bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating acylated and total ghrelin and galanin in children with insulin‐treated type 1 diabetes: relationship to insulin therapy, metabolic control and pubertal development
Authors: Celi F. , Bini V. , Papi F. , Santilli E. , Ferretti A. , Mencacci M. , Berioli M. G. , De Giorgi G. , Falorni A. 
Published: July 2005

SummaryObjective  To study the circulating levels of two gut‐derived peptides in children with type 1 (insulin‐dependent) diabetes mellitus (IDDM).Research Design and Methods  Plasma levels of ghrelin, both total ghrelin (TG) and the acylated form (AG), and galanin and their relationships with insulin dosage, metabolic control, IGFBP‐1, body mass and pubertal development were evaluated in 91 children, aged 11·1 ± 2·7 years, affected by IDDM and treated with insulin. Ninety‐one healthy children were selected as controls.Results  Body mass index (BMI)‐adjusted levels of both forms of ghrelin were reduced in IDDM compared with healthy subjects, with greater values in prepubertal than pubertal IDDM subjects. A negative association was found between AG and fasting insulin serum levels and insulin resistance [measured by using the homeostasis model assessment of insulin resistance (HOMA IR)] among the healthy children. IDDM children showed a negative association of their plasma ghrelin (both acylated and total) with daily insulin dosage, and the three adiposity indices (BMI, skinfold thickness and percentage fat mass). IGFBP‐1 levels were higher among the IDDM children without any association with ghrelin serum values. BMI‐adjusted plasma levels of galanin were higher among IDDM compared to healthy subjects, irrespective of sex or pubertal development. Greater values for galanin were found among pubertal than prepubertal subjects in both groups without any significant differences between the genders. A positive association was found between galanin and BMI in both groups and between galanin and haemoglobin A1c (HbA1c) among the IDDM children. No relationship existed between either galanin and fasting serum insulin among the healthy subjects or galanin and both insulin dosage or duration of treatment among the IDDM subjects.Conclusions  The associations found between both ghrelin and galanin with adiposity indices could be considered as an indirect signal of involvement of the two peptides in the development of the nutritional status of the IDDM adolescents. The reduction in both forms of ghrelin could be involved in the development of the body mass increase of IDDM subjects with opposite effects, either influencing insulin sensitivity or exerting a compensatory restraint of feeding.
Thyrotropin receptor gene mutations and TSH resistance: variable expressivity in the heterozygotes
Authors: Camilot Marta , Teofoli Francesca , Gandini Alberto , Franceschi Roberto , Rapa Anna , Corrias Andrea , Bona Gianni , Radetti Giorgio , Tatò Luciano 
Published: July 2005

SummaryObjective  TSH resistance ranges from overt nonautoimmune hypothyroidism to subclinical hypothyroidism, defined as mild hyperthyrotrophinaemia but a euthyroid state clinically. To date, 23 inactivating mutations of the TSH receptor (TSHR) gene have been proven responsible for the clinical condition, but an absence of mutations in the TSHR gene has been reported for several cases of TSH resistance as well. In this paper, we aimed to investigate the actual role of the TSHR gene in the development of both subclinical and congenital hypothyroidism.Patients  14 hypothyroid newborns, 116 subclinical hypothyroid subjects and 120 healthy controls.Measurements  Through denaturing high performance liquid chromatography (DHPLC), we screened for mutations the TSHR gene (the proximal promoter, the exons and their flanking regions), and evaluated the association between serum TSH and functionally characterized alleles identified.Results  In the hypothyroid patients, one patient was heterozygous for a new missense variation, E34K, whereas two others patients were either homozygous or heterozygous for the P162A substitution. In the subclinical hypothyroid subjects, we detected only heterozygous substitutions: they are mostly new (123–124insTGCA, P27T, R46P, 555–561delTATTCTT, D403N, W488R, M527T), while six correspond to already published mutations (P162A, R109Q, L252P and three C41S). We only focused on those mutations that had been functionally characterized in vitro, and in whom serum TSH was available from family members.Conclusions  A single grossly mutated allele (such as C41S or 555–561del) invariably leads to a condition of subclinical hypothyroidism, whereas in case of heterozygous carriers of mutations partially affecting the receptor function (such as P162A or L252P), a remarkable variable expressivity was detected among individuals belonging to different generations.
The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women
Authors: Schaap Laura A. , Pluijm Saskia M. F. , Smit Jan H. , Van Schoor Natasja M. , Visser Marjolein , Gooren Louis J. G. , Lips Paul 
Published: July 2005

SummaryObjective  The objective of this study was to examine whether low levels of oestradiol and testosterone are associated with impaired mobility, low muscle strength and the incidence of falls in a population‐based sample of older men and women.Design  Cross‐sectional population‐based study, based on data of the Longitudinal Ageing Study Amsterdam (LASA), including 623 men and 663 women, aged 65–88 years.Measurements  Serum levels of oestradiol, testosterone, albumin and sex hormone‐binding globulin (SHBG) were measured. Physical performance, functional limitations and muscle strength were assessed, and a follow‐up on falls was performed prospectively within 3 years.Results  After adjustment for age, level of education, alcohol use, physical activity, chronic disease and body mass index (BMI), men in the highest quartile of the oestradiol/SHBG ratio had significantly higher physical performance scores than men in the lowest quartile (β = 0·103). Serum levels of total testosterone were positively associated with muscle strength (β = 0·085). Calculated bioavailable testosterone levels were positively associated with physical performance and muscle strength (β = 0·128 and 0·109 respectively). No associations of oestradiol levels with mobility were seen in women. Levels of oestradiol and testosterone were not associated with falls.Conclusions  It can be concluded that low levels of sex hormones were associated with impaired mobility and low muscle strength in men, but not in women. Levels of sex hormones were not associated with the incidence of falls neither in men, nor in women.
High prevalence of differentiated thyroid carcinoma in acromegaly
Authors: Tita Patrizia , Ambrosio Maria Rosaria , Scollo Claudia , Carta Anna , Gangemi Pietro , Bondanelli Marta , Vigneri Riccardo , Uberti Ettore C. degli , Pezzino Vincenzo 
Published: July 2005

SummaryObjective Acromegaly is a chronic disease caused by increased GH secretion and associated with a greater risk of developing both benign and malignant tumours. In the present study we evaluated the prevalence of thyroid disorders and thyroid malignancies in a series of acromegalic subjects.Design and patients We studied, retrospectively, a continuous series of 125 acromegalic patients referred to the Endocrinology Centres at the University Hospitals of Catania and Ferrara, Italy, over a 22‐year period.Measurements Diagnosis and management of acromegaly were based on standardized criteria. In all patients thyroid function and morphology were evaluated by serum free T4, free T3, TSH measurements and ultrasound scanning, respectively. Fine‐needle aspiration biopsy (FNAB) was performed in all solid‐mixed thyroid nodules of diameter greater than 1 cm. IGF‐1 expression was assessed by semiquantitative immunohistochemical analysis in some patients with differentiated thyroid cancer.Results Abnormal thyroid function was found in eight cases (6%). A diffuse or nodular goitre was present in 102 cases (82%). Thyroidectomy was performed in 17 patients. Histological examination revealed a differentiated thyroid cancer in seven of the patients. No significant association of thyroid cancer with GH or IGF‐1 levels was found. Semiquantitative assessment of IGF‐1 expression by immunohistochemistry revealed a more intense staining in thyroid cancer from acromegalic subjects than in papillary thyroid cancer from nonacromegalic subjects.Conclusions The frequency of thyroid disorders in our series of acromegalic subjects was similar to that previously observed in these patients. However, the prevalence of thyroid cancer was not only strikingly elevated (5·6%) in comparison to the estimated prevalence in the general population (0·093%), but it was even higher than that reported for acromegalic subjects. Sustained exposure to high serum IGF‐1 levels is likely to play a role in the development of thyroid cancer in this disease. An additive role for the autocrine/paracrine action of locally produced IGF‐1 is also possible. Our results suggest that thyroid function and morphology should be carefully monitored in all acromegalic patients.
Treatment of acromegaly with octreotide‐LAR: extensive experience in a Brazilian institution
Authors: Jallad Raquel S. , Musolino Nina R. C. , Salgado Luiz R. , Bronstein Marcello D. 
Published: July 2005

SummaryObjective  Somatostatin analogues have become the mainstay of the medical treatment of acromegaly. The aim of our study was to evaluate the efficacy and tolerability of octreotide‐LAR (OCT‐LAR) treatment in acromegalic patients.Design  Prospective open trial.Patients and methods  Eighty acromegalic patients (46 women; 18–80 years) were treated with OCT‐LAR. Mean ± SD duration of follow‐up was 16·6 ± 6·6 months (6–24 months). Twenty‐eight patients received OCT‐LAR as primary treatment. The target was to achieve normal IGF‐I levels. Clinical activity was evaluated by symptom score and fasting samples for GH and IGF‐I serum concentrations, obtained under basal conditions as well as during treatment. Pituitary tumour volume was assessed by magnetic resonance imaging of the sella. A tumour volume reduction of at least 25% was considered significant.Results  Clinical improvement was attained in most patients. Fifty‐nine (74%) of them attained mean GH < 2·5 ng/ml and 33 (41%) achieved normal IGF‐I by the 24th month of treatment. GH and IGF‐I control increased throughout treatment. Regarding the 46 patients treated for at least 12 months there was a significant decrease of GH and IGF‐I levels by the third month compared to basal levels, persisting with no subsequently variation.In the patient group that achieved normal serum IGF‐1 during treatment (controlled group: n = 43) 20 patients maintained normal levels up to the latest follow‐up, whereas 23 of them once again showed altered serum IGF‐1‐values of some measurements during follow‐up, despite dose maintenance or elevation.Baseline percentage of the upper limit of IGF‐I normal range, GH levels by the third month and length of treatment were predictive factors of IGF‐I normalization. Tumour shrinkage occurred in 76% of primary patients. Among 21 diabetic patients, four worsened and five improved glycaemic control, based on glycated haemoglobin. One previously intolerant patient progressed to overt diabetes. Nine patients developed gall bladder sludge, other nine patients acquired microlithiasis and one patient developed gallstone pancreatitis.Conclusion  OCT‐LAR is an effective agent in alleviating symptoms, suppressing GH, normalizing IGF‐I and inducing tumour shrinkage in many acromegalic patients. Overall, OCT‐LAR is well tolerated and should be recommended for nonsurgically cured acromegalics, and also be considered as primary therapy for selected cases, mainly for those with a low probability of surgical cure.
The somatostatin analogue SOM230, compared with octreotide, induces differential effects in several metabolic pathways in acromegalic patients
Authors: Van Der Hoek Joost , Van Der Lelij Aart‐Jan , Feelders Richard A. , De Herder Wouter W. , Uitterlinden Piet , Poon Kwai W. , Boerlin Viktor , Lewis Ian , Krahnke Tillmann , Hofland Leo J. , Lamberts Steven W. 
Published: July 2005

SummaryObjective  Recently, our first clinical study with the novel multiligand somatostatin (SRIF) analogue SOM230 in acromegalic patients showed that SOM230, due to its beneficial inhibitory effects on GH levels compared with octreotide (OCT), might increase the number of patients that can be biochemically controlled. Since SRIF analogues are also known to interact with other metabolic pathways, IGF‐I, IGFBP‐1, glucose and insulin concentrations on the control day (CD) and on treatment days following a single s.c. injection SOM230 100 and 250 µg, were compared to those following OCT 100 µg.Design and patients  Randomized, cross‐over, double‐blinded proof‐of‐concept trial in 12 patients with active acromegaly.Results  Free IGF‐I levels were suppressed after 24 h by OCT, SOM230 250 and 100 µg, whereas at 48 h only both SOM230 dosages still induced these inhibitory effects. Circulating IGFBP‐1 levels (AUC; 0830–1430 h) compared with CD, increased sharply after OCT (from 48 to 237 µg/l/h; P < 0·001 vs. CD), while SOM230 250 and 100 µg elicited a lower and dose‐dependent effect (163 and 90 µg/l/h, respectively, P < 0·05 vs. CD and OCT). Neither insulin nor GH levels showed statistically significant correlation with IGFBP‐1 levels either after SOM230 or OCT. An early rise in glucose levels 1 h postinjection with SOM230 250 µg compared with OCT and CD was observed 8·3 ± 0·8, 4·4 ± 0·5 and 4·9 ± 0·4 mmol/l, respectively: P < 0·05). SOM230 250 µg (19 ± 4 vs. 46 ± 3 mU/l on CD: P < 0·05), although clearly less potent than OCT (5·4 ± 0·4 mU/l: P < 0·01 vs. CD), inhibited insulin release. Since these corresponding absolute insulin levels cannot entirely explain this hyperglycaemic effect of SOM230, other mechanisms seem involved in this glucose rise. If SOM230 would influence glucose homeostasis in peripheral target tissues of insulin action, expression of SS‐receptors (sst) seems a logical necessity. In normal human liver tissues, analysed by quantitative polymerase chain reaction (PCR), the average sst1 mRNA expression level appeared significantly higher compared with sst2 (n = 6, relative copy number 161 ± 46 vs. 57 ± 6; P < 0·05). Fat tissue expressed both sst1 and sst2 mRNA, whereas in muscle only sst2 mRNA was found.Conclusion  Both dosages of SOM230 inhibit free IGF‐I in a more sustained fashion compared to OCT, implying longer duration of action. The superior action of OCT compared with SOM230 in stimulating IGFBP‐1 levels, suggests direct regulation of IGFBP‐1 by SRIF analogues via sst2. Finally, expression of only sst1 and sst2 in target tissues of insulin action, might point towards additional modulatory effects by SOM230 on glucose homeostasis.
Final height after treatment of early puberty in short adopted girls with gonadotrophin releasing hormone agonist with or without growth hormone
Authors: Mul D. , Oostdijk W. , Waelkens J. J. J. , Drop S. L. S. 
Published: July 2005

SummaryObjective  To compare final height data after treatment with gonadotrophin releasing hormone agonist (GnRHa) alone or in combination with growth hormone (GH) in short adopted girls with early puberty.Design  A randomized controlled trial.Patients and methods  Twenty‐six girls with onset of puberty before 10 years of age were treated for 3 years with either GnRHa alone (group A, n = 12) or with GnRHa and GH (group B, n = 14). Mean age at start of treatment was 9·6 years in both groups, bone age was 10·7 (SD 1·1) years in group A and 11·6 (0·8) years in group B.Results  Initial height prediction with average Bayley & Pinneau tables was 149·8 (5·6) and 146·8 (4·8) cm, respectively. Bone age at discontinuation of treatment was 12·3 (0·9) and 13·0 (0·6) years in group A and B, respectively.Height gain defined as the difference between initial height prediction and attained final height, was significantly different between group A and B (5·2 (3·7) and 8·2 (3·4) cm, P < 0·05) using average tables for height prediction. With accelerated tables for prediction the numbers were −1·0 (3·6) and 3·3 (3·5) cm, respectively.At final height, there was no significant difference in height: group A: 155·0 (5·6) cm and group B: 155·0 (5·5) cm.Conclusions  After 3 years of GnRHa treatment in adopted girls with early puberty, FH is significantly higher than initial height prediction. The addition of GH resulted in a limited further increase in height gain. In the interpretation of the results methodological issues concerning height prediction have to be taken into account.
Relation of anti‐TPO autoantibody titre and T‐lymphocyte cytokine production patterns in Hashimoto's thyroiditis
Authors: Karanikas Georgios , Schuetz Matthias , Wahl Katharina , Paul Matthias , Kontur Sylvester , Pietschmann Peter , Kletter Kurt , Dudczak Robert , Willheim Martin 
Published: July 2005

SummaryObjective  Cytokines produced by cytotoxic T cells or autoantibodies lead to thyroid cell damage and/or cell death in Hashimoto's thyroiditis (HT). Anti‐TPO autoantibodies (TPOAb) are the most frequently represented autoantibodies in the sera of patients with HT. Data describing the quantitative correlation between TPOAb titre and cytokine pattern are missing so far. To our knowledge this is the first study systematically evaluating the correlation of possible parameters of disease activity such as changes in CD4 and CD8 T‐cell cytokine production and of TPOAb titre.Methods  Twenty‐four consecutive patients (aged 29–58) with verified HT under levothyroxine therapy were included in the present study. The patients were divided into two groups. Group I: 12 HT patients with a high TPOAb titre (> 1000 U/ml), group II: 12 HT patients with a low TPOAb titre (< 100 U/ml). All patients underwent intracellular cytokine detection in CD4 and CD8 T cells of peripheral blood mononuclear cells (PBMC) by flow cytometry. Twelve healthy volunteers matched in sex and age consisted the control group (group III).Results  T cells from patients with a high TPOAb titre (group I) had significantly higher percentages of cells producing IFN‐γ compared to healthy donors (group III). A detailed analysis of cytokine production patterns revealed that this was accompanied by an increased frequency of single IFN‐γ positive cells, i.e. cells not expressing other cytokines tested, such as IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐13 or TNF‐β. Similarly, patients in group I also showed higher percentages of TNF‐α positive cells than healthy donors (group III). In this case, cells expressing TNF‐α alone as well as cells coexpressing TNF‐α and IFN‐γ were found at significantly higher frequencies. On the other hand, cytokine production patterns of patients with a low TPOAb titre (group II) showed significant difference neither to patients of group I nor to healthy donors (group III).Conclusion  Taken together, we were able for the first time to demonstrate that high TPOAb titre correlates with increased frequencies of T cells producing Th/Tc1 cytokines, probably responsible for thyroid cell damage and/or death in Hashimoto's thyroiditis.
Hypocortisolism in survivors of severe acute respiratory syndrome (SARS)
Authors: Leow Melvin Khee‐Shing , Kwek Daniel Seow‐Khee , Ng Alan Wei‐Keong , Ong Kian‐Chung , Kaw Gregory Jon‐Leng , Lee Lawrence Soon‐U 
Published: July 2005

SummaryObjective  Following the severe acute respiratory syndrome (SARS) outbreak, many survivors were observed to suffer from psychosomatic symptoms reminiscent of various endocrine disorders. Hence, we sought to determine the existence of any chronic endocrine sequelae in SARS survivors.Design, patients, measurements  Sixty‐one survivors of SARS prospectively recruited were analysed for hormonal derangements 3 months following recovery. Patients with pre‐existing endocrine disorders were excluded. Any endocrine abnormalities diagnosed were investigated and treated where indicated up to a year. Serial evaluation facilitated characterization of trends and prognostication of any endocrinological aberrations.Results  Twenty‐four (39·3%) patients had evidence of hypocortisolism. The hypothalamic–pituitary–adrenal (HPA) axis dysfunction of the majority resolved within a year. Two (3·3%) of the hypocortisolic cohort had transient subclinical thyrotoxicosis. Four (6·7%) were biochemically hypothyroid, being comprised of three with central hypothyroidism and one with primary hypothyroidism. Two of the three with central hypothyroidism had concomitant central hypocortisolism. Eight had subnormal DHEAS levels.Conclusions  These preliminary findings highlight a possible aetiologic role of SARS‐associated coronavirus in causing a reversible hypophysitis or direct hypothalamic effect, with the HPA axis affected more frequently than the HPT axis.
The effects of thyroxine replacement on the levels of serum asymmetric dimethylarginine (ADMA) and other biochemical cardiovascular risk markers in patients with subclinical hypothyroidism
Authors: Ozcan Omer , Cakir Erdinc , Yaman Halil , Akgul Emin Ozgur , Erturk Kivilcim , Beyhan Zeynel , Bilgi Cumhur , Erbil Mehmet Kemal 
Published: July 2005

SummaryBackground  The relationship between subclinical hypothyroidism (SH) and cardiovascular disease (CVD) is still under debate. The purpose of the present study was to evaluate plasma total homocysteine (tHcy), high sensitive C‐reactive protein (hsCRP), small dense low‐density lipoprotein (sdLDL), l‐arginine and asymmetric dimethylarginine (ADMA) concentrations and their relationship to nitric oxide (NO) production, measured as plasma nitrite‐plus‐nitrate (NOx) concentration, in patients with SH before and after thyroxine replacement therapy and compared with control group values.Design  Eighty‐four women with SH and 33 healthy women as controls matched to the patient group for sex, age and body mass index (BMI), were enrolled in this study. Lipoprotein profile, tHcy, hsCRP, sdLDL, ADMA, l‐arginine and NOx were measured in pre‐ and post‐treatment blood samples.Results  The pretreatment total cholesterol (TC), LDL‐C, hsCRP, ADMA and l‐arginine levels were significantly higher and NOx levels were lower than in the control group. After treatment, hsCRP, ADMA and l‐arginine levels were significantly reduced and sdLDL and NOx levels were significantly increased.Conclusion  The present study demonstrated an elevation of hsCRP and ADMA plasma levels of patients with SH associated with a reduction in NO production, which may contribute to some cardiovascular alterations. The elevated ADMA and hsCRP levels were reduced after thyroxine replacement. Also the sdLDL levels of SH patients were found to be lower than the control group values whereas TC and LDL were elevated. Even though we found an elevation in sdLDL levels after treatment, those values were still not higher than in the control group.