bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low level of glucocorticoid receptor messenger ribonucleic acid in pituitary adenomas manifesting Cushing's disease with resistance to a high dose‐dexamethasone suppression test
Authors: Mu Yi‐Ming , Takayanagi Ryoichi , Imasaki Kyosuke , Ohe Kenji , Ikuyama Shoichiro , Yanase Toshihiko , Nawata Hajime 
Published: March 2003

OBJECTIVESThe overnight 8‐mg dexamethasone suppression test is often used to differentiate Cushing's disease, due to an oversecretion of ACTH from the pituitary gland, from other kinds of Cushing's syndrome. However, a few patients with ACTH‐producing pituitary adenoma show no suppression of plasma cortisol after the administration of 8 mg of dexamethasone. To clarify the relationship between the level of glucocorticoid receptor (GR) in the pituitary adenoma and the sensitivity to dexamethasone in Cushing's disease, we thus examined the levels of GRα and GRβ mRNAs in the pituitary adenomas in six patients who were proven at surgery to have pituitary ACTH‐producing adenomas.MATERIALSTotal RNA was extracted from six pituitary adenomas and pituitary tissue adjacent to one of the adenomas, and the mRNA levels of GRα, GRβ, pro‐opiomelanocortin (POMC) and β‐actin in these samples were sampled by quantitative RT–PCR.RESULTSThe GRα mRNA levels in the adenomas from the two patients who showed no response to the 8‐mg dexamethasone suppression test were significantly lower than those in the adenomas of four patients who showed suppression. The GRβ mRNA level was much lower than that of GRα mRNA but not significantly different among the six adenomas.CONCLUSIONSThese results suggest strongly that decreased expression of GRα in pituitary adenomas may be the major reason for the marked insensitivity to the 8‐mg dexamethasone suppression test observed in two patients with Cushing's disease.
The efficacy of DDAVP is related to the circadian rhythm of urine output in patients with persisting nocturnal enuresis
Authors: Hunsballe J. M. , Hansen T. K. , Rittig S. , Pedersen E. B. , Djurhuus J. C. 
Published: March 2003

OBJECTIVEDesmopressin may be a useful treatment in some, but not all, patients with nocturnal enuresis. We have evaluated a relation between nocturnal urine output in patients with primary monosymptomatic nocturnal enuresis and the treatment response to synthetic vasopressin.DESIGNAdolescent or adult enuretics and normal subjects were enrolled in the study and admitted to hospital for a 24 hour investigation of the diurnal variation in urine output, plasma vasopressin (AVP) and plasma atrial natriuretic peptide (ANP). The enuretics were characterized prior to investigation as either 1‐desamino‐8‐D‐arginine vasopressin (DDAVP) responders or non‐responders. During admission the fluid intake was restricted to 25 ml/kg per day.PATIENTSTwenty‐four patients (15–37 years) with primary monosymptomatic nocturnal enuresis and 9 normal subjects (24–31 years).MEASUREMENTSCirculating levels of AVP, ANP, plasma electrolytes and plasma osmolality were measured (1400, 2000, 2300, 0200, 0500 and 0800 hours) together with urine volume, urine osmolality and urine electrolytes during daytime and nighttime. Tubular reabsorptive capacity for water, osmoles and creatinine were assessed as well as urinary and fractional excretion rates of sodium and potassium.RESULTSControls and DDAVP non‐responders had a significant decrease in urine output at night concomitant with a significant plasma AVP amplitude in peak/nadir values although both groups lacked a significant nocturnal increase in AVP. In contrast, in DDAVP responders there was no circadian variation in urine output and thus a nocturnal polyuria together with no oscillation in plasma AVP. The DDAVP responding group had a nocturnal urine production significantly larger than the two other groups. However, the mean 24 hour AVP levels were similar in all groups. The excessive urine production at night in DDAVP responders was accompanied by nocturnal natriuresis due to an increased fractional excretion of sodium. In contrast, nocturnal antidiuresis in controls and DDAVP non‐responding enuretics coincided with diminished sodium excretion. Average ANP levels were elevated in both enuretic groups compared to normals, whereas a circadian variation was detected only in the latter.CONCLUSIONIt is concluded that DDAVP responsiveness is linked to the nocturnal urine production and that no pathophysiological role can be ascribed to AVP or ANP in DDAVP refractory adolescent and adult enuretics. Moreover, it is suggested that an abnormal tubular handling of sodium may contribute to the nocturnal polyuria seen in DDAVP responders.
Effects of growth hormone treatment on serum levels of insulin‐like growth factors (IGFs) and IGF binding proteins 1–4 in postmenopausal women
Authors: Kassem M. , Brixen K. , Mosekilde L. , Blum W. F. , Flyvbjerg A. 
Published: March 2003

BACKGROUND AND OBJECTIVEInsulin‐like growth factor binding proteins (IGFBPs) modulate the actions and bioavailability of insulin‐like growth factors (IGFs), however, their regulation in vivo is incompletely understood. In this study we investigated the effects of different doses of growth hormone (GH) on circulating levels of IGFs and IGFBPs.DESIGNThe study was double‐blind and placebo‐controlled. Patients were treated with either GH in doses of 0.05, 0.10, or 0.20 IU/kg/day of placebo for one week.PATIENTSForty post‐menopausal women aged 52–73 years with low bone mass.MEASUREMENTSSerum IGF‐I and IGF‐II were measured by RIA while IGFBP‐1–3 were measured by Western ligand blot (WLB) and compared with determinations by specific immunoassays. IGFBP‐4 was measured by WLB alone.RESULTSBoth IGF‐I (P < 0.001) and IGF‐II (P < 0.01) increased significantly during GH treatment. Additionally, IGFBP‐1 (P < 0.001) and IGFBP‐2 (P < 0.001) decreased significantly while IGFBP‐3 (P < 0.001) and IGFBP‐4 (P < 0.05) increased all in a dose‐dependent manner. Stepwise (backwards) multiple regression analyses showed that the changes in IGF‐I and IGF‐II, and age correlated with the change in serum IGFBP‐1. Both GH‐dosage, the increase in IGF‐II, and body mass index correlated with the decrease in IGFBP‐2. Furthermore, the increase in serum IGF‐I, IGF‐II, and triiodothyronine correlated with the increase in IGFBP‐3. Moreover, GH‐dosage correlated with the increase in serum IGFBP‐4.CONCLUSIONGH significantly increased serum IGF‐I, IGF‐II, IGFBP‐3, and IGFBP‐4 and decreased serum IGFBP‐1 and IGFBP‐2 in post‐menopausal women.
Serum oestradiol and oestrogen‐receptor gene polymorphism are associated with bone mineral density independently of serum testosterone in normal males
Authors: Ongphiphadhanakul B. , Rajatanavin R. , Chanprasertyothin S. , Piaseu N. , Chailurkit L. 
Published: March 2003

OBJECTIVESThe physiological effects of oestrogens on bone in men were largely unanticipated until recently, when oestrogen deficiency in males with aromatase deficiency and oestrogen resistance was found to cause osteoporosis and delayed fusion of epiphyses despite sufficient serum testosterone. This raises the possibility that in normal men oestrogens rather than androgens are of physiological importance in bone maturation. In the present study, we examined the association of serum oestradiol (E2) compared to that of free testosterone (FT) with bone mineral density (BMD) in normal men. The effect of oestrogen receptor (ER) gene polymorphism on BMD in men was also addressed.SUBJECTSEighty‐one Thai men aged 20–79 years. All were healthy and did not take medication which may affect calcium and bone metabolism. BMD was assessed by DEXA. Dietary calcium was assessed by a 3‐day dietary record. Serum E2 and FT concentrations were measured by radioimmunoassay. Polymorphism at intron 1 of the α isoform of ER gene was determined by PCR–RFLP. Small p represents the presence of the restriction site while capital P indicates the absence of the restriction site.RESULTSSerum FT decreased with increasing age (r = −0.58, P < 0.0001) while E2 did not. However, there was a positive association between E2 and FT (r = 0.28, P < 0.05). Serum FT was related to BMD at femoral neck (r = 0.26, P < 0.05) and Ward's triangle (r = 0.30, P < 0.01) while E2 was related to BMD at anteroposterior (AP) lumbar spine (r = 0.29, P < 0.05), femoral neck (r = 0.23, P < 0.05) and femoral trochanter (r = 0.27, P < 0.05). Besides FT and E2, age, body weight, fat mass and fat‐free mass were also correlated to BMD at various skeletal sites. Using stepwise multiple linear regression to control for the confounding effects among these factors, fat‐free mass was found to be strongly associated with BMD at most skeletal sites. Serum E2 was related to BMD independently of other factors including FT at AP lumbar spine (r = 0.22, P < 0.05), femoral neck (r = 0.26, P < 0.01), femoral trochanter (r = 0.22, P < 0.05) and Ward's triangle (r = 0.26, P < 0.01) while serum FT was not associated with BMD at any site after controlling for E2 and other related factors. Concerning ERα gene polymorphism, 27 (33.3%) of the subjects had pp genotype, while 42 (51.9%) and 12 (14.8%) Pp and PP genotypes, respectively. After controlling for age, body weight, fat mass, fat‐free mass, calcium intake, FT and E2, the presence of P allele was associated with higher BMD at AP L2‐L4 (P < 0.05).CONCLUSIONSSerum oestradiol is more related to bone mass than free testosterone in normal men. Oestrogen‐receptor gene polymorphism is also associated with bone mass in men independently of oestradiol levels. Serum oestradiol together with oestrogen‐receptor genotype may partly determine bone mass in males.
Rosai‐Dorfman disease presenting as a pituitary tumour
Authors: Kelly W. F. , Bradey N. , Scoones D. 
Published: March 2003

A 45‐year‐old woman had pyrexia, headaches, collapse and hyponatraemia. Intracerebral abscess, bacterial meningitis and subarachnoid haemorrhage were excluded. She was given intravenous antibiotics and gradually recovered. One month later she was readmitted with diplopia, headache and vomiting. Serum sodium was low (107 mmol/l) and a diagnosis of inappropriate ADH secretion was made. MRI scan showed a suprasellar tumour arising from the posterior pituitary gland. A skin rash gradually faded. Serum cortisol, prolactin, gonadotrophins and thyroid hormone levels were low. A pituitary tumour was removed trans‐sphenoidally, she had external pituitary radiotherapy, and replacement hydrocortisone and thyroxine. She was well for 12 months when she developed progressive weakness and numbness of both legs. Examination suggested spinal cord compression at the level of T2 where MRI scanning showed an intradural enhancing mass. This spinal tumour was removed and her neurological symptoms disappeared. Nine months after this she developed facial pain and nasal obstruction. CT scan showed tumour growth into the sphenoid sinus and nasal cavities. A right Cauldwell‐Luc operation was done and residual tumour in the nasal passages was treated by fractionated external radiotherapy and Prednisolone.Histological examination of the specimens from pituitary, spinal mass, and nasal sinuses showed Rosai‐Dorfman disease, a rare entity characterized by histiocytic proliferation, emperipolesis (lymphophagocytosis) and lymphadenopathy. Aged 48 she developed cranial diabetes insipidus. Although Rosai–Dorfman syndrome is rare, it is being reported with increasing frequency, and should be borne in mind as a possible cause of a pituitary tumour.
Y‐chromosome identification by PCR and gonadal histopathology in Turner's syndrome without overt Y‐mosaicism
Authors: Mendes Judite R. T. , Strufaldi Maria Wany L. , Delcelo Rosana , Moisés Regina C. M. S. , Gilberto Vieira José , Kasamatsu Teresa S. , Francis Galera Marcial , Andrade Joyce A. D. , Verreschi Ieda T. N. 
Published: March 2003

OBJECTIVEThe frequency of gonadoblastoma is high in patients with Turner's syndrome bearing cells with Y or partial Y‐chromosome. About 60% of patients with Turner's syndrome have a 45,X karyotype. In 30% of them a Y‐sequence is disclosed by DNA analysis. To identify patients at risk of developing gonadoblastoma, a PCR based assay with SRY, ZFY and DYZ3 specific primers was carried out to detect different Y‐sequences in the DNA of peripheral lymphocytes from patients with Turner's syndrome.DESIGN AND PATIENTSPeripheral blood karyotypes from 36 patients with Turner's syndrome were studied. Patients with proven Y‐chromosomal material were excluded. Genomic DNA was extracted from peripheral blood. SRY and ZFY genes and DYZ3 repetion of Y‐chromosome were amplified by PCR. Patients with clinical signs of hyperandrogenism or with positive Y‐sequences by PCR underwent gonadectomy. The gonadal tissues were examined for Y‐sequences using PCR, morphology and immunohistochemical study.MEASUREMENTSTurner's syndrome and signs of hyperandrogenism were evaluated both clinically and through laboratory tests. Haematoxylin and eosin staining was employed in gonadal morphology studies. The presence of testosterone was detected by immunohistochemistry using a monoclonal antibody.RESULTSTwo patients who had Y‐positive blood samples and three hyperandrogenic (2 hirsutes, 1 virilized) Y‐negatives underwent gonadectomy. PCR was carried out on their gonadal tissue. The tissue from the two patients without hyperandrogenism was Y‐positive. The gonadal tissue from the three hyperandrogenics was Y‐negative. Gonadal morphology disclosed hilus cell hyperplasia in the 3 hyperandrogenic Y‐negatives and in one Y‐positive patient; stromal luteoma and hyperthecosis in the virilized patient, cystadenofibroma in one hirsute patient and gonadoblastoma in one Y‐positive. Testosterone was detected immunohistochemically in the hilus cell hyperplasia, stromal luteoma and hyperthecosis found in the hyperandrogenic patients.CONCLUSIONSThe molecular study was sensitive and useful in the evaluation of patients at risk of developing gonadoblastoma. Other nontumour, gonadotrophin‐dependent and Y‐independent mechanisms which deserve the same medical approach may be involved in the genesis of hyperandrogenic signs in Turner's syndrome.
Rapid leptin decrease in immediate post‐exercise recovery
Authors: Duclos M. , Corcuff J.‐B. , Ruffie A. , Roger P. , Manier G. 
Published: March 2003

OBJECTIVELeptin concentrations in humans are known to decrease in response to fasting. The aim of this work was to investigate whether leptin levels might also be modified by exercise‐induced negative energy balance.SUBJECTSEight male runners reported in the morning from 0800 to 1200 h for (i) one resting session (sitting) and (ii) one exercise‐and‐rest session (2 h run and 2 h rest).MEASUREMENTSPlasma leptin, free fatty acids (FFA), glycerol, cortisol and salivary cortisol were assayed in both sessions at 1200 h.RESULTSAfter exercise‐and‐rest the leptin concentrations were lower than after rest (1.7 ± 0.1 vs 2.5 ± 0.2 μg/l, P < 0.05), i.e. a mean decrease of 30.3 ± 4.5% (range 9.5–45.8). Plasma FFA, glycerol and cortisol concentrations increased: FFA 0.78 ± 0.08 vs 0.18 ± 0.04 mmol/l, glycerol 0.13 ± 0.01 vs 0.04 ± 0.01 mmol/l, and cortisol 428 ± 36 vs 279 ± 27 nmol/l. A negative correlation was found between plasma FFA and leptin levels (r = − 0.5, P < 0.05) and between plasma glycerol and leptin levels (r = − 0.5, P < 0.05). No correlation was found between leptin and cortisol levels.CONCLUSIONSIn normal subjects with low body fat, a strenuous exercise‐and‐rest lowers leptin levels by a mean of 30%. A role of lipolysis possibly via increased plasma free fatty acids and glycerol levels is suggested. Cortisol does not seem to be involved.
The impact of gender, puberty and body mass on reference values for urinary growth hormone (GH) excretion in normally growing non‐obese and obese children
Authors: Bona  , Petri  , Rapa  , Conti  , Sartorio  
Published: March 2003

OBJECTIVEThere is a lack of normal reference data on urinary GH (u‐GH) excretion in children. We have investigated the impact of age, gender, pubertal development and body mass on reference values for u‐GH excretion in normally growing non‐obese and obese children.STUDY DESIGNu‐GH levels were evaluated in 1153 healthy normal children (aged 5–14) and in 684 obese children (body mass index, BMI: > 75th). u‐GH levels (ng/8 h) were determined by ELISA as the mean value of three consecutive first morning voidings.RESULTSReference values (5–95th centile) for u‐GH excretion in obese and non‐obese children of both sexes are reported. In normal prepubertal children median u‐GH levels were relatively stable and superimposable in the two sexes; subsequently, u‐GH levels increased, reaching a peak value at 13 years in both sexes. Significant increments (P < 0.0001) in u‐GH levels were shown at B2 for females and at G3 for males. A slight decline was evident at 14 years. In obese children, median u‐GH concentrations were significantly lower than those recorded in normal children of prepubertal age and at all stages of puberty (except in females at B2), in spite of their comparable normal height. u‐GH levels significantly increased at puberty also in obese children, although the pubertal rise was significantly (P < 0.001) lower (1.7‐fold in both sexes) than that observed in normal children (2.5‐fold in boys and 2.3‐fold in girls). A multiple regression analysis showed that both chronological age (beta: 0.20), BMI (beta: − 0.11), gender (beta: − 0.04) and pubertal stage (beta: 0.25) contributed significantly to the physiological variation in u‐GH levels (multiple R: 0.44, P < 0.00001).CONCLUSIONSThis study provides reference values for u‐GH in normally growing non‐obese and obese children, analysing the impact of gender, puberty and body mass on this parameter. In agreement with previous studies, which demonstrate blunted GH‐responses to provocative stimuli and reduced nocturnal GH concentration, obese children have significantly lower u‐GH levels than age‐matched normal weight children, both before and during puberty.
Effect of carbenoxolone on the plasma renin activity and hypothalamic–pituitary–adrenal axis in congenital adrenal hyperplasia due to 21‐hydroxylase deficiency*
Authors: Irony Ilan , Cutler Gordon B. 
Published: March 2003

OBJECTIVETo test the hypothesis that carbenoxolone, an inhibitor of 11β‐hydroxysteroid dehydrogenase, might augment the ACTH‐suppressing and mineralocorticoid activities of hydrocortisone without a corresponding increase in peripheral hydrocortisone effects, we assessed the effects of carbenoxolone in patients with congenital adrenal hyperplasia.DESIGNAND PATIENTS Six patients with classic 21‐hydroxylase deficiency (5 salt‐losing, 1 nonsalt‐losing) were enrolled in this study. The study protocol involved 3 treatment periods (except for patient 3): phase 1, hydrocortisone and fludrocortisone; phase 2, hydrocortisone, fludrocortisone and carbenoxolone; phase 3, hydrocortisone and carbenoxolone. Patient 3 was not treated with fludrocortisone at baseline, so she participated only in phase 1 (hydrocortisone only) and phase 2 (hydrocortisone and carbenoxolone). Hydrocortisone and fludrocortisone dosages were kept the same during the study except for the discontinuation of fludrocortisone during phase 3.MEASUREMENTSPlasma adrenal androgens or their precursors (androstenedione, 17‐hydroxyprogesterone, and testosterone, and urine pregnanetriol); plasma cortisol, cortisol‐binding globulin, ACTH, apparent cortisol metabolic clearance, 24‐h urine 17‐hydroxysteroids, and urine free cortisol; mineralocorticoid activity, as measured by plasma renin activity, body weight, plasma potassium, and mean blood pressure; fasting insulin/glucose ratio, protein balance, % eosinophils in peripheral blood, and total urine pyridinoline and deoxypyridinoline; TRH stimulation of TSH and pyridostigmine/GHRH stimulation of growth hormone.RESULTSCompared to phase 1, the addition of carbenoxolone (with or without concurrent fludrocortisone administration) produced statistically significant decreases of 20–50% in mean plasma 17‐hydroxyprogesterone, androstenedione, and renin activity. Since carbenoxolone also decreased the apparent metabolic clearance rate of cortisol by 20%, other measures of systemic glucocorticoid activity were examined. Carbenoxolone did not produce a cushingoid appearance or increase body weight, blood pressure, blood glucose or plasma insulin levels. Carbenoxolone also did not suppress stimulated GH levels, but did decrease TRH‐stimulated TSH levels by approximately 20% (P < 0.05).CONCLUSIONCarbenoxolone can augment the adrenal androgen‐suppressing activity of hydrocortisone in patients with 21‐hydroxylase deficiency. These observations support the hypothesis that selective inhibition of enzymes that metabolize cortisol may lead to new approaches to improve the treatment of congenital adrenal hyperplasia.
Leptin concentrations in Prader‐Willi syndrome before and after growth hormone replacement
Authors: Myers Susan E. , Davis Ajuah , Whitman Barbara Y. , Santiago Julio V. , Landt Michael 
Published: March 2003

OBJECTIVEThis study explored leptin concentrations in Prader‐Willi syndrome (PWS), a genetic disorder characterized by significant obesity and presumed hypothalamic dysfunction. The potential interaction of leptin metabolism with the growth hormone (GH) axis was also studied.STUDY DESIGNPlasma leptin concentrations and percent body fat were determined by radioimmunoassay and dual energy x‐ray absorptionmetry, respectively, in 23 children with Prader‐Willi syndrome and 23 children with exogenous obesity.RESULTSLog plasma leptin concentrations were positively correlated with percentage body fat in PWS (r = 0.844) and exogenous obesity (r = 0.869). When the regression lines for the two groups were compared, there were no differences in their slopes (P = 0.737) or intercepts (P = 0.701). Administration of recombinant human growth hormone to PWS children for 12 months significantly reduced both percentage body fat and plasma leptin concentrations, but the relationship of log plasma leptin to percentage body fat was unchanged.CONCLUSIONPrader‐Willi syndrome is not accompanied by deranged leptin concentrations and there was no evidence of an interaction of the GH axis with leptin metabolism in these GH‐deficient children.