cholesterol efflux in MetS.
Relation of plasma homocysteine levels to atherosclerotic vascular disease and inflammation markers in type 2 diabetic patients
Authors: Akalin Aysen , Alatas Ozkan , Colak Omer 
Published: January 2008

ObjectiveBoth hyperhomocysteinemia and increased inflammatory activity are shown to be associated with atherosclerosis. The relation of inflammatory activity to homocysteine (Hcy) levels is not well established. In the present study, we aimed to evaluate the relation of plasma Hcy levels to atherosclerotic vascular disease and inflammatory activity in type 2 diabetic patients.Design and methodsIn total 90 type 2 diabetic patients were included in the study. Of these patients, 41 had established atherosclerotic vascular disease and 49 had no evidence of atherosclerotic vascular disease. Hcy levels and markers of inflammation, namely C-reactive protein, fibrinogen, erythrocyte sedimentation rate, interleukin-6, and tumor necrosis factor α (TNFα), were measured. Glucose regulation, C-peptide, lipid parameters, and renal functions were also studied.ResultsBoth Hcy levels and inflammation markers were all significantly elevated in patients with atherosclerotic vascular disease when compared with patients without vascular disease. Reduced renal functions were responsible for the majority of Hcy elevation in patients with vascular disease. Also, renal functions were significantly associated with both Hcy levels and inflammatory markers. There was no correlation between Hcy levels and inflammation markers except for TNFα.ConclusionsInflammatory activity and Hcy levels are increased in type 2 diabetic patients with atherosclerotic vascular disease. Impairment of renal functions is the key factor that affects both Hcy levels and inflammation markers. Inflammation is not involved in the process by which Hcy leads atherosclerosis in type 2 diabetes.
Restoration of ovulation after unilateral ovariectomy in a woman with McCune–Albright syndrome: a case report
Authors: Lavoué Vincent , Morcel Karine , Bouchard Philippe , Sultan Charles , Massart Catherine , Grall Jean-Yves , Lumbroso Serge , Laurent Marie-Christine 
Published: January 2008

IntroductionMcCune–Albright syndrome (MAS) is characterized by peripheral precocious puberty, café-au-lait spots, and polyostotic fibrous dysplasia. This syndrome is due to a post-zygotic mutation of the GNAS1 gene with mosaic distribution and unilateral predominance. Clinical manifestations depend on the tissues carrying the mutation. We describe the ovarian function before and after unilateral ovariectomy in a woman with MAS and bilateral distribution of the GNAS1 gene mutation.Case reportA 33-year-old patient, previously diagnosed as having MAS, presented irregular menstrual cycles (30–180 days) and monophasic temperature curves. Transvaginal ultrasound and blood tests were repeated at 3-day intervals over 3 months. Findings included a persistent quiescent left ovary, a persistent polycystic right ovary, constantly high estradiol-17β (E2) levels, and very low FSH and LH levels. She also presented severe persistent pelvic pain. Because of unilateral ovarian activity, a unilateral right ovariectomy was performed as well as biopsy of the remaining left ovary. A GNAS1 gene mutation was identified in both ovaries. A regular monthly menstrual cycle was immediately restored. On day 3 of the menstrual cycle, E2 level was 30 pg/ml, FSH level was 7.5 mIU/ml, and LH level was 6.4 mIU/ml. On day 17, pelvic ultrasound showed one follicle of 25 mm in the left ovary. On day 21, the progesterone level was 13.1 ng/ml.DiscussionThis is the first report of ovulation being restored following unilateral ovariectomy in an adult patient suffering from severe MAS with GNAS1 gene mutation identified in both ovaries.
Hypothalamic–pituitary insufficiency following infectious diseases of the central nervous system
Authors: Schaefer S , Boegershausen N , Meyer S , Ivan D , Schepelmann K , Kann P H 
Published: January 2008

ObjectiveHypothalamic–pituitary insufficiency may have diverse causes. The aim of this study was to determine the incidence of hypothalamic–pituitary insufficiency in patients with previous infectious diseases of the central nervous system (CNS) of different etiologies and mild-to-moderate clinical course.DesignPatient series. Basal and stimulated (insulin tolerance test) pituitary function testing was performed in 19 patients with previous neuroborreliosis, encephalitis, or meningitis following an interval of between 10 and 56 months (mean 26.1±13.1 months) after the acute event.ResultsFour patients (21%; two males, two females) showed an isolated corticotropic insufficiency (peak cortisol <181.25 μg/l during the insulin tolerance test). Two patients (11%, males) showed borderline gonadotropic insufficiency (basal testosterone between 2.4 and 3.0 μg/l). No patient had somatotropic or thyrotropic insufficiency or evidence for diabetes insipidus; all had prolactin concentrations within the reference range.ConclusionsHypothalamic–pituitary dysfunction and especially isolated corticotropic insufficiency may develop in a relevant proportion of patients after infectious diseases of the CNS.
Preliminary data on biochemical remission of acromegaly after somatostatin analogs withdrawal
Authors: Ronchi Cristina L , Rizzo Erica , Lania Andrea G , Pivonello Rosario , Grottoli Silvia , Colao Annamaria , Ghigo Ezio , Spada Anna , Arosio Maura , Beck-Peccoz Paolo 
Published: January 2008

ObjectiveIt is still unknown whether prolonged treatment with somatostatin analogs (SSTa) may cause a long-lasting disease remission in GH-secreting adenomas after drug discontinuation. The aim of the present study was to investigate the evolution of GH/IGF-I secretion and tumor mass after SSTa withdrawal in patients affected by acromegaly.Patients and DesignA total of 27 patients with acromegaly (12de novoand 15 previously operated) were treated with SSTa for a median period of 48 months and considered optimally controlled in hormonal and neuroradiological terms. None of them were previously irradiated.MethodsBasal GH, post-glucose GH nadir, IGF-I, clinical signs/symptoms, and metabolic parameters were evaluated after 12–16 weeks from drug withdrawal. Only patients who met the current criteria for disease remission remained in drug suspension being periodically re-evaluated for biochemical/clinical data and neuroradiological imaging.ResultsAfter 12–16 weeks withdrawal, 15 of the 27 patients had disease relapse and restarted SSTa, while 12 were considered ‘in disease remission’ (44% of total). Glucose metabolism improved in both euglycemic and diabetic patients after short-term SSTa discontinuation. Only one of the ten patients who reached 24 weeks withdrawal showed biochemical disease recurrence. On the whole, five of the patients still in remission after 6 months have already prolonged the follow-up over 12 months (median: 24 months), without clinical and biochemical/neuroradiological evidence of disease recurrence.ConclusionsThese preliminary data indicate a successful withdrawal of SSTa at least in a subset of well-responsive patients with acromegaly and challenge the previously held concept that medical therapy is always a lifelong requirement.