CiteULike: omalbams Jensen

A Prospective Study of Gastric Carcinoids and Enterochromaffin-Like Cell Changes in Multiple Endocrine Neoplasia Type 1 and Zollinger-Ellison Syndrome: Identification of Risk Factors

Marc Berna — 2008-05-11T23:45:51-00:00

J Clin Endocrinol Metab, Vol. 93, No. 5. (1 May 2008), pp. 1582-1591.

Context: Multiple endocrine neoplasia type 1 (MEN1) patients frequently develop Zollinger-Ellison syndrome (ZES). These patients can develop proliferative changes of gastric enterochromaffin-like (ECL) cells and gastric carcinoids (ECL-cell tumors). ECL-cell changes have been extensively studied in sporadic ZES patients and can be precursor lesions of gastric carcinoids, but little is known about factors influencing their severity or development of carcinoids in MEN1/ZES patients. Objectives: Our objective was to prospectively analyze ECL-cell changes and gastric carcinoids (ECL-cell tumors) in a large series of MEN1/ZES patients to detect risk factors and deduct clinical guidelines. Setting and Patients: Fifty-seven consecutive MEN1/ZES patients participated in this prospective study at two tertiary-care research centers. Interventions and Outcome Measures: Assessment of MEN1, gastric hypersecretion, and gastroscopy with multiple biopsies was done according to a fixed protocol and tumor status. ECL-cell changes and alpha-human chorionic gonadotropin staining were assessed in each biopsy and correlated with clinical, laboratory, and MEN1 features. Results: ECL-cell proliferative changes were universally present, advanced changes in 53% and carcinoids in 23%. Gastric nodules are common and are frequently associated with carcinoids. Patients with high fasting serum gastrin levels, long disease duration, or a strong alpha-human chorionic gonadotropin staining in a biopsy are at higher risk for an advanced ECL-cell lesion and/or gastric carcinoid. Conclusions: Gastric carcinoids and/or advanced ECL-cell changes are frequent in MEN1/ZES patients, and therefore, regular surveillance gastroscopy with multiple routine biopsies and biopsies of all mucosal lesions are essential. Clinical/laboratory data and biopsy results can be used to identify a subgroup of MEN1/ZES patients with a significantly increased risk for developing gastric carcinoids, allowing development of better surveillance strategies. 10.1210/jc.2007-2279

DHEA in elderly women and DHEA or testosterone in elderly men.

KS Nair — 2007-10-21T23:39:35-00:00

N Engl J Med, Vol. 355, No. 16. (19 October 2006), pp. 1647-1659.

BACKGROUND: Dehydroepiandrosterone (DHEA) and testosterone are widely promoted as antiaging supplements, but the long-term benefits, as compared with potential harm, are unknown. METHODS: We performed a 2-year, placebo-controlled, randomized, double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA. Among the men, 29 received DHEA, 27 received testosterone, and 31 received placebo. Among the women, 27 received DHEA and 30 received placebo. Outcome measures included physical performance, body composition, bone mineral density (BMD), glucose tolerance, and quality of life. RESULTS: As compared with the change from baseline to 24 months in the placebo group, subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 microg per milliliter (9.2 micromol per liter) in men and by 3.8 microg per milliliter (10.3 micromol per liter) in women. Among men who received testosterone, the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter (1.1 nmol per liter), as compared with the change in the placebo group. A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements. Neither hormone altered the peak volume of oxygen consumed per minute, muscle strength, or insulin sensitivity. Men who received testosterone had a slight increase in fat-free mass, and men in both treatment groups had an increase in BMD at the femoral neck. Women who received DHEA had an increase in BMD at the ultradistal radius. Neither treatment improved the quality of life or had major adverse effects. CONCLUSIONS: Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. (ClinicalTrials.gov number, NCT00254371 [ClinicalTrials.gov].).

Effects of Two Years of Testosterone Replacement on Insulin Secretion, Insulin Action, Glucose Effectiveness, Hepatic Insulin Clearance and Postprandial Glucose Turnover in Elderly Men.

Rita Basu — 2007-05-24T17:00:08-00:00

Diabetes Care (11 May 2007)

Objective: To determine if, and if so the mechanism by which, testosterone replacement improves carbohydrate tolerance. Research Design and Methods: Fifty-five elderly men with relative testosterone deficiency ingested a labeled mixed meal and underwent a frequently sampled labeled IVGTT before and after treatment with either placebo or testosterone patch (5 mg/day) for two years. Results: Despite restoring bioavailable testosterone to values observed in young men, the change (24 month minus baseline values) in fasting and postprandial glucose, insulin, C-peptide concentrations, meal appearance, glucose disposal and endogenous glucose production were virtually identical to those observed after two years of placebo. The change over time in insulin and C-peptide concentrations post intravenous glucose injection also did not differ. Furthermore, the change over time in insulin action and glucose effectiveness (measured with the unlabeled and labeled "oral" and "intravenous" minimal models), as well as insulin secretion and hepatic insulin clearance (measured with the C-peptide model) did not differ in the testosterone and placebo groups. Conclusions: We conclude that two years of treatment of elderly men with testosterone does not improve carbohydrate tolerance nor does it alter insulin secretion, insulin action, glucose effectiveness, hepatic insulin clearance or the pattern of postprandial glucose metabolism. Thus testosterone deficiency is unlikely to be the cause of the age associated deterioration in glucose tolerance commonly observed in elderly men.