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V Parameswaran

Publications and source records attributed to V Parameswaran.

At least 19 recordsLinked to original sources
PubMed2007

Development and characterization of two new cell lines from milkfish (Chanos chanos) and grouper (Epinephelus coioides) for virus isolation.

Two new cell lines, SIMH and SIGE, were derived from the heart of milkfish (Chanos chanos), a euryhaline teleost, and from the eye of grouper (Epinephelus coioides), respectively. These cell lines were maintained in Leibovitz's L-15 supplemented with 20% fetal bovine serum (FBS). The SIMH cell line was subcultured more than 50 times over a period of 210 days and SIGE cell line has been subcultured 100 times over a period of 1 1/2 years. The SIMH cell line consists predominantly of fibroblastic-like cells. The SIGE cell line consists predominantly of epithelial cells. Both the cell lines were able to grow at temperatures between 25 and 32 degrees C with an optimum temperature of 28 degrees C. The growth rate of these cells increased as the proportion of FBS increased from 2% to 20% at 28 degrees C with optimum growth at the concentrations of 15% or 20% FBS. Seven marine fish viruses were tested to determine the susceptibility of these cell lines. The SIGE cell line was found to be susceptible to nodavirus, MABV NC-1 and Y6, and the infection was confirmed by cytopathic effect (CPE) and reverse transcriptase-polymerase chain reaction. When these cells were transfected with pEGFP-N1 vector DNA, significant fluorescent signals were observed, suggesting that these cell lines can be a useful tool for transgenic and genetic manipulation studies. Further, these cell lines are characterized by immunocytochemistry using confocal laser scanning microscopy (CFLSM).

Animals↗
PubMed2006

Establishment of embryonic cell line from sea bass (Lates calcarifer) for virus isolation.

A continuous cell line was established from blastula stage embryos of sea bass (Lates calcarifer). The sea bass embryonic cells were maintained in Leibovitz's L-15 supplemented with 15% fetal bovine serum. The embryonic cell line was sub-cultured more than 70 passages over a period of 1.5 years and is designated as Sahul Indian sea bass embryonic (SISE) cell line. The cells were able to grow at temperatures between 25 and 32 degrees C with an optimum temperature of 28 degrees C. The growth rate of sea bass embryonic cells increased as the FBS proportion increased from 2 to 20% at 28 degrees C with optimum growth at the concentration of 15 or 20%. Polymerase chain reaction products were obtained from embryonic cells and blastula of sea bass with primer sets of microsatellite markers of sea bass. Four fish viruses were tested on this cell line to determine its susceptibility to these viruses and this cell line was found to be susceptible to IPNV VR-299 and nodavirus, and the infection was confirmed by cytopathic effect (CPE) and RT-PCR. Further, this cell line was characterized by immunocytochemistry using confocal-laser-scanning microscopy (CFLSM), transfection with pEGFP-N1, proliferate marker (BrdU).

Animals↗
PubMed2003

A randomized controlled trial of phytoestrogen supplementation, growth and bone turnover in adolescent males.

OBJECTIVE: To assess the effect of phytoestrogens on bone turnover and growth in adolescent boys. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Single school in northwest Tasmania. PARTICIPANTS: Adolescent boys (treatment n=69, placebo n=59, mean age 16.8 y). INTERVENTIONS: Six weeks of isoflavone supplementation (Novasoy, 50 mg daily of isoflavone equivalents). Bone turnover markers (bone specific alkaline phosphatase (BAP) and pyridinoline creatinine ratio (PYR)) were measured at baseline and follow-up. RESULTS: Despite marked increases in urinary genistein and daidzein in the treatment arm (both P<0.001), there were no significant differences in BAP, PYR or short-term height or weight change. This applied to both intention-to-treat and per protocol analysis. Neither was there a significant correlation between urinary genistein and daidzein levels and BAP or PYR. CONCLUSIONS: Phytoestrogen supplementation to the level of usual Japanese dietary intake has no measurable effect on bone turnover in adolescent boys. Longer-term studies of bone density may be desirable but it is unlikely that there will be a large effect in either girls or boys given the lower endogenous oestrogen levels in boys.

Adolescent↗
PubMed2002

Recurrent iodine deficiency in Tasmania, Australia: a salutary lesson in sustainable iodine prophylaxis and its monitoring.

Even mild iodine deficiency during early childhood and pregnancy has the potential to impair neurological development. Often considered a problem of developing nations, a number of industrialized countries are at risk of deficiency. Despite past success with intentional and unintentional iodine fortification, recurrence of deficiency is an ever-present risk. Tasmania, an island state of the Commonwealth of Australia, has a history of endemic iodine deficiency, which was successfully eliminated by iodine prophylaxis initiated in 1950. In this report we describe a formal assessment of iodine nutrition in the Tasmanian population, 50 yr after initiation of the prophylaxis program. The requirements and obstacles to achieving sustainable iodine prophylaxis in an otherwise affluent community are considered. A cross-sectional study was undertaken during the yr 2000. Urinary iodine excretion (UIE) and thyroid ultrasonography were assessed in a representative statewide sample of school-age children. Children (n = 225) aged 4 to 17 yr from throughout Tasmania were studied. The sample comprised 99 girls and 126 boys. The median UIE was 84 microg/liter (87 microg/liter for males and 81 microg/liter for females), with UIE 50 microg/liter or less in 20%. Based on age-specific World Health Organization/International Council for the Control of Iodine Deficiency Disorders normative data for thyroid volume, the prevalence of elevated thyroid volume was 5.3% for boys and 3.5% for girls. However, after correcting the World Health Organization/International Council for the Control of Iodine Deficiency Disorders reference data, the prevalence increased to 24.6% for boys and 20.7% for girls. No significant difference in the thyroid volumes was found between males and females in this study. These data confirm the recurrence of mild iodine deficiency in Tasmania. The failure of sustained iodine prophylaxis highlights the universal importance of persistent surveillance, use of sustainable measures, public awareness, and a specific legislative framework for managing ongoing iodine prophylaxis. Our findings also emphasize the importance of accurate reference data for assessment thyroid volume.

Adolescent↗
PubMed2000

Phenotype and phenocopy: the relationship between genotype and clinical phenotype in a single large family with multiple endocrine neoplasia type 1 (MEN 1).

BACKGROUND: The 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 PATIENTS: We 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. RESULTS: A 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. CONCLUSION: Multiple 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.

Adult↗
PubMed1999

Octreotide improves biochemical, radiologic, and symptomatic indices of gastroenteropancreatic neoplasia in patients with multiple endocrine neoplasia type 1 (MEN-1). Implications for an integrated model of MEN-1 tumorigenesis.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant tumor syndrome associated with parathyroid, gastroenteropancreatic (GEP), and pituitary neoplasia. Gastrinoma and GEP malignancy are common life-threatening endocrine complications of MEN-1. An effective management strategy for these disorders remains to be determined. The authors attempted to determine the role of the somatostatin analogue, octreotide, in ameliorating features of hypergastrinemic GEP neoplasia associated with MEN-1. METHODS: Five MEN-1 patients with hypergastrinemia and either symptoms of GEP neoplasia or hepatic metastases received a trial of octreotide, 100 microg subcutaneously, three times daily for 3 months. RESULTS: Treatment with octreotide was associated with a rapid symptomatic and biochemical response. In all patients serum gastrin fell to < 25% of the pretreatment value. The serum glycoprotein-alphasubunit (a marker of enterochromaffin-like [ECL] cell hyperplasia, gastric carcinoidosis, and disseminated enteropancreatic malignancy) was elevated at baseline in three patients. In each case the serum glycoprotein-alphasubunit normalized after treatment with octreotide. Hepatic metastases were present in two patients at baseline. The size of the metastases diminished by up to 15% during the period of octreotide treatment. Four patients reported symptoms prior to treatment: lethargy, easy fatigability, and generalized musculoskeletal discomfort. A marked symptomatic improvement occurred in each case. No patient experienced side effects related to octreotide therapy and all elected to remain on treatment after completion of the trial. CONCLUSIONS: Octreotide is a safe and effective adjunct to surgical strategies for the management of GEP neoplasia in hypergastrinemic MEN-1 patients.

Aged↗
PubMed1999

Osteoporosis in multiple endocrine neoplasia type 1: severity, clinical significance, relationship to primary hyperparathyroidism, and response to parathyroidectomy.

BACKGROUND: Sporadic primary hyperparathyroidism (PHPT) occurs most frequently in postmenopausal women. Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal-dominant disease in which mild to moderate PHPT develops in most gene carriers by 20 years of age. Primary hyperparathyroidism associated with MEN 1 is typically recurrent, despite initially successful subtotal parathyroidectomy. Osteoporosis is considered a complication of sporadic PHPT and an indication for parathyroidectomy. In the setting of MEN 1, however, the relationship of bone mass to PHPT, fracture risk, and parathyroidectomy is unknown. HYPOTHESIS: Parathyroidectomy improves bone mineral density for patients with primary hyperparathyroidism in the setting of MEN 1. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Twenty-nine women with MEN 1 belonging to a single family with a history of MEN 1. INTERVENTIONS: Parathyroidectomy. MAIN OUTCOME MEASURES: Bone mineral density (BMD) and history of skeletal fracture. RESULTS: Osteopenia and osteoporosis were diagnosed in 41% and 45% of patients, respectively. Forty-four percent of patients with uncontrolled PHPT had severe osteopenia (T score, <-2.0) by 35 years of age. Reduction in BMD was greatest at the femoral neck. Reduced BMD was associated with an increased likelihood of skeletal fracture (P = .05). Patients with uncontrolled PHPT had lower femoral neck and lumbar spine BMDs than those in whom PHPT was controlled by parathyroidectomy (P = .005 and .02, respectively). Successful parathyroidectomy improved femoral neck and lumbar spine BMDs by a mean +/- SEM of 5.2% +/- 2.5% and 3.2% +/- 2.9%, respectively. CONCLUSIONS: Osteoporosis is a frequent and early complication of PHPT in MEN 1. Despite difficulty in achieving a cure of PHPT in MEN 1, parathyroidectomy has an important role in the optimization of BMD for patients with MEN 1.

Adult↗
PubMed1999

Vitamin D levels in prepubertal children in Southern Tasmania: prevalence and determinants.

OBJECTIVE: To describe the prevalence and determinants of 25-hydroxy D3(25(OH)D) in children. DESIGN: Cross-sectional study. SETTING: Southern Tasmania between June and November 1997. SUBJECTS: Two hundred and one 8-y old male and female children taking part in a cohort study whose principal endpoints were blood pressure and high-density lipoprotein (HDL) cholesterol. RESULTS: The mean 25(OH)D level was 79 nmol/l (s.d. 29.5, median 73, range 12-222). Boys had higher levels than girls (82.1 vs 72.8 nmol/l, P=0.02). 25(OH)D was associated with sunlight exposure in winter school holidays (r=0.20, P=0.005) and winter weekends (r=0.16, P=0.02), the month after school holidays (87.5 vs 69.5 nmol, P<0.0001) and body mass index (r=-0.23, P=0.001). Dietary intake of vitamin D was low (mean 40 IU/day, range 5.2-384) and was not associated with 25(OH)D levels (r=0.01, P=0.91). Variation in skin melanin density was weakly associated with 25(OH)D (r=0.09, P=0.19). CONCLUSIONS: Sunlight is the major determinant of vitamin D stores in our population. Neither variation in skin type within Caucasians nor diet modified this association to any significant extent. Extrapolation of these findings to sunlight bone mass associations in a very similar population suggests that a minimum level of around 50 nmol/l in the population is required for optimal bone development in prepubertal children but this needs to be confirmed with further controlled trials of vitamin D supplementation and bone mass. SPONSORSHIP: Arthritis Foundation of Australia, Roche Pharmaceuticals.

Body Mass Index↗
PubMed1998

Enteropancreatic malignancy associated with multiple endocrine neoplasia type 1: risk factors and pathogenesis.

BACKGROUND: Enteropancreatic malignancy is an important cause of morbidity and mortality associated with multiple endocrine neoplasia type 1 (MEN 1). However, the risk factors and mechanisms of the tumorigenesis of this malignancy are poorly understood. METHODS: The authors conducted a retrospective study of factors associated with the development of malignant enteropancreatic tumor in 69 patients with MEN 1 belonging to a single family. RESULTS: Metastatic enteropancreatic tumor and gastrinoma were identified in 20% and 36% of patients, respectively. Compared with MEN 1 patients who did not have an immediate family history of enteropancreatic malignancy, MEN 1 patients with a first-degree relative affected by enteropancreatic malignancy had an increased risk of developing disseminated tumor (odds ratio, 3.7; P < 0.05). In addition, hypergastrinemia and advanced age were both associated with a significant increase in the risk of enteropancreatic malignancy. Elevated serum glycoprotein alpha subunit levels were associated with enterochromaffin-like cell hyperplasia, gastric carcinoid formation, and disseminated enteropancreatic tumor in hypergastrinemic patients (P < 0.05). CONCLUSIONS: Disease modifier factors act in concert with the MEN 1 gene to modulate the development of enteropancreatic neoplasia. It is possible to identify MEN 1 patients at high risk for developing aggressive enteropancreatic tumors. Heritable disease modifier factor(s) affecting enteropancreatic malignancy appear to reside at loci distinct from that of the MEN 1 gene.

Adenoma↗
PubMed1998

The outcome of subtotal parathyroidectomy for the treatment of hyperparathyroidism in multiple endocrine neoplasia type 1.

BACKGROUND: The efficacy of subtotal parathyroidectomy for the treatment of hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) is unclear. The long-term outcome and optimal timing of operation remain controversial. OBJECTIVE: To determine the long-term outcome of parathyroidectomy for primary hyperparathyroidism in the presence of MEN 1. DESIGN: Case series and retrospective analysis. SETTING: Tertiary referral center. PATIENTS: Patients with MEN 1 from 2 families. INTERVENTIONS: Subtotal parathyroidectomy, ie, resection of 3 1/2 parathyroid glands from each patient. MAIN OUTCOME MEASURES: Recurrence of hyperparathyroidism. RESULTS: Thirty-seven patients underwent subtotal parathyroidectomy. Overall, persistent postoperative hypoparathyroidism developed in 24%, normocalcemia was maintained in 46%, and hyperparathyroidism recurred in 30%. However, after adjustment for the duration of follow-up (by using the Kaplan-Meier method), the cumulative recurrence rates for hyperparathyroidism were 15% at 2 years, 23% at 4 years, 55% at 8 years, and 67% after 8 years. Early recurrence of hyperparathyroidism (within 5 years of operation) was less likely to develop in patients in whom ionized calcium levels of 1.00 mmol/L (4.00 mg/dL) or less were achieved during the perioperative period than in patients in whom this degree of hypocalcemia failed to develop (P=.01). CONCLUSIONS: While relatively long periods of disease remission are possible after subtotal parathyroidectomy, our results indicate that recurrent hyperparathyroidism eventually develops in most patients with MEN 1.

Adult↗
PubMed1997

A population-based study of the relationship between salt intake, bone resorption and bone mass.

OBJECTIVE: To explore the relationship between urinary sodium (the best measure of salt intake), urinary calcium, urinary deoxypyridinoline (DPYR) and bone mass. DESIGN: Cross-sectional study. SETTING: Population based sample of healthy Hobart residents. SUBJECTS: One hundred and fifty-four (M = 34, F = 120) subjects invited to take part from a systematic sample of the electoral roll and a single newspaper advertisement. RESULTS: In both sexes, urinary sodium correlated moderately with urinary DPYR (r = 0.32, P < 0.0001) and urinary calcium (r = 0.37, P < 0.0001). In multivariate analysis, the combination of urinary sodium, total body bone area, age and sex explained 22% of the variation in log-transformed DPYR (P < 0.00001). In univariate analysis, both urinary sodium and urinary DPYR were strongly associated with bone mineral content and bone mineral density at all sites but this association disappeared after adjustment for confounders particularly body weight. CONCLUSIONS: This study has shown that salt intake is associated with markers of bone resorption in a population-based sample of males and females and appears likely to be a risk factor for osteoporosis despite the lack of a demonstrable association between bone mass and a single measure of urinary sodium excretion. Further studies are needed to define the effect of salt intake on bone mass and fractures more clearly. These studies will need to be either longitudinal or interventional in design with repeated measures of urinary sodium so that habitual sodium intake can be accurately assessed and regression dilution bias can be minimised.

Adult↗
PubMed1996

Adrenal lesions in a large kindred with multiple endocrine neoplasia type 1.

OBJECTIVE: To review the prevalence and natural history of adrenal lesions occurring in patients from a single kindred with multiple endocrine neoplasia type 1 (MEN-1). DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Medical records of 33 patients from the Tasman 1 MEN-1 kindred who had undergone abdominal computed tomographic (CT) scanning were reviewed. In 30 patients, the results of abdominal ultrasonographic examinations were available for correlation with CT scan. Computed tomographic and ultrasound scans of 18 patients were reviewed by a radiologist blinded to the patients' clinical details. Three patients underwent adrenalectomy, and the histopathologic material was reviewed. MAIN OUTCOME MEASURES: Computed tomographic and ultrasound scans. RESULTS: Adrenal lesions were detected in 12 patients (36%) by CT scan examination. Ultrasound imaged 58% of these lesions. Pancreatic lesions were present in all cases of adrenal disease. Follow-up was available for 8 patients with adrenal disease. Over 5.5 years, 6 patients (75%) had stable disease, 1 patient had an adrenal lesion that enlarged by 5 mm, and 1 patient had a lesion that enlarged by 50 mm. Adrenal histopathologic material was available in 3 patients. Macronodular cortical hyperplasia was present in 2 patients and a cortical adenoma present in 1 patient. Another kindred had bilateral macronodular cortical hyperplasia at autopsy. CONCLUSIONS: Adrenal lesions are common in MEN-1 and occur in association with pancreatic disease. Abdominal CT scan is more sensitive than ultrasonographic examination in detecting adrenal disease. Primary hypersecretory syndromes of the adrenal glands appear to be rare, and the majority of lesions follow an indolent clinical course.

Adrenal Gland Neoplasms↗
PubMed1996

Sporadic primary hyperparathyroidism in the setting of multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia involving the parathyroid glands, the endocrine pancreas, the duodenum, and the anterior pituitary. The most commonly involved gland is the parathyroid gland, which has been found to be abnormal in 90% to 95% of all patients with MEN 1. The disease process is invariably multiglandular and histologically described as either hyperplasia or multiple adenoma, although the histological distinction between the 2 entities remains difficult and controversial. The prevalence of MEN 1 is approximately 0.002 in 100, whereas the prevalence of sporadic primary hyperparathyroidism due to a solitary adenoma is estimated to be as high as 1 in 100.(2.3) We report herein the first case of sporadic primary hyperparathyroidism in the setting of MEN 1 based on clinical, biochemical, pathological, and genetic studies.

Adenoma, Oxyphilic↗
PubMed1996

Somatotrophinomas in multiple endocrine neoplasia type 1: a review of clinical phenotype and insulin-like growth factor-1 levels in a large multiple endocrine neoplasia type 1 kindred.

PURPOSE: Within the spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN-1), widely disparate prevalence rates for somatotrophinomas have been described. Studies that combine multiple, small MEN-1 kindreds report pituitary disease in 60% to 65% of patients, somatotrophinomas accounting for 27% to 37% of total pituitary lesions. However, reports based on large MEN-1 family screening programs have produced lower prevalence rates for pituitary adenomas (9% to 40%), of which somatotrophinomas comprise up to 14%. We sought to determine the prevalence of both biochemical and clinically overt growth hormone (GH) hypersecretion in the largest reported MEN-1 genealogy, the Tasman 1 kindred. PATIENTS AND METHODS: The Tasman 1 MEN-1 kindred contains 165 members with established MEN-1. We reviewed the records of 124 MEN-1 patients for evidence of acromegaly or gigantism. To determine if clinical criteria underestimate the occurrence of biochemical GH hypersecretion, a subset of 33 patients was assessed for elevated levels of serum insulin-like growth factor-1 (IGF-1). RESULTS: No cases of acromegaly or gigantism were detected in the 124 patients reviewed. Of the 33 patients screened with IGF-1, 13 had previously diagnosed pituitary lesions--11 prolactinomas and 2 nonsecretory lesions. The IGF-1 levels were normal in all patients studied. There were no significant differences in mean IGF-1 values between patients with and without pituitary lesions. CONCLUSIONS: This report represents the largest study of growth hormone secretion patterns thus far described in MEN-1. The apparent absence of somatotrophinomas in a kindred of this size is unexpected. These results support the existence of kindred-specific MEN-1 phenotypes. We conclude that the pathogenesis of GH-secreting adenomas in MEN-1 is influenced by secondary factors acting in synergy with the well-documented primary MEN-1 gene defect on chromosome 11q13.

Adenoma↗
PubMed1996

Prolactinomas in a large kindred with multiple endocrine neoplasia type 1: clinical features and inheritance pattern.

Multiple endocrine neoplasia type 1 (MEN 1) is associated with neoplasia and hyperfunction of the parathyroid and pituitary glands, pancreatic islet cells, and neuroendocrine cells of the gut. The inheritance pattern is autosomal dominant, and the underlying genetic defect is situated at chromosome 11q13. The MEN 1 gene behaves as a defective copy of a normally constitutive tumor suppressor gene. Development of the MEN 1 phenotype, however, is a multistep and multifactorial process. The Tasman 1 genealogy is the largest MEN 1 pedigree detected to date. Thus far, 90 related members with MEN 1 have been screened for evidence of prolactinoma. Prolactinomas were found in 18 patients (20%). Prolactinomas were not evenly distributed in the genealogy; in 2 branches of the overall genealogy prolactinomas were present in 50% or more of MEN 1-affected members. The familial distribution of prolactinomas in these branches was consistent with an autosomal dominant mode of inheritance. In the remainder of the pedigree, prolactinomas were uncommon and did not display this inheritance pattern. This pedigree represents one of the largest published MEN 1 genealogies in which the risk of developing prolactinoma follows an autosomal dominant pattern of transmission. It is the first to demonstrate an inheritance pattern for prolactinomas acting in addition to, yet distinct from, the inheritance of the underlying MEN 1 gene defect. These findings are consistent with the existence of an undefined second genetic defect involved in the pathogenesis of prolactinoma in MEN 1.

Adult↗
PubMed1996

Spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN 1): clinical, biochemical, and radiological features of pituitary disease in a large MEN 1 kindred.

Prolactinomas and somatotropinomas are reported to be the pituitary lesions most frequently associated with multiple endocrine neoplasia type 1 (MEN 1). However, few reports have documented the full spectrum of pituitary disease in this condition. We report herein the clinical, biochemical (PRL, alpha-subunit, insulin-like growth factor-I, cortisol, and thyroid function), and radiological (magnetic resonance imaging and computerized tomography scan) characteristics of pituitary disease occurring in a single MEN 1 pedigree containing 165 MEN 1-affected members. Pituitary lesions were detected in 30 (18%) of 165 patients overall. In the subgroup of MEN 1 patients (n = 131) living after recognition of MEN 1 in the kindred, pituitary lesions were detected in 25 (19%). In 76% of patients with pituitary lesions, the diagnosis was made by prospective screening; the remainder sought medical attention for symptomatic pituitary disease. Prolactinomas accounted for 76%, and nonfunctioning adenomas accounted for the remaining 24%. alpha-Subunit elevation was observed in 29% of 41 patients tested, and an aggressive alpha-subunit secreting macroadenoma developed in 1 subject with a previously documented prolactinoma. Progression of pituitary disease occurred in 47% of patients with prolactinoma. There were no cases of Cushing's disease, thyrotropinoma, or somatotropinoma. We conclude that 1) in addition to prolactinomas, nonfunctioning pituitary tumors are common in MEN 1; 2) alpha-subunit hypersecretion is frequent in MEN 1; 3) comprehensive screening may identify many clinically significant but asymptomatic pituitary lesions; and 4) prolactinomas occurring in MEN 1 may behave more aggressively than sporadic prolactinomas.

Adenoma↗
PubMed1994

Multiple endocrine neoplasia type 1 (MEN1) in two Asian families.

Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disease characterized by neoplasia of the parathyroid glands, anterior pituitary and endocrine pancreas, is rarely reported in Asian populations. The MEN1 gene, mapped to chromosome 11q13 but yet to be cloned, has been found to be homogeneous in Caucasian populations through linkage analysis. Here, two previously unreported Asian kindreds with MEN1 are described; linkage analysis using microsatellite polymorphic markers in the MEN1 region was carried out. The first kindred, of Mongolian-Chinese origin, is a multigeneration family with over 150 living members, eight of whom are affected to date. The second kindred is of Chinese origin consisting of four affected members. Linkage to chromosome 11q13 was confirmed in both kindreds, supporting evidence for genetic homogeneity. A recombination in the larger kindred localizes the gene distal to marker D11S956, consistent with its placement from previous studies. We also show that it is feasible to use these markers for predictive testing, as four gene carriers were detected in 13 family members with unknown disease status in the first kindred.

Adult↗