bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal circadian rhythm and increased non‐pulsatile secretion of thyrotrophin in Sheehan's syndrome
Authors: Maccagnan Paulo , Oliveira Juliana H. A , Castro Vania , Abucham Julio 
Published: March 2003

OBJECTIVEIt has previously been shown that patients with postpartum pituitary necrosis (Sheehan's syndrome, SS) have paradoxically increased TSH levels and loss of the nocturnal TSH surge. This study sought to determine the circadian and pulsatile characteristics of TSH secretion underlying those abnormalities.DESIGN AND PATIENTSChronobiological and cluster analyses of 24‐h TSH profiles were performed in nine SS patients (43–61 years, median = 52 years) and nine healthy female controls (33–47 years, median = 42 years).MEASUREMENTSSerum concentrations of T3, T4, free T4 (fT4) and cortisol were measured by radioimmunoassay; TSH, GH, PRL and LH were determined by immunometric assays.RESULTSAll patients and controls showed significant circadian TSH rhythms, but the percentage amplitude was decreased (7.5% vs. 21.3%, P < 0.0001) and the acrophase was markedly displaced in SS patients, occurring between 0315 h and 1515 h in seven/nine patients and in two/nine controls (P = 0.057). Patients showed increased total 24‐h TSH secretion (6054 ± 2293 vs. 2193 ± 340 mU/l/min, mean ± SE, P = 0.04) due to increased non‐pulsatile or tonic 24‐h TSH secretion (5631 ± 2105 vs. 1925 ± 301 mU/l/min, P = 0.026), but no difference was detected in pulsatile secretion (424 ± 191 vs. 268 ± 41, P = 0.82). The contribution of non‐pulsatile to total TSH secretion was also increased in SS patients (93.8% vs. 87.6%, P = 0.002). No significant changes were found in TSH pulse frequency, amplitude, duration or interpeak interval. When cluster parameters were individually analysed in two distinctive 12‐h periods corresponding to acrophase and nadir, patients showed increased non‐pulsatile TSH secretion in both periods, but no differences were found in pulsatile TSH secretion, pulse frequency or amplitude. The increment of TSH secretion during the acrophase in SS patients was exclusively due to increased non‐pulsatile TSH secretion, as opposed to controls who displayed significant increments in both non‐pulsatile and pulsatile TSH secretions.CONCLUSIONSSheehan's syndrome patients have increased total TSH secretion due to increased tonic TSH secretion. A circadian TSH rhythm is still present in these patients, but shows decreased magnitude and markedly displaced acrophase.
Sensitivity and specificity of the fine needle aspiration biopsy of the thyroid: clinical point of view
Authors: Čáp  , Ryška  , Řehořková  , Hovorková  , Kerekes  , Pohnětalová  
Published: March 2003

INTRODUCTIONThe rates of sensitivity and specificity of fine needle aspiration biopsy (FNAB) for the diagnosis of thyroid malignancy differ considerably among various reported series. These values are influenced by three factors: (a) whether only clearly positive and negative results are considered, or whether the commonly encountered 10–20% of indeterminate/suspicious ones are included; (b) whether adenomas are considered as neoplasms in one group with carcinomas; and (c) whether only histologically proven cases are used in calculations or whether patients with benign clinical follow‐up are included.AIMThe aim of the study was to evaluate the sensitivity and specificity of FNABs performed at this institution in the last 7 years from the clinical point of view, considering only benign vs. suspicious/malignant FNAB results (indicating surgery), and benign (including adenomas) vs. malignant definitive histology.STUDY DESIGNRetrospective study comparing pre‐operative FNAB results with definitive histological examination after operation.PATIENTSA total of 2492 FNABs were performed in 2100 patients (1875 women and 225 men); their ages ranged from 9 to 85 years, with a median of 46 years. Clinical diagnosis was multinodular goitre in 1330, single nodule in 591, Hashimoto's thyroiditis in 147 and subacute thyroiditis in 32 cases. In 148 instances, the nodule was cystic. A history of previous treatment for carcinoma of the thyroid was present in 12 patients. Five hundred and thirty‐six patients subsequently underwent thyroid surgery.STATISTICSThe values of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were calculated.RESULTSThe sensitivity was 86%, specificity 74%, PPV 34%, NPV 97% and diagnostic accuracy 75%.CONCLUSIONSThe specificity and positive predictive value are low when fine needle aspiration biopsy results are divided into two categories only (these being indication for surgery or not), and when only suspicious/malignant fine needle aspiration biopsies with subsequent malignant histology are considered to be true positive. Nevertheless, the ability to discriminate 11.7% of patients with a 34% probability of malignancy (suspicious/malignant cytology) from 81.2% of patients (benign cytology) with a probability of only 3% is very helpful.
Increased risk for endocrine autoimmunity in Italian type 2 diabetic patients with GAD65 autoantibodies
Authors: Gambelunghe Giovanni , Forini Francesca , Laureti Stefano , Murdolo Giuseppe , Toraldo Gianluca , Santeusanio Fausto , Brunetti Paolo , Sanjeevi Carani B. , Falorni Alberto 
Published: March 2003

OBJECTIVEGlutamic acid decarboxylase (GAD)65 autoantibodies (GAD65Ab) in type 2 diabetic subjects with secondary failure to sulphonylurea treatment identify the so‐called latent autoimmune diabetes of the adult (LADA). The aim of our study was to estimate the risk for endocrine autoimmunity in type 2 diabetic subjects with GAD65Ab.DESIGN AND PATIENTSWe analysed serum samples from 600 adult subjects with a clinical diagnosis of type 2 diabetes mellitus for the presence and levels of GAD65Ab and antibodies directed against the islet autoantigen IA‐2/ICA512 (IA‐2/ICA512Ab). All the patients had been treated initially with hypoglycaemic agents and/or diet for at least 1 year. GAD65Ab+ subjects were studied for the presence of thyroid peroxidase autoantibodies (TPOAb), 21 hydroxylase autoantibodies (21OHAb) and frequency of HLA class II haplotypes.RESULTSGAD65Ab were found in 67/600 (11%) and IA‐2/ICA512Ab in 12/600 (2%) subjects (P < 0.0001). The presence of GAD65Ab, but not that of IA‐2/ICA512Ab, was significantly associated with insulin therapy, low BMI (P < 0.0001) and low basal C‐peptide (P < 0.01). Islet‐cell antibodies (ICA) were detected in 43/67 (64%) GAD65Ab+ and in 10/12 (83%) IA‐2/ICA512Ab + subjects. TPOAb occurred more frequently in GAD65Ab+ (16/67, 24%) than in GAD65Ab‐subjects (9/174, 5%) (P < 0.0001). 21OHAb were detected only in GAD65Ab+ subjects (3/67, 4.5%) (P = 0.03 vs. GAD65Ab‐subjects). None of the 21OHAb+ subjects had metabolic or clinical signs of adrenal dysfunction. HLA‐DRB1*03‐DQA1*0501‐DQB1*0201 (DR3‐DQ2) was significantly more frequent in GAD65Ab+ subjects than in healthy controls (OR = 5.42, corrected P < 0.0026). The presence of TPOAb was significantly associated with DR3‐DQ2 (P = 0.024).CONCLUSIONSOur study demonstrates that the presence of GAD65Ab identifies a subgroup of type 2 diabetic patients with high risk for thyroid and adrenal autoimmunity, and that both GAD65Ab and TPOAb are associated with the presence of HLA‐DR3‐DQ2, in these patients.
The use of insulin‐like growth factor 1 reference values for the diagnosis of growth hormone deficiency in prepubertal children
Authors: Bussières Laurence , Souberbielle Jean‐Claude , Pinto Graziella , Adan Luis , Noel Michele , Brauner Raja 
Published: March 2003

OBJECTIVEThis study was done to determine whether the use of reference values obtained in children with idiopathic short stature (ISS) improved the clinical value of serum insulin‐like growth factor I (IGF‐1) as a tool for diagnosing GH deficiency (GHD) in prepubertal children.PATIENTS AND METHODSSerum IGF‐1 was measured with a new IRMA kit (IGFI‐RIA CT, Cis Bio, Gif sur Yvette, France) in 168 prepubertal normal children and in prepubertal children with ISS (n = 68), organic GHD due to a craniopharyngioma (oGHD, n = 15) and permanent idiopathic GHD (iGHD, n = 28).RESULTSIGF‐1 was lower (P < 0.001) in iGHD than in either ISS or oGHD and was below the fifth percentile of the normal range in 29/68 ISS (43%), 8/15 oGHD (53%) and 28/28 (100%) iGHD patients. Three oGHD (20%) and two iGHD (7%) patients had a serum IGF‐1 below the fifth percentile of the normal group but above the fifth percentile of the ISS group. Thus, a serum IGF‐1 below the fifth percentile of the normal group distinguished between normal children and iGHD with 100% sensitivity, between normal and oGHD with 53% sensitivity and between normal and all GHD (idiopathic + organic) with 84% sensitivity; the overall specificity was only 57%. Conversely, a serum IGF‐1 below the fifth percentile of the ISS population distinguished between ISS and iGHD with 93% sensitivity, between ISS and oGHD with 33% sensitivity and between ISS and all GHD with 72% sensitivity; the overall specificity was then 95%.CONCLUSIONSA serum IGF‐1 within the normal range virtually excludes idiopathic GHD but does not rule out organic GHD, whereas an IGF‐1 below the ISS range is strongly in favour of GHD, after exclusion of poor nutritional status and/or liver disease. An IGF‐1 below the normal range but in the idiopathic short stature range gives no definitive conclusion even when it is associated with a low GH peak. Thus, whereas reference values obtained in normal children must be used to interpret serum IGF‐1 in short prepubertal children, reference data obtained in idiopathic short stature children should also be taken into account.
Oral glucose tolerance testing but not intravenous glucose administration uncovers hyper‐responsiveness of hypothalamo–pituitary–adrenal axis in patients with adrenal incidentalomas
Authors: Beuschlein F. , Borgemeister M. , Schirra J. , Göke B. , Fassnacht M. , Arlt W. , Allolio B. , Reincke M. 
Published: March 2003

OBJECTIVEModern imaging techniques are detecting adrenal incidentalomas with increasing frequency. Recent data suggests food‐dependent hypercortisolism in a subgroup of patients with bilateral macronodular hyperplasia due to aberrant adrenal responsiveness to gastric inhibitory polypeptide (GIP). We studied the putative influence of food intake on the hypothalamo–pituitary–adrenal (HPA) axis in patients with adrenal incidentalomas and possible mediation by GIP.PATIENTS AND MEASUREMENTSWe examined 15 mildly obese patients with adrenal incidentalomas, eight healthy, lean subjects, and seven obese patients with the metabolic syndrome, who were matched for body weight and age. Each individual underwent oral glucose tolerance testing (OGTT, 75 g glucose), i.v. glucose administration (IVGTT, 30 g glucose over 1 h) and i.v. glucose plus GIP infusion (body weight adapted leading to physiological postprandial GIP serum levels) on three occasions. Plasma glucose, ACTH and cortisol were measured from blood samples taken every 15 minutes from time − 30 minutes to + 75 minutes.RESULTSOGTT, i.v. glucose administration and GIP infusion led to comparable glucose values within the groups. In contrast to normal subjects and patients with the metabolic syndrome, patients with adrenal incidentalomas had significantly higher mean cortisol values after oral glucose intake as compared to i.v. glucose administration or GIP infusion. The increase in cortisol levels was preceded by a corresponding ACTH increase. No significant effect of GIP administration on cortisol or on ACTH secretion could be detected.CONCLUSIONSPatients with adrenal incidentalomas showed an abnormal responsiveness of the pituitary–adrenal axis to oral glucose administration. The cortisol peaks in these patients seemed to be ACTH‐mediated and were not induced by GIP.
Oral dehydroepiandrosterone (DHEA) replacement therapy in women with Addison's disease
Authors: Gebre‐Medhin Gennet , Husebye Eystein S. , Mallmin Hans , Helström Lotti , Berne Christian , Karlsson F. Anders , Kämpe Olle 
Published: March 2003

OBJECTIVEPatients with primary adrenocortical failure (Addison's disease) have abnormally low levels of DHEA and androgens relative to age. To define a suitable dose, the effect of oral dehydroepiandrosterone (DHEA) replacement therapy in women with Addison's disease (n = 9) was evaluated.DESIGN AND MEASUREMENTSDHEA was administered as a daily oral dose of either 50 mg (n = 5) or 200 mg (n = 4). Blood sampling and measurements of insulin sensitivity (as measured with euglycemic insulin clamp technique) and body composition (as measured by dual energy X‐ray absorptiometry) were performed before and during DHEA treatment and at a 3‐month follow up.RESULTSDHEA and DHEA(S) levels were restored to normal in those patients receiving 50 mg whereas DHEA(S) level was slightly above the normal reference value in those receiving 200 mg. Circulating levels of androgens (androstenedione, testosterone and testosterone/SHBG ratio) were normalized in all patients. A slight rise in IGF‐1 levels was seen in both groups as was a decrease in the levels of low and high density lipoproteins. No effect on blood glucose levels or insulin sensitivity was seen and no change of body composition was observed. No serious side‐effects were seen, but some of the patients experienced increased apocrine sweat secretion (n = 7), itchy scalp (n = 2) and acne (n = 7), all of which were reversed when DHEA was discontinued.CONCLUSIONA daily replacement dose of 50 mg of DHEA results in near physiological levels of DHEA, DHEA(S) androstenedione and testosterone in women with Addison's disease, without severe side‐effects.
Influence of exogenous melatonin on catecholamine levels in postmenopausal women prior and during oestradiol replacement
Authors: Cagnacci Angelo , Zanni Anna Lisa , Veneri Maria Grazia , Menozzi Renata , Volpe Annibale , Rio Graziano Del 
Published: March 2003

OBJECTIVEIn young individuals melatonin administration reduces circulating norepinephrine. Some effects of melatonin are reduced in elderly women and are modulated by gonadal steroids. Accordingly, the influence of melatonin on catecholamine levels was investigated in postmenopausal women without and with oestradiol replacement.DESIGNPrior to and after 2 months of transdermal oestradiol (50 μg/day), women were studied on two consecutive days, on which they received placebo or 1 mg of melatonin orally in a randomised and double‐blind fashion.PATIENTSFourteen healthy postmenopausal women.MEASUREMENTSResting levels of epinephrine and norepinephrine and their responses to both a cold stimulus, performed by placing a hand in a basin of water and ice for 2 minutes, and to 10 minutes of upright position (upright test).RESULTSPrior to oestradiol, melatonin did not modify baseline or stimulated catecholamine levels. In contrast, during oestradiol, melatonin tended to reduce, although not significantly, baseline norepinephrine levels (P = 0.053), and significantly reduced peak values (P = 0.0061) and integrated norepinephrine response (P = 0.0076) to the cold stimulus. Responses of norepinephrine to the upright test were not modified, while those of epinephrine were increased (P = 0.042). During, but not prior to oestradiol replacement, modifications induced by melatonin (melatonin day‐placebo day) in the norepinephrine response to the cold (r 2 = 0.457; P = 0.0079) and the upright (r2 = 0.747; P = 0.0001) tests were linearly and inversely related to the responses of the placebo day.CONCLUSIONSMelatonin does not modulate adrenergic activity in postmenopausal women without hormone replacement therapy. Oestradiol replacement restores the capability of melatonin to modulate adrenergic activity, particularly the norepinephrine response to stimuli.
Body proportions during 6 years of GH treatment in children with short stature born small for gestational age participating in a randomised, double‐blind, dose–response trial*
Authors: Sas Theo C. J. , Gerver Willem‐Jan M. , De Bruin Rob , Mulder Paul G. H. , Cole Tim J. , De Waal Wouter , Hokken‐Koelega Anita C. S. 
Published: March 2003

The aim of this study was to assess body proportions in children with short stature born small for gestational age (SGA) before and during 6 years of growth hormone (GH) treatment.A prospective randomised double‐blind dose–response study comparing the effects of 3 vs. 6 IU GH/m2/day.Seventy‐nine children with short stature (height SD‐score < −1·88) born small for gestational age (birth length SD‐score < −1·88).Before and during GH treatment, height, sitting height (SH), hand (Hand) and foot length (Foot), biacromial (Biac) and biiliacal diameter (Biil) were measured. All results were adjusted for age and sex, and expressed as SD‐scores (SDS) using reference values for healthy Dutch children. To describe the size of SH, Hand, Foot, Biac, and Biil in relation to height, these values were adjusted for the SDS of height.At baseline, these short children had small hands and feet and narrow shoulders and pelvis compared to healthy peers. Height and SH, were, however, even more affected. Consequently, on average, these children had relatively large hands and feet, and relatively broad shoulders and pelvis compared to their height, but a normal sitting height in proportion to height. In most of the individuals, the values for body proportions were, however, within the normal range. During 6 years of GH treatment the SD‐scores of all measurements increased significantly towards values more close to zero. The mean size of Hand, Foot, and Biil decreased in proportion to height. The mean SH increased relatively more than height, however, to values well within the normal range. The mean Biac in relation to height had not changed after 6 years of GH treatment. No differences in the 6‐year changes in body proportions were found between the two GH dosage groups.Untreated short children born small for gestational age have, on average, relatively large hands and feet, and broad shoulders and pelvis, but a normal sitting height compared to height. The increase in height during 6 years of GH treatment is accompanied by an improvement of the proportions of the size of hands, feet, and biiliacal diameter, in relation to height. The increase in height appeared to be the result of the increase in sitting height as well as leg length, but the sitting height SD‐score increased slightly more than that of leg length. The changes in body proportion during GH treatment were dose‐independent. Thus, 6‐year continuous GH treatment with either 3 or 6 IU/m2/day in children with short stature born small for gestational age does not negatively influence body proportions.
Optimal dosage interval for depot somatostatin analogue therapy in acromegaly requires individual titration
Authors: Jenkins P. J. , Akker S. , Chew S. L. , Besser G. M. , Monson J. P. , Grossman A. B. 
Published: March 2003

The recent introduction of the depot somatostatin analogues octreotide LAR and lanreotide represent major advances in the medical treatment of acromegaly. However, it is uncertain whether the recommended dose intervals of 4 weeks and 10–14 days, respectively, are applicable to all patients.To determine the optimum intervals between depot injections of either octreotide LAR and lanreotide for the suppression of serum GH and IGF‐I in patients with acromegaly.Twenty‐seven patients with acromegaly were randomly allocated to receive either three injections at 4 week intervals of octreotide LAR (n = 18) or five injections at 14 day intervals of lanreotide (n = 11); two patients participated in both arms. Prior to the first injection, at 4 and 6 weeks after the last injection of LAR, and at 10, 14 and 21 days after the last injection of lanreotide, serum mean GH and IGF‐I levels were measured.In the LAR‐treated group, at 4 and 6 weeks after the third injection 13 patients (72%) and 12 patients (67%), respectively, had a mean GH < 5 mU/l. IGF‐I was normalized in 12 and 11 patients at these times. In the lanreotide‐treated group, five (45%), four (36%) and three (27%) patients, respectively, had a GH < 5 mU/l at 10, 14 and 21 days after the last injection and eight, six and five patients had a normal serum IGF‐I.There is marked variability in individual patient responses to depot somatostatin analogues. The establishment of optimal drug intervals requires careful assessment. For octreotide LAR many patients may be as adequately controlled with 6 weekly injections as with 4 weekly injections. It is important to measure serum GH profiles at intervals after initiating therapy with these drugs to individualize doses for each patient and hence minimize cost.
Hypertension is a major risk factor for aortic root dilatation in women with Turner's syndrome
Authors: Elsheikh M. , Casadei B. , Conway G. S. , Wass J. A. H. 
Published: March 2003

Women with Turner's syndrome (TS) have a threefold increase in mortality, primarily as a result of their cardiovascular complications. Recently, the risk of fatal aortic dissection has come to light as a major cause of mortality in women with TS. The aim of this study was to assess the prevalence of aortic root dilatation in a group of women with TS and to investigate the factors contributing to its development.Thirty‐eight women with TS attending a dedicated adult Turner clinic were examined clinically and by M‐mode and two‐dimensional echocardiography on at least one occasion. Aortic root dilatation was defined as an aortic root diameter greater than the 95th centile for body surface area. Fasting serum lipid concentrations were measured in all women. Additionally, 18 subjects underwent noninvasive assessment of central arterial stiffness using applanation tonometry.Fifty percent of subjects were hypertensive and a similar number had an abnormal echocardiogram. A bicuspid aortic valve was present in 33% of subjects, 16 women (42%) had ascending aortic root dilatation. This was associated with a bicuspid aortic valve in four women and hypertension in 11. Two women had isolated aortic root dilatation. Aortic root diameter was significantly associated with systolic blood pressure (r = 0·5, P = 0·003) and left ventricular thickness (r = 0·5, P = 0·02). There was no association with serum lipids or arterial compliance.Structural cardiac abnormalities are present in up to 50% of women with Turner's syndrome. Aortic root dilatation is a significant risk in women with Turner's syndrome and is closely dependent on blood pressure. Aortic root dilatation does not appear to be related to atherosclerosis and is more likely to be due to a mesenchymal defect. Regular surveillance of the aortic root diameter is essential in all women with Turner's syndrome and hypertension should be treated aggressively when present in order to minimize the risk of potentially fatal aortic dissection.