bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasonography for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism: comparison with 99mtechnetium sestamibi scintigraphy
Authors: Haber Richard S. , Kim Chun K. , Inabnet William B. 
Published: March 2003

Summaryobjective To determine the utility of ultrasonography for the preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism, and to compare this method with 99mtechnetium sestamibi scintigraphy.design The results of ultrasonography for localization of enlarged parathyroid glands were determined in 120 consecutive patients with primary hyperparathyroidism and compared with findings at surgery (n = 86) and with the results of 99mtechnetium sestamibi scintigraphy (n = 99).patients All patients had biochemically documented primary hyperparathyroidism based on elevated serum calcium and ‘intact’ parathyroid hormone measured by immunoassay. Patients with prior parathyroid surgery or secondary hyperparathyroidism were excluded.measurements High‐resolution ultrasonography was performed by a single observer. 99mTechnetium sestamibi scintigraphy was performed using early and delayed (2‐h) views, and correlated with simultaneous thyroidal 123I uptake in most patients.results Ultrasonography detected putative enlarged parathyroid glands in 92 of 120 unselected patients (77%). It correctly predicted surgical findings in 64 of 86 patients undergoing surgery (74%), including 61 of 72 patients with solitary eutopic parathyroid adenomas (84%), but only two of eight patients with solitary ectopic adenomas, and only one of six patients with multigland parathyroid disease.Sestamibi scintigraphy was positive in 87 of 99 unselected patients (88%), a higher proportion than ultrasonography (P < 0·05), reflecting superior sensitivity for the detection of ectopic parathyroid adenomas. For 74 patients undergoing parathyroid surgery who underwent both imaging tests there was no statistically significant difference between ultrasonography and sestamibi scintigraphy in ability to correctly predict surgical findings (74%vs. 82%, respectively) or in positive predictive value (93%vs. 90%, respectively). However, sestamibi scintigraphy was clearly more sensitive for ectopic parathyroid adenomas, providing correct localization in 8/8 cases. When one test was negative, testing with the second method was usually positive, improving the likelihood of a positive result to 98% when both tests were employed.conclusions Ultrasonography can be a sensitive and accurate method for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism, comparable in overall utility to sestamibi scintigraphy. These results suggest that a strategy of initial testing with one or the other method, followed by the alternate imaging test if the first test is negative, would provide correct parathyroid imaging in most patients without prior parathyroid surgery.
In vitro effect of human recombinant leptin and expression of leptin receptors on growth hormone‐secreting human pituitary adenomas
Authors: Giusti Massimo , Bocca Liliana , Florio Tullio , Corsaro Alessandro , Spaziante Renato , Schettini Gennaro , Minuto Francesco 
Published: March 2003

Summaryobjective and study design Leptin is a circulating hormone secreted by adipose tissue and a few other tissues. It has recently been demonstrated that leptin and leptin receptors are expressed in normal and adenomatous pituitary cells. The aim of this study was to investigate the effect of recombinant human leptin on GH release from adenomatous GH‐secreting cells in culture. Specimens were obtained from 10 patients with acromegaly who had undergone selective transsphenoidal adenomectomy. Cells (2 × 105/well) preincubated for 24 h with leptin (10−10−10−8 m) or control medium were exposed to GHRH for 2 h. The GH released into the medium was measured before and after GHRH incubation. The expression of leptin receptor isoforms was evaluated by reverse‐transcriptase polymerase chain reaction (RT‐PCR) in cells obtained from five adenomas.results After the first incubation, there was a slight dose‐dependent leptin‐induced decrease in GH released into the medium. A significant increase in GH release after GHRH was noted from cells previously exposed to leptin in comparison with cells incubated with medium alone. Expression of leptin receptors was found in two out of five GH‐secreting adenomas evaluated.conclusions Our data confirm that some, but not all, GH‐secreting adenomas express leptin receptors. Leptin seems to exert both a slight inhibitory effect on spontaneous GH secretion and a stimulatory effect on GHRH‐stimulated GH secretion from GH‐secreting adenomatous tissue.
Suprasellar germ cell tumours: specific problems and the evolution of optimal management with a combined chemoradiotherapy regimen
Authors: Janmohamed S. , Grossman A. B. , Metcalfe K. , Lowe D. G. , Wood D. F. , Chew S. L. , Monson J. P. , Besser G. M. , Plowman P. N. 
Published: March 2003

Summaryobjective Suprasellar germ cell tumours are rare, and there are few series of patients outlining the problems in diagnosis and management, and providing clear guidelines for optimal therapy. We have therefore reviewed our own series of 11 such patients who were managed in a joint endocrinology/clinical oncology setting.patients and design A retrospective case review assessment of all patients seen within a given time. Clinical, biochemical and radiological findings were reviewed, the types of therapy administered noted, and the responses to treatment analysed.results In the years 1977–2001, 11 patients with suprasellar (SS) germ cell tumours (GCT) were seen (germinomatous : nongerminomatous = 8 : 3). SSGCT had an approximately equal sex incidence (M : F, 6 : 5), in contrast to pineal tumours, the commonest site of origin of intracranial GCT and which occur predominantly in men. The median age at presentation was 20 years (range 6–49 years) with a median duration of symptoms before diagnosis of 17 months (range 1–35 months). Polyuria was the commonest presenting symptom (10 patients). Diabetes insipidus occurred in all patients, as did partial or complete anterior pituitary failure. Visual failure was present in 55% of cases. Anorexia, weight loss and disturbed thirst sensation were also common. Positron emission tomography scanning was occasionally useful in the evaluation of suprasellar tumours/pituitary stalk lesions deemed too risky to biopsy. A ‘central nervous system‐friendly’ chemoradiotherapy regimen comprising vincristine, etoposide and carboplatin and differential daily dose irradiation, usually administered using a partial transmission block technique, produced a 5‐year survival of 100% with low morbidity. Treatment did not correct previously abnormal endocrine function although it did improve vision in three of six patients.conclusions We therefore emphasize the use of techniques other than biopsy in the diagnosis of these patients, note the problems in the management of their fluid control, and highlight the favourable response to a combined chemotherapy‐radiotherapy protocol.
Serum leptin and CD4+ T lymphocytes in HIV+ children during highly active antiretroviral therapy
Authors: Matarese G. , Castelli‐Gattinara G. , Cancrini C. , Bernardi S. , Romiti M. L. , Savarese C. , Di Giacomo A. , Rossi P. , Racioppi L. 
Published: March 2003

Summaryobjective Because leptin, the adipocyte‐derived hormone, affects thymocyte survival, proliferation of naïve T lymphocytes and the production of proinflammatory cytokines, we aimed to investigate the role of this molecule in immunoreconstitution during highly active antiretroviral therapy (HAART).design Prospective longitudinal cohort study. A series of 20 HIV+ children were studied. The subjects were grouped by their increase in serum leptin levels after HAART.methods All participants were weight‐stable, free of endocrine disorders and opportunistic infections and equally distributed for sex (males, n= 10; females, n= 10). Body mass index (BMI), serum lipids, leptin, CD4+ T cells and HIV‐1 RNA were measured before initiation of HAART and after a 2‐year follow‐up.results Serum leptin concentration positively correlated with CD4+ lymphocyte number before treatment. HAART significantly reduced viraemia and increased serum levels of lipids in all patients, whereas a significant increase in CD4+ cells and serum leptin was observed in the majority of patients. Notably, in children where HAART was not effective in increasing CD4+ lymphocyte counts, serum leptin did not increase.conclusion To our knowledge, these findings reveal for the first time a novel link among CD4+ T lymphocytes, serum leptin and highly active anteretroviral theraphy.
Glucocorticoid receptor gene polymorphisms in ACTH‐secreting pituitary tumours
Authors: Antonini S. R. R. , Latronico A. C. , Elias L. L. K. , Cukiert A. , Machado H. R. , Liberman B. , Mendonca B. B. , Moreira A. C. , Castro M. 
Published: March 2003

Summaryobjective The inhibitory action of glucocorticoids on the hypothalamic‐pituitary axis is disrupted in ACTH‐secreting pituitary tumours. The molecular events leading to the development of these tumours and their relative resistance to glucocorticoids are unknown. We investigated the presence of mutations and polymorphisms of the glucocorticoid receptor (GR) gene in corticotropinoma and their possible relationship with the tissue‐specific resistance to glucocorticoids.design and methods DNA or RNA was extracted from 18 corticotropinomas and the GR gene was amplified by the polymerase chain reaction (PCR) or reverse transcriptase‐PCR followed by automated direct sequencing.results We did not identify any mutation in the coding region and the exon–intron boundary regions of the GR gene. The polymorphism AAT > AGT at codon 363 (N363S) was found in 17% and the polymorphism AAT > AAC at codon 766 (N766N) in 11% of tumours, both in heterozygous state. The polymorphisms at codons 22 and 23, at introns 3 and 4, and at codon 618, previously described in normal population, were not observed.conclusions Our results show that GR gene mutations are rare and unlikely to contribute to the glucocorticoid resistance observed in corticotropinomas. Polymorphisms in the GR gene might confer a selective advantage to tumorigenesis in corticotropinoma. However, there was no relationship between GR gene polymorphism and clinical presentation, tumour size or surgery outcome, suggesting that tumour growth may not be directly related to alterations of the GR gene structure.
Sequence analysis of the PRKAR1A gene in sporadic somatotroph and other pituitary tumours
Authors: Kaltsas Gregory A. , Kola Blerina , Borboli Ninetta , Morris Damian G. , Gueorguiev Maria , Swords Frankie M. , Czirják Sándor , Kirschner Lawrence S. , Stratakis Constantine A. , Korbonits Márta , Grossman Ashley B. 
Published: March 2003

Summaryobjective Carney complex (CNC) is an autosomal dominant multiple neoplasia syndrome featuring cardiac, endocrine, cutaneous and neural tumours, as well as a variety of pigmented lesions of the skin and mucosa. Pituitary GH‐secreting tumours are found in approximately 10% of patients with CNC. One of the genes responsible for CNC, the PRKAR1A gene located on human chromosome 17q22‐24, has recently been cloned. This represents a putative tumour suppressor gene, coding for the type 1α regulatory subunit of protein kinase A (PKA), which is found to be mutated in approximately half of the patients with CNC. However, it is currently unclear as to whether similar mutations occur in sporadic pituitary tumours. We have therefore investigated a series of GH‐secreting and other pituitary tumours for sequence abnormalities in the PRKAR1A gene. The mRNA produced by the PRKAR1A undergoes decay if it codes for a truncated protein; we therefore also determined PRKAR1A mRNA levels in the tumours, and compared them with known mutant PRKAR1A‐carrying lymphocyte samples.methods We extracted RNA from a series of pituitary tumours, reverse transcribed it to cDNA, and directly sequenced the PRKAR1A coding sequence in 17 GH‐secreting, three prolactin‐secreting, three ACTH‐secreting, one FSH‐secreting and 10 nonfunctioning pituitary tumours. Lymphocyte and tumour tissue RNA from two patients with CNC was used as positive controls. Using duplex polymerase chain reaction (PCR) with the PRKAR1A and the ‘housekeeping’ gene GAPDH, we determined the relative expression of the PRKAR1A gene in the unknown as well as in the positive control samples.results and conclusion No mutations were found in any of the exons sequenced. Relative mRNA expression was not decreased in any of the sporadic pituitary tumour samples. The present data thus do not suggest a major role for the PRKAR1A tumour suppressor gene in sporadic GH‐secreting or other pituitary tumours.
The effect of exogenous melatonin on stimulated neurohypophysial hormone release in man
Authors: Forsling Mary L. , Williams A. J. 
Published: March 2003

Summaryobjective Melatonin is known to have a dose‐dependent effect on basal neurohypophysial hormone release in man, low physiological doses being stimulatory and high doses inhibitory. We have performed a study to determine if this is true also for stimulated release.design This was a double‐blind randomized crossover study with subjects being given oral doses of melatonin (0·5 mg or 5·0 mg) or placebo, before infusion of hypertonic saline or exercise.subjects Studies were performed on a total of 24 male subjects aged 19–23 years, who were entrained to a normal light–dark cycle and who refrained from taking heavy exercise, alcohol and smoking for 24 h prior to study.measurements Plasma vasopressin, oxytocin, sodium and osmolality and packed cell volume were measured in control samples and at regular intervals after the administration of melatonin and the challenge tests. Blood pressure and urine flow, sodium potassium and osmolality were determined during hypertonic saline infusion and blood pressure and pulse rate during exercise.results Plasma vasopressin increased during hypertonic saline infusion and exercise, the responses being attenuated by 5·0 mg melatonin and augmented with 0·5 mg melatonin. Although exercise had no effect on oxytocin release, there was a small but statistically significant (P < 0·05) increase in plasma oxytocin after hypertonic saline administration, which was inhibited by 5·0 mg and augmented by 0·5 mg melatonin.conclusions Melatonin modulates the neurohypophysial response to different stimuli, low doses enhancing the response. This effect could contribute to the night‐time increase in circulating concentrations of the hormones.
Early growth, pubertal development, body mass index and final height of patients with congenital adrenal hyperplasia: factors influencing the outcome
Authors: Manoli I. , Kanaka‐Gantenbein Ch. , Voutetakis A. , Maniati‐Christidi M. , Dacou‐Voutetakis C. 
Published: March 2003

Summaryobjective The management of children with congenital adrenal hyperplasia (CAH) remains a challenge, especially with regard to growth potentials. The objective of our analysis was to uncover the factors that influence the growth and final height of patients with CAH.design The linear growth pattern and body mass index (BMI) at different developmental stages (birth to 2 years, 2 years to puberty initiation and puberty initiation to final height) and the final height achieved were analysed retrospectively in 48 patients with 21‐hydroxylase deficiency; 17 with the salt‐wasting (SW) form, 25 with the simple virilizing (SV) and six with the nonclassical (NC) form.results Mean final height (FH) and FH‐SDS were, respectively, 170·8 ± 5·6 m and −0·57 ± 0·8 in males and 156·7 ± 6 cm and −0·61 ± 1 in females with the SW form, 166·1 ± 6·1 cm and −1·05 ± 1 in males and 151·6 ± 5·4 cm and −1·4 ± 1 in females with the SV form and 159·7 ± 6·9 cm and 0·3 ± 1·4 in females with the NC form. In subjects with the SW form, height SDS at 2 years, at puberty initiation and at FH were −0·18 ± 0·9, 0·11 ± 1·28 and −0·6 ± 1·0, respectively. FH achieved was not different from target height (TH) in the SW group, but it was significantly lower than TH in the SV group (P = 0·003). FH in the SW group showed a positive correlation to the height achieved at 2 years of age (r = 0·68, P = 0·019), and height at 2 years was negatively related to the hydrocortisone dose in the birth to 2‐year period (r = −0·79, P = 0·011). FH showed no correlation to hydrocortisone dose at any of the three developmental periods studied. BMI‐SDS were not different in the various forms of CAH and showed no correlation to FH or hydrocortisone dose. Age at menarche was comparable to that in our general population.conclusions Under our conditions of management, the final height of patients with the salt‐wasting form was comparable to the target height and to the most favourable literature data. The patients with the simple virilizing form fare less well, mainly due to delayed diagnosis and consequent advancement of bone age and early puberty. In salt‐wasting patients, height at 2 years is comparable to normals, it is influenced by the hydrocortisone dose and is related to the final height. Some height is lost during puberty. Hence, monitoring treatment over the first 2 years and during puberty is critical for the outcome in these patients.
Effects of slow‐release octreotide on urinary metanephrine excretion and plasma chromogranin A and catecholamine levels in patients with malignant or recurrent phaeochromocytoma
Authors: Lamarre‐Cliche Maxime , Gimenez‐Roqueplo Anne‐Paule , Billaud Eliane , Baudin Eric , Luton Jean‐Pierre , Plouin Pierre‐François 
Published: March 2003

Summaryobjective Somatostatin receptors are present on human phaeochromocytomas. Catecholamine concentrations may decrease following short‐term administration of somatostatin agonists to patients with phaeochromocytomas. We carried out a prospective study on 10 patients with malignant or recurrent phaeochromocytomas to examine the clinical and hormonal effects of three monthly intramuscular injections of 20 mg slow‐release octreotide.design and measurements Patients underwent somatostatin receptor scintigraphy using 111In‐pentetreotide before slow‐release octreotide was administered. The patients’ symptoms, blood pressure, blood glucose concentrations, glycosylated haemoglobin concentra‐tions, plasma insulin and noradrenaline concentrations, and the levels of two putative markers of tumour burden, urinary metanephrine excretion and plasma chromogranin A concentration, were recorded before the first injection and 28 days after the third injection.results Slow‐release octreotide did not significantly alter symptoms, blood pressure, blood glucose concentrations, plasma catecholamine and chromogranin A concentrations or metanephrine excretion. Median glycosylated haemoglobin concentrations increased from 5·3% to 6·0% (P = 0·03). Patients whose tumours took up 111In‐ pentetreotide did not differ from those whose tumours did not after slow‐release octreotide treatment in terms of symptoms, blood pressure, blood glucose, plasma catecholamine and chromogranin A concentrations or metanephrine excretion.conclusion Our data suggest that slow‐release octreotide is of limited value for the long‐term treatment of patients with malignant or recurrent benign phaeochromocytomas.
High prevalence and increasing incidence of Addison's disease in western Norway
Authors: Løvås Kristian , Husebye Eystein S. 
Published: March 2003

Summaryobjective Estimates of the prevalence of Addison's disease in Caucasians have varied from 39 to 117 per million. We have carried out an epidemiological study to obtain a confident point prevalence estimate in the Norwegian population for the end of 1999, and to find out whether the incidence is changing.patients and methods The patients were identified by a search through registers of 10 hospitals and consultant endocrinologists serving a population of 916 000. The completeness of the list was tested by a survey of general practitioners in one district, and by the member list of the local Addison Association in another district.results We identified 128 patients with Addison's disease (59 men and 69 women), yielding a prevalence of 140 per million. Recorded mean incidence in the past decade was 0·62 per 100 000 per year. Fifty‐one patients (40%) had concomitant endocrine diseases. The aetiology was almost exclusively idiopathic or autoimmune.conclusions We found a higher prevalence of Addison's disease in western Norway than has previously been reported anywhere. Our findings support the hypothesis of a rising incidence of autoimmune adrenal insufficiency.
Two Italian kindreds with familial hypocalciuric hypercalcaemia caused by loss‐of‐function mutations in the calcium‐sensing receptor (CaR) gene: functional characterization of a novel CaR missense mutation
Authors: Cetani Filomena , Pardi Elena , Borsari Simona , Tonacchera Massimo , Morabito Eugenia , Pinchera Aldo , Marcocci Claudio 
Published: March 2003

Summaryobjectives Description of two unrelated Italian kindreds with familial hypocalciuric hypercalcaemia (FHH), an autosomal dominant disease mostly caused by heterozygous inactivating mutations of the Ca2+ sensing receptor (CaR).patients and design We studied 11 members of the two families. Genomic DNA was isolated from peripheral blood leucocytes in all family members and in 50 unrelated Italian controls. Total serum and ionized calcium, PTH, creatinine, phosphate, magnesium, and urinary calcium clearance to creatinine clearance ratio were measured. Direct sequencing of the entire coding region of the CaR was performed in the probands. Functional studies were performed in COS‐7 cells transiently expressing the mutated CaR.results In the proband of family A direct sequencing revealed a novel heterozygous Y218C missense mutation in exon 4. The same mutation was identified in the affected but not in the unaffected family members or in any of the 50 unrelated Italian controls. Transient expression of the Y218C CaR in COS‐7 cells revealed a blunted Ca2+‐evoked accumulation of inositol trisphosphates, indicating that the Y218C is a loss‐of‐function mutation. Cotransfection experiments showed that the mutant receptor had no impact on the function of the wild‐type receptor, suggesting that a reduced expression of the normal CaR, rather than a dominant‐negative effect, accounted for the functional impairment. In the proband of family B an already described heterozygous P55L missense mutation in exon 2 of the CaR gene was found. The same mutation was identified in the affected family members.conclusions We described two familial hypocalciuric hypercalcaemia kindreds with loss‐of‐function mutations of the Ca2+ receptor gene and identified a novel heterozygous mutation (Y218C) characterized by a blunted response to Ca2+ stimulation compared to the wild‐type receptor and no interference with the function of the wild‐type Ca2+ receptor.