bluuebunny/crossref_metadata_2025_split huggingface dataset:
L‐Arginine and insulin‐tolerance tests in the diagnosis of adult growth hormone deficiency: influence of confounding factors
Authors: Fisker  , Jørgensen  , Ørskov  , Christiansen  
Published: March 2003

OBJECTIVEIn the attempt to define a GH stimulation test with high specificity and reproductibility, few studies have addressed the influence of potential interfering external factors on the test result. We therefore tested the influence of physical activity (admission to hospital on test morning) and mild heat exposure on the GH response to l‐arginine stimulation test (Arg) and insulin‐tolerance test (ITT).DESIGNOne Arg stimulation test and one ITT were performed in all subjects during standard conditions (overnight hospital stay, 10 hours fasting). In addition, each subject was randomized to undergo either two additional Arg tests, or two ITTs, performed under two different conditions: admission to hospital on the morning of the test and during standard conditions except for heat exposure before testing. The four tests were performed in random order.PATIENTSTwenty‐two patients (six women, 16 men) (mean age ± SEM, 38.3 ± 5.3 years and 36.1 ± 2.7 years, respectively) presenting with pituitary disease and a group of healthy age and gender‐matched normal subjects (six women, 13 men) (age 38.3 ± 4.8 years and 35.7 ± 2.4 years, respectively) participated.MEASUREMENTSDuring the GH‐stimulation tests serum GH, cortisol, blood glucose, and plasma glucagon were measured and compared in the three different test conditions.RESULTSDuring standard conditions, peak GH response was higher in the ITT compared to the Arg test in the control group (23.4 ± 3.6 mU/l vs 11.6 ± 2.0 mU/l, P = 0.004), and the specificity of the ITT was higher (18/19 versus 13/19, P = 0.047). Minor heat exposure before the ITT (temperature rise 0.24 ± 0.05°C, range 0.0–0.5°C) did not change the GH response in the healthy adults whereas admission to hospital on the morning of the test reduced the GH response significantly (P < 0.05). The lowest blood glucose did not change in the three situations and did not correlate with peak GH during the ITT. In the patients there were no significant differences between the GH response during different conditions. Plasma glucagon did not significantly differ between the different test conditions in the control group (P = 0.88), but there was a significant decrease in the glucagon response to the test performed after hospital admission on the test morning in the patients (P < 0.025). Serum cortisol response in the control group did not differ in the three situations.CONCLUSIONSSince provocative GH responses are influenced by external factors, conditions should be standardized to optimize the reproductibility and specificity of the tests. Furthermore the higher specificity of the insulin‐tolerance test as compared to the arginine stimulation test was confirmed.
Corticosteroid metabolism in human granulosa‐lutein cells
Authors: Thomas  , Thomas  , Tetsuka  , Mason  , Hillier  
Published: March 2003

OBJECTIVEThe aims of this study were to determine the type and level of 11β‐hydroxysteroid dehydrogenase (11βHSD) in human granulosa‐leutein cells (GLE) shortly before ovulation and to correlate activity with the outcome of treatment in patients undergoing in vitro fertilization and embryo transfer (IVF/ET).DESIGNGLC from 32 patients undergoing IVF/ET were tested for type and level of 11βHSD activity in relation to treatment outcome.PATIENTSPeriovulatory follicles were aspirated by ultrasound guided transvaginal puncture following a standard controlled ovarian stimulation protocol, ∼36 h after administering an ovulation‐inducing dose of human chorionic gonadotrophin (HCG). GLC were separated from follicular fluid by density‐gradient centrifugation and taken for measurement of 11βHSD activity in vitro; oocytes were used for IVF/ET.MEASUREMENTSInterconversion of cortisol (F) and cortisone (E), and dexamethasone (D) and 11‐dehydrodexamethasone (DHD) was measured in standardized assays comprising incubation of GLC with 3H‐labelled substrate, with separation of substrate and product by thin‐layer radiochromatography.RESULTSConversion of F to E varied from 10.5 to 30.9% while that of E to F was between 2.4 and 44.6%. In the GLC of 25 patients in whom both activities were measured, dehydrogenase (F to E) activity predominated in 13 and reductase (E to F) in 12. By contrast, D (substrate for 11βHSD2 but not 11βHSD1) showed less than 1% metabolism in this system while DHD (substrate for 11βHSD1 and 11βHSD2) was converted significantly (65.6–90.5%) to D in the four patients tested. There was no significant difference in the interconversion of F and E between patients who became pregnant and those who did not.CONCLUSIONSThe dehydrogenase and oxoreductase reactions catalysed by 11βHSD both occur in granulosa‐lutein cells at the time of follicular rupture, probably due to 11βHSD1. A lack of measurable conversion of dexamethasone to 11‐dehydrodexamethasone suggests that dehydrogenation due to 11βHSD2 is low or absent. Neither type nor level of 11βHSD activity measured under the present assay conditions correlates with IVF outcome.
A study of the association between a polymorphism in the CTLA‐4 gene and postpartum thyroiditis
Authors: Waterman E. A. , Watson P. F. , Lazarus J. H. , Parkes A. B. , Darke C. , Weetman A. P. 
Published: March 2003

OBJECTIVEPostpartum thyroiditis (PPT) is an autoimmune thyroid disease which shares immunological and clinical features with autoimmune hypothyroidism and Graves' disease, and is believed to be caused by a combination of genetic and environmental factors. Recently, an association has been described between Graves' disease or autoimmune hypothyroidism and a polymorphism in the CTLA‐4 gene, which encodes a T cell receptor for the B7 family of ligands, and we wished to test whether a similar association exists with PPT.DESIGNA population‐based case‐control study of a CTLA‐4 gene microsatellite polymorphism was performed, to look for an association with PPT.PATIENTSCaucasoid women (n = 122) were studied; 58 had thyroid antibodies (against thyroglobulin or thyroid peroxidase) alone during the postpartum period (PPT−) and 64 had thyroid antibodies and some form of postpartum thyroid dysfunction (PPT+).RESULTSThere was no significant difference between this whole group of women and 161 local Caucasoid thyroid antibody‐negative women for the CTLA‐4106 base pair (AT)n microsatellite polymorphism (relative risk = 1.3; P = 0.3), nor did the PPT+ group differ from controls when analysed separately (P = 0.2). When the postpartum women were subdivided in groups according to clinical pattern of PPT and the type of thyroid antibodies, there were no associations within the subgroups.CONCLUSIONSNo significant association exists between postpartum thyroiditis and a polymorphism in the CTLA‐4 gene. Furthermore, a natural variation in the prevalence of the polymorphism in healthy UK populations underscores the need to select appropriately matched normal subjects in future case‐control studies.
Growth hormone induced increase in serum IGFBP‐3 level is reversed by anabolic steroids in substance abusing power athletes
Authors: Karila Tuomo , Koistinen Hannu , Seppälä Markku , Koistinen Riitta , Seppälä Timo 
Published: March 2003

OBJECTIVEBody builders may use growth hormone (GH) and anabolic steroids to increase fitness and muscle mass. GH increases serum concentrations of IGF‐I and IGFBP‐3. The combined effects of GH and anabolic androgenic steroids on IGFBP‐3 and IGF‐I levels are not known under authentic substance‐abusing conditions. The aim of this study was to investigate this in substance‐abusing power athletes.DESIGN AND PATIENTSNine healthy, non‐obese and non‐competing male power athletes, all aggressive substance abusers, used GH and/or anabolic steroids independently of this study. Blood samples were taken both during and between the drug intake. Sixteen substance non‐abusing wrestlers served as controls.MEASUREMENTSSerum IGF‐I concentration was measured by radioimmunoassay and the IGFBP‐3 concentration was measured by two immunofluorometric assays, one detecting proteolytic fragments of IGFBP‐3. The capacity of serum to proteolytically cleave IGFBP‐3 was studied by the proteolysis assay.RESULTSWhile growth hormone increased the IGFBP‐3 and IGF‐I concentrations, anabolic steroids decreased the same. Concomitant use of growth hormone and anabolic steroids decreased the IGFBP‐3 concentration in five out of six abuse periods in spite of the fact that the IGF‐I concentration remained elevated in four of them. However, in two men who were on low calorie diet both the IGF‐I and IGFBP‐3 concentrations decreased during combined GH/anabolic steroid abuse. No proteolytic fragmentation of IGFBP‐3 was observed.CONCLUSIONMassive abuse of anabolic steroids decreases both the basal and GH‐stimulated IGFBP‐3 concentrations, whereas its effects on serum IGF‐I concentration are variable and affected by low calorie diet. This study demonstrates that detection of GH doping by measuring the IGF‐I and/or IGFBP‐3 levels has notable confounding factors.
Regulation and tissue distribution of the human sodium iodide symporter gene
Authors: Ajjan R. A. , Kamaruddin N. A. , Crisp M. , Watson P. F. , Ludgate M. , Weetman A. P. 
Published: March 2003

OBJECTIVEIodide uptake by the thyroid gland is mediated by the sodium iodide symporter (NIS). In the present report, we have analysed the factors that modulate human NIS mRNA expression and iodide uptake in primary thyroid follicular cell (TFC) cultures. In addition, NIS mRNA tissue distribution was investigated.METHODSPrimary thyroid follicular cell cultures were treated with human recombinant TSH with or without cytokines for 72 h. Subsequently, NIS gene expression and iodide uptake were analysed using reverse transcription–polymerase chain reaction (RT–PCR) and 125I uptake, respectively. Human tissue samples were investigated for NIS gene expression using both RT–PCR and Northern blotting.RESULTSHuman TSH increased both NIS gene expression and iodide uptake in TFC cultures in a dose‐dependent manner. Using concentrations of 0.1 U/l of hTSH, a minor increase in NIS gene expression was detected without a detectable increase in iodide uptake. IL‐1α,TNFα and IFNγ at concentrations of 105 U/l all inhibited TSH‐induced NIS gene expression and iodide uptake. In these experiments, there was a good correlation between NIS mRNA expression and iodide uptake. Using RT–PCR higher levels of NIS mRNA were detected in Graves' disease (GD) compared to multi‐nodular goitre tissue samples. Stomach and salivary gland tissue also expressed NIS mRNA, whereas low levels were found in the mammary gland and extraocular muscle tissue. No expression was detected in the ovary, oesophagus, colon, extraocular fat or skin. In contrast, Northern blot analysis failed to detect NIS in stomach, salivary gland, intestinal fat or non‐toxic multi‐nodular goitre tissue samples, although this was present in GD thyroid tissue.CONCLUSIONTSH upregulates sodium iodide symporter gene expression and iodide uptake in primary thyroid follicular cell cultures, and this induction is modulated by cytokines. Variable levels of sodium iodide symporter mRNA are present in different tissue samples, with high expression evident in Graves' disease thyroid tissue.
Clinical features associated with metastasis and recurrence of differentiated thyroid cancer in children, adolescents and young adults
Authors: Welch Dinauer Catherine A. , Michael Tuttle  , Robie Daniel K. , McClellan Donald R. , Svec Rita L. , Adair Carol , Francis Gary L. 
Published: March 2003

OBJECTIVEDifferentiated thyroid cancer (DTC), including papillary (PTC) and follicular (FTC) variants, is unusual in children and accounts for only 10% of all cases. For that reason, knowledge of the clinical features which predict recurrence is limited. We reviewed 170 cases of childhood DTC to determine if specific clinical or pathological findings were associated with increased risk of recurrence.DESIGNThis was a retrospective study of children and adolescents with DTC registered in the Department of Defense Automated Centralized Tumor Registry.PATIENTSWe reviewed 137 cases of PTC and 33 cases of FTC diagnosed between 1953 and 1996 at ≤ 21 years of age.RESULTSIn the PTC group (median follow‐up 6.6 years, range 2 month — 39.5 years), only one patient died, but 21 developed local and 6 developed distant recurrence. By univariate analysis, recurrence was more common in patients with multifocal (odds ratio 7.5) or large tumours (odds ratio 4.1), and in those with palpable cervical lymphadenopathy (odds ratio 3.0) or metastasis at diagnosis (odds ratio 2.8). By multivariate analysis focality was the best predictor of recurrence (P = 0.0019). In the FTC group (median follow‐up 5 years, range 6 month — 38.1 years), no patient died of disease, but 5 developed recurrence. As with PTC, recurrence was more likely in patients with multifocal tumours (odds ratio 22.0).CONCLUSIONSDifferentiated thyroid cancer in children and adolescents has low mortality, but a high risk of recurrence. Young patients with large, multifocal tumours that are already metastatic at diagnosis have the greatest risk of recurrence.
Serum vascular endothelial growth factor (VEGF) in the normal menstrual cycle: association with changes in ovarian and uterine Doppler blood flow
Authors: Agrawal Rina , Conway G. S. , Sladkevicius P. , Payne N. N. , Bekir J. , Campbell S. , Tan S. L. , Jacobs H. S. 
Published: March 2003

OBJECTIVETo investigate whether changes in circulating serum vascular endothelial growth factor (VEGF) concentrations during the menstrual cycle are associated with changes in blood flow within the ovaries and uterus.PATIENTS AND MEASUREMENTSSerum VEGF concentrations were measured and pulsed and colour Doppler blood flow waveforms recorded within the ovarian stroma and uterine arteries during the early follicular, the immediate preovulatory and the mid‐luteal phases of the menstrual cycle of 14 healthy women.RESULTSMean (±SD) serum VEGF concentrations rose from 2.44 ± 0.1 ng/ml in the early follicular phase to 3 ± 0.8 ng/ml in the pre‐ovulatory phase and to 4.4 ± 0.9 ng/ml in the mid‐luteal phase (P < 0.0001) of the menstrual cycle. Mean peak systolic blood flow velocity (PSV) and time‐averaged maximum flow velocity (TAMXV) were higher within the ovarian stroma of the ovary bearing the dominant follicle and the uterine arteries in the pre‐ovulatory and mid‐luteal phase than in the same sites during the early follicular phase of the menstrual cycle. PSV rose significantly from the early follicular phase (11 ± 6 cm/s) to 14 ± 4 cm/s in the pre‐ovulatory phase and further in the mid‐luteal phase (26 ± 7 cm/s, P = 0.0001). Within the uterine arteries, mean PSV rose significantly from 28 ± 9 cm/s in the early follicular phase to 31 ± 8 cm/s in the pre‐ovulatory phase and further in the mid‐luteal phase (44 ± 11 cm/s, P < 0.005). Serum VEGF correlated with serum progesterone concentrations in the luteal phase (r = 0.85, P < 0.001), with serum oestradiol concentrations in the early follicular (r = 0.67, P = 0.009), pre‐ovulatory (r = 0.57, P = 0.03) and luteal phases (r = 0.68, P < 0.005) and with serum testosterone in the early follicular phase (r = 0.63, P = 0.01).CONCLUSIONSCyclical changes in serum vascular endothelial growth factor concentrations are associated with coincident changes in ovarian and uterine blood flow.
Multiple endocrine neoplasia type 1 (MEN1): clinical heterogeneity in a large family with a nonsense mutation in the MEN1 gene (Trp471Stop)
Authors: Valdés N. , Pérez de Nanclares G. , Alvarez V. , Castaño L. , Díaz‐Cadórniga F. , Aller J. , Coto Eliecer 
Published: March 2003

OBJECTIVEFamilial multiple endocrine neoplasia type 1 (MEN1) is an hereditary dominant trait characterized by tumours of the parathyroids, anterior pituitary and endocrine pancreatic glands, among others. The MEN1 gene has recently been cloned, and MEN1‐mutations have been identified in several families as well as in a number of sporadic cases. The aim of this study was to search for mutations in a large MEN1‐family in order to define the clinical heterogeneity among mutation‐carriers. We also analysed DNA from several tumour tissues in order to test the ‘two hit’ model for inactivation of the MEN1 gene.PATIENTS AND METHODSWe searched for mutations in the MEN1‐gene in members of a large MEN1‐family. A total of 11 affected and 4 healthy at risk individuals were analysed. DNA was obtained and exons 1 to 10 of the MEN1‐gene were PCR‐amplified and subjected to automated‐direct sequencing. In addition, we isolated DNA from parathyroid tumours of two family members, and compared this DNA with that of the normal tissue counterpart to define if the normal copy of the MEN1‐gene was deleted.RESULTSG to A change at nucleotide 7640 (exon 10) that would convert Trp to Stop at codon 471 was found. This mutation was identified in eleven affected individuals, as well as in four healthy (asymptomatic) family members. These patients showed a wide spectrum of clinical symptoms and ages of presentation. Comparison of normal and tumour DNAs showed the loss of the normal (non‐mutated) copy of MEN1 gene in the tumour tissue.CONCLUSIONThe different ages of disease presentation and the heterogeneity of symptoms among carriers of the Trp471Stop mutation, which would lead to the synthesis of a truncated non‐functional protein, suggest that clinical heterogeneity is a characteristic of MEN1 independent of the type of mutation. Finally, the lack of amplification of the normal MEN1‐allele on DNA from parathyroid tumours of two family members indicates that MEN1 is a tumour suppressor gene, the second hit that inactivates the normal copy in mutation carriers being a deletion.
A trial of growth hormone therapy in well‐controlled hypophosphataemic rickets
Authors: Cameron  , Sochett  , Daneman  , Kooh  
Published: March 2003

OBJECTIVEConventional therapy of hypophosphataemic rickets (HR) with oral phosphate and calcitriol does not always result in normal linear growth. Recombinant human growth hormone (rhGH) offers theoretical advantages as an adjunctive therapy. We aimed to determine the effects of adjunctive rhGH therapy in children with well‐controlled HR.PATIENTSIn this report, 5 prepubertal children (aged 3.5–10.9 years) with well‐controlled HR on conventional therapy were given adjunctive standard dose rhGH therapy for one year.DESIGN AND MEASUREMENTSHeight, growth velocity, metabolic markers of calcium and phosphate metabolism, body composition, bone mineral density, wrist and knee X‐rays, and renal sonography were assessed at regular intervals. Height and growth velocities were also calculated 12 months after ceasing rhGH therapy.RESULTSAfter 12 months therapy with rhGH, no significant biochemical or radiological benefits were observed. A significant increase in height SD score was observed (P = 0.023), but this was not associated with any increase in the growth velocity SD score and appears to have been due to catch‐up growth caused by conventional therapy alone. When rhGH therapy was ceased, no significant decreases in mean height SD or growth velocity SD scores were observed.CONCLUSIONSIn well‐controlled hypophosphataemic rickets patients receiving conventional therapy, adjunctive therapy with standard dose rhGH offers no benefits in linear growth or rachitic disease markers.
The influence of hydrocortisone substitution on the quality of life and parameters of bone metabolism in patients with secondary hypocortisolism
Authors: Wichers Maria , Springer Wolfram , Bidlingmaier Frank , Klingmüller Dietrich 
Published: March 2003

OBJECTIVEHydrocortisone replacement regimes remain rather empirical and produce serum cortisol profiles very different from normal physiology. We have analysed the effects of different dosages of hydrocortisone (HC) replacement therapy on the health perception and general well‐being of patients with secondary hypocortisolism. We also evaluated the effects of these regimens on bone metabolism.DESIGNIn a prospective randomized double‐blind study, 3 groups of 3 patients were treated with 3 different dosages of HC (15, 20 and 30 mg/day), in different sequences, each sequence for two weeks.PATIENTSNine adult patients with complete secondary hypocortisolism.MEASUREMENTSSerum cortisol, ACTH, aldosterone, renin, alkaline phosphatase, bone specific alkaline phosphatase, osteocalcin, PTH, C‐telopeptides of type‐I collagen, sodium, potassium, phosphate; urinary free cortisol, pyridinium cross‐links, urine sodium, potassium and phosphate were measured at the beginning and after each week of the study.For quality of life assessment the patients completed three different questionnaires, the Basler Befindlichkeits‐Skala (BBS), the Befindlichkeits‐Skala (Bf‐S), the Beschwerde‐Liste (BL) each week.RESULTSWith increasing doses of 15, 20 and 30 mg hydrocortisone a significant increase of free urinary cortisol was achieved (298 ± 26 nmol/day, 454 ± 43, 819 ± 59, respectively; P < 0.01). The mean scores of the psychological questionnaires did not change significantly during the whole study (BBS 81.8 ± 3.9; 82.8 ± 3.9, 83.6 ± 3.9; Bf‐S 15.9 ± 3.4, 11.3 ± 2.6, 12.5 ± 2.8; BL 15.7 ± 2.3, 14.4 ± 2.5, 14.8 ± 2.6, respectively). Osteocalcin decreased significantly (2.3 ± 0.49, 2.1 ± 0.42, 1.8 ± 0.38, P < 0.01) with increasing HC doses but remained within the normal range. The other investigated parameters were within or nearly within the normal range in all patients at the beginning and did not change during the study.CONCLUSIONDosages of 15, 20 or 30 mg hydrocortisone/day have equivalent effects on quality of life in patients with secondary hypocortisolism. With 15 or 20 mg hydrocortisone/day the patients feel nearly as well and content as normal healthy individuals. Since long‐term treatment with a high replacement dose of glucocorticoids (hydrocortisone 30 mg/day) induces bone loss, this risk can be avoided with a substitution dosage of 20 mg or even 15 mg hydrocortisone/day, without influencing the well‐being of the patient.
Ontogeny of serum leptin concentrations in the human
Authors: Geary M. , Herschkovitz R. , Pringle P. J. , Rodeck C. H. , Hindmarsh P. C. 
Published: March 2003

OBJECTIVESerum leptin concentrations reflect the fat mass of an individual. Fetal growth is rapid and it might be expected that major changes in circulating leptin concentrations in the fetus and neonate take place. We have studied the ontogeny of serum leptin concentrations in cord blood samples obtained by cordocentesis between 14 and 32 weeks of gestation and in samples obtained at term.PATIENTSCordocentesis samples from 10 appropriately grown for gestational age (AGA) and 10 intrauterine growth restricted (IUGR) fetuses. The results were compared with cord serum leptin concentrations obtained in 39 term healthy pregnancies.RESULTSIn the AGA and term pregnancies serum leptin concentrations changed little up until 38 weeks of gestation when there was an increase in concentration (Pre 38 weeks 3.5 μg/l (SEM 0.3); Post 38 weeks 5.6 μg/l (SEM 0.7): Mann Whitney P = 0.03). Serum leptin concentrations were similar in the AGA and IUGR fetuses (AGA 5.9 μg/l (SEM 3.0); IUGR 4.2 μg/l (SEM 1.5): Mann–Whitney P = ns). Serum leptin was strongly related to birth weight (r = 0.58; P < 0.001) and birth length (r = 0.32; P = 0.05) in the term babies but not in the AGA or IUGR groups.CONCLUSIONSerum leptin concentrations in the fetus appear to be independent of gestational age and only rise towards the end of gestation. This late change probably reflects the changes in the accretion of body fat. There appears to be little difference in serum leptin concentrations between AGA and IUGR fetuses.