The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 1 17a-19a
Copyright © 2008 by The Endocrine Society
Endocrinology & Metabolism News
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Endocrine Discovery
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Treatment with the CETP inhibitor torcetrapib in 15,067 patients with cardiovascular disease or type 2 diabetes without known cardiovascular disease was associated with increased mortality in a randomized trial.
(N Engl J Med [Nov. 22, 2007] 357 (21):2109)
In a meta-analysis of studies examining the relationship between cholesterol and cardiovascular mortality, 61 studies with 900,000 subjects showed that, for every 38 mg/dl decrease in total cholesterol, cardiovascular mortality risk decreased by half (HR 0.44), one-third (HR 0.66), and one-sixth (HR 0.83) in both men and women at ages 40–49, 50–69, and 70–89 years, with no apparent threshold.
(Lancet [Dec. 1, 2007] 370 (9602):1829)
Fenofibrate therapy for type 2 diabetes patients was associated with a decrease in diabetic retinopathy requiring laser therapy (RR 0.69) for macular edema, proliferative retinopathy, or other ophthalmological conditions. This effect was independent of plasma lipid changes in a randomized placebo-controlled trial in 9795 patients aged 50–75 years.
(Lancet [Nov. 17, 2007] 370 (9600):1687)
Obese individuals receiving the CB1 cannabinoid receptor antagonist rimonabant for one year lost 4.7 kg weight, but suffered more depression and anxiety compared to those on placebo group, based on a meta-analysis of four double-blind, randomized controlled trials including 4105 participants.
(Lancet [Nov. 17, 2007] 370 (9600):1706)
In glucocorticoid-treated patients, teriparatide proved more effective than alendronate: increasing lumbar spine bone mineral density more (7.2±0.7% vs. 3.4±0.7%, P<0.001 and reducing incident vertebral fractures (0.6% vs. 6.1%, P=0.004), although not other fractures, in an 18-month randomized, double-blind, controlled trial.
(N Engl J Med [Nov. 15, 2007] 357 (20):2028)
The incidence of differentiated thyroid cancer has increased in Ontario between 1990 and 2001 due to an increase in diagnosis of small (
2 cm) tumors, whereas the incidence of larger tumors has been unchanged—suggesting that the increase reflects more common detection by medical imaging. There was a disproportionate increase among women and those older than 45 years.
(CMAJ [Nov. 20, 2007] 177 (11):1357)
In obese men, PSA testing may be less effective for diagnosing prostate cancer due to hemodilution that lowers measured PSA concentrations, based on a retrospective study of 13,000 male prostate cancer patients who underwent radical prostatectomy.
(JAMA [Nov. 21, 2007] 298 (19):2275)
Traumatic non-spine fractures in older individuals were associated with both low BMD and increased subsequent fracture risk, similar to their higher risk of low-trauma non-spine fractures, in two prospective US cohort studies of women (n=6,022 followed for 9 years) and men (5995 followed for 5 years) 65 years or older.
(JAMA [Nov. 28, 2007] 298 (20):2381)
Physical fitness, as assessed by a maximal exercise test, predicted all-cause mortality in 2603 adults aged 60 years or older (33 versus 8 deaths per 1,000 in the top and bottom incremental fifths of fitness, p<0.001). Furthermore, fitness predicted survival independent of overall or abdominal adiposity, although BMI and waist circumference remained predictive of death in the unfit.
(JAMA [Dec. 5, 2007] 298 (21):2507)
A pro-osteoclastogenic effect of PPAR-
was observed in a mouse model of osteoclast-specific PPAR- deletion, in which the mice developed osteopetrosis with increased bone mass. Furthermore, PPAR- activation by rosiglitazone increased osteoclast differentiation, implying that it might accelerate bone resorption.
(Nat Med [Dec. 2007] 13 (12):1496)
Mice under-expressing apoptosis-inducing factor, an obligatory mitochondrial protein for respiratory chain function, were unexpectedly found to be protected against diet-induced obesity and to have improved glucose tolerance, reduced fat mass, and enhanced insulin sensitivity.
(Cell [Nov. 2, 2007] 131 (3):476)
Small molecule activators of the NAD+-dependent deacetylase SIRT1, which modulates pathways responding to caloric restriction, improved insulin sensitivity, lowered plasma glucose, and increased mitochondrial capacity—suggesting that such agents could represent a new therapeutic approach to treatment of type 2 diabetes.
(Nature [Nov. 29, 2007] 450 (7170):712)
Decreased embryonic implantation, pregnancy rate, and litter size were observed in matings with p53-/- female mice, but not p53 knockout male mice, an effect that was related to downstream p53 regulation of leukemia inhibitory factor (LIF), a cytokine required for successful implantation.
(Nature [Nov. 29, 2007] 450 (7170):721)
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Endocrine Research
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The Science article first reporting visfatin to be a novel adipocyte protein with insulinomimetic properties
(Science [Jan. 21, 2005] 307 (5708):426
) has been retracted by the authors. Subsequent studies by others have shown that visfatin is identical to pre-B cell colony-enhancing factor and failed to confirm its putative insulin-like actions. (For more information, see: http://www.the-scientist.com/news/display/53772/)
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Endocrine Practice
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New diagnostic codes in the 9th Revision of ICD-9 includes designations for glucocorticoid deficiency, mineralocorticoid deficiency, aseptic necrosis of the jaw, family history of multiple endocrine neoplasia, family history of other endocrine and metabolic diseases, and genetic susceptibility to multiple endocrine neoplasia. The following codes have been deleted: corticoadrenal insufficiency, and polyglandular activity in multiple endocrine adenomatosis. (For additional information on ICD-9 diagnosis code changes, please see: http://www.cdc.gov/nchs/icd9.htm)
Physicians spent 112 minutes per week providing unreimbursed care outside of office visits to patients with chronic illness in a cross-sectional study of 16 academic geriatricians’ activities during three randomly selected 1-week periods.
(Ann Intern Med [Nov. 20, 2007] 147 (10):693)
NIH released booklets to explain special considerations for hemoglobin A1c testing in diabetes patients with sickle cell trait or other hemoglobinopathies. These booklets are online at http://www.diabetes.niddk.nih.gov/dm/a-z.asp.
The American Society of Health-System Pharmacists announced a nationwide shortage of injectable levothyroxine in 200 and 500 mcg vials from Bedford Laboratories and APP Pharmaceuticals; Bedford anticipates return of supplies by late January. (For more information, see: http://www.ashp.org/s_ashp/bulletin.asp)
FDA approved use of recombinant TSH (Thyrogen®) for postoperative ablation of remnant thyroid tissue in the management of patients with differentiated thyroid cancer. For more information, see: http://www.medicalnewstoday.com/articles/92042.php
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Endocrine Education & Training
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Starting 2008, Endocrine fellowship training programs and applicants will participate for the first time in the National Resident Matching Program, which provides residents fellowship matching services to more than 30 medical subspecialties.
Endocrinology program officers welcome this move, says Dr. Alan Dalkin, president of the Association of Program Directors in Endocrinology, Diabetes, and Metabolism.
"A selection process that was sometimes stressful and chaotic in the past will become orderly," says Dr. Dalkin. "It will allow both candidates and programs to interview more widely, paralleling the successful match for residencies and most other subspecialty fellowships."
Programs received candidates’ application materials on December 1, 2007 through the Electronic Residency Application System, in anticipation of submitting their respective choices, beginning April 9, 2008. Match results will be revealed at noon EST on June 18, 2008. (For more information, see: http://www.nrmp.org/fellow/match_name/msmp/dates.html)
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Endocrine Policy
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Almost 90 million Americans—more than one out of three people under 65—lacked medical insurance at some point during 2006–2007, according to a Families USA report based on U.S. Census Bureau data. (For more information, go to: http://familiesusa.org/assets/pdfs/wrong-direction.pdf)
Labeling of rosiglitazone now includes a black box warning that the drug "can cause or worsen heart failure" and that it can increase risk of angina and myocardial infarction, especially in patients also taking nitrates or insulin. (For more information, go to: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01743.html)
New legislation requires that NIH-funded clinical trials initiated after September 27, 2007, or ongoing as of December 26, 2007 must have been be registered in full by December 26, 2007 or 21 days after the first patient is enrolled, whichever is later. (For more information, see: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-014.html)
FDA has requested manufacturers to update prescribing information for all desmopressin formulations to include new information about the risk of severe hyponatremia and seizures. Because of these potential complications, desmopressin intranasal formulations are no longer indicated for treating primary nocturnal enuresis and the drug should be interrupted during acute illnesses that could lead to fluid and/or electrolyte imbalance. (For more information, see: http://www.fda.gov/cder/drug/InfoSheets/HCP/desmopressinHCP.htm).
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Endocrinologists
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Yuri Nikiforov, of University of Pittsburgh Medical Center, was awarded the American Thyroid Association’s 2007 Van Meter Award, which honors an investigator younger than age 45 who has made outstanding contributions to thyroid research.
Kenneth White has received the Fuller Albright Award of the American Society for Bone and Mineral Research for his work related to phosphate metabolism and FGF23. The award is given in recognition of meritorious scientific accomplishment in the bone and mineral field.
Michael Whyte received the Frederic C. Bartter Award of the American Society for Bone and Mineral Research, for his work on genetic disorders of bone and mineral metabolism. The Bartter award is given in recognition of outstanding clinical investigation in disorders of bone and mineral metabolism.
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Milestones in Endocrinology
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Fifty years ago, Franz Gross proposed that renin promoted aldosterone secretion via angiotensin II, and that resulting sodium retention exerted negative feedback on renin release.
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In the Journal 25 Years Ago
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Insulin resistance in nonobese patients with polycystic ovarian disease. Chang RJ, Nakamura RM, Judd HL, Kaplan SA.
(J Clin Endocrinol Metab [Aug. 1983] 57:356)
"...our results indicated that in PCO patients, a significant degree of insulin resistance exists, which clearly is not related to obesity or acanthosis nigricans. The positive correlation of serum T and A (sic) to insulin secretion in the study suggests that the insulin resistance in PCO may be, in part, a consequence of hyperandrogenism."
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Footnotes
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Readers are encouraged to suggest items for Endocrinology and Metabolism News by email (sherman@endo-society.org). Submissions will be considered based on their significance and timeliness.
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