bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidentally discovered pituitary lesions: high frequency of macroadenomas and hormone‐secreting adenomas — results of a prospective study
Authors: Feldkamp  , Santen  , Harms  , Aulich  , Mödder  , Scherbaum  
Published: March 2003

OBJECTIVEWith increasing use of computed tomography and magnetic resonance imaging, pituitary adenomas are being discovered incidentally with increasing frequency. However, limited data are available concerning the clinical importance and natural history of such ‘incicentalomas’. We have undertaken a prospective study to investigate changes in adenoma size and endocrine and visual function in patients with incidentally discovered intrasellar masses.PATIENTS AND METHODSOur study included 67 patients with incidentalomas of the pituitary gland during a 5‐year period (1992–96). 50 of these patients were followed up prospectively over a mean period of 2.7 years. Initially, all patients underwent endocrine testing and ophthalmological examinations as well as magnetic resonance imaging or computed tomography scans. These investigations were repeated after 3 months and then annually.RESULTS42 (62.7%) out of 67 patients with incidentalomas had microadenomas whereas 37.3% had macroadenomas. Macroadenomas were found more frequently in men (52.2%). Visual field defects could be documented in 4.5% of the patients. Partial deficiency of anterior pituitary function was present in 14.9%. Eight patients (11.9%) had prolactinomas. An increase in adenoma size was detected in 3.2% of the microadenomas and in 26.3% of the macroadenomas within the follow‐up period.CONCLUSIONMacroadenomas and hormone secreting adenomas are not uncommon in patients with pituitary incidentalomas. Macroadenomas should be closely monitored for tumour enlargement. All patients should undergo biochemical assessment and ophthalmological examination, since endocrine dysfunction or visual field defects may be present at the time a pituitary incidentaloma is detected.
Outcome of transphenoidal surgery for acromegaly and its relationship to surgical experience
Authors: Ahmed  , Elsheikh  , Stratton  , Page  , Adams  , Wass  
Published: March 2003

BACKGROUNDA number of surgical series have been reported on the treatment of acromegaly and their results vary widely. The acceptable definition of remission has changed in recent years and it is known, though in a small series, that growth hormone levels of > 5 mU/l are still associated with an increased mortality from the condition. We have analysed data at this centre and examined the outcome of transphenoidal surgery for acromegaly, compared our results with recently published series from other centres and also assessed factors which might effect outcome including whether there is any demonstrable effect of the experience of the surgeon on outcome.PATIENTS AND METHODSWe have analysed data from all of our 139 patients in whom follow up data are available who have undergone initial transphenoidal surgery for acromegaly by one surgeon at this centre, between 1974 and 1995. Follow up was for a median of 5 years (range 1 month to 17 years).RESULTS67% of patients achieved the criterion for remission (mean GH < 5 mU/l). Success was related to tumour size and preoperative growth hormone values. Thus 91% of patients with microadenomas were in remission postoperatively compared to 46% of patients with macroadenomas. Analysis of the results according to the year of operation showed an improvement in success rates with time. More than 15 years ago, the success rate according to the growth hormone criteria set was 48% and the failure rate 52%. In contrast in the last 5 years analysed, the overall success rate was 74% with a failure rate of 26% (P < 0.04). The success rate for microadenomas was 50% initially, then remained 100%. The case mix was analysed and no change was found.  We have also demonstrated an improvement in pituitary function (including normalization of preoperative elevated prolactin) with time so that pre 1981 16% of patients' pituitary function improved peri‐operatively but 10 years later this figure had risen to 34% (P < 0.03). There was no change over time in the development of pituitary hypofunction, complication rate or recurrence rate.CONCLUSIONSurgical treatment is a safe and effective treatment for acromegaly and remains the first choice of treatment for most acromegalic patients. The results of this centre compare favourably with series from other centres. We have demonstrated improved results, both in terms of post operative growth hormone values and pituitary function tests with time and increasing neurosurgical experience. We conclude that outcome for the surgical treatment for acromegaly is best achieved with one surgeon specialising in pituitary surgery. Improved operative outcome thus achieved has major cost implications and avoids the necessity for consideration of postoperative radiotherapy and the use of expensive growth hormone suppressing drugs in the postoperative period.
The effects of age and gender on parathyroid hormone dynamics
Authors: Haden Susan T. , Brown Edward M. , Hurwitz Shelley , Scott Jennifer , Fuleihan Ghada El‐Hajj 
Published: March 2003

BACKGROUND AND AIMSHyperparathyroidism is a risk factor for bone loss. An age‐related increase in parathyroid hormone (PTH) level has been demonstrated in several studies. It has been suggested that the type II osteoporotic syndrome, a condition of increased prevalence among elderly women, may be at least partially caused by elevations in intact parathyroid hormone (iPTH) levels. To date, however, the effects of age and gender per se on PTH dynamics in healthy subjects independent of other risk factors such as vitamin D deficiency and/or impaired renal function that can impact on parathyroid function, remain unknown. In this study, we used citrate and calcium (Ca) infusions to characterize the impact of age and gender on PTH dynamics in normal subjects.SUBJECTS AND METHODSTwelve young women with mean age ± SD of 26.4 ± 1.6 years, 12 young men with mean age of 26.6 ± 1.3 years, 12 older women with mean age of 68.6 ± 1.3 years and 12 older men with mean age of 67.2 ± 1.6 years were studied. The sigmoidal curves relating serum iPTH to serum levels of ionized Ca (Cai) were characterized by maximal and minimal iPTH levels, the set‐points (levels of Cai causing half‐maximal suppression of iPTH), and the slopes of the curves at the set‐points.RESULTSBaseline serum Ca, Cai, 25 hydroxyvitamin D [25(OH)D] and 1,25 dihydroxyvitamin D [1,25(OH)2D3] levels, as well as the set‐points, slopes and minimal values of the sigmoidal curves relating Cai to iPTH, did not differ among the four groups. iPTH levels at baseline were slightly but not significantly higher in the older age groups (P = 0.18). The maximal iPTH level was 25% higher in the older women than in the younger women, although this difference was not significant (P = 0.29). However, the integrated iPTH responses calculated from the areas under the curves (AUC) of iPTH levels vs. time during the calcium and citrate infusions were significantly higher in postmenopausal women than in young women during both infusions and in older men than in young men during the calcium infusion. There was no effect of gender on serum iPTH levels.CONCLUSIONSIn both women and men, ageing per se, independent of changes in vitamin D economy or renal function, is associated with an increase in integrated PTH secretory response to changes in serum calcium. No alterations in the Cai/iPTH set‐point were present. The biological relevance of these modest increments in integrated iPTH levels during dynamic testing in older healthy men and women remain uncertain.
The innate immune response and type 2 diabetes: evidence that leptin is associated with a stress‐related (acute‐phase) reaction
Authors: Pickup John C. , Chusney Gary D. , Mattock Martin B. 
Published: March 2003

OBJECTIVELeptin is produced by adipose tissue and controls food intake and body weight. Although blood levels of leptin reflect energy stores, cytokines also stimulate leptin production from fat. Because we have proposed that type 2 diabetes mellitus is associated with a cytokine‐mediated acute‐phase or stress response, part of the innate immune system, we sought evidence that leptin is increased in type 2 diabetes partly as a stress response, independently of obesity and sex.DESIGNWe selected two groups of type 2 diabetic patients with either a low acute‐phase response (< 2.30 mmol/l serum concentration of the acute‐phase marker sialic acid) or high response (> 2.30 mmol/l sialic acid), but pair‐matched for body mass index (BMI) and sex.PATIENTSTwenty type 2 diabetic subjects (11 male, 9 female) in each group, whose body mass index (BMI) and age were comparable (mean ± SD: 28.8 ± 3.8 vs. 28.9 ± 3.8 kg/m2, and 60.7 ± 8.9 vs. 61.9 ± 12.3 years, low vs. high acute‐phase responders, respectively). The glycaemic control was also similar in each group (glycated haemoglobin: 9.1 ± 2.2 vs. 8.9 ± 1.9%).MEASUREMENTSSerum concentrations of sialic acid, leptin, interleukin‐6 (IL‐6) (the major cytokine mediator of the acute‐phase response) and cortisol were assayed in fasting venous blood samples from patients and the results compared.RESULTSSerum leptin concentration was increased in the high compared to the low acute‐phase group (median 13.2 (range 3.6–55) vs. 8.1 (2.0–22.5) μg/l, P = 0.004). IL‐6 and cortisol concentrations were also higher in the high‐stress group (1.9 (1.0–6.4) vs. 1.4 (0.4–7.5) ng/l, P = 0.02; and 409 (180–875) vs. 290 (157–705) nmol/l, P = 0.02, respectively). Leptin was strongly correlated with BMI (r = 0.61, P < 0.001), but also with sialic acid (r = 0.40, P = 0.01) and IL‐6 (r = 0.38, P = 0.04).CONCLUSIONSSerum leptin concentrations in type 2 diabetes are partly related to an acute‐phase or stress response, independent of BMI and sex. The association of hyperleptinaemia with elevated serum cortisol provides a mechanism for leptin resistance in type 2 diabetes (glucocorticoids inhibit the central action of leptin). This study provides further support for the theory that type 2 diabetes is asociated with chronic innate immune activation.
Determinants of thyroid volume in healthy French adults participating in the SU.VI.MAX cohort
Authors: Barrère Xavier , Valeix Pierre , Preziosi Paul , Bensimon Michel , Pelletier Bruno , Galan Pilar , Hercberg Serge 
Published: March 2003

OBJECTIVETo study the relative importance of determinants of thyroid volume.DESIGNCross‐sectional study on a sample of subjects issued from the SU.VI.MAX cohort.SUBJECTS2987 French subjects (1713 women aged 35–60 years and 1274 men aged 45–60 years). None of them had previous or present thyroid disease.MEASUREMENTSThyroid volume was determined by ultrasound. Serum TSH and free thyroxine (fT4) were measured in duplicate. Urinary iodine and urinary thiocyanate were assayed in random morning urine samples.RESULTSFor both sexes, thyroid volume (ml) was positively correlated with weight, height, body mass index and body surface area (P = 0.0001) and negatively with age for females (P = 0.0009). When the urinary iodine concentration was adjusted for urinary thiocyanate concentration and their interaction, the thyroid volume was negatively correlated with urinary iodine (males P = 0.02, females P = 0.006) and positively correlated with urinary thiocyanate (males P = 0.0001, females P = 0.004). Mean thyroid volume was greater among active smokers than non‐smokers (males P < 0.0001, females P = 0.0004) and was greater among former smokers than among non‐smokers (males P = 0.0001, females = 0.004). Free T4 and thyroid volume were positively correlated for both sexes (P = 0.0001). TSH was negatively correlated with thyroid volume for both groups (P = 0.0001). Female users of oral contraception (aged 35–45 years) had a smaller thyroid volume than non‐users (P = 0.0009).CONCLUSIONSThe state of borderline iodine deficiency observed in France, in association with a slightly goitrogenic environment, may result in sustained stimulation of the thyroid, independently of TSH level, and is of paramount importance in the formation of goitre. Smoking may affect the thyroid, inducing marked long‐lasting thyroid enlargement.
The influence of renal and cardiovascular abnormalities on blood pressure in Turner syndrome
Authors: Nathwani  , Unwin  , Brook  , Hindmarsh  
Published: March 2003

INTRODUCTIONPatients with Turner syndrome (TS) are at an increased risk of morbidity and mortality from cardiovascular disease. This study was undertaken to establish the prevalence of hypertension in patients with TS and to establish to what extent cardiovascular or renal abnormalities contribute to the measured blood pressure.PATIENTS AND METHODS62 patients with TS, age 5.4–22.4 years, had 24 h‐ABPM (ambulatory blood pressure monitoring), echocardiography, renal imaging and measurement of recumbent plasma renin activity (PRA). Blood pressure was compared with population standards.RESULTS21% of the TS study population had mean systolic and 17% mean diastolic 24 h‐ABPM measurements above the 95th percentile for age and sex (i.e. mild hypertension). Borderline blood pressure (i.e. 90th to 95th percentile) was found in another 17% of the patients. 57% of the patients had a blunted (i.e. less than 10%) fall in the night‐time blood pressure. 24% of the patients had a detectable cardiac abnormality, 42% a detectable renal abnormality and 52% were found to have raised plasma renin activity. The presence of a cardiac or renal abnormality had no significant effect on blood pressure. Blood pressure of patients on growth and/or pubertal therapy was not different from those patients on no such treatment.CONCLUSIONOver 30% of patients with Turner syndrome were found to be mildly hypertensive and over 50% had an abnormal diurnal blood pressure profile. In this study we were unable to demonstrate that the presence of renal or cardiac abnormalities had an effect on recorded blood pressure. The use of growth hormone and oestrogen to manage growth failure and pubertal delay did not seem to affect blood pressure. This study suggests that there is a high prevalence of raised blood pressure in Turner syndrome patients. The 24 h‐ambulatory blood pressure monitoring profile suggests that this may be secondary in origin, but we were unable to demonstrate an underlying mechanism with the renal and cardiac investigations performed.
Cushing's syndrome associated with a chemodectoma and a carcinoid tumour
Authors: Tremble  , Buxton‐Thomas  , Hopkins  , Kane  , Bailey  , Harris  
Published: March 2003

We present a case of Cushing's syndrome where 111In‐octreotide scanning provided evidence for the presence of two neuroendocrine tumours. Uptake in the right neck corresponded to a chemodectoma, but there was no change in the clinical condition or fall in ACTH levels following surgical resection. Uptake in the left chest was assumed to relate to a bronchial carcinoid, but a tumour could not initially be localized on magnetic resonance imaging (MRI), spiral CT scanning or on selective venous sampling.A 1 cm bronchial carcinoid tumour was identified post‐mortem which immunostained for ACTH. This case demonstrates that 111ln‐octreotide scanning is a useful technique for identifying the source of ectopic ACTH production in difficult cases of Cushing's syndrome. Reliance should not be placed solely on standard imaging techniques to localize the tumour prior to surgery. Although rare, the possibility of a non‐ACTH secreting neuroendocrine tumour should also be considered in patients with ectopic ACTH syndrome, who have positive 111In‐octreotide scans.
Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?
Authors: Koziell A. , Charmandari E. , Hindmarsh P. C. , Rees L. , Scambler P. , Brook C. G. D. 
Published: March 2003

SummaryDysfunction of the Wilms’Tumour gene (WT1), a transcription factor critical for normal development and function of the urogenital tract, can result in both tumorigenesis and urogenital abnormalities. The association of WT1 gene mutations with most cases of Denys‐Drash syndrome is well described. More recently WT1 mutations have also been described In a related condition, Frasier syndrome. We report a case where genetic analysis showed a WT1 mutation typically associated with Frasier syndrome: a 1228 + 5 guanine to adenine substitution at the 3’alternative splice donor site in intron 9. The case provides a focus for the discussion of recent evidence that Denys Drash and Frasier syndrome form two ends of a spectrum of disorders. In addition, it illustrates the increasing significance of genetic investigation within clinical practice for diagnostic, prognostic and therapeutic purposes and the importance of karyotype analysis in phenotypically normal girls with renal disease.
Optic chiasmal herniation — an under recognized complication of dopamine agonist therapy for macroprolactinoma
Authors: Jones S. E. , James R. A. , Hall K. , Kendall‐Taylor P. 
Published: March 2003

The initial presentation of macroprolactinoma with visual field impairment, especially in males, is well recognized. Successful treatment with dopamine agonist therapy is characterized by a reduction in hyperprolactinaemia and often rapid and progressive resolution of the visual impairment.A small proportion of patients may subsequently develop a secondary deterioration in both their visual fields and visual acuities despite normalization of prolactin levels and tumour shrinkage. When pituitary apoplexy can be excluded this may result from traction on the optic chiasm which is pulled down into the now partially empty sella.We report a series of seven patients in whom chiasmal traction is believed to be the cause of their secondary deterioration in visual acuity occurring after dopamine agonist therapy for macroprolactinoma. The clinical history of two patients both of whom had rapid resolution of field defect with bromocriptine therapy but subsequently developed a recurrence of their bitemporal hemianopia is detailed. In both patients MRI scanning showed not only tumour involution but also marked optic chiasm herniation into the pituitary fossa. Surgical treatment was considered too risky; but on reduction of bromocriptine dosage the field defect improved in both cases; there was a modest elevation of prolactin and a degree of tumour re‐expansion. The latter is believed to have released tethering of the optic chiasm and/or its vascular supply and thus obviated the need for surgery.Regular monitoring of visual fields in patients with macroprolactinoma receiving medical treatment is therefore important. Early recognition of secondary field loss due to chiasmal herniation enables correction of the visual field loss by manipulation of the medical therapy.
Urine calcium and urine sodium concentrations are not related, after adjustment for urine magnesium
Authors: Stein  , Flicker  , Scherer  , Mead  , Walton  , Chick  , Di Carlantonio  , Zajac  , Wark  
Published: March 2003

BACKGROUND AND OBJECTIVESUrine calcium correlates with urine sodium. The aims of this study were to investigate whether the urine sodium–calcium relationship persists into old age and whether it holds after adjustment for urine magnesium.DESIGNCross‐sectional descriptive analysis.PATIENTSResidents of two aged care institutions (median age 84 years) who were not taking diuretics, calcium or vitamin D supplements.MEASUREMENTSEarly morning urine calcium, sodium and magnesium, plasma creatinine and serum 25‐hydroxyvitamin D and parathyroid hormone.RESULTSUrine calcium correlated with urine sodium (r = 0.29, P < 0.01) and with urine magnesium (r = 0.56, P < 0.001). After adjustment for urine magnesium, the relationship between urine sodium and urine calcium was no longer significant. Forty‐five percent of the interindividual variation in urine calcium was explained by a linear model on the basis of urine magnesium and plasma creatinine.CONCLUSIONThe data indicate that a correlation between urine sodium and calcium persists in very old age. However, this correlation no longer holds after adjustment for urine magnesium. Further studies examining urine calcium excretion should also consider urine magnesium.
Monitoring serum insulin‐like growth factor‐I (IGF‐I), IGF binding protein‐3 (IGFBP‐3), IGF‐I/IGFBP‐3 molar ratio and leptin during growth hormone treatment for disordered growth
Authors: Tillmann  , Patel  , Gill  , Whatmore  , Price  , Kibirige  , Wales  , Clayton  
Published: March 2003

OBJECTIVESerum IGF‐I levels are monitored during GH replacement treatment in adults with GH deficiency (GHD) to guide GH dose adjustment and to minimize occurrence of GH‐related side‐effects. This is not routine practice in children treated with GH. The aim of this study was to evaluate changes in (1) serum IGF‐I, IGFBP‐3 and IGF‐I/IGFBP‐3 molar ratio, and (2) serum leptin, an indirect marker of GH response, during the first year of GH treatment in children with disordered growth.DESIGNAn observational prospective longitudinal study with serial measurements at five time points during the first year of GH treatment was carried out. Each patient served as his/her own control.PATIENTSThe study included 31 patients, grouped as (1) GHD (n = 20) and (2) non‐GHD (Turner syndrome n = 7; Noonan syndrome n = 4), who had not previously received GH treatment.MEASUREMENTSSerum IGF‐I, IGFBP‐3 and leptin levels were measured before treatment and after 6 weeks, 3 months, 6 months and 12 months of GH treatment, with a mean dose of 0.5 IU/kg/wk in GHD and 0.7 IU/kg/wk in non‐GHD groups. IGF‐I, IGFBP‐3 and the calculated IGF‐I/IGFBP‐3 molar ratio were expressed as SD scores using reference values from the local population.RESULTSIn the GHD group, IGF‐I SDS before treatment was lower compared with the non‐GHD (−5.4 ± 2.5 vs. −1.8 ± 1.0; P < 0.001). IGF‐I (−1.8 SDS ± 2.2) and IGFBP‐3 (−1.1 SDS ± 0.6) levels and their molar ratios were highest at 6 weeks and remained relatively constant thereafter. In the non‐GHD group, IGF‐I levels increased throughout the year and were maximum at 12 months (0.3 SDS ± 1.4) while IGFBP‐3 (1.1 SDS ± 0.9) and IGF‐I/IGFBP‐3 molar ratio peaked at 6 months. In both groups, IGF‐I SDS and IGF‐I/IGFBP‐3 during treatment correlated with the dose of GH expressed as IU/m2/week (r‐values 0.77 to 0.89; P = 0.005) but not as IU/kg/week. Serum leptin levels decreased significantly during GH treatment in the GHD (median before treatment 4.0 μg/l; median after 12 months treatment 2.4 μg/l; P = 0.02) but not the non‐GHD (median before treatment 3.0 μg/l; median after 12 months treatment 2.6 μg/l). In the GHD group, serum leptin before treatment correlated with 12 month change in height SDS (r = 0.70, P = 0.02).CONCLUSIONSThe pattern of IGF‐I, IGFBP‐3 and their molar ratio during the first year of GH treatment differed between the GHD and non‐GHD groups. Calculation of GH dose by surface area may be preferable to calculating by body weight. As a GH dose‐dependent increase in serum IGF‐I and IGF‐I/IGFBP‐3 may be associated with adverse effects, serum IGF‐I and IGFBP‐3 should be monitored routinely during long‐term GH treatment. Serum leptin was the only variable that correlated with first year growth response in GHD.