Search PubMed⌕ Search

Biomedical subjects

S L Chew

Publications and source records attributed to S L Chew.

At least 19 recordsLinked to original sources
PubMed2006

Growth hormone deficiency and replacement in patients with treated Cushing's Disease, prolactinomas and non-functioning pituitary adenomas: effects on body composition, glucose metabolism, lipid status and bone mineral density.

BACKGROUND/AIMS: This study was designed to determine whether previous Cushing's disease (CD) or prolactinoma (PRL) could exert adverse effects additional to those of growth hormone (GH) deficiency as a consequence of variable degrees of prior hypogonadism or hypercatabolism. We report the effects of 5 years GH treatment in 124 GH deficiency adults; 42 patients with non-functioning pituitary adenomas (NFPA), 43 with treated PRL and 39 with treated CD. METHODS: Fasting plasma glucose, HbA(1c), lipoprotein profile, anthropometry and bone mineral density (BMD) were measured at baseline, 6 months and annually up to 5 years. RESULTS: Mean body mass index remained unchanged in the PRL group and tended to increase in the NFPA group. In contrast, body mass index decreased in the CD group. Decreases in waist and waist/hip ratio were seen in all groups at 6 months. Decreases in total cholesterol and low-density lipoprotein cholesterol were seen in all groups and remained sustained at 5 years. Plasma glucose and HbA(1c) increased at 6 months. Subsequently, plasma glucose returned to baseline values at 5 years; in contrast, HbA(1c )remained unchanged at the end of the study. Baseline lumbar spine and hip BMD were lower in the PRL and CD groups than in the NFPA group, decreased over 1 year in all groups and subsequently increased by 2 years in NFPA with a subsequent increase in lumbar spine BMD in PRL and CD groups delayed to 3-5 years. CONCLUSIONS: Baseline characteristics and response to GH replacement are qualitatively similar in NFPA, PRL and CD patients. Because improvements in BMD occur later in PRL and CD patients, an extended trial of GH therapy may be indicated in those patients who were commenced on GH therapy as an additional treatment for reduced BMD.

Adenoma↗
PubMed2006

Benefits of screening in von Hippel-Lindau disease--comparison of morbidity associated with initial tumours in affected parents and children.

Von Hippel-Lindau (VHL) is a rare autosomal dominant syndrome characterised by the association of retinal and CNS haemangioblastomas, phaeochromocytoma and renal cell carcinoma. If a child of an affected parent has inherited a VHL mutation or the parent's mutation cannot be identified, then clinical screening is recommended. We report the clinical features in three parent-offspring pairs where the parents have presented clinically with renal cell carcinoma, phaeochromocytoma, cerebellar haemangioblastoma and retinal haemangioma, and the children have undergone pre-symptomatic screening. During the first screening a 13-year-old boy was diagnosed with bilateral phaeochromocytoma and later developed an endolymphatic sac tumour at 19 years. A right phaeochromocytoma was found in a 12-year-old girl who was screened from the age of 4 years and in a 13-year-old boy screened from 5 years of age. All children were asymptomatic at the time of diagnosis. These families demonstrate that clinical screening of children at risk of VHL can detect tumours before the first symptoms arise with a consequent reduction in morbidity. These observations strongly support the recommendation to undertake screening of the children of VHL patients.

Adolescent↗
PubMed2006

Pharmacokinetics of a new testosterone transdermal delivery system, TDS-testosterone in healthy males.

AIMS: The Transdermal Delivery System (TDS) is a liquid formulation that can be applied to the skin via a metered pump spray to deliver drug to the systemic circulation. The aims of this study were to assess the ability of the TDS preparation to deliver testosterone systemically, and to characterize the pharmacokinetic profiles of the hormone in healthy males. METHODS: An open label, comparative, randomized placebo controlled study involving three treatments and three periods with a minimum of a 1 week washout period was conducted. Twelve healthy males received 50 mg TDS-testosterone, TDS-placebo, and 50 mg of a commercially available topical testosterone preparation (Androgel, 1% topical testosterone gel). RESULTS: The mean AUC(0,12 h) was higher following application of TDS-testosterone (61.8 ng ml-1 h), compared with Androgel (57.7 ng ml-1 h) and TDS-placebo (50.7 ng ml-1 h. The mean Cmax (0,12 h) was similar for TDS-testosterone (6.6 ng ml-1) and Androgel (6.5 ng ml-1) and these values were higher than those for TDS-placebo (5.7 ng ml-1). Analysis of variance showed that the 90% confidence intervals on the relative difference of the ratio for the AUC(0,12 h) and the Cmax (0,12 h) between TDS-testosterone and Androgel, were contained within the bioequivalence limit (80, 125%) (Cmax 89.2, 112.3% and AUC 93.5, 120.5%). Serum testosterone concentrations were lower following TDS-Placebo and were not bioequivalent either to the gel or spray. CONCLUSIONS: The TDS preparation was shown to deliver testosterone systemically to humans and the concentrations of the hormone in the 12 h following TDS administration were bioequivalent to an existing topical delivery gel.

Administration, Cutaneous↗
PubMed2006

Selective parathyroid venous sampling in patients with complicated hyperparathyroidism.

OBJECTIVE: The role of preoperative localisation of abnormal parathyroid glands remains controversial but is particularly relevant to the management of patients with recurrent or persistent hyperparathyroidism and familial syndromes. We report our experience of the use of selective parathyroid venous sampling (PVS) in the localisation of parathyroid disease in such patients. DESIGN: We report a retrospective 10-year experience (n = 27) of the use of PVS in complicated primary hyperparathyroidism and contrast the use of PVS with neck ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) and sestamibi imaging modalities. RESULTS: In 14 out of 25 patients who underwent surgery PVS results were completely concordant with surgical and histological findings and 88% of patients achieved post-operative cure. Out of 13 patients referred after previous failed surgery, 12 underwent further surgery which was curative in 9. In total PVS yielded useful positive (n = 13) and/or negative information (n = 6) in 19 out of 25 patients undergoing surgery. Using histology as the gold standard, 59% of PVS studies were entirely consistent with histology, as compared with 39% of ultrasound scans, 36% of sestamibi scans and 17% of MRI/CT scans. CONCLUSIONS: PVS is a valuable adjunct to MRI/CT and sestamibi scanning in selected patients with complicated hyperparathyroidism when performed in an experienced unit.

Adult↗
PubMed2005

Tumour surveillance imaging in patients with extrapituitary tumours receiving growth hormone replacement.

OBJECTIVE: GH replacement is widely used in the management of patients with adult-onset (AO)-GH deficiency (GHD). In most cases, AO-GHD arises as a result of pituitary/peripituitary tumours and/or their treatment, but the effect of GH replacement on recurrence/regrowth of these tumours is unknown. The aim of this study was to examine the effect of GH replacement in a group of patients with primary tumours of the parasellar region, many of which (e.g. craniopharyngioma, glioma or germ cell tumours) might be anticipated to have a higher recurrence rate than secretory and nonsecretory anterior pituitary tumours. PATIENTS AND DESIGN: We report here our experience of prospective imaging in 50 consecutive patients (21 males; mean age 45.9 years) with nonanterior pituitary parasellar tumours treated with GH. All had severe GHD (peak serum GH 9 mU/l or less on dynamic testing) and were treated with an identical dose-titration regimen to maintain serum IGF-I concentrations between the median and upper end of the age-adjusted normal range. The primary diagnoses were: craniopharyngioma (28), germ cell tumour (8), arachnoid cyst (4), meningioma (4), glioma (4) and mensenchymal tumour (2). External pituitary irradiation had been given to 37 (74%) of patients. Measurements Surveillance imaging (magnetic resonance imaging (MRI) 70%, computed tomography (CT) 16%, both 14%) was performed at baseline (prior to GH), at 6--12 months, and then again yearly or as clinically indicated. Median follow-up was 36 months (range 7--129 months). All images were reviewed by the same radiologist. RESULTS: Four patients had an apparent increase in tumour volume but in only one patient was it considered necessary to abandon GH replacement. In two of the four cases marginal increases in cystic parasellar tumours were not progressive; and in the fourth case apparent recurrence of a suprasellar germ cell tumour was shown to be acellular fibrous tissue only on biopsy. In all other cases either the appearances were unchanged or the amount of tissue was reduced during long-term follow-up on GH. CONCLUSIONS: Overall, GH appears safe with respect to tumour recurrence over this time period in this patient group. Comparison with similar prospective series in patients not receiving GH replacement is desirable.

Adult↗
PubMed2004

Obstructive sleep apnea presenting as pseudopheochromocytoma: a case report.

Sudden arousal from sleep causes a transient surge in sympathetic nervous activity. Repeated arousals, as occur in obstructive sleep apnea (OSA), are well documented to cause a more prolonged sympathetic overactivity and consequent elevations in 24-h urinary catecholamine levels. We describe here a series of five patients, each presenting with a clinical and biochemical picture indistinguishable from that of pheochromocytoma. Thorough investigations have failed to find catecholamine-secreting tumor in any of these subjects, but all have been diagnosed with OSA. Primary treatment of OSA with nasal continuous positive airways pressure has led to normalization of systemic blood pressure and urinary catecholamines. Pseudopheochromocytoma is therefore a rare, but treatable, presentation of obstructive sleep apnea.

Adrenal Gland Neoplasms↗
PubMed2003

Rapid desensitisation of the GH secretagogue (ghrelin) receptor to hexarelin in vitro.

Ghrelin, the recently identified hormone with GH-secreting and appetite-inducing effects, acts on the GH secretagogue receptor (GHS-R). GHS-R belongs to the G protein-coupled 7 transmembrane domain receptors and activates the phospholipase C pathway; it then leads to the release of GH from somatotroph cells via an elevation of intracellular calcium concentration. Both in vivo and in vitro studies demonstrated that the effect of GH secretagogues (GHS) could be desensitised similar to most receptor stimulation systems. We have studied whether acute desensitisation of the GHS-R occurs in response to the GHS hexarelin in vitro in terms of intracellular calcium concentration. Chinese hamster ovary cells were transiently transfected with cDNA encoding the human type 1a GHS-R. The presence of messenger RNA was confirmed with RT-PCR, while no GHS-R was observed in mock-transfected cells. Calcium responses to the peptide GHS analogue hexarelin were measured using the fluorescent indicator fura-2. Cells were stimulated with the peptide GHS, hexarelin, at concentrations between 10(-10) and 10(-7) M. Cells transfected with the GHS-R cDNA demonstrated a significant and specific calcium response to hexarelin that was not observed in mock-transfected cells. Marked desensitisation of the calcium response to hexarelin was observed 2-5 min after the first dose of hexarelin (10(-7) M) was administered. These data show directly for the first time the desensitisation of the GHS receptor signal at the second messenger level. The desensitisation of the receptor may play a major role in the regulation of effect of circulating or locally produced ghrelin both in the GH and in the appetite-regulating system or in other systems where ghrelin has been shown to be active, such as the cardiovascular system or cell proliferation.

Animals↗
PubMed2003

Stereotactic radiosurgery XVI: a treatment for previously irradiated pituitary adenomas.

We report the use of stereotactic radiosurgery delivered through an adapted linear accelerator [stereotactic multiple arc radiation therapy (SMART)] for pituitary adenomas not cured by conventional therapy. All 21 patients had undergone conventional radiotherapy (45-50 Gy); 18 had also undergone prior surgery. This cohort comprised 13 patients with somatotrope adenomas, four with corticotrope adenomas, one with a lactotrope adenoma, and three with nonfunctioning pituitary adenomas (median follow-up: 33 months, range: 3-72 months). SMART has proven effective, safe, and rapidly acting. We observed an accelerated reduction in GH and IGF-I levels in acromegaly, with normalization of GH and IGF-I levels in 58%. Mean GH fell from 21.1 mU/liter to 7.9 mU/liter (7 ng/ml to 2.6 ng/ml, P < 0.01, median 25 months) faster than our predicted fall to 50% at 2 yr with conventional radiotherapy. Mean IGF-I fell from 624 ng/ml to 384 ng/ml (P < 0.001). Tumor growth was controlled in two of three nonfunctioning pituitary adenomas, and three of four corticotrope adenomas. There were no adverse effects from SMART. Notably there have been no visual sequelae or further loss of anterior pituitary function in this heavily pretreated group. Our data indicate that SMART is an effective complementary therapy for pituitary adenomas that have displayed a suboptimal response to conventional therapy including external irradiation.

Acromegaly↗
PubMed2002

Suprasellar germ cell tumours: specific problems and the evolution of optimal management with a combined chemoradiotherapy regimen.

OBJECTIVE: 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.

Adolescent↗
PubMed2002

Pancreatic lesions in von Hippel-Lindau disease.

OBJECTIVE: Von Hippel-Lindau disease is an inherited neoplasia syndrome. The main endocrine manifestations are phaeochromocytoma and paraganglioma. The presence of pancreatic disease has also been variably reported. This study was undertaken to describe the prevalence, nature, natural history and clinical associations of pancreatic lesions in von Hippel-Lindau disease. PATIENTS AND DESIGN: A retrospective analysis of the case notes of 17 consecutive patients. Average duration of follow-up was 5.5 years. Clinical, biochemical, genetic and radiological testing was routinely performed. RESULTS: Eleven (64.7%) patients had pancreatic lesions either on computed tomography or magnetic resonance imaging. Serous microcystic adenomas and multiple cysts were the commonest findings, but solid lesions were also found. The commonest clinical association was diabetes mellitus in patients with extensive serous microcystic adenomas. None of the pancreatic lesions showed evidence of biochemical function. All patients with pancreatic lesions also had renal lesions. Mutations were found at several points in the gene and there was no apparent association between pancreatic lesions and a particular mutation. CONCLUSIONS: Pancreatic lesions are very common in von Hippel-Lindau disease and all patients had coexisting renal lesions. The main clinical correlate was diabetes mellitus, but otherwise the lesions were clinically and biochemically silent.

Adenoma↗
PubMed2002

Growth hormone replacement does not increase serum prostate-specific antigen in hypopituitary men over 50 years.

OBJECTIVE: Epidemiological studies have shown an increased risk for prostate carcinoma in men with serum IGF-I in the upper part of the age-related reference range. Recombinant human GH (rhGH) is widely used in patients with GH deficiency, usually raising the serum IGF-I levels into the normal range: safety surveillance is therefore mandatory, with particular regard to neoplasia. The aim was to examine whether rhGH replacement in hypopituitary adults is associated with changes in serum prostate-specific antigen (PSA) as a surrogate marker of changes in prostatic growth. DESIGN AND METHODS: A prospective longitudinal study was used with a median follow-up of 22 (range 2.5-32) months, in which 41 men aged over 50 years with adult onset hypopituitarism and GH deficiency during rhGH replacement were examined. Serum PSA and IGF-I were measured at baseline and at latest follow-up. RESULTS: Mean serum PSA remained unchanged during rhGH replacement, with a median follow-up of 2 years. No correlation was found between the individual changes in serum IGF-I and changes in serum PSA. CONCLUSIONS: These data are reassuring thus far regarding the safety of GH replacement in relation to the prostate in this patient group.

Aged↗
PubMed2001

Pseudoexon activation as a novel mechanism for disease resulting in atypical growth-hormone insensitivity.

Inherited growth-hormone insensitivity (GHI) is a heterogeneous disorder that is often caused by mutations in the coding exons or flanking intronic sequences of the growth-hormone receptor gene (GHR). Here we describe a novel point mutation, in four children with GHI, that leads to activation of an intronic pseudoexon resulting in inclusion of an additional 108 nt between exons 6 and 7 in the majority of GHR transcripts. This mutation lies within the pseudoexon (A(-1)-->G(-1) at the 5' pseudoexon splice site) and, under in vitro splicing conditions, results in inclusion of the mutant pseudoexon, whereas the wild-type pseudoexon is skipped. The presence of the pseudoexon results in inclusion of an additional 36-amino acid sequence in a region of the receptor known to be involved in homo-dimerization, which is essential for signal transduction.

Female↗
PubMed2001

Paraganglioma genes.

Explore the source record for details and available documents.

Adrenal Gland Neoplasms↗
PubMed2001

Treatment of metastatic carcinoid tumours, phaeochromocytoma, paraganglioma and medullary carcinoma of the thyroid with (131)I-meta-iodobenzylguanidine [(131)I-mIBG].

OBJECTIVE: Meta-iodo-benzyl-guanidine labelled with 131-iodine [(131)I-mIBG] has been used extensively for imaging tumours originating from the neural crest but experience with its therapeutic use is limited, particularly for non-catecholamine secreting tumours. In order to assess the therapeutic response and potential adverse effects of the therapeutic administration of (131)I-mIBG, we have reviewed all patients who had received this form of treatment in our department. DESIGN: Retrospective analysis of the case notes of patients with neuroendocrine tumours who received treatment with (131)I-mIBG and were followed-up according to a defined protocol in a given time frame. PATIENTS: Thirty-seven patients (18 with metastatic carcinoid tumours, 8 metastatic phaeochromocytoma, 7 metastatic paraganglioma and 4 metastatic medullary carcinoma of the thyroid) treated with (131)I-mIBG over a 15-year period were included in this analysis. MEASUREMENTS: The symptomatic, hormonal and tumoural responses before and after (131)I-mIBG therapy over a median follow-up duration of 32 months (range 5-180 months) were recorded. Of the 37 patients (22 males; median age 51 years, range 18-81 years), 15 were treated with (131)I-mIBG alone whereas the other 22 received additional therapy. RESULTS: A total of 116 therapeutic (131)I-mIBG doses were administered [mean cumulative dose 592 mCi (21.9 GBq); range 200-1592 mCi (7.4-58.9 GBq)]. None of the patients showed a complete tumour response. However, 82% of patients treated with (131)I-mIBG alone and 84% who received additional therapy showed stable disease over the period of follow-up. Overall survival during the period of the study was 71%. The overall 5-year survival rate was 85% (95% confidence interval, 72-99%) for all patients and 78% (95% confidence interval, 55-100%) for the carcinoid group alone, according to Kaplan-Meier analysis. Symptomatic control was achieved in all the patients treated with (131)I-mIBG alone, and in 72% of those receiving additional therapy. Hormonal control was noted in 50% and 57% of patients, respectively. (131)I-mIBG therapy was safe and well tolerated. Serious side-effects necessitating the termination of (131)I-mIBG therapy were seen in only 2 of our patients. CONCLUSIONS: (131)I-mIBG therapy produces symptomatic and hormonal improvement and moderate tumour regression/stabilization in patients with metastatic neuroendocrine tumours with minimal adverse effects. It may be a valuable alternative or additional therapeutic option to the currently available conventional treatment modalities.

3-Iodobenzylguanidine↗
PubMed2001

Investigating familial endocrine neoplasia syndromes in children.

Familial endocrine neoplasia syndromes multiple endocrine neoplasia (MEN) type 1, MEN type 2 and von Hippel Lindau (VHL) can now be diagnosed genetically in childhood. Paediatric endocrinologists must therefore be prepared to investigate and manage these children. This paper provides an overview of the major features of these syndromes and suggests protocols for regular screening of children known to be at risk of developing these disorders.

Child, Preschool↗
PubMed2001

Comparison of somatostatin analog and meta-iodobenzylguanidine radionuclides in the diagnosis and localization of advanced neuroendocrine tumors.

A comparison has been made of [(123)I]meta-iodobenzylguanidine ([(123)I]MIBG) and [(111)In]pentetreotide scintigraphy in 54 patients with a variety of neuroendocrine tumors of whom 46 patients had metastatic disease. [(111)In]Pentetreotide scintigraphy was more sensitive in detecting metastatic lesions, as demonstrated on computed tomography and/or magnetic resonance scanning, than [(123)I]MIBG: 67% vs. 50% for carcinoid tumors (n = 24), 91% vs. 9% for pancreatic islet cell tumors (n = 12), 100% vs. 60% for medullary thyroid carcinomas (n = 5), and 75% vs. 100% for pheochromocytomas/paragangliomas (n = 4). In only 2 patients were lesions seen with [(123)I]MIBG scanning that were not apparent with [(111)In]pentetreotide. With the exception of pancreatic islet cell tumors, both radionuclides exhibited a similar sensitivity in detecting hepatic metastases, whereas in three patients the two radionuclides exerted a complementary role as different deposits exhibited uptake to only 1 or the other radionuclide. Hepatic metastases were the most important clinical predictor of a positive scan for both radionuclides. Neither elevated 5-hydroxyindoleacetic acid levels nor any other hormonal marker was predictive of a positive scan. In 8 patients with clinical and/or hormonal evidence of a neuroendocrine tumor but negative conventional radiology, [(111)In]pentetreotide scintigraphy was more sensitive than [(123)I]MIBG (37.5% vs. 12.5%) in detecting lesions. In conclusion, scintigraphy with [(111)In]pentetreotide detects more metastatic lesions than [(123)I]MIBG in patients with carcinoid and pancreatic islet cell tumors and medullary thyroid carcinomas; [(123)I]MIBG scintigraphy may be more sensitive for sympathoadrenomedullary tumors. The radionuclides may exert a complementary role in the detection and treatment of neuroendocrine tumors in occasional patients, as areas of different pattern of uptake were identified within the same patient. These data have implications not only for staging such tumors, but also for identifying patients who might benefit from treatment using either [(131)I]MIBG or radioactive somatostatin analogs.

3-Iodobenzylguanidine↗