bluuebunny/crossref_metadata_2025_split huggingface dataset:
Audit of selected patients with nonfunctioning pituitary adenomas treated without irradiation — a follow‐up study
Authors: Turner  , Stratton  , Byrne  , Adams  , Wass  
Published: March 2003

OBJECTIVENon‐functioning pituitary adenomas (NFA) are the commonest type of pituitary macroadenoma. Although the initial definitive management of these tumours is almost always trans‐sphenoidal surgery, the use of postoperative radiotherapy remains controversial. Radiotherapy has been shown to significantly reduce the risk of tumour regrowth. An audit of patients with NFAs treated with trans‐sphenoidal surgery without irradiation was performed at our centre five years ago, and suggested that careful selection and follow‐up could avoid the need for adjuvant radiotherapy. We have repeated this audit to assess the longer term effects of this management strategy.METHODS AND PATIENTSThe case notes and imaging of the original cohort of 65 of 73 patients (50 males, mean age 52) who had undergone trans‐sphenoidal surgery (TSA) for NFA between July 1979 and 1992, had not received irradiation and were followed up by imaging were reviewed. Tumour regrowth was defined as enlargement of the pituitary tumour. Mean follow‐up was 76 months (range 12–173).RESULTSPituitary tumour regrowth has occurred in 21 of the 65 patients (32%) during a mean follow‐up of 76 months compared with 8/73 (11%) in 1994 (P = 0.002). The tumour regrowth was detected at a mean of 5.4 years (range 2–14 years). Lifetable analysis of the whole unirradiated group showed 82% recurrence free survival at 5 years (95% confidence limits 72–92%), and 56% at 10 years (95% confidence limits 38–74%). Eight (12%) patients required a second surgical procedure (6 TSA and 2 craniotomies). There was no relationship between recurrence and whether a total surgical removal was thought to have been performed.CONCLUSIONDespite careful selection of patients with non‐functioning pituitary adenomas, tumour regrowth occurs in a significant proportion. These results show that continued follow‐up in these patients is essential as significantly more patients showed evidence of tumour regrowth at this second assessment compared with the 1994 data. Until we are able to predict which tumours are likely to regrow postoperatively, radiotherapy should be considered for all patients with non‐functioning pituitary adenomas as even in carefully selected cases, the regrowth rate is approaching 50% at 10 years.
Endogenous inhibitors of 11β–hydroxysteroid dehydrogenase type 1 do not explain abnormal cortisol metabolism in polycystic ovary syndrome
Authors: Walker Brian R. , Rodin Andrew , Taylor Norman F. , Clayton Richard N. 
Published: March 2003

OBJECTIVEThe aetiology of enhanced adrenal androgen secretion in polycystic ovary syndrome is poorly understood. Previous reports suggest that enhanced peripheral metabolism of cortisol results in decreased negative feedback suppression of ACTH secretion, either by enhanced inactivation of cortisol by 5α‐reductase or impaired reactivation of cortisol by 11β–hydroxysteroid dehydrogenase type 1 (11β–HSD1). Endogenous inhibitors of hepatic 11β–HSD1 can be extracted from urine. We have tested the hypothesis that these are increased in patients with polycystic ovary syndrome.DESIGNA case‐control study.PATIENTS57 patients with polycystic ovary syndrome and 27 healthy control women.MEASUREMENTSAliquots from 24 h urine samples were extracted with Sep‐Paks and incubated with rat liver microsomes in which 11β–HSD1 activity was quantified by conversion of 3H‐corticosterone to 3H‐11‐dehydrocorticosterone.RESULTSInhibition of 11β–HSD1 activity was not different in extracts from patients compared with controls (40.8 ± 18.9 arbitrary units in patients vs. 42.7 ± 16.6 in controls, mean (± SEM, P > 0.60) and did not correlate with ratios of cortisol metabolites in urine or with body mass index.CONCLUSIONSThe altered cortisol metabolism in polycystic ovarian syndrome, which is consistent with impaired 11β–HSD1 activity, cannot be accounted for by increased production of measurable endogenous inhibitors of this enzyme.
Raised plasminogen activator inhibitor‐1 (PAI‐1) is not an independent risk factor in the polycystic ovary syndrome (PCOS)
Authors: Atlorno William U. , Fox Robert , Condon John E. , Shaw Stephen , Friend J. , Prentice Archibald G. , Wilkin Terence J. 
Published: March 2003

SummaryBACKGROUND It has been postulated that an insulln‐driven increase in plasminogen activator inhibitor‐1 (PAI‐1) levels may link insulin resistance to anovulatory infertility in women with PCOS and that It may place them at increased risk of thromboembolic disease. However, previous studies have been conflicting because many have failed to control for body mass index (BMI) which may affect PAI‐1. The aim of this study was to investigate PAI‐1 activity in women with PCOS and to compare it with unaffected controls of a similar BMI.DESIGN AND PATIENTS 41 Women with Pcos and 25 weight‐matched controls participated in this cross‐sectional study. Patients were evaluated clinically and by pelvic ultrasound and fasting blood samples were taken for haematological and biochemical tests. MEASUREMENTS PAI‐1 activity, insulin, glucose, trlglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, FSH, LH, PRL, testosterone, SHBG, 17–hydroxyprogesterone, plasminogen, fibrinogen (α2 antiplasmin, blood pressure and insulin sensitivity with a homeostasis model assessment (HOMA) computer programme.RESULTS There was no significant difference in BMI or in (log) PAI‐1 activity in women with PCOS compared with controls (BMI 29.5 ± 5.6 vs. 28.4 ± 6.3 kg/m2, P=0.25 and PAI‐12.56 (SD 0.85) vs. 2.14 (SD 0.98) au/ml, P=0.07). The median fasting insulin level was significantly higher (17 (4.6–134.5) vs. 9.6 (3.7–41.5) mU/l, P<0.01), and insulin sensitivity signiflcantly lower In the PCOS group, (43.17% (5.48–160) vs. 82.8% (21.8–193), P<0.01). Women with PCOS also had a significantly higher free androgen index, LW/FSH ratio and a lower HDL/total cholesterol ratio. However blood pressure and all other lipid and haematological measurements were not significantly different between both groups. There were significant positive correlations between (log) PAL1 activity and BMI (ρ= 0.61), triglycerides (ρ= 0.49) and fasting insulin (ρ= 0.60) and a negative correlation with HDL cholesterol (ρ=−0.46). Triglyceride concentrations showed the most Significant relationship with (log) PAI‐1 activity on multiple regression. 29% of PCO women (12/41) gave a positive family history of thrombosis compared to 8% (2/25) in the control group. CONCLUSION Plasminogen activator inhibitor‐1 activity is not raised in women with PCOS independent of obesity and these results do not support the hypothesis that it may contribute to their anovulatory infertility, or increase their risk of thrombosis. The only significant metabolic features of the PCOS independent of obesity are insulin resistance, hyperinsu‐linaemia and lower HDUtotal cholesterol ratio. The higher frequency of a positive family history of thrombosis in these women nevertheless requires further explanation.
Is monoclonality in pituitary adenomas synonymous with neoplasia?
Authors: Levy Andy 
Published: March 2003

SummaryThe objective of clonality analysis is to help differentiate hyperplasia from neoplasia. If the clonality of different pituitary subpopulations is skewed rather than uniform it is possible that a physiological trophic response could, by displacing trophically inert cells, give rise to a potentially evanescent monoclonal expansion in the absence of spontaneous somatic mutation. Such a clonal temtory model would allow for the presence of cellular subsets (a feature difficult to explain in terms of classical neoplasia) and account for a number of unusual characteristics of pituitary adenomas including monoclonality, cyclical activity, lack of oncogene involvement. spontaneous resolution and quantitative but not qualitative changes in secretory activity seen, for example, in Cushing's disease.
Oestrogen‐receptor‐α gene polymorphism affects response in bone mineral density to oestrogen in post‐menopausal women
Authors: Ongphiphadhanakul B. , Chanprasertyothin S. , Payatikul P. , Tung S. Sae , Piaseu N. , Chailurkit L. , Chansirikarn S. , Puavilai G. , Rajatanavin R. 
Published: March 2003

OBJECTIVEAn oestrogen‐receptor‐α (ERα) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ERα gene polymorphism is associated with a functional difference, we assessed the response in bone mineral density (BMD) to oestrogen therapy in post‐menopausal women in relation to ERα gene polymorphism.PATIENTS AND MEASUREMENTSSubjects consisted of 124 Thai post‐menopausal women. Sixty‐three of the women were less than 6 years post‐menopausal and 61 were more than 10 years post‐menopausal with vertebral or femoral osteoporosis as defined by BMD T‐score less than − 2.5. Subjects were randomly allocated to receive 0.3 mg (n = 67) or 0.625 mg (n = 57) of conjugated equine oestrogen (CEE). All subjects also took 5 mg medroxyprogesterone acetate. Vertebral and femoral neck BMD were measured at baseline and 1 year after treatment. Data were expressed as mean ± SEM. Capital P represents the absence of the restriction site while lower‐case p indicates the presence of the restriction site.RESULTSFor subjects on 0.625 mg CEE, BMD at L2–4 increased significantly after 1 year in those with pp (n = 20) Pp (n = 29) and PP genotypes (n = 8) (P < 0.001). However, in subjects on 0.3 mg CEE, BMD at L2–4 increased significantly after 1 year in subjects with Pp (n = 34, + 7.6 ± 1.5%, P < 0.001) and PP genotypes (n = 13, + 6.9 ± 1.0%, P < 0.001), but not in those with pp genotype (n = 20, + 2.3 ± 2.1%, P = NS). After adjusting for age and years since menopause, the change in vertebral BMD was still lower in those without the P allele compared to those with the P allele (P < 0.05). Femoral BMD did not significantly change regardless of dose of CEE and genotype.CONCLUSIONSWe conclude that ERα gene polymorphism affects skeletal response to oestrogen in post‐menopausal women. The effect of ERα gene polymorphism appears to be site‐specific and does not relate to biochemical markers of bone turnover. Determination of ERα genotype may help identify post‐menopausal women who will have more skeletal benefit from oestrogen therapy.
Increase of adhesion molecules, fibrinogen, type‐1 plasminogen activator inhibitor and orosomucoid in growth hormone (GH) deficient adults and their modulation by recombinant human GH replacement
Authors: Kvasnička Jan , Marek Josef , Kvasnička Tomáš , Weiss Vladimír , Marková Markéta , Štìěpán Jan , Umlaufová Anna 
Published: March 2003

OBJECTIVEGH deficiency (GHD) is usually associated with a higher incidence of cardiovascular disease (CVD). The aim of this study was to establish whether patients with GHD, like those with CVD, show an increase in fibrinogen (FBG), type‐1 plasminogen activator inhibitor (PAI‐1), acute phase response proteins (APR), and soluble adhesion molecules. The effect of recombinant human GH (rhGH) replacement, on these parameters was also investigated.PATIENTS AND DESIGNConcentrations of PAI‐1 antigen (Ag), adhesion molecules sE‐selectin, sP‐selectin, and intercellular adhesion molecule‐1 (sICAM‐1), FBG and levels of APR orosomucoid (ORM), and ‘negative APR’ transferrin (TRF) were established in 11 panhypopituitary (PHP) patients (eight men and three women, age median 39.0 years, body mass index (BMI) 27.49 ± 3.89 kg/m2) before and after 12‐month replacement with rhGH. Control values were obtained by examination of 33 healthy age and sex matched subjects (24 men and nine women with BMI 24.16 ± 1.99 kg/m2).RESULTSPHP patients had higher concentrations of ORM (0.80 ± 0.25, vs. 0.61 ± 0.20 g/l; P = 0.05), FBG (3.22 ± 0.48, vs. 2.57 ± 0.47 g/l; P = 0.001), PAI‐1 Ag (97.12 ± 33.23, vs. 44.11 ± 21.40 μg/l; P = 0.001), sE‐selectin (72.42 ± 28.35, vs. 42.80 ± 12.60 μg/l; P = 0.004), sP‐selectin (221.26 ± 75.12, vs. 104.79 ± 26.01 μg/l; P = 0.001) sICAM‐1 (409.75 ± 137.78, vs. 228.10 ± 37.54 μg/l; P = 0.001), and lower levels of TRF (2.14 ± 0.40, vs. 2.76 ± 0.39 g/l; P = 0.001) than controls. After 12‐month rhGH replacement the patients showed an increase of TRF (2.64 ± 0.84 g/l, P = 0.037) and decrease of soluble adhesion molecules (sE‐selectin 57.98 ± 27.04 μg/l, P = 0.01, sP‐selectin 121.74 ± 50.42 μg/l, P = 0.007; and sICAM‐1 279.95 ± 88.32 μg/l, P = 0.005), which then, similarly to the ORM (0.67 ± 0.12 g/l) and FBG level (2.82 ± 0.51 g/l), did not statistically differ from the values in the control group.CONCLUSIONrhGH replacement led to modulation of the ‘inflammatory response’ in panhypopituitary patients. This modulation occurred locally at vascular endothelium level where after rhGH replacement, sE‐selectin, sP‐selectin and sICAM‐1 concentrations decreased, a similar effect as in the systemic inflammatory response, as was also apparent from the changes in acute phase response protein levels.
Phenotype and phenocopy: the relationship between genotype and clinical phenotype in a single large family with multiple endocrine neoplasia type 1 (MEN 1)
Authors: Burgess John R. , Nord Brita , David Ruben , Greenaway Tim M. , Parameswaran Venkateswaran , Larsson Catharina , Shepherd Joseph J. , Teh Bin T. 
Published: March 2003

BACKGROUNDThe majority of reports describing the natural history and prognosis of multiple endocrine neoplasia type 1 (MEN 1) utilize phenotypic rather than molecular genetic criteria to establish a diagnosis of MEN 1.OBJECTIVES AND PATIENTSWe sought to determine the spectrum of endocrine abnormality amongst 152 members (64 gene carriers and 88 noncarriers) of a large MEN 1 family in whom a determination of MEN 1 status had previously been made by phenotype screening. The predictive utility of both clinical and molecular screening techniques are described.RESULTSA novel IVS2–3 (C‐G) MEN1 mutation was identified in affected members of this family. Seven (10%) of 71 individuals satisfying clinical diagnostic criteria for MEN 1 were found to be genetically negative (excluded by mutation analysis and haplotyping) for MEN 1. These cases of MEN 1 phenocopy comprised four cases of primary hyperparathyroidism, two ‘nonsecretory’ pituitary adenoma and one case of coincident prolactinoma and hyperparathyroidism. Three of the patients with hyperparathyroidism had previously required parathyroidectomy and each had achieved normocalcaemia following parathyroid resection. Predictive genetic testing prospectively identified three children with the MEN 1 genotype. Serum calcium was normal at the time of their initial molecular genetic diagnosis. In each case hyperparathyroidism subsequently developed during adolescence.CONCLUSIONMultiple endocrine neoplasia type 1 phenocopy is an important differential diagnosis in patients exhibiting an multiple endocrine neoplasia type 1 phenotype. This is a relevant consideration, particularly when the diagnosis of multiple endocrine neoplasia type 1 is made using sensitive, but nonspecific, criteria such as mild hyperparathyroidism, pituitary micoadenoma, and hyperprolactinaemia. Confirmatory genetic testing should be undertaken to confirm clinical diagnoses of multiple endocrine neoplasia type 1.
Growth hormone deficiency and replacement in elderly hypopituitary adults
Authors: Monson John P. , Abs Roger , Bengtsson Bengt‐Åke , Bennmarker Helge , Feldt‐Rasmussen Ulla , Hernberg‐Ståhl Elizabeth , Thorén Marja , Westberg Björn , Wilton Patrick , Wüster Christian 
Published: March 2003

OBJECTIVEAlthough elderly hypopituitary adults demonstrate an increase in total and central fat compared with age‐matched controls and are distinguishable from control subjects in terms of growth hormone (GH) responsiveness on dynamic testing, there are few data available on response to GH replacement. The objective of this study was to compare the baseline characteristics and longitudinal response to GH replacement in patients aged > 65 years with that observed in younger patients enrolled in KIMS (Pharmacia and Upjohn International Metabolic Database). KIMS is a physician‐managed, open, long‐term surveillance study of adult GH‐deficient patients receiving GH replacement. Patients were entered and data provided by interested physicians.PATIENTSBaseline characteristics were studied in 109 patients (66 males) aged > 65 years commencing GH replacement at time of entry into KIMS and the effects of GH replacement on blood pressure, lipids and quality of life in 64 patients who had completed at least 6 months of GH replacement. Data were compared with baseline data on 863 patients aged < 65 years with adult onset GH deficiency, who had not received GH for at least 6 months prior to entry into KIMS, 220 of whom went on to complete > 6 months GH therapy in KIMS.RESULTSBlood pressure, cholesterol and LDL cholesterol were positively correlated with age, particularly in females, and older patients had a predictably higher prevalence of diabetes mellitus and history of hypertension. The frequency of previous fractures was increased in females but not in males aged > 65 years. Body mass index, waist/hip ratio and quality of life (AGHDA score) was similar in both groups prior to commencement of GH therapy. GH replacement doses were similar in younger and older patients and the percentage of patients with serum IGF‐I of > 2SD above the age‐related normal mean was not significantly different between the groups (< 65 years, 20%; > 65 years, 11%). After 6 months of GH replacement significant improvements were evident in waist circumference, waist/hip ratio, diastolic blood pressure, total and LDL cholesterol and AGHDA score in patients aged < 65 years. Similar significant reductions in total and LDL cholesterol were evident in patients > 65 years. In addition, male patients aged > 65 years demonstrated significant reductions in diastolic blood pressure and AGHDA score but no change in waist circumference whereas females aged > 65 years demonstrated a trend to reduction in waist circumference and AGHDA score.CONCLUSIONSThese data, derived from the largest series of GH‐treated hypopituitary patients published to date, confirm similar baseline characteristics and positive benefit from GH replacement in older compared with younger hypopituitary patients particularly in relation to quality of life.
Growth and endocrine disorders in multisystem Langerhans' cell histiocytosis
Authors: Nanduri V. R. , Bareille P. , Pritchard J. , Stanhope R. 
Published: March 2003

INTRODUCTIONLangerhans' cell histiocytosis is a rare disorder, with diabetes insipidus occurring in up to half of patients. Causes of growth failure include the illness itself, treatments used and growth hormone insufficiency.PATIENTS AND METHODSWe identified all patients with an endocrinopathy secondary to Langerhans' cell histiocytosis (LCH). Growth data were analysed from all patients with multisystem involvement.RESULTSOf 144 patients with multisystem LCH, 50 had an endocrinopathy, 49 of whom had diabetes insipidus. Growth hormone insufficiency (GHI) was present in 21 patients, seven of whom had other anterior pituitary deficiencies as well (gonadotrophin deficiency + GHI n = 2, gonadotrophin deficiency + TSH deficiency + GHI n = 2, panhypopituitarism n = 3). GH insufficiency, the development of which appeared to be independent of pituitary radiation, occurred at a median age of 8.3 years (4.7–18 years) and at a median interval of 3.5 years (0–11.8 years) after diagnosis of LCH. The median height SDS at diagnosis of growth hormone insufficiency was −2.9. Thirteen of the patients with growth hormone insufficiency attained final height with a median height SDS of −1.2. The final height SDS of 15 patients without GH insufficiency was closer to target height SDS, but not statistically different from that of the GH insufficient group.CONCLUSIONSGH therapy significantly improves growth in GH insufficient patients with Langerhans' cell histiocytosis. Early institution of GH therapy may further improve height outcome. However, most children with Langerhans' cell histiocytosis regardless of endocrine function, failed to reach target height.
Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly
Authors: Chanson P. , Boerlin V. , Ajzenberg C. , Bachelot Y. , Benito P. , Bringer J. , Caron P. , Charbonnel B. , Cortet C. , Delemer B. , Escobar‐Jiménez F. , Foubert L. , Gaztambide S. , Jockenhoevel F. , Kuhn J. M. , Leclere J. , Lorcy Y. , Perlemuter L. , Prestele H. , Roger P. , Rohmer V. , Santen R. , Sassolas G. , Scherbaum W. A. , Schopohl J. , Torres E. , Varela C. , Villamil F. , Webb S. M. 
Published: March 2003

BACKGROUND AND OBJECTIVEThe most effective option for the medical treatment of patients with acromegaly is the use of somatostatin analogues. Long‐acting depot formulations for intramuscular injection of two somatostatin analogues have recently become available: octreotide acetate LAR (Sandostatin®LAR®, Novartis Pharma AG) and lanreotide SR (Somatuline®, Ipsen Biotech). We wished to compare efficacy of octreotide LAR and lanreotide SR in acromegalic patients.PATIENTS AND METHODSA group of 125 patients with acromegaly (67 females; mean age, 47 years; 59 patients had previous pituitary irradiation) from 26 medical centres in France, Spain and Germany were studied. Before the study, all patients had been treated with intramuscular injections of lanreotide SR (mean duration, 26 months) at a dose of 30 mg which was injected every 10 days in 64 and every 14 days in 61 patients, respectively. All patients were switched from lanreotide SR to intramuscular injections of 20 mg of octreotide LAR once monthly for three months. In order to obtain efficacy and safety data of lanreotide SR under study conditions, it was decided to randomly assign at day 1, in a 3 : 1 ratio, the time point of the treatment switch; 27 of the patients were randomly assigned to continue the lanreotide SR treatment for the first 3 months of the study (group A); they were on octreotide LAR 20 mg from month 4–6. The other 98 patients were assigned to be switched to treatment with octreotide LAR 20 mg at day 1 (group B). In group B patients, octreotide LAR treatment was continued until month 6, with an adjustment of the dose based on GH levels obtained at month 3.RESULTSThe mean GH concentration decreased from 9.6 ± 1.3 mU/l at the last evaluation on lanreotide SR to 6.8 ± 1.0 mU/l after three injections of octreotide LAR (P < 0.001). The percentages of patients with mean GH values ≤ 6.5 mU/l (2.5 μg/l) and ≤ 2.6 mU/l (1.0 μg/l) at the last evaluation on lanreotide SR were 54% and 14%, and these values increased after 3 months treatment with octreotide LAR to 68% and 35% (P < 0.001), respectively. IGF‐I levels were normal in 48% at the last evaluation on lanreotide SR and in 65% after 3 months on octreotide LAR (P < 0.001). Patients with pre‐study pituitary irradiation had lower mean GH and IGF‐I concentrations. But the effects of the treatment change did not differ between the irradiated and the nonirradiated patients. In general both drugs were well tolerated.CONCLUSIONOctreotide LAR 20 mg administered once monthly was more effective than lanreotide SR 30 mg administered 2 or 3 times monthly in reducing GH and IGF‐I in patients with acromegaly.