bluuebunny/crossref_metadata_2025_split huggingface dataset:
Life expectancy following surgery for pituitary tumours
Authors: Bates A. S. , Bullivant B. , Sheppard M. C. , Stewart P. M. 
Published: March 2003

OBJECTIVEHypopituitarism, predominantly al‐though not exclusively due to nonfunctioning pituitary tumours, has been associated with reduced life expectancy. Mortality from vascular diseases contributed significantly to the overall increase in mortality in some, but not all of the studies published to date. The aim of this study was to contribute further data to the debate regarding the putative association of vascular mortality with hypopituitarism.DESIGN AND PATIENTSA retrospective case note review of patients undergoing pituitary surgery in Birmingham, between 1/1/70 and 1/1/92. Subjects were identified from neurosurgical and neuropathology records. 348 patients were identified of which 197 were male (median age at surgery 48.4, range 11–79 years) and 151 female (median age at surgery 47.8, range 9–78 years). All cause mortality and mortality from vascular disease was compared to the general population of the UK using the Person Years computer programme.RESULTSThere was a small increase in all cause mortality (SMR 1.2; 95% CI 0.95–1.55), but this was not statistically significant in this study (P = 0.06). Mortality from vascular disease was reduced (SMR 0.7; 95% CI 0.5–1.1; P = 0.03) particularly in the female cohort (SMR 0.5; 95% CI 0.2–1.0; P < 0.01) with the male subjects having similar mortality to that expected in an age and sex matched control population (SMR 0.9; 95% CI 0.5–1.4; P = 0.26).CONCLUSIONAlthough patients with pituitary deficiency may be subject to a small increase in all cause mortality, the results of this study do not support the view that hypopituitarism is associated with a significant increase in vascular disease. There is a pressing need for a large prospective study with comprehensive data collection, including both endocrine data and information regarding clinical outcome, to clarify this issue. In the interim it would seem prudent to base the need for GH replacement therapy on quality of life issues rather than any potential for increased longevity.
Discrepancy between serum leptin values and total body fat in response to the oral growth hormone secretagogue MK‐677
Authors: Svensson  , Carlsson  , Carlsson  , Jansson  , ‐Å. Bengtsson  
Published: March 2003

OBJECTIVEGrowth hormone (GH) treatment decreases total body fat while this effect has not yet been documented for the oral GH secretagogue MK‐677. In the present study, the effects of MK‐677 treatment on serum levels of leptin, thyroid hormones and testosterone were determined.DESIGNThis was a randomized, double‐blind, and parallel study. Twenty‐four healthy obese males, 19–49 years of age, with body mass index (BMI) > 30 kg/m2 and a waist:hip ratio > 0.95, were treated with MK‐677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks.RESULTSMK‐677 treatment increased serum leptin levels and leptin/body fat ratio at 2 weeks of treatment (P < 0.05 vs. placebo) but no significant change was observed at 8 weeks. An increase in serum free 3, 5, 3′‐triiodothyronine (free T3) was not detected until 8 weeks of MK‐677 treatment (P < 0.05 vs. placebo). Peak serum thyroid stimulating hormone (TSH) concentration after MK‐677 administration was similar to that after placebo administration at initiation of treatment and at 2 weeks. At 8 weeks of MK‐677 treatment, mean peak serum TSH concentration was increased (P < 0.05 vs. placebo) although it remained within the normal range. Serum peak values of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were similar after MK‐677 and placebo administration. MK‐677 treatment reduced serum total testosterone (P < 0.05 vs. placebo) although total testosterone/sex hormone‐binding globulin (SHBG) ratio (an index of free testosterone) was not changed.CONCLUSIONTreatment with the oral GH secretagogue MK‐677 transiently increased serum leptin levels and leptin/body fat ratio at 2 weeks of treatment, and increased serum free T3 after 8 weeks. These results indicate that MK‐677 treatment is able to affect circulating factors of importance for adipose tissue mass and fuel metabolism.
Expression of the androgen metabolizing enzyme UGT2B15 in adipose tissue and relative expression measurement using a competitive RT–PCR method
Authors: Tchernof André , Lévesque Éric , Beaulieu Martin , Couture Patrick , Després Jean‐Pierre , Hum Dean W. , Bélanger Alain 
Published: March 2003

OBJECTIVESWe have demonstrated previously that obesity in men was significantly associated with low plasma testosterone levels and higher concentrations of the androgen metabolite androstane‐3α,17β‐diol glucuronide, suggesting that androgen metabolism and elimination is increased in this condition. The objective of the present study was to investigate whether adipose tissue was a site of expression of the androgen metabolizing enzymes UDP‐glucuronosyltransferases (UGT) 2B15 and 2B17.DESIGN AND PATIENTSSubcutaneous and visceral adipose tissue was obtained from male patients subjected to various abdominal surgeries.MEASUREMENTS AND RESULTSBy performing reverse transcriptase–PCR (RT–PCR) amplification of mRNA extracted from adipose tissue samples, UGT2B15 transcript was detected in both subcutaneous and omental adipose tissue while UGT2B17 transcript expression was very low, or undetectable. A quantitative, competitive RT–PCR method was established and used to quantify UGT2B15 messenger RNA. The level of UGT2B15 expression was also measured in other human tissues. Although the major sites of expression were the liver and the lung, expression in adipose tissue was similar to levels found in the prostate, testis and mammary gland.CONCLUSIONSThese results demonstrate for the first time that both subcutaneous and visceral adipose tissue express androgen metabolizing enzyme UGT2B15 mRNA and further support the role of adipose tissue as a site of steroid metabolism.
Increased MEN1 mRNA expression in sporadic pituitary tumours
Authors: McCabe  , Gittoes  , Sheppard  , Franklyn  
Published: March 2003

BACKGROUNDThe MEN1 gene on chromosome 11q13 encodes a tumour suppressor gene, mutations in which cause multiple endocrine neoplasia (MEN) type 1 syndrome. Loss of heterozygosity (LOH) at this locus is a common finding amongst sporadic pituitary tumours. We have therefore screened the MEN1 gene for mutations in sporadic pituitary tumours and, as the gene is a putative tumour suppressor, have quantified mRNA expression in tumorous and normal pituitaries to assess the role of MEN1 in pituitary tumorigenesis.SUBJECTS AND DESIGNThirty‐one nonfunctioning pituitary tumours, 8 GH secreting, 2 TSH‐secreting tumours and 1 corticotrophinoma have been assessed for the presence of MEN1 mutations, to examine the hypothesis that MEN1 mutations may contribute to the pathogenesis of sporadic pituitary neoplasms. In addition, quantitative changes in the pretranslational expression of the tumour suppressor gene MEN1 have been determined in 42 pituitary tumours and 6 normal pituitaries using semiquantitative reverse transcriptase PCR.RESULTSNo novel or previously published mutations were apparent in the MEN1 coding regions of any tumours studied, although several polymorphisms were identified. Transcriptional changes of the gene, assessed by semiquantitative RT‐PCR, indicated that nonfunctioning and GH‐secreting pituitary tumours are associated with significantly increased pretranslational expression of the MEN1 gene. In addition, the single corticotrophinoma showed increased expression compared to normal, as did one of the two TSH‐omas.CONCLUSIONCoding mutations of the putative tumour suppressor gene MEN1 are unlikely to contribute to pituitary tumorigenesis in sporadic nonfunctioning, GH‐secreting and TSH‐secreting adenomas. Changes in pretranslational expression of MEN1 were observed in pituitary tumours, suggesting that changes in the level of MEN1 expression, rather than coding changes, may be of functional importance in influencing sporadic pituitary tumorigenesis.
Serum IGF‐I and IGFBP‐3 concentrations do not accurately predict growth hormone deficiency in children with brain tumours
Authors: Weinzimer Stuart A. , Homan Sarah A. , Ferry Robert J. , Moshang Thomas 
Published: March 2003

OBJECTIVEThe growth hormone (GH)‐dependent growth factors insulin‐like growth factor‐I (IGF‐I) and IGF‐binding protein‐3 (IGFBP‐3) may be superior to provocative GH testing in diagnosing GH deficiency (GHD) in children. In adults with brain tumours (BT) and GHD, however, provocative GH testing more accurately reflects GHD than either IGF‐I or IGFBP‐3. We assessed growth factor levels in children with GHD due to BT with respect to brain tumour type, pubertal stage, growth velocity, bone age delay, and body mass index (BMI).DESIGNRetrospective case review of all patients followed at our centre with GHD following treatment of BT.PATIENTS72 children (51 M, 21 F) with BT diagnosed with GHD by clinical and auxological criteria, including provocative GH testing, in whom pre‐GH treatment IGF‐I and IGFBP‐3 levels were obtained.MEASUREMENTSAuxological data, including height, weight, growth velocity, and pubertal stage; and biochemical data, including GH response to provocative GH testing and pre‐GH treatment serum IGF‐I and IGFBP‐3 concentrations.RESULTSIGF‐I levels were normal (above −2 SD) in 19 of 70 children (27%), and IGFBP‐3 levels were normal in 21 of 42 (50%). In children with GHD, pubertal stage correlated significantly with both IGF‐I (r = 0.328, p < 0.006) and IGFBP‐3 (r = 0.364, P < 0.02). Normal IGF‐1 levels were found in 1/15 children with craniopharyngioma (Cranio) (7%), 10/30 with primitive neuroectodermal tumours (PNET) (33%), and 5/12 children with hypothalamic/chiasmatic glioma (HCG) (42%) (P < 0.05). IGFBP‐3 levels were normal in 4/13 Cranio patients (31%), 8/15 PNET patients (53%), and 6/8 HCG patients (75%) (P = ns). Tanner staging varied significantly among tumour types: mode = 1 for Cranio and PNET vs. mode = 3 for HCG (P < 0.03). BMI did not differ between patients with low vs. normal growth factor levels.CONCLUSIONSLow IGF‐I levels were more predictive of growth hormone deficiency than low IGFBP‐3 levels in our brain tumour patients, but both were poor predictors of growth hormone deficiency in children with hypothalamic‐chiasmatic glioma and in pubertal children. Serum IGF‐I and IGFBP‐3 levels, therefore, do not always reflect growth hormone deficiency in children with brain tumours, particularly in those with hypothalamic‐chiasmatic glioma or those already in puberty.
The course of Graves' ophthalmopathy is not influenced by near total thyroidectomy: a case‐control study
Authors: Marcocci  , Bruno‐Bossio  , Manetti  , Tanda  , Miccoli°  , Iacconi  , Bartolomei  , Nardi  , Pinchera  , Bartalena  
Published: March 2003

OBJECTIVEThe relationship between the method of treatment of hyperthyroidism due to Graves' disease and the course of Graves' ophthalmopathy is debated. Antithyroid drug therapy is associated with no change, or even amelioration, of ophthalmopathy. Although controversial, radioiodine may be followed by progression of eye disease, preventable by glucocorticoid administration. Whether thyroidectomy affects the course of ophthalmopathy is uncertain.DESIGNIn a case control study, the course of non‐severe Graves' ophthalmopathy after thyroidectomy was investigated and the results compared with those observed in patients treated with methimazole.PATIENTSThirty patients with Graves' hyperthyroidism and non‐severe/absent ophthalmopathy were treated with near‐total thyroidectomy (Group 1, Tx), after achievement of euthyroidism with methimazole. After surgery, all patients started levothyroxine replacement therapy. Sixty patients treated with methimazole, matched for age, sex, duration of hyperthyroidism, degree of ocular involvement and smoking habits, were used as controls (Group 2, MMI).MEASUREMENTSPatients were seen every 1–2 months for 12 months for thyroid tests and ocular evaluation.RESULTSIn Group 1, ocular parameters did not change in 17 of 18 patients with pre‐existing ophthalmopathy, and in 12 patients without ophthalmopathy. Eye manifestations worsened only in one (3.3%) patient with pre‐existing ophthalmopathy. In Group 2, ocular parameters did not change in 58 patients (33 with, and 25 without ophthalmopathy), while new ophthalmopathy occurred in two without pre‐existing eye disease. One of the 30 patients treated by surgery (3.3%) had permanent hypoparathyroidism.CONCLUSIONSTreatment of Graves' hyperthyroidism with near‐total thyroidectomy in patients with non‐severe or absent pre‐existing ophthalmopathy is not associated in the short term with significant effects on the course of ophthalmopathy.
Serum levels of growth hormone binding protein in children with normal and precocious puberty: relation to age, gender, body composition and gonadal steroids
Authors: Juul Anders , Fisker Sanne , Scheike Thomas , Hertel Thomas , Müller Jørn , Ørskov Hans , Skakkebæk Niels E. 
Published: March 2003

AIMTo study the regulation of GHBP serum levels by gonadal steroids in normal and precocious puberty.STUDY PROTOCOLWe studied GHBP levels in relation to age, sex, pubertal maturation, body composition as well as to circulating IGF‐I and gonadal steroid levels in 320 healthy children. Furthermore, we studied the regulation of circulating GHBP in 33 girls with central precocious puberty before and during gonadal suppression with GnRH agonist.METHODSGHBP was determined by a time‐resolved fluoroimmunoassay (GHBP TR‐FIA) based on a commercially available immunoassay for GH, the DELFIA GH assay.RESULTSIn healthy children GHBP levels were significantly higher in normal girls compared with boys, and there was no significant increase in GHBP in puberty in both sexes. GHBP levels did not correlate with height (SDS), age, pubertal stage, IGF‐I or testosterone/oestradiol levels in boys and girls, respectively. There were significant correlations between BMI and GHBP in boys and girls (R 2 = 0.14 and R 2 = 0.12, both P < 0.0001). Furthermore, GHBP correlated highly significantly with the percentage body fat, determined by BIA in 43 healthy girls (R 2 = 0.40, P < 0.0001). GHBP levels were significantly higher in girls with central precocious puberty (CPP) (1.31 SDS (1.26), mean (SD)) compared to prepubertal controls (P < 0.0001), and above + 2 SD in 10 out of 33 patients. In girls with CPP, GHBP correlated inversely with oestradiol before treatment (R 2 = 0.26, P < 0.01) and there was a tendency towards a positive correlation with BMI (R 2 = 0.13, P = 0.078). By contrast, there were no signficant correlations between GHBP and IGF‐I or height SDS. Gonadal suppression with GnRH agonist treatment caused a transient significant increase of 0.57 SD after 2 months of treatment (P < 0.001), but decreased to baseline levels hereafter.CONCLUSIONWe conclude that in children, as in adults, body fat is the primary determinant for the circulating level of GHBP, and that the difference in body fat is probably the main factor for the higher levels of serum GHBP in girls compared with boys, as well as for the negative influence of testosterone levels in boys and of oestrogen levels in girls. The elevation in GHBP levels observed in girls with central precocious puberty is probably due their higher body fat content.
Treatment of pituitary‐dependent Cushing's syndrome: long‐term results of unilateral adrenalectomy followed by external pituitary irradiation compared to transsphenoidal pituitary surgery
Authors: Nagesser S. K. , van Seters A. P. , Kievit J. , Hermans J. , van Dulken H. , Krans H. M. J. , van de Velde C. J. H. 
Published: March 2003

SummaryBACKGROUND The preferred treatment of Cushing's disease (CD) nowadays is transsphenoidal pituitary surgery (TPS). Prior to TPS, patients at the Leiden University Medical Centre were treated by unilateral adrenalectomy followed by external pituitary irradiation (UAPI). We report on long‐term results of both UAPl and TPS and compare remission, relapse rates, and complications.PATIENTS AND METHODS A retrospective Study was carried out on 130 patients with CD. Patients with pituitary macroadenoma were excluded. Eighty‐six and 44 patients underwent UAPl and TPS, respectively. Of these patients, 85 and 41 were evaluable for long‐term results.RESULTS Remission following UAPl and TPS was identical at 64% (54/85 and 27/41). Cumulative relapse was also comparable ‐ 17% (9/54) and 22% (6/27), respectively, ‐ for UAPl and TPS, although the mean follow‐up periods were different ‐ 21.4 years and 8.5 years, respectively. Cumulative disease‐free survival curves after UAPl and TPS are identical until 5 years of follow‐up, but diverge thereafter indicating more sustained remissions following UAPl (P=0.17, Wilcoxon statistic). Pituitary dysfunction following UAPl (36%) and pituitary surgery (55%) likewise did not dlffer significantly. However, pituitary dysfunction was an immediate event after TPS, whereas it developed after a mean interval of 17.8 years following UAPI.Low‐dose dexamethasone testing during follow‐up had no value in predicting therapeutic outcome.CONCLUSIONS The results of unilateral adrenalectomy followed by external pituitary irradiation do not Justify that this therapy is totally abandoned in favour of transsphenoidal pituitary surgery. Unilateral adrenalectorny followed by external pituitary irradiation is a valid therapeutic modality for the treatment of Cushing's disease, and could be considered as alternative to bilateral adrenalectomy and under some circumstances to transsphenoidal pituitary surgery.
Association of thyrotrophin receptor antibodies with the clinical features of Graves' ophthalmopathy
Authors: Gerding Martin N. , van der Meer Jolanda W. C. , Broenink Margreet , Bakker Onno , Wiersinga Wilmar M. , Prummel Mark F. 
Published: March 2003

OBJECTIVEGraves' ophthalmopathy (GO) and Graves' hyperthyroidism are closely associated diseases and thought to be caused by the same autoimmune process. An obvious explanation for this would be the presence of autoantibodies reacting with an autoantigen present in the orbit and the thyroid gland. The TSH‐Receptor (TSH‐R) antibodies are a likely candidate, because they cause Graves' hyperthyroidism and the TSH‐R appears to be present also in orbital tissues. If TSH‐R antibodies are responsible for the ophthalmopathy one would expect their titres to correlate with clinical characteristics of the eye disease. The aim of the present study is to see whether TSH‐R antibodies are related to the activity and severity of the thyroid‐associated ophthalmopathy.DESIGN AND PATIENTSTSH‐R antibody levels were measured as TBII (TRAK assay), and TSI (cAMP response of a TSH‐R transfected cell line) in serum of 63 patients with untreated moderately severe GO, accompanying Graves' thyroid disease; all patients had been euthyroid for > 2 months.RESULTSTBII and TSI titres were strongly related to each other. TBII or TSI titres did not correlate with thyroidal or orbital disease duration, nor with TPO antibody levels. In contrast, we found a striking and highly significant correlation between the Clinical Activity Score (CAS) of the eye disease, and both TBII (r = 0.54; P < 0.0001) and TSI (r = 0.50; P < 0.0001). In addition, a weaker but significant relation was found between proptosis (in mm) and TBII (r = 0.36; P = 0.004) and TSI (r = 0.49; P = 0.0001). No correlation was found with eye muscle motility.CONCLUSIONTSH‐R antibody levels correlate directly with clinical features of Graves' ophthalmopathy. The results support the hypothesis of a pathogenetic role of TSH‐R antibodies and the TSH‐R in the orbit of Graves' ophthalmopathy patients.
Ablation of the thyroid remnant and 131I dose in differentiated thyroid cancer
Authors: Doi Suhail A.R. , Woodhouse Nicholas J.Y. 
Published: March 2003

AIMSTo compare the efficacy of remnant ablation following a single low dose (specific activity of 131I administered, 1074–1110 MBq) vs. a single high dose (mostly 2775–3700 MBq) of 131I in patients with differentiated thyroid cancer and to determine whether or not the extent of surgery influences outcome.METHODSNineteen studies have reported the results of low dose 131I ablation. Of these, 11 met our criteria for a comparative analysis. Two additional cohorts of ours were added and these were analysed in two groups based on the extent of surgery (near‐total [NT; Woodhouse1] vs. sub‐total [ST; Woodhouse2]). There were 518 low dose and 449 high dose patients in all.RESULTSThe average failure of a single low dose was 46 ± 28% (SD). Meta‐analysis revealed a statistically significant advantage for a single high over a single low dose and a pooled reduction in relative risk of failure of the high dose of about 27% (P < 0.01). From this we estimate that for every seven patients treated one more would be ablated given a high rather than a low dose (assuming a low dose failure risk of 50%). Also, a significantly greater proportion of patients are ablated after a single high or low dose, if they underwent near‐total as opposed to sub‐total thyroidectomy (summary relative risk (RR) 1.4; P < 0.05).CONCLUSIONHigh dose 131I is more efficient than low dose for remnant ablation particularly after less than total thyroidectomy. Results suggest that patients with differentiated thyroid cancer should routinely have a total thyroidectomy followed by high dose 131I (2775–3700MBq) for ablation of the remnant.
Corpus luteum response to exogenous HCG during the mid‐luteal phase of the menstrual cycle
Authors: Tay  , Lenton  
Published: March 2003

OBJECTIVETo assess a range of exogenous HCG regimes designed to simulate the endocrine environment occurring in biochemical, single and multiple pregnancies and to study the response of the corpus luteum to those regimes.DESIGNProspective clinical study.PATIENTSTwenty‐five normally cycling women aged 24–35 years were given one of four regimes of HCG injections designed to mimic the HCG concentrations found following spontaneous implantation. Regimes A, B, C and D were designed with starting HCG doses of 60, 140, 250 and 1000 iu, respectively. The daily HCG injections were then increased to give a doubling concentration every 30 h for regime A, every 27 h for regime B, every 24 h for regimes C and D. HCG administration was started on either days 7 or 8 after the LH peak.MEASUREMENTSPlasma HCG and progesterone concentrations.RESULTSSubjects given regime A failed to demonstrate any rescue of the corpus luteum despite low‐detectable amounts of HCG in the circulation equivalent to those seen in some biochemical pregnancies. In contrast, subjects given regimes B and C demonstrated prompt increases in progesterone secretion immediately after the first HCG injection achieving HCG and progesterone concentrations in plasma similar to those seen in normal singleton pregnancies. Subjects given regime D also showed rapid rescue of the corpus luteum but this time achieved plasma HCG concentrations in the range normally seen in multiple pregnancies. All subjects in regimes B, C and D secreted significantly higher amounts of progesterone than those in regime A (P < 0.001). However, despite the greater amounts of HCG used in regime D, the amount of progesterone produced was not significantly different from regimes B or C.CONCLUSIONSThe exogenous HCG regimes used in this study successfully mimicked the hormonal environment found in biochemical, single and multiple pregnancies and elicited appropriate corpus luteum responses.