bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urocortin expression in the human central nervous system
Authors: Iino Kazumi , Sasano Hironobu , Oki Yutaka , Andoh Noriaki , Shin Ryong‐Woon , Kitamoto Tetsuyuki , Takahashi Kazuhiro , Suzuki Hiroyoshi , Tezuka Fumiaki , Yoshimi Teruya , Nagura Hiroshi 
Published: March 2003

OBJECTIVE AND STUDY DESIGNUrocortin is a recently identified neuropeptide of the corticotrophin‐releasing factor (CRF) family in the mammalian brain and has been demonstrated to stimulate ACTH secretion from pituitary cells, but its expression in human brain tissue including the hypothalamus has not been examined. In this study, we first examined urocortin expression in the hypothalamus (20 cases) and pituitary stalks (17 cases) of human brain obtained from autopsy using immunohistochemistry and mRNA in situ hybridization.RESULTSNeither urocortin immunoreactivity nor mRNA hybridization signals were detected in the hypothalami and pituitary stalks while CRF immunoreactivity was detected in the paraventricular nuclei of the hypothalami in 10/20 cases and in nerve fibres of the stalks in 17/17 cases. These results indicate that urocortin does not act on the hypothalamo‐pituitary‐adrenal axis, at least not in the same manner as CRF in humans. We then examined urocortin expression in various portions of the brain in 7 cases. Both urocortin immunoreactivity and mRNA hybridization were detected in Purkinje cells of the cerebellum and anterior horn cells of the spinal cord in specimens examined. Urocortin expression was, however, variably seen in superior olivary nuclei (two out of six cases examined) and in the Edingar‐Westphal nuclei (one out of three cases examined).CONCLUSIONSThe distribution of urocortin in the human central nervous system suggests that urocortin may work as a neurotransmitter like other neuropeptides in the human.
Prevalence, predictors and patterns of postoperative polyuria and hyponatraemia in the immediate course after transsphenoidal surgery for pituitary adenomas
Authors: Hensen Johannes , Henig Anja , Fahlbusch Rudolf , Meyer Martin , Boehnert Markus , Buchfelder Michael 
Published: March 2003

OBJECTIVEDisturbances of osmoregulation, leading to diabetes insipidus and hyponatraemia are well known complications after surgery in the sella region. This study was performed to examine the prevalence and predictors of polyuria and hyponatraemia after a complete and selective removal of pituitary adenomas was attempted via the transnasal–transsphenoidal approach.DESIGN1571 patients with pituitary adenomas (238 Cushing's disease, 405 acromegaly, 534 hormonally inactive adenomas, 358 prolactinoma, 23 Nelson's syndrome, and 13 thyrotropinoma) were daily examined within a 10‐day postoperative inpatient observation period. Prevalence of patterns of polyuria (> 2500 ml) and oliguria/hyponatraemia (< 132 mmol/l) were surveyed as well as predictors of postoperative morbidity.RESULTS487 patients (31%) developed immediate postoperative hypotonic polyuria, 161 patients (10%) showed prolonged polyuria and 37 patients (2.4%) delayed hyponatraemia. A biphasic (polyuria‐hyponatraemia) and triphasic (polyuria‐hyponatraemia‐polyuria) pattern was seen in 53 (3.4%) and 18 (1.1%) patients, respectively. Forty‐one patients (2.6%) displayed immediate postoperative (day 1) hyponatraemia. Altogether, 8.4% of patients developed hyponatraemia at some time up to the 10th day postoperative, with symptomatic hyponatraemia in 32 patients (2.1%). Risk analysis showed that patients with Cushing's disease had a fourfold higher risk of polyuria than patients with acromegaly and a 2.8‐fold higher risk for postoperative hyponatraemia. Younger age, male sex, and intrasellar expansion were associated with a higher risk of hypotonic polyuria, but this was not considered clinically relevant.CONCLUSIONSThe analysis illustrates that disturbances in osmoregulation resulting in polyuria and pertubations of serum sodium concentration are of very high prevalence and need observation even after selective transsphenoidal surgery for pituitary adenomas, especially in patients with Cushing's disease.
Blood pressure and Turner syndrome
Authors: Nathwani  , Unwin  , Brook  , Hindmarsh  
Published: March 2003

INTRODUCTIONElevated blood pressure (BP) is an important predictor of morbidity and mortality from cardiovascular disease. Patients with Turner syndrome (TS) have a higher morbidity and mortality in middle age than the normal population. As BP in childhood or early adulthood is predictive of BP later in adult life, we assessed manual and 24 h ambulatory BP in patients with TS to determine whether the BP pattern is altered at an early stage in these patients who are known to be at risk of cardiovascular disease.PATIENTS AND METHODSWe studied manual and 24 h ambulatory BP profiles in 75 girls with Turner syndrome, age range 5.4–22.4 years. A monitor with an oscillometric device (SpaceLabs model 90207) and an appropriate sized cuff was used. BP was measured during the day‐time (0800–2000 h) and the night‐time periods (2200–0800 h). The BP measured were compared with population standards. The effect of different growth promoting agents on BP was also evaluated.RESULTSMean manual and 24 h ambulatory BP measurements were 118/77 mmHg (range 95/60–140/102) and 115/70 mmHg (range 93/57–154/99), respectively. There was minimal difference between the two methods with a positive bias of 2.4 mmHg for diastolic BP and a negative bias of 2.1 mmHg for systolic BP. The mean standard deviation scores (SDS) corresponding to the mean BP recordings were 24 h systolic + 0.81 (range − 1.26 to + 4.45), 24 h diastolic + 0.43 (range − 0.85 to + 3.42), day‐time systolic + 1.08 (range − 0.95 to + 4.72), day‐time diastolic + 0.70 (range − 0.94 to + 3.71), night‐time systolic + 0.22 (range −2.2 to + 3.64) and night‐time diastolic − 0.18 (range −2.0 to + 2.43). The SDS for both the mean 24 h and day‐time systolic and diastolic BP were shifted to the right of the normal distribution. 57% of the girls had less than the normal 10% reduction in nocturnal systolic blood pressure. 17% had diastolic and 21% had systolic blood pressure above the 95th percentile for age and sex. There was no significant difference in the BP SDS between girls on no treatment and those receiving treatment.CONCLUSIONOver 50% of girls with Turner syndrome have an abnormal BP circadian rhythm, which is similar to adult patients with secondary hypertension. Patients with Turner syndrome have higher blood pressure measurements compared to published population standards, as evidenced by the shift to the right of both the systolic and diastolic BP SDS. These findings suggest that girls with Turner syndrome should be carefully monitored in childhood and adulthood for blood pressure and other cardiovascular risk factors.
Influence of different genotypes on 17‐hydroxyprogesterone levels in patients with nonclassical congenital adrenal hyperplasia due to 21‐hydroxylase deficiency
Authors: Bachega Tânia A. S. S. , Billerbeck Ana E. C. , Marcondes José A. M. , Madureira Guiomar , Arnhold Ivo J. P. , Mendonca Berenice B. 
Published: March 2003

OBJECTIVEThe diagnosis of the nonclassical form of 21‐hydroxylase (NC‐21OH) deficiency, established before molecular studies, is based on basal 17OH‐progesterone (17OH‐P) values > 15 nmol/l or ACTH‐stimulated 17OH‐P values > 30 nmol/l. This disease is caused by mutations in the structural gene that can be grouped into three categories: A, B and C, according to the predicted level of enzymatic activity. So, the genotype of the nonclassical form is a combination of mutations that cause moderate impairment of enzymatic activity in one allele and mutations which cause total (A), severe (B: 3%) or moderate (C: 20–60%) impairment of enzymatic activity in the other allele.DESIGNWe analysed the influence of the different genotypes on 17OH‐P levels in 58 patients with the nonclassical form of 21OH deficiency.RESULTSAfter screening for 18 mutations through Southern blotting, allele‐specific polymerase chain reaction (PCR) and enzyme restriction, mutations were identified in 73% of the alleles. Patients with mutations identified in both alleles were divided into groups A/C (n = 18), B/C (n = 3) and C/C (n = 15). The basal and ACTH‐stimulated 17OH‐P levels in patients with A/C genotype ranged from 1.2 to 153 and 72–363 nmol/l, and in C/C genotype ranged from 0.9 to 72 and 51–363 nmol/l, respectively (P < 0.05 for stimulated levels). The lowest value of ACTH‐stimulated 17OH‐P levels in fully genotyped patients was 51 nmol/l. Patients with the A/C genotype presented androgen excess symptoms earlier than patients with the C/C genotype.CONCLUSIONSThese data suggest an influence of genotype on phenotype and on 17OH‐P levels. The high frequency of unidentified mutant alleles in nonclassical 21‐hydroxylase deficiency suggests that ACTH‐stimulated values of 17OH‐P between 30 and 51 nmol/l have overestimated this diagnosis. Genotyping more patients with nonclassical 21‐hydroxylase deficiency will help to redefine the cut‐off value for ACTH‐stimulated 17OH‐P for correct diagnosis of this disease.
Embolization in combination with radioiodine therapy for bone metastases from differentiated thyroid carcinoma
Authors: Van Tol K. M. , Hew J. M. , Jager P. L. , Vermey A. , Dullaart R. P. F. , Links T. P. 
Published: March 2003

BACKGROUNDThe outcome for patients with bone metastases from differentiated thyroid carcinoma is worse compared to the overall prognosis of patients with differentiated thyroid carcinoma. The aim of this study is to evaluate the effect of embolization with concomitant radioiodine treatment on the serum thyroglobulin (Tg) level, pain and neurological symptoms in patients with large bone metastases from differentiated thyroid carcinoma.PATIENTS AND METHODSFive symptomatic patients, who presented with a large unresectable bone metastasis of differentiated thyroid carcinoma were treated with radioiodine and embolization. The effect of this combined treatment was compared to the effect of radioiodine without embolization in a previously treated control group of 6 patients. Serum Tg levels, pain and neurological symptoms were scored. Both groups were treated similarly with total thyroidectomy followed by ablation with 5.55 GBq 131I and a second dose of 5.55 GBq 131I three months later, except for embolization in the embolization group, which took place between the 2 radioiodine treatments.RESULTSIn the embolization group, serum Tg at the second 131I therapy had decreased by 88.7% (median, range: 77.1–99.3%), which was significantly more compared to the decrease of serum Tg in the control group (18.6%, range: −4.7–95%, P < 0.05). CT‐scanning showed a median volume reduction of the metastasis after radioiodine treatment combined with embolization of 52.5% (range: 39–80%). Both strategies resulted in a rapid relief of pain and neurological symptoms. Embolization was not accompanied with severe complications.CONCLUSIONSThis preliminary study suggests that embolization of bone metastases of differentiated thyroid carcinoma in combination with radioiodine treatment results in a significant initial reduction of serum Tg level compared to radioiodine treatment alone. This suggests a beneficial reduction in tumour burden. In this patient category, embolization appears to be a safe and well tolerated procedure.
Low birth weight is not associated with clinically overt thyroid disease: a population based twin case‐control study
Authors: Brix Thomas Heiberg , Kyvik Kirsten Ohm , Hegedüs Laszlo 
Published: March 2003

OBJECTIVEIn recent years low birth weight has been proposed as a risk factor for the development of several chronic diseases in adult life, including diabetes and subclinical autoimmune thyroid disease. The association could, however, also be due to genetic or environmental factors affecting both birth weight and adverse health outcomes in adult life. Moreover, it is at present unknown whether or not low birth weight is associated with an increased risk of developing clinically overt thyroid disease. The aim of the present study was to investigate the impact of birth weight and several other birth characteristics on the development of clinically overt thyroid disease.DESIGNA twin case‐control study of same sex twin pairs.PATIENTSOne hundred and thirty‐one same sex twin pairs (262 twin individuals) discordant for clinically overt thyroid disease, ascertained from a population based nation‐wide twin register.MEASUREMENTSInformation about birth weight, birth length, birth order (first vs. second born), and prematurity was obtained from the original midwife records.RESULTSForty‐nine twin pairs were discordant for clinically overt autoimmune thyroid disease (Graves' disease = 35 and Hashimoto's thyroiditis = 14) and 82 pairs were discordant for overt nonautoimmune thyroid disease (Simple goitre = 79 and toxic nodular goitre = 3). Overall, there was no difference in birth weights between probands and the healthy co‐twins in monozygotic (MZ, n = 39) or in dizygotic (DZ, n = 92) pairs (MZ: mean ± SE: 2619 ± 93 g vs. 2553 ± 89 g, P = 0.40; DZ: 2576 ± 45 g vs. 2585 ± 49, P = 0.86). By means of logistic regression, the impact of other birth characteristics such as birth length, birth order (first vs. second born), and prematurity was tested. None of the variables reached statistical significance. Subdividing the twin pairs into those discordant for clinically overt Graves' disease, Hashimoto's thyroiditis, and nonautoimmune thyroid disease did not change the results.CONCLUSIONSThis is the first study of the effect of birth weight and other birth characteristics on the subsequent development of clinically overt thyroid disease in which maternal, socioeconomic, and to a high degree, genetic factors have been controlled for. Our study did not show any effect of birth weight or any of the other birth characteristics on the risk of developing clinically overt autoimmune or nonautoimmune thyroid disease.
Urinary GH and IGF‐I excretion in nine year‐old children: relation to sex, current size and size at birth
Authors: Fall C. H. D. , Clark P. M. , Hindmarsh P. C. , Clayton P. E. , Shiell A. W. , Law C. M. 
Published: March 2003

OBJECTIVESTo study the relationship of 24‐hour urinary growth hormone (GH) and IGF‐I excretion in childhood to sex and body size. To test the hypothesis that small size at birth followed by postnatal catch‐up growth is associated with elevated IGF‐I production.DESIGN AND SUBJECTSFollow‐up study of a cohort of 183 healthy children born in Salisbury, UK.MEASUREMENTSWeight and height, 24‐h urinary growth hormone (uGH) and IGF‐I (uIGF‐I) excretion, and systolic and diastolic blood pressures.RESULTSAt 9 years of age, 24‐h uIGF‐I excretion, but not uGH excretion, was strongly related to current weight (P < 0.001) and height (P < 0.001). Urinary GH and IGF‐I excretion were positively correlated (r = 0.15, P = 0.05). Boys excreted more uIGF‐I per unit uGH than girls (uIGF‐I/uGH molar ratio 32.1 compared to 21.0; P for difference = 0.002). There were no significant relationships of uGH, uIGF‐I or uIGF‐I/uGH molar ratio with birthweight, birthlength or head circumference at birth, nor with blood pressure at 9 years. ‘Catch‐up’ growth, indicated by an increase in height SD scores between birth and 9 years, was associated with higher IGF‐I excretion (P = 0.01) and occurred in children with taller parents (P < 0.001).CONCLUSIONSBoys appear to be more sensitive to GH than girls, generating more uIGF‐I in relation to uGH. Urinary IGF‐I excretion at 9 years is related to both absolute height and to the degree of catch‐up in height from birth. Our results suggest that IGF‐I production is strongly influenced by genetic factors, but also by either the degree to which intrauterine growth falls short of genetic growth potential, or the process of postnatal catch‐up growth that follows.
Over‐expression of hepatocyte growth factor/scatter factor (HGF/SF) and the HGF/SF receptor (cMET) are associated with a high risk of metastasis and recurrence for children and young adults with papillary thyroid carcinoma
Authors: Ramirez Raul , Hsu Daniel , Patel Aneeta , Fenton, Cydney , Dinauer Catherine , Tuttle R. Michael , Francis Gary L. 
Published: March 2003

OBJECTIVEThe study determined if hepatocyte growth factor/scatter factor (HGF/SF) or the HGF/SF receptor (cMET) might be important for metastasis in thyroid cancer.DESIGNWe examined HGF/SF and cMET expression by immunohistochemistry in a retrospective group of benign and malignant thyroid lesions from children and young adults, and correlated the intensity of expression with clinical outcome.PATIENTSPatients included 42 children and young adults with papillary thyroid carcinomas (PTC), seven with follicular thyroid carcinomas (FTC), two with medullary thyroid carcinomas (MTC), 14 with benign thyroid disorders, and two with normal thyroids.MEASUREMENTSExpression of cMET was graded from 0 (absent) to 4 (intense); and HGF/SF expression was graded from 0 (absent–minimal) to 3 (diffuse and intense).RESULTScMET staining was greater in PTC (mean intensity 2.3 ± 0.4 vs. 0.8 ± 0.2, P < 0.005) and FTC (2.4 ± 0.6 vs. 0.8 ± 0.2, P = 0.04) than benign lesions (0.8 ± 0.2) or normal thyroids (0.4 ± 0.5). PTC with intense cMET staining had shorter disease free survival (P = 0.05) and increased HGF/SF staining (r = 0.39, P = 0.017). HGF/SF correlated with the extent of disease at diagnosis (r = 0.33, P = 0.049). Patients with PTC were stratified into quartiles based on combined cMET and HGF/SF staining. Those with intense cMET and HGF/SF staining were younger (P = 0.05), and had reduced disease free survival (P = 0.03).CONCLUSIONSWe conclude that increased cMET and HGF/SF expression is associated with a high risk for metastasis and recurrence in children and young adults with papillary thyroid carcinoma.
Immunohistochemical detection of somatostatin receptor types 1–5 in medullary carcinoma of the thyroid
Authors: Papotti Mauro , Kumar Ujendra , Volante Marco , Pecchioni Carla , Patel Yogesh C. 
Published: March 2003

BACKGROUND We have analysed the distribution of the five somatostatin receptors (sst1–5) by immunohistochemistry in a large retrospective series of 51 medullary carcinoma of the thyroid (MCT) specimens and correlated the pattern of sst expression with expression of somatostatin (SRIF) peptide, tumour pathology and clinical outcome.MEASUREMENTS Immunohistochemistry was performed with rabbit polyclonal antipeptide antibodies directed against the extracellular domains or cytoplasmic tail of human (h) sst1–5. SRIF immunoreactivity was investigated in parallel paraffin sections.RESULTS Eighty‐five percent of the tumours were positive for one or more sst, localized to both tumour cells as well as surrounding peritumoural structures, especially blood vessels. Forty‐nine percent of the tumours were positive for sst1, 43% for sst2, 47% for sst3, 4% for sst4, and 57% for sst5. Fifty‐one percent of tumours expressed one or two sst subtypes; 33% were positive for three or more sst isoforms. All five sst receptors were detected in only two cases. Tumours expressing octreotide sensitive subtypes (sst2,3,5) accounted for 75% of the series. 50% of the tumours co‐expressed SRIF suggesting tumour cell regulation by endogenous SRIF via paracrine/autocrine circuits. There was no correlation between sst1–5 expression and age, sex, tumour size or stage, histological type or clinical outcome. Simultaneous analysis of primary tumour and lymph node metastases revealed a similar pattern of sst immunoreactivity indicating that sst expression is not modified in the course of disease progression.CONCLUSIONS With the exception of sst4, medullary carcinoma of the thyroid display a rich but heterogeneous expression of sst subtypes. Immunohistochemical typing of sst receptor expression using specific antireceptor antibodies represents an ideal approach for characterizing sst subtype expression in medullary carcinoma of the thyroid for optimizing receptor targeted diagnosis and therapy with somatostatin analogs.
The release of leptin and its effect on hormone release from human pituitary adenomas
Authors: Korbonits Márta , Chitnis Meenali M. , Gueorguiev Maria , Norman Dennis , Rosenfelder Nicola , Suliman Mohamed , Jones T. Hugh , Fabbri Kate Noonan Andrea , Besser G. Michael , Burrin Jacky M. , Grossman Ashley B. 
Published: March 2003

BACKGROUND Leptin is the protein product of the obese gene, known to play an important role in body energy balance. The leptin receptor exists in numerous isoforms, the long isoform being the major form involved in signal transduction. Leptin expression has recently been demonstrated in the human pituitary, both in normal tissue and in pituitary adenomas. The long isoform of the leptin receptor has also been shown to be present in pituitary adenomas; however, contrasting results have been obtained regarding its expression in the normal human pituitary.AIM The aim of this study was (i) to investigate the presence and pattern of distribution of leptin mRNA and the long isoform of its receptor mRNA in the normal pituitary and in different types of pituitary adenomas with RT‐PCR; (ii) to study leptin secretion from human pituitary tumours in culture and (iii) to assess in vitro pituitary hormone release following stimulation with human leptin.RESULTS Leptin receptor long isoform expression was detected in 2/4 GH‐secreting adenomas, 12/17 non‐functioning adenomas, 5/9 ACTH‐secreting adenomas, 1/2 prolactinomas, 2/2 FSH‐secreting adenomas and 5/5 normal pituitaries. The receptor long isoform did not segregate with any particular tumour type, and varying levels of expression were detected between the tissues studied. Leptin mRNA was detected at a low level of expression in 2/7 GH‐secreting adenomas, 9/14 non‐functioning adenomas, 2/3 ACTH‐secreting adenomas, 1/3 prolactinomas and 1/3 FSH‐secreting adenomas. We were unable to detect leptin mRNA in any of the five normal pituitaries removed at autopsy; however, immunostaining of a non‐tumorous pituitary adjacent to an adenoma removed at transsphenoidal surgery showed scattered leptin positive cells. Culture of pituitary adenomas showed that 16/47 released leptin into the incubation media. Leptin release did not correlate with tumour type or with any of the other pituitary hormones released. In vitro leptin stimulation of pituitary tumours caused stimulation of FSH and α‐subunit secretion from a non‐functioning adenoma and TSH secretion from a somatotroph adenoma.CONCLUSION We conclude that not only is leptin stored within the pituitary, but it may also be released from pituitary cells and modulate other pituitary hormone secretion. Pituitary leptin may therefore be a novel paracrine regulator of pituitary function.