bluuebunny/crossref_metadata_2025_split huggingface dataset:
β3‐adrenoreceptor gene polymorphism and leptin. Lack of relationship in type 2 diabetic patients
Authors: Vendrell  , Gutierrez  , Broch  , Fernandez‐Real  , Aguilar  , Richart  
Published: March 2003

INTRODUCTIONThe β3‐Adrenergic receptor (β3AR) and leptin are molecules involved in the regulation of energy balance. Recently, a mutation in the β3AR gene (Trp64Arg) has been reported to be associated with features of insulin resistance, weight gain and early onset of Type 2 Diabetes Mellitus. The aim of this study was to determine the frequency and clinical characteristics of the Trp64Arg mutation in the β3AR gene in Type 2 diabetic patients, its relationship with leptin levels, and its role in microangiopathic complications.SUBJECTS AND METHODS187 Type 2 diabetic patients and 100 unrelated non‐diabetic subjects were studied. There was no difference between the diabetic and nondiabetic subjects in the frequency of the Trp64 and Arg64 alleles (92.5% vs. 92.3% and 7.5% vs. 7.7%, respectively). Type 2 diabetic patients were divided into two groups according to the presence (n = 27) or absence of the mutation (n = 160).RESULTSMutation of the β3AR gene was not associated with any differences either in the clinical and metabolic parameters or microangiopathic complications. Type 2 diabetic patients carrying the Arg64 allele tended to have a lower diabetes duration, but this was not statistically significant. Plasma leptin levels were not different according to the β3AR genotype.CONCLUSIONSThe Trp64Arg mutation is not a major determinant of Type 2 diabetes and its microangiopathic complications. Moreover, this mutation was not clinically relevant in leptin regulation.
Secondary adrenal insufficiency associated with autoimmune disorders: a report of twenty‐five cases
Authors: Kasperlik‐Załuska A. A. , Czarnocka B. , Czech W. , Walecki J. , Makowska A. M. , Brzeziński J. , Aniszewski J. 
Published: March 2003

OBJECTIVEAddison's disease is frequently a component of autoimmune polyendocrinopathies while secondary adrenal insufficiency associated with autoimmune disorders is believed to be a rare event. We present a series of patients with secondary adrenal insufficiency coexisting with autoimmune diseases and/or antithyroid autoantibodies.DESIGN AND PATIENTSAmong a group of 102 patients with secondary adrenal failure of unknown origin diagnosed at the Department of Endocrinology of the Centre for Postgraduate Medical Education (Warsaw, Poland) we have identified a group with associated autoimmune disorders. Thyroid abnormalities occurred most frequently. Other diseases included insulin‐dependent diabetes mellitus, pernicious anaemia, vitiligo, premature ovarian failure and autoimmune thrombocytopaenia. There were 23 women and one man aged 17–72 years at the time of investigation. Additionally, we included a woman with Addison's disease in whom the ACTH deficiency appeared 18 years after the onset of primary adrenal hypofunction.MEASUREMENTSPituitary–adrenal function tests comprised urinary excretion of 17‐hydroxycorticosteroids in basal conditions and during a 2‐day tetracosactrin test, plasma concentrations of ACTH and cortisol, and a 2‐day metyrapone test (in eight cases). Thyroid function and immunity tests were: TSH, thyroxine, the antithyroglobulin, antimicrosomal and anti‐peroxidase autoantibodies. Other endocrine studies included: serum LH, FSH and PRL.RESULTSThe 17‐hydroxycorticosteroid values, both basally and during stimulation tests were consistent with a diagnosis of secondary adrenal insufficiency. Serum cortisol and plasma ACTH concentrations were low. In 14 patients primary hypothyroidism was confirmed by low T4 levels. In three patients subclinical primary hypothyroidism was revealed (elevated TSH levels). Three patients who had a past history of Graves' disease were euthyroid at the time of investigation. Twenty‐three patients had antibodies against peroxidase. Most patients had gonadotrophins and PRL values within normal limits.CONCLUSIONSThe co‐existence of autoimmune disorders with secondary adrenal insufficiency suggests an autoimmune aetiology for the ACTH deficiency.
Different immunohistochemical patterns of TGF‐β1 expression in benign and malignant adrenocortical tumours
Authors: Boccuzzi Adriana , Terzolo Massimo , Cappia Susanna , De Giuli Paolo , De Risi Carolina , Leonardo Eugenio , Bovio Silvia , Borriero Mirella , Paccotti Piero , Angeli Alberto 
Published: March 2003

OBJECTIVETransforming growth‐factor β1 (TGF‐β1) influences a number of specific functions of adrenocortical cells in several animal species. The aim of our study was to evaluate by immunohistochemical analysis the presence and distribution of TGF‐β1 in normal adrenal tissue and in different adrenal tumours.PATIENTSWe analysed 8 functioning (5 adenomas and 3 carcinomas) and 15 non functioning (6 adenomas and 9 carcinomas) adrenal tumours and 6 normal adrenal glands.RESULTSIn normal adrenal glands, the glomerulosa and the reticularis zones displayed diffuse cytoplasmic staining, while the fasciculata zone was almost completely negative. Functioning adenomas displayed cytoplasmic staining restricted to compact cells while in nonfunctioning adenomas, prevalently composed by clear cells, no staining was observed. Overall, adrenal carcinomas were characterized by the lack of cytoplasmic positivity and by sporadic positive cells around vessels both in functioning and in nonfunctioning tumours.CONCLUSIONSTGF‐β1 expression is associated with active steroid secretion in normal adrenal tissue, as well as in benign cortical adenomas, while this relationship is lost in primary adrenal malignancies. These data provide indirect evidence for a regulatory role played by TGF‐β1 on steroid secretory pathways.
Kallmann's syndrome: is it always for life?
Authors: Quinton  , Cheow  , Tymms  , Bouloux  , Wu  , Jacobs  
Published: March 2003

OBJECTIVEKallmann's syndrome (KS) is defined by the association of olfactory deficit with irreversible, congenital gonadotrophin deficiency (IHH). We present evidence for the existence of a variant form of KS, in which endogenous gonadotrophin secretion recovers spontaneously in later life.DESIGNLongitudinal clinical study.PATIENTSFive men with anosmia or severe hyposmia, who originally presented in their late teens or early twenties as a result of severe pubertal delay and were thus presumed to have KS.RESULTSSpontaneous onset of endogenous gonadotrophin secretion, evidenced by progressive normalization of testicular volume and of serum testosterone concentration, occurred in these men over a period of years following the initial diagnosis.CONCLUSIONSThis variant form of Kallman's syndrome is not well recognized and may well be under‐diagnosed. Once full virilization has been induced, males with congenital gonadotrophin deficiency whose testes have significantly increased in size should be reassessed, off androgen replacement therapy, to identify those who no longer require treatment.
Correlation between urinary cortisol and 6‐sulphatoxymelatonin rhythms in field studies of blind subjects
Authors: Skene  , Lockley  , James  , Arendt  
Published: March 2003

OBJECTIVEBlind individuals have different types of circadian rhythm disorders. In order to study these in the field reliable markers of circadian phase are required. The aim of the present study was to determine the usefulness of urinary cortisol as a marker rhythm in field studies. This was assessed by investigating the relationship between the cortisol rhythms and the previously determined melatonin rhythms from a large sample of blind people with different types of circadian rhythm disorders.DESIGNField studySUBJECTRegistered blind subjects (n = 49) classified as having light perception or better (n = 19, 12 men, 7 women, aged 23–61 years) or having no conscious perception of light (n = 30, 24 men, 6 women, aged 19–72 years) were studied in their normal environment.MEASUREMENTSequential 4‐hourly urine samples (plus an overnight sample) were collected for 48 h each week for 3–5 weeks. Urinary cortisol and 6‐sulphatoxymelatonin were measured by radioimmunoassay.RESULTIrrespective of the type of circadian rhythm (entrained or free‐running), there was a significant correlation between the characteristics of the 6‐sulphatoxymelatonin and cortisol rhythms in the blind subjects.CONCLUSIONUrinary cortisol is recommended as a useful marker of circadian phase in field studies in addition to urinary 6‐sulphatoxymelatonin measurements.
Adrenal and gonadal contributions to urinary excretion and plasma concentration of epitestosterone in men — effect of adrenal stimulation and implications for detection of testosterone abuse
Authors: Kicman Andrew T. , Coutts Sarah B. , Cowan David A. , Handelsman David J. , Howe Chris J. , Burring Surrinder , Wu Frederick C. W. 
Published: March 2003

OBJECTIVEThe ratio of urinary testosterone (T) to epitestosterone (EpiT) is used to detect T abuse in sport. Also, plasma or urinary concentrations of EpiT have been measured to assess testicular steroidogenesis during hormonal male contraception. Further investigations are required to evaluate the relative contributions of the testis and adrenal to EpiT production. To this purpose, we have compared basal urinary EpiT glucuronide and plasma EpiT and the response to synthetic adrenocorticotrophic hormone (ACTH) stimulation between eugonadal and hypogonadal men.DESIGN AND SUBJECTSThe basal urinary excretion rate of EpiT glucuronide was determined in 34 eugonadal men. Six men, clinically diagnosed as hypogonadal, and 6 out of the 34 eugonadal men previously described, received an intramuscular injection of synthetic ACTH depot (1 mg) at 0800 h on two consecutive days. Blood samples were collected prior to and then at 1.5, 8, 24, 25.5, 32 and 48 h with respect to the first administration (0 h). 24‐h urine specimens were collected from 0800 h on days 1 and 2 (baseline) and 3 and 4 (stimulation).MEASUREMENTSPlasma EpiT, T and cortisol were measured by RIA and urinary EpiT and T, following glucuronide hydrolysis, by gas chromatography‐mass spectrometry (extract combines aglycones with a minor amount of urinary free steroids).RESULTSBasal excretion rates of EpiT glucuronide in eugonadal men (range:62–751 nmol/24 h) were considerably greater than in hypogonadal men (range: 3–34 nmol/24 h). Mean basal plasma EpiT in eugonadal men (1.32 ± 0.08 nmol/l) were greater than in hypogonadal men (0.68 ± 0.04 nmol/l). In each group, synthetic ACTH stimulation increased plasma cortisol 4‐fold. In eugonadal men, plasma and urinary EpiT were unchanged whereas plasma and urinary T glucuronide decreased in response to ACTH. In hypogonadal patients, ACTH increased plasma and urinary EpiT while plasma T remained unchanged.CONCLUSIONThe testes are the major source of epitestosterone, the adrenal contribution being relatively modest. Following adrenal stimulation, urinary epitestosterone glucuronide increases considerably in hypogonadal men but this increase is masked in eugonadal men because testicular production is probably suppressed by the ACTH‐induced rise in cortisol. Activation of the adrenal cortex results in no change or only a small decrease in the urinary T/EpiT ratio in eugonadal men.
A novel mutation in the TPO gene in goitrous hypothyroid patients with iodide organification defect
Authors: Santos Cecilia L. S. , Bikker Hennie , Rego Katia G. M. , Nascimento Antonio C. , Tambascia Marcos , De Vijlder Jan J. M. , Medeiros‐Neto Geraldo 
Published: March 2003

OBJECTIVETo screen and subsequently sequence the TPO gene for mutations in patients with congenital goitre, hypothyroidism and evidence for an organification defect (positive perchlorate discharge test).PATIENTSWe have studied seven hypothyroid and congenitally goitrous patients from three unrelated families.DESIGN AND MEASUREMENTSWe have measured serum thyroid hormone levels, 131I uptake, serum TSH and serum Tg concentrations. Denaturing gradient gel electrophoresis (DGGE) of PCR amplified genomic DNA was used to screen for mutations in the TPO gene.RESULTSDGGE identified the presence of two frameshift mutations: a GGCC duplication in exon 8 (homozygous in one family and heterozygous in the other family) and a heterozygous insertion of a single nucleotide (C) at position 2505‐2511 in exon 14. In addition, we have detected an alteration in exon 11, not yet described in the literature, derived from a single nucleotide substitution of a C to G at position 2008, altering the well‐conserved amino acid domain among the peroxidases superfamily. This mutation in exon 11 was present in two families that showed heterozygous mutation for exon 8 or for exon 14.CONCLUSIONSThese results could support the hypothesis for a putative compound heterozygosity pattern in the affected patients. The altered phenotype (goitre and hypothyroidism since birth) seems justifiable in view of the possible inactivating character of this novel mutation in exon 11.
Growth hormone (GH) replacement therapy reduces serum sialic acid concentrations in adults with GH‐deficiency: a double‐blind placebo‐controlled study
Authors: Christ Emanuel R. , Cummings Michael H. , Lumb Peter J. , Crook Martin A. , Sönksen Peter H. , Russell‐Jones David L. 
Published: March 2003

OBJECTIVESPatients with adult GH‐deficiency are thought to have an increased risk of cardiovascular disease. Sialic acid (SA) concentrations have been proposed as a marker of atherosclerotic disease probably related to an inflammatory response of the arterial wall. SA as a marker of cardiovascular disease in adult GH‐deficiency and its relation to changes in fasting lipid profile and hormone concentrations have not yet been investigated.PATIENTSWe performed a randomised, double‐blind placebo‐controlled study in 18 patients with adult GH‐deficiency before and after 3 months GH replacement therapy (0.036 U/kg/d; GH‐treated group: 6 females, 3 males; age: 47.3 ± 5.4 years., mean ± SEM; placebo‐group: 5 females, 4 males; mean age 50.2 ± 4.7). In addition, SA concentrations were measured in 18 sex and age matched healthy control subjects.METHODSBlood samples were obtained after an overnight fast. Serum SA, triglycerides and cholesterol were measured using enzymatic methods. Lipoprotein classes were separated by ultracentrifugation. Insulin and IGF‐I were determined by radioimmunoassay, HbA1C was measured by anion exchange liquid chromatography.RESULTSSA concentrations of the patients with adult GH‐deficiency were not significantly different compared to the control group (GH‐deficient group: 2.29 ± 0.02 mmol/l, mean ± SEM vs. control group: 2.09 ± 0.13 mmol/l, P = 0.25). Before GH replacement therapy SA concentrations correlated positively with the patients age (r = 0.45; P < 0.04) and fasting insulin concentrations (r = 0.5; P < 0.03) but not with fasting lipid profile. GH replacement therapy significantly increased IGF‐I (GH: + 27 ± 2.6 vs. placebo: + 1.0 ± 0.8 nmol/l, P < 0.001) and fasting insulin concentrations (GH: + 71.9 ± 8.0 vs. placebo: + 19.6 ± 22.6 pmol/l, P < 0.04) compared to placebo therapy. SA concentrations (GH: − 0.41 ± 0.15 vs. placebo: − 0.01 ± 0.12 mmol/l, P < 0.05), total cholesterol (GH: − 0.71 ± 0.16 vs. placebo: 0.23 ± 0.21 mmol/l, P < 0.003) and LDL‐cholesterol (− 0.71 ± 0.14 vs. placebo: − 0.12 ± 0.21 mmol/l P < 0.04) significantly decreased after GH replacement therapy compared to placebo therapy. No significant correlation between changes in SA concentrations and changes in lipid profile were observed following GH replacement therapy.CONCLUSIONThese results suggest that, firstly, GH replacement therapy may have a beneficial effect on the pathogenesis of atherosclerosis despite the increase in insulin concentrations, a surrogate marker of insulin resistance, secondly, the proposed beneficial effect of GH on the atherosclerotic process is likely to be multifactorial and cannot only be explained by changes in lipid profile and finally, SA might be a useful marker for the process of atherosclerotic disease in interventional studies.
Increased pressor response to noradrenaline in pituitary dependent Cushing's syndrome
Authors: Heaney Anthony P. , Hunter Steven J. , Sheridan Brian , Brew Atkinson  
Published: March 2003

OBJECTIVESThe mechanism of hypertension in Cushing's syndrome remains undetermined. Some studies have demonstrated an increased sensitivity to pressor agents but it is not clear if patients with Cushing's syndrome of different aetiologies demonstrate this finding. We have examined pressor sensitivity in a group of patients with Cushing's disease (pituitary dependent hypercortisolism) by measuring blood pressure during incrementally increasing infusions of noradrenaline.METHODSEight subjects (7 female, 1 male), aged 42.2 ± 4.5 years (mean ± SEM) with Cushing's disease were studied. Eight age‐ and sex‐matched control subjects were also studied. Four of the eight controls and five patients with Cushing's disease had elevated blood pressure. All medication for this had been stopped at least seven days prior to the study. After subjects ate a light breakfast, ECG leads and a sphygmomanometer were attached, an intravenous cannula was inserted and all subjects then rested quietly for 60 minutes. Noradrenaline was then infused intravenously for 10‐minute periods at concentrations of 0.01, 0.03, 0.07, 0.11 and 0.18 μg/kg/minute.RESULTSOn the day of the study the baseline blood pressures and pulse rates in the patients with Cushing's disease (blood pressure; 138/87 ± 6/3 mmHg, pulse 76.5 ± 4.8 beats/minute) and controls (blood pressure; 126/86 ± 6/6 mmHg, pulse 71.2 ± 3.7 beats/minute) were not significantly different. The mean change in diastolic blood pressure from baseline at the time of the peak increase or when the test was stopped was 21.5 ± 4.7 mmHg in Cushing's disease compared to 7.0 ± 2.5 mmHg in controls (P = 0.03). The mean change in mean arterial pressure from baseline at the time of the peak increase or when the test was stopped was 22.0 ± 4.0 mmHg in Cushing's disease compared to 13.0 ± 2.4 mmHg in controls (P = 0.03). No significant difference in mean change of systolic pressure (26.0 ± 4.6 vs. 25 ± 4.0 mmHg) or pulse rates (− 11.1 ± 1.8 vs. − 4.7 ± 2.6) was seen in the group with Cushing's disease as compared to the control group.CONCLUSIONSWe conclude that patients with pituitary–dependent Cushing's syndrome have enhanced pressor diastolic and mean arterial responses to noradrenaline and this may be an important underlying mechanism for the hypertension seen in this particular group of Cushing's syndrome patients.
Syndrome of body fat redistribution in HIV‐1‐infected patients: relationships to cortisol and catecholamines
Authors: Renard Eric , Fabre Jacqueline , Paris Françoise , Reynes Jacques , Bringer Jacques 
Published: March 2003

OBJECTIVEAlterations of body fat distribution have been recently reported in HIV‐infected patients. We aimed to investigate whether the hormones modulating adipose tissue metabolism could be implicated.SUBJECTSWe investigated twenty‐eight HIV‐infected patients who had developed abdominal fat, combined with peripheral lipodystrophy in 25 cases and ‘buffalo hump’ in 2 cases, but who had otherwise improved on antiretroviral therapies. Twelve patients with no change in body fat, matched for age, disease control and treatment, were studied as controls.MEASUREMENTSBody composition was assessed by bioelectrical impedance analysis. Subcutaneous (SAT) and visceral (VAT) compartments of total abdominal adipose tissue (TAT) were measured by computed tomography. Resting metabolic rate (RMR) was assessed by indirect calorimetry. Endocrine investigations included plasma thyroid hormones, cortisol, testosterone, oestradiol and 24‐hour urinary free cortisol (UFC) and catecholamines.RESULTSDespite similar body mass index, the patients with body fat alterations showed significantly larger VAT and higher VAT:TAT ratio than controls (P = 0.002 and 0.0001, respectively). In these patients, RMR was significantly higher than estimated according to the Harris‐Benedict formula (+ 19.7 ± 11.6 %, P = 0.0001) and correlated with VAT (r = 0.58, P = 0.003) and 24‐hour urinary output of catecholamines (r = 0.67, P = 0.002), that was significantly increased in comparison withcontrols (1737 ± 1228 vs 476 ± 292 nmol, P = 0.013). We also found a significant correlation between VAT and UFC (r = 0.41, P = 0.042) that was absent in controls, although levels of UFC were similar in the two groups.CONCLUSIONSOur data suggest that body fat redistribution may involve cortisol and catecholamine actions. While high release of catecholamines may enhance RMR through increased lipolysis, cortisol may promote central fat storage. These effects might be related both to persistent hormonal responses to stress becoming inappropriate while disease control improved and to an increased sensitivity of visceral adipose tissue to cortisol in affected patients.
Sexual dimorphism in circulating monomeric and dimeric inhibins in normal boys and girls from birth to puberty
Authors: Bergadá  , Rojas  , Ropelato  , Ayuso  , Bergadá  , Campo  
Published: March 2003

BACKGROUND AND OBJECTIVEInhibins are peptides, mainly of gonadal origin, that suppress FSH production. Dimeric forms of inhibin (A and B) have been proposed as peripheral markers of Sertoli and granulosa cell function. The aim of this study was to establish the relationship between circulating dimeric and monomeric inhibins, and gonadotrophins and sex steroids, in normal boys and girls from birth to puberty.SUBJECTSOne hundred and forty‐six normal children (females: 57; males: 89) were studied.MEASUREMENTSSerum LH and FSH were measured by an immunofluorometric assay. Serum oestradiol and testosterone were measured by radioimmunoassay. Serum inhibin A and B, and Pro‐αC, were measured by specific two‐site enzyme‐linked immunosorbent assays.RESULTSIn boys from birth to 6 months of age, the mean serum inhibin B concentration was as high (477 ± 53.7 ng/l) as that found at puberty (400 ± 70.2 ng/l). After the first year, inhibin B gradually decreased to reach its lowest concentration (153 ± 23.6 ng/l) at age 4–6 years. At approximately age 10, it rose progressively to reach pubertal concentrations. Pro‐αC showed a similar pattern but at lower concentrations. Inhibin A was not detected at any age. In girls from birth to 6 months, inhibin B levels (83.0 ± 18.3 ng/l) were approximately 50% lower than those found at puberty (181 ± 25.7 ng/l). After 6 months of age, these levels dropped (17.5 ± 1.6 ng/l) and remained low until the prepubertal years. Thereafter, they increased to pubertal concentrations. The serum inhibin A concentration after birth (29.9 ± 8.7 ng/l) was similar to that found at puberty (18.3 ± 5.7 ng/l); after 6 months, it fell to undetectable levels until the prepubertal years.CONCLUSIONThe sex difference in serum levels of gonadotrophins is associated with sex differences in the levels and proportions of circulating dimeric and monomeric inhibins.