bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoimmune thyroid syndrome in women with Turner's syndrome—the association with karyotype
Authors: Elsheikh M. , Wass J.A.H. , Conway G.S. 
Published: March 2003

OBJECTIVE Females with Turner's syndrome (TS) are at an increased risk of developing autoimmune thyroid disease. Studies assessing the influence of karyotype on thyroid autoimmunity in adults with TS have yielded conflicting results but have been limited by small numbers. The aim of this study was to determine the frequency of thyroid autoimmunity in a large cohort of women with TS and to assess the influence of karyotype on the development of thyroid disease.DESIGN, PATIENTS AND MEASUREMENTS Data were available for 145 women with TS attending a dedicated adult Turner clinic. The mean age was 26 years (range 16–52 years). Information regarding the presence of thyroid disease, karyotype, thyroid autoantibodies and thyroid function was recorded in all. The chi‐squared test with Yates' correction was used to assess the association between karyotype and thyroid autoimmunity.RESULTS Forty‐one per cent of women with TS had positive thyroid autoantibodies and 16% of women were hypothyroid on replacement therapy with thyroxine. However, 83% of women with an X‐isochromosome had positive thyroid autoantibodies compared with 33% of women with other karyotypes (P < 0·0001). Women with an isochromosome‐X karyotype were also significantly more likely to become frankly hypothyroid and require thyroxine compared with other karyotypes (37·5% isochromosome‐X vs. 14% 45, X vs. 6% other karyotypes P = 0·0034).CONCLUSIONS In this large cohort of women with TS we have shown that the risk of developing autoimmune thyroid disease is particularly high in women with an X‐isochromosome, suggesting that a gene on the long arm of the X chromosome (Xq) may play an important pathogenetic role in the development of autoimmune thyroid disease.
Sensitive LH and FSH assays for monitoring low serum levels in men undergoing steroidal contraception
Authors: Robertson David M. , Pruysers Enid , Stephenson Tanneale , Pettersson Kim , Morton Sue , McLachlan Robert I. 
Published: March 2003

BACKGROUND AND OBJECTIVES Current immunoassays for detecting serum FSH and LH are not sufficiently sensitive to detect the markedly reduced levels in men undergoing steroidal hormonal treatment for contraceptive purposes. The purpose of this study was to increase the sensitivity of available LH and FSH immunofluorometric (Delfia®) assays in order to allow a better understanding of the importance of gonadotrophin suppression in achieving the optimal suppression of sperm count.DESIGN AND PATIENTS Assay conditions were modified by increasing serum sample volume, the inclusion of either FSH‐ or LH‐depleted serum to reduce the resulting matrix effects and extending incubation times. The microassays were applied to serum from 10 men administered testosterone enanthate with or without depot medroxyprogesterone acetate for 12 weeks as part of a contraceptive trial.RESULTS The assay sensitivities were increased to 0·005 IU/l for LH and 0·010 IU/l for FSH, representing a five‐ to six‐fold increase in sensitivity compared with existing assays. In the clinical trial, serum LH levels were suppressed to near or below the level of assay detection (mean 0·014 IU/l < 0·4% of pretreatment values) while in eight of 10 men, plasma FSH levels were detectable (0·04–0·07 IU/l, 1–5% of pretreatment values). These FSH levels would not have been detected by current assays.CONCLUSIONS The increased sensitivities of the LH and FSH assays enabled the detection of gonadotrophins that were < 0·4% of pretreatment serum levels. Using these methods, serum LH was suppressed to nondetectable or near nondetectable levels while serum FSH was highly suppressed but still detectable in the majority of men undergoing steroidal treatment for contraceptive purposes.
Effects of fasting and pegvisomant on the GH‐releasing hormone and GH‐releasing peptide‐6 stimulated growth hormone secretion
Authors: Muller A. F. , Janssen J. A. M. J. L. , Lamberts S. W. J. , Bidlingmaier M. , Strasburger C. J. , Hofland L. , Van Der Lely A. J. 
Published: March 2003

OBJECTIVE Pegvisomant is a mutated GH molecule which prevents functional dimerization and subsequent activation of the growth hormone receptor. Pegvisomant and fasting both lead to GH resistance.DESIGN AND PATIENTS We performed a double‐blind placebo‐controlled cross‐over study comparing the effects of pegvisomant and fasting on the GH‐releasing hormone (GHRH)‐ and GH‐releasing peptide‐6 (GHRP‐6)‐stimulated GH‐release before and after 3 days of fasting in 10 healthy lean male subjects. We also performed a single‐arm open label study under nonfasting conditions in five of these subjects. On day 1, in random order, at 0800 h, a GHRP‐6 or GHRH test was performed. At 1600 h, a GHRH (if the first test was a GHRP‐6 test) or GHRP‐6‐test (if the first test was a GHRH test) was done. After the second test either pegvisomant (80 mg as a single subcutaneous injection) or placebo was administered. On day 4, GHRP‐6 and GHRH tests were performed in the same order as on day 1. During the cross‐over study, subjects fasted from 2400 h on day 1 until the end of the study.MEASUREMENTS During the GH stimulation tests, blood samples were drawn every 15 min from 15 to 120 min. GH was determined in all samples. Total insulin‐like growth factor (IGF)‐I and free IGF‐I were determined from the samples at 0 min only.RESULTS Three days of fasting alone and pegvisomant alone as well as in combination increased GH concentrations, whereas a decrease in serum‐free, but not total, IGF‐I concentrations was observed. On day 4, fasting and pegvisomant, either alone or in combination, significantly increased GH concentrations after GHRH compared to baseline. Pegvisomant alone did not increase GH concentrations after GHRP‐6 administration. Fasting alone increased GH levels after GHRP‐6 administration. The combination of fasting and pegvisomant had a synergistic effect on GH release after GHRP‐6.CONCLUSION These human in vivo data suggest that: (1) circulating free IGF‐I, and not total IGF‐I, is the major component in the negative feedback on GH secretion; (2) increased pituitary GHRH receptor expression plays a role in the mechanism whereby fasting leads to increased GH concentrations; (3) in vivo, GHRP‐6 sensitivity seems to be regulated primarily by metabolic factors and not by changes in GH–IGF‐I axis.
Seasonal variation in glucocorticoid receptor binding characteristics in human mononuclear leucocytes
Authors: Blackhurst G. , McElroy P. K. , Fraser R. , Swan R. L. , Connell J. M. C. 
Published: March 2003

OBJECTIVE Glucocorticoid sensitivity varies between individuals and between tissues in the same individual. Although some of this variation is explained by the activity of the 11β‐hydroxysteroid dehydrogenase enzymes, the possibility that glucocorticoid receptor sensitivity is modulated remains unexplored. This study examined glucocorticoid receptor binding in leucocytes and assessed the effects of seasonal hormonal variation on receptor binding.PATIENTS AND MEASUREMENTS Two populations were studied. In the first, 318 healthy subjects were studied over 2 years with a single measurement of receptor binding made on each. In the second study nine healthy male subjects each had receptor binding measurements made at 3‐week intervals over 1 year.RESULTS In both populations there was significant seasonal variation in receptor binding. In the first population Kd for dexamethasone was highest in November and lowest in July (8·37 ± 0·5 nmol/l vs. 1·58 ± 0·7, mean ± SEM P < 0·00001) and the number of receptor sites per leucocyte was highest in January and lowest in June (10 440 ± 580 vs. 4969 ± 302, P < 0·00001). In multivariate analysis, climate was the main determinant for both Kd and the number of receptor sites per cell: increases in day length and environmental temperature reduced Kd and the number of receptor sites per cell. Co‐incubation with physiological concentrations of melatonin raised Kd without affecting receptor number. Co‐incubation with forskolin lowered Kd suggesting that melatonin might act through the ML1 receptor class by inhibiting adenylyl cyclase. No correlations were found with 0900 h plasma cortisol.CONCLUSIONS The results suggest that the glucocorticoid receptor might be modulated by season. Melatonin might mediate part of these effects. The lack of correlation with cortisol suggests that it is not an important determinant of receptor binding and that leucocyte receptors are regulated differently from central receptors.
Polycystic ovary syndrome after precocious pubarche: ontogeny of the low‐birthweight effect
Authors: Ibáñez Lourdes , Valls Carme , Potau Neus , Marcos Maria Victoria , De Zegher Francis 
Published: March 2003

OBJECTIVE Young girls with precocious pubarche (PP) are at increased risk of developing polycystic ovary syndrome (PCOS), including hyperinsulinism, dyslipidaemia and ovarian hyperandrogenism, particularly if PP itself was preceded by a low birthweight. Resistance to insulin is thought to be a key factor in the pathogenesis of this sequence. We aimed to elucidate the peripubertal ontogeny of the low birthweight effect on hyperinsulinism, dyslipidaemia and ovarian dysfunction after PP.PATIENTS AND DESIGN We obtained fully longitudinal data from 51 girls with a history of PP and compared normal‐birthweight (n = 26) with low‐birthweight (n = 25) girls (birthweight SD score 0·0 ± 0·2 vs. − 2·4 ± 0·2) for measurements obtained at diagnosis of PP (mean age 7·0 years), in early puberty (10·4 years) and after menarche (14·3 years).MEASUREMENTS Fasting serum lipids and lipoproteins, together with insulin responses to an oral glucose load, were assessed at diagnosis of PP, in early puberty and after menarche; serum gonadotropins were measured in early puberty and after menarche; ovarian function was examined postmenarche.RESULTS Comparisons of endocrine‐metabolic results between normal‐ and low‐birthweight PP girls showed no detectable differences before puberty. The hypertriglyceridaemia and elevated LDL‐cholesterol levels characterizing low‐birthweight PP girls became detectable by early puberty; reduced insulin sensitivity was not evident until postmenarche, when the tendency to ovarian dysfunction also became obvious. Body mass indices of normal‐ and low‐birthweight subgroups were identical in early puberty and postmenarche.CONCLUSIONS These longitudinal data show that, in PP girls, the endocrine‐metabolic risk conferred by prenatal growth restraint is not readily detectable until puberty or postmenarche, and is not attributable to a higher body mass index.
Lack of influence of the androgen receptor gene CAG‐repeat polymorphism on sex steroid status and bone metabolism in elderly men
Authors: Van Pottelbergh I. , Lumbroso S. , Goemaere S. , Sultan C. , Kaufman J. M. 
Published: March 2003

OBJECTIVEPopulation means for serum testosterone (T) levels in healthy men decrease with ageing but there is considerable interindividual variability of serum T in elderly men. Ultimate androgen action is mediated through the androgen receptor. Subtle differences in androgen sensitivity might contribute to serum T variability through the T negative feedback regulation. The androgen receptor gene (AR) contains in exon 1 a polymorphic trinucleotide CAG‐repeat, whose length modulates androgen receptor action. The aims of the study were to assess the potential contribution of the AR CAG‐repeat polymorphism in the interindividual variability of serum T and in the determination of bone metabolism in ambulatory elderly men.DESIGN AND PATIENTSWe used cross‐sectional baseline data of a longitudinal study investigating the process of ageing, in particular the changes in hormonal status and bone metabolism, in a cohort of 273 community‐dwelling healthy men, between age 71 and 86 years.MEASUREMENTSAR CAG‐repeat length was determined by automated DNA sequencing of exon 1 of the AR gene. Serum T, sex hormone binding globulin, LH and oestradiol were measured by specific immunoassays. Bone mineral density (BMD) was determined by dual energy X‐ray absorptiometry. Bone turnover was assessed by measurement of serum bone‐specific alkaline phosphatase, serum osteocalcin, serum C‐terminal type I procollagen peptide, serum and urinary C‐terminal telopeptides of type I collagen and urinary deoxypyridinoline levels, with use of immunoassays.RESULTSNo significant association was found between the AR CAG‐repeat length and either total or free T, LH or the androgen sensitivity index (LHxT). BMD measurements at the hip and the forearm were not associated with AR CAG‐repeat length and there was no association of this AR polymorphism with any of the biochemical markers of bone turnover. Results were not different after adjustments for age and body mass index.CONCLUSIONSThe findings of the present study do not support the view that in community‐dwelling, healthy elderly men the androgen receptor gene CAG‐repeat polymorphism has a substantial impact on interindividual variability of serum testosterone levels or on the determination of bone turnover and bone mineral density.
Dehydroepiandrosterone sulphate is increased and dehydroepiandrosterone‐response to corticotrophin‐releasing hormone is decreased in the hyperthyroid state compared with the euthyroid state
Authors: Yamakita Noriyoshi , Murai Toshihiro , Kokubo Yoshiaki , Hayashi Makoto , Akai Akifumi , Yasuda Keigo 
Published: March 2003

OBJECTIVE Dehydroepiandrosterone (DHEA) and DHEA‐sulphate (S) have been suggested to play protective roles in many pathological states, some of which are observed in hyperthyroidism. If DHEA and DHEA‐S levels change in hyperthyroidism, they might participate as a possible causative link with such pathophysiological changes in hyperthyroidism. However, the CRH–ACTH–DHEA system in hyperthyroidism has not been clearly defined. We examined plasma levels of DHEA and DHEA‐S together with ACTH and cortisol in both hyperthyroid (Hyper) and euthyroid states (Eu).METHODS Eighteen patients (5 men and 13 women, aged 46·9 ± 2·8 years) with Graves' disease were studied before treatment and again in the euthyroid state following treatment with methimazole. A 100 µg hCRH stimulation test and a low‐dose (0·5 µg) 1–24 ACTH stimulation test were performed on separate days. Basal levels and Δ area under the response curve (AUC) were compared between Hyper and Eu.RESULTS DHEA‐S was higher in Hyper than in Eu. However, basal DHEA did not differ between Hyper and Eu. The ratio of DHEA to DHEA‐S was lower in Hyper than in Eu. ΔAUC of DHEA during a CRH test was lower in Hyper than in Eu. However, ΔAUC of DHEA during an ACTH test was similar in both Hyper and Eu. Basal ACTH was higher in Hyper than in Eu. In both CRH and ACTH tests, ΔAUC of cortisol response was lower in Hyper than in Eu, although the basal cortisol level was not different.CONCLUSION The balance of the conversion between DHEA‐S and DHEA in the hyperthyroid state favoured DHEA‐S. Similar to cortisol, the DHEA response in the CRH test in hyperthyroidism seemed to be insufficiently compensated for by increased ACTH, although the DHEA response to low‐dose ACTH was similar in the hyperthyroid and euthyroid states. Increased DHEA‐S might play some role in the pathological states in many organs in hyperthyroidism.
CTLA‐4 gene A–G polymorphism and childhood Graves’ disease
Authors: Yung E. , Cheng P. S. , Fok T. F. , Wong G. W. K. 
Published: March 2003

Summaryobjective Graves’ disease is associated with a polymorphism at position 49 in exon 1 of the cytotoxic T‐lymphocyte‐associated antigen‐4 (CTLA‐4) gene in Caucasians and Japanese. A high incidence of childhood Graves’ disease has been documented in Hong Kong Chinese. The aims of this study were to investigate the CTLA‐4 gene A–G polymorphism association in Chinese children with Graves’ disease.patients and design One hundred and twenty‐three Chinese children with Graves’ disease (104 girls and 19 boys) and 158 racially matched healthy controls were recruited for the study. Genomic DNA was extracted from venous blood samples. The dimorphism at position 49 A–G was analysed by polymerase chain reaction, single‐strand conformation polymorphism and restriction fragment‐length polymorphism analysis.results The genotype distribution and allele frequencies of children with Graves’ disease differed significantly from those of the controls (P = 0·0023 and P = 0·022, respectively). The presence of at least one G allele (GG or AG) was associated with an increased risk of Graves’ disease (OR = 6·8, 95% CI = 2·0–36·1; P = 0·001).conclusions This study confirms that CTLA‐4 49 A–G polymorphism is associated with Graves’ disease in Chinese children. The CTLA‐4 49 G allele confers an increased risk of childhood Graves’ disease.
Subjective health status in Norwegian patients with Addison’s disease*
Authors: Løvås Kristian , Loge Jon Håvard , Husebye Eystein S. 
Published: March 2003

Summaryobjective  Many patients with Addison’s disease have complaints that might be related to the disease or to its treatment. However, only a few studies have addressed the subjective health status of patients with adrenocortical failure. The aim of the present study was to assess the subjective health status with special emphasis on fatigue among patients with Addison’s disease.subjects, design and measurement   In a postal survey, 79 patients with confirmed primary adrenal failure (Addison’s disease) completed the Short Form 36 (SF‐36) and the Fatigue questionnaires. The subjective health status in Addison’s disease was compared with normative data from the general population.results  General health and vitality perception were most consistently impaired in the patients with Addison’s disease. The scores on physical functioning and role‐physical were low in women. Social functioning and role‐emotional scores were also lower than normal in the female patients, but this was confined to the patients with autoimmune polyendocrine syndromes. Patients with autoimmune polyendocrine syndromes tended to have lower scores than patients with solitary Addison’s disease. The level of fatigue was higher than normal for both men and women. Working disability at ages 18–67 years was 26%, compared with 10% in the corresponding general Norwegian population. The high working disability increased with age and was higher in subgroups with concomitant endocrine diseases. Most subjective health parameters were lower among the disabled compared to the patients in work.conclusions  Patients with Addison’s disease under replacement therapy with cortisone acetate and fludrocortisone have reduced general health perception and vitality, and increased fatigue. Female patients reported reduced physical function, which might be due to adrenal androgen depletion. Mental health seems more influenced by concomitant endocrine diseases, but mental fatigue might be a specific feature in adrenal failure. The patient population is heterogeneous, with normal findings in a substantial proportion but markedly reduced subjective health status and working ability in many others. Thus, there might be potential for further refinement of replacement therapy.
Erythrocyte Na+,K+‐ATPase and nasal potential in pseudohypoaldosteronism*
Authors: Bistritzer Tzvy , Kerem Eitan , Berkovitch Matitiahu , Rapoport Micha J. , Evans Sandra , Aladjem Mordechai 
Published: March 2003

Summaryobjectives Pseudohypoaldosteronism type 1 (PHA1) is a rare inherited disorder characterized by salt‐wasting due to target organ unresponsiveness to mineralocorticoids. PHA1 comprises two clinically and genetically distinct entities; isolated renal and systemic forms.design The aim of this study was to investigate red blood cell (RBC) Na+,K+‐ATPase activity and nasal potential difference (PD) in two pairs of unrelated dyzygous twins; one with the systemic form of the disease (PHA1‐S) and the second with the isolated renal form (PHA1‐R). Total and ouabain‐sensitive ATPase activities were measured spectrophotometrically by a method that couples ATP hydrolysis with NADH oxidation. Maximal PD and response to amiloride perfusion were evaluated by a standard technique.results In the twins with PHA1‐S, persistently low activity of RBC Na+,K+‐ATPase was found during a 6‐year follow‐up. Normalization of plasma renin activity (PRA) and plasma aldosterone was observed at the end of the first year of life. Maximal nasal PD was low and there was no significant response to amiloride. In the twins with PHA1‐R, RBC Na+,K+‐ATPase activity was very low at the time of diagnosis and normalized at the age of 6–8 months. PRA reverted gradually to normal values, whereas aldosterone levels remained high during the 6 years of follow‐up. Maximal nasal PD and response to amiloride were normal.conclusions The observed differences in RBC Na+,K+‐ATPase activity and nasal PD response to amiloride between the two pairs of twins support the contention of different basic pathogenic mechanisms in the two forms of PHA1.
Trisomy of the short stature homeobox‐containing gene (SHOX), resulting from a duplication‐deletion of the X chromosome
Authors: Adamson K. A. , Cross I. , Batch J. A. , Rappold G. A. , Glass I. A. , Ball S. G. 
Published: March 2003

SummaryThe Turner syndrome (TS) is a complex disorder associated with almost invariant short stature and gonadal dysgenesis, as well as a variety of other major organ malformations. Recently, a homeobox‐containing gene entitled short‐stature homeobox‐containing gene (SHOX), was isolated from a minimal short stature gene interval from the pseudoautosomal region of Xp (and Yp). Together with the demonstrable escape of SHOX from X‐inactivation, this suggested SHOX to be a strong candidate gene for the short stature component of TS, and as SHOX haploinsufficiency appears to be the molecular basis of a mesomelic short statured skeletal dysplasia (Leri–Weill syndrome), this suggested that SHOX protein expression levels may confer a dosage effect on human stature. However, in this communication we report a normal statured female with gonadal dysgenesis, due to the inheritance of a recombinant duplication‐deletion X‐chromosome. The karyotype of the proband was 46,X,rec(X)dup(Xp)inv(X)(p11·22q21·2)mat and fluorescentin situhybridization of her metaphases with a SHOX cosmid confirmed the proband to be trisomic forSHOX. This communication suggests the relationship between levels of SHOX expression and human stature to be more complex than envisaged previously. The presence of normal stature in our patient rather than tall stature is likely to represent the natural variation seen in patients with transcription factor disorders.