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The Endocrine Society |
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Endocrine Discovery |
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 Top Endocrine Discovery Endocrine PolicyNew Guidelines Established for...Endocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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Thyroid hormone replacement therapy was not shown to have a favorable effect on cardiovascular mortality and morbidity, symptoms, and quality of life in adults with subclinical hypothyroidism in a review of 12 randomized controlled trials comparing thyroid hormone replacement therapy with placebo. (Cochran Database Syst Rev [2007]3:CD003419)
The annual incidence of diabetes in the U.S. increased by 23% between 1994–1995 and 2003–2004, and its prevalence increased by 62% in a study examining trends in diabetes incidence in persons aged 65 years or older in the Medicare population. (Arch Intern Med [January 28, 2008] 168 (2):192)
Cardiovascular events were more prevalent in patients with primary aldosteronism than in a matched cohort with essential hypertension (35% versus 11%, P <.001), but there was no difference in events over a mean 7.4 years of treatment with either spironolactone or surgery. (Arch Intern Med [January 14, 2008] 168 (1):80)
Ergocalcferol reduced the risk of subsequent falls in the winter and spring, but not in the summer or autumn in a 1 year prospective randomized trial of ergocalciferol 1000 U/day or placebo in elderly Australian women with a history of falling. (Arch Intern Med [January 14, 2008] 168 (1):103)
In men 60 years and older, low serum testosterone was independently associated with risk of low trauma fracture, especially of the hip in a prospective cohort study. (Arch Intern Med [January 14, 2008] 168 (1):47)
In men aged 60–80 with low serum testosterone, testosterone therapy increased lean body mass and decreased fat mass, but did not affect functional mobility, muscle strength, cognitive function, bone mineral density, quality of life, and or the prevalence of the metabolic syndrome in a 1 year prospective randomized trial. (JAMA [January 2, 2008] 299 (1):39)
In patients with schizophrenia, combined metformin plus lifestyle change was most effective to induce weight loss in a randomized trial comparing it with lifestyle intervention or metformin alone to treat antipsychotic medication-induced weight gain. (JAMA [January 9/16, 2008] 299 (2):185)
Hydrocortisone did not improve survival or reversal of shock in a randomized placebo controlled trial of hydrocortisone therapy in patients with septic shock and a decreased response to cosyntropin. (N Engl J Med [January 10, 2008] 358 (2):111)
Increasing selenium intake to augment T4-to-T3 conversion in an elderly population was found ineffective in elevating the serum T3 level in a double-blind, placebo-controlled trial. (Am J Clin Nutr [February 2008] 87 (2):370)
Calcium supplementation in healthy postmenopausal women was associated with trends toward more cardiovascular events. (BMJ [February 2, 2008] 336 (7638):262)
The proapoptotic BCL-2 family member BAD plays a physiologic role in glucose-stimulated pancreatic insulin secretion, an action that depends on the phosphorylation of its BH3 sequence, restoring mitochondrial respiration and correcting the insulin secretory response in islets that are Bad-deficient. (Nat Med [February 2008] 14 (2):144)
Dok1, a known multisite adapter molecule involved in insulin signaling also regulates adiposity, with increased Dok1 expression in the white adipose tissue of mice fed a high-fat diet, while Dok1-deficiency adipocytes hypertrophied less in response to high fat intake. Dok1-deficient mice were also leaner with better glucose tolerance and insulin sensitivity than wild-type mice. In additional experiments, the Dok1 effect was related to its interference with ERK’s inhibitory effect on PPAR-gamma. (Nat Med [February 2008] 14 (2):188)
Stomach Banding More Beneficial than Drugs in Curing Diabetes
The first randomized trial comparing surgically induced loss of weight with conventional drug and weight loss therapy for management of type 2 diabetes in obese patients found that laparoscopic adjustable gastric banding led to much better control of glucose levels and higher rates of diabetes remission, as reported by Australian researchers in the January 23 issue of JAMA.
"... We can do minor things to the gut and have this incredible effect on diabetes,"
John Dixon, Ph.D., on his finding that stomach banding surgery staves off type 2 diabetes.
John B. Dixon, M.D., of the Monash University in Melbourne, and his colleagues enrolled 60 obese patients (BMI 30–40) with recently diagnosed type 2 diabetes to either undergo surgery or be treated with a combined diet and exercise program. Five times as many patients who underwent stomach banding had remission of their diabetes compared to those on conventional therapy. The surgery group also lost an average of 20% of their body weight, while the other group lost only 1%. Among those who lost 10% of their body weight in both groups, 87% were able to stop taking all diabetes medications within a year.
"It’s a very exciting area to think that we can do minor things to the gut and have this incredible effect on diabetes," said Dixon. While the results are promising, other researchers are still waiting to see what will be the long-term effects of these surgeries. "It’s encouraging data, but we’d like to know what the 5-,10-, and 15- year follow-up will be," said endocrinologist Marc-Andre Cornier, M.D., at the University of Colorado Denver.
Each year 2.9 million people die from diabetes and its complications, and the World Health Organization projects that these deaths will increase by more than 50% in the next 10 years without urgent action. Over 250,000 lap band surgeries have been performed worldwide, yet researchers estimate that only about 1% of those who meet eligibility criteria for the surgery receive it. (JAMA [January 23, 2008] 299 (3): 316)
Reported Deaths Partially Halts Major Diabetes Study
The recent abandonment of a tight glycemic control arm in the major NIH-funded ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial was based on an unexpected paradox in the relationship between blood glucose control and cardiovascular events in patients with type 2 diabetes. However, many leading diabetes researchers expressed the view that it was too early to be sure what was responsible for the unexpected finding.
On February 1, 2008, the National Heart, Lung, and Blood Institute announced it will stop the intensive glycemic control arm of the ACCORD study 18 months early due to a higher death rate in patients in whom the therapeutic goal was to control their glucose levels to achieve a hemoglobin A1C of around 6%.
For decades, there has been this general belief among diabetes researchers and clinicians that intense glucose management can reduce heart disease events, for which diabetes patients are at increased risk. The trial had enrolled more than 10,000 patients between the ages of 40 and 82 with type 2 diabetes, with cardiovascular disease or one or two risk factors for heart disease. Those in the blood glucose level lowering arms received the intensive treatment targeting blood sugar to a hemoglobin A1C level either below 6% or, standard treatment, 7.0 to 7.9%. Early results revealed that 257 of those in the intensive treatment group died compared with 203 with standard treatment—a difference of 3 per 1,000 participants each year. Patients in the intensive treatment group will now receive the standard treatment, as researchers explore why lowering blood glucose intensively would lead to increased mortality.
"I don’t think anybody was anticipating this outcome," said Dr. Steven Kahn, M.D., associate director of the Diabetes Endocrinology Research Center at the University of Washington in Seattle. "In fact, if anything, the idea was that it was going to go in the opposite direction."
Other diabetes researchers suggest that caution should be exercised in interpreting the preliminary data report. "We shouldn’t rush to judgment. We need to review the findings once they appear as a published manuscript," said Dr. Bernard Zinman, M.D., director of the Leadership Sinai Centre for Diabetes in Toronto. "The clinical practice recommendation of an A1c less than 7% or lower, if it can be achieved safely, remains entirely appropriate."
Not all of the earlier results from the study were discouraging. ACCORD researchers point out that the causes of death did not appear to be related to hypoglycemia or any of the medications used to treat diabetes, including rosiglitazone (Avandia), which recently has been suspected of increasing myocardial infarction risk in patients with diabetes.
What these results highlight, said Martin Abrahamson, director of the Joslin Diabetes Center in Boston, Mass., is that individualized therapy for diabetes patients should still be stressed. "We can’t put every single person with diabetes in a single bucket," said Abrahamson. "We should still however adhere to the current guidelines of treatment which do not encourage normalization of glucose but which do encourage individualization of treatment goals based on a variety of factors including the presence of co-morbid conditions, age of the patient, risk for hypoglycemia, and expected longevity."
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Endocrine Policy |
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TopEndocrine DiscoveryEndocrine PolicyNew Guidelines Established for...Endocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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In a move that stunned many researchers, legislators, and patient advocacy groups, President Bush’s top science advisor, John Marburger, released a memo on January 22 declaring that the White House will not provide potassium iodide (KI) for protection against radioiodine exposure to the estimated 18 million of people who live 10 to 20 miles from a nuclear power plant in the U.S.
Although the 2002 Bioterrorism Preparedness and Response Act of 2002 ordered stockpiling and distribution of KI to populations living within 20 miles of a nuclear power plant, a loophole in the bill allowed the White House to reassess the distribution requirement if officials determine that there was a better way to prevent cancer. Marburger’s memo invoked that loophole by stating that the pills "offer negligible additional protection" against radiation exposure for residents who live 10 miles away from a nuclear reactor. It argued that evacuation and protection from contaminated food would be more effective ways to combat the potential cancer risk.
Scott Burnell, spokesperson of the U.S. Nuclear Regulatory Commission, pointed out that the government already stockpiles the pills for the 4.7 million people who live within 10 miles of a nuclear plant, a move that he claimed was "out in the forefront in and around the world." He said that the White House’s decision was based on the review of a multi-agency committee that concluded there was no scientific basis for expanding the distribution of KI out to 20 miles. However, a 2004 report by the National Academy of Sciences recommended that in the event of a nuclear incident, the pills should be available to all, especially infants, children, and pregnant and lactating women and recommended both local and national stockpiling, even in areas outside the 10-mile "emergency planning zone" around a nuclear reactor.
Lewis E. Braverman, M.D., an international authority on thyroid cancer and iodine effects, expressed his disagreement and frustration with the policy. "This is a political decision that has little to do with protecting the at-risk population from radiation exposure to the thyroid in addition to evacuation and restriction of contaminated foods," he said.
Richard T. Kloos, M.D, Secretary and Chief Operating Officer of the American Thyroid Association concurred. "The current decision by the White House is disappointing and is reminiscent of one purchasing the minimal necessary car insurance coverage and hoping that one does not regret the decision to error on the side of under protection," he said. "Unfortunately, the theoretical concepts of efficient evacuation and clean food are much easier said than done as the events of Hurricane Katrina demonstrated–despite the advantage of advanced warning. In contrast, iodine prophylaxis can be given to households ahead of time and, therefore, could be readily available when needed."
Rep. Edward J. Markey (D-MA), who co-authored the 2002 law, expressed outrage over the current White House decision. "It is inexcusable that the White House would decide to leave children and their families totally unprotected from a potential meltdown or terrorist attack on a nuclear power plant," he said, "especially when the cost of protecting these Americans is mere pennies per pill."
ThyCa: Thyroid Cancer Survivors’ Association, a patient support and advocacy organization, also expressed dismay about the White House decision. Gary Bloom, ThyCa executive director and cancer survivor, said, "We agree with the thyroid cancer specialists that KI and evacuation are a key means to prevent thyroid cancer for those at risk. We would never want others to get thyroid cancer if there’s a way to prevent it."
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New Guidelines Established for Preventing Terrorism from Fringe Animal Rights Groups |
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TopEndocrine DiscoveryEndocrine PolicyNew Guidelines Established for...Endocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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The number of campaigns of harassment and intimidation against animal researchers, often at researchers’ homes and involving their families, has increased sharply. The society claims that its members have reported more attacks in the first six months of 2007 than in the five-year period from 1999 to 2003.
"Not only have there been more attacks but the character of these attacks have changed," said Jeffrey Kordower, Ph.D., Chair of the society’s Committee on Animals in Research who helped put out the document, Best Practices for Protecting Researchers and Research: Recommendations for Universities and Institutions. In the past, animal rights groups would break into labs, disturb the animals, and destroy data and lab property. Now these types of attacks include bombs being put into homes of investigators as well as harassment of their families.
On February 5, Edythe London, a neuroscientist at the University of California, Los Angeles, who uses monkeys in her research regarding nicotine addiction, had her house firebombed by an unknown group. This incident occurred months after the Animal Liberation Front used a garden hose to flood her house—causing $30,000 in damages.
The first step toward protecting animal researchers was when the U.S. Congress passed the Animal Enterprise Terrorism Act, on November 27, 2006, giving the Department of Justice the authority to "apprehend, prosecute, and convict individuals committing animal enterprise terror." However, the Society for Neuroscience feels that a more proactive approach could be done at the university, state, and local legislative levels as well. Among other recommendations, the document calls for universities to show support and commitment to these researchers, actively pursue further federal, state, and local legislation to protect animal research, as well as develop special security ready to deal with both on- and off-campus attacks.
"Responsible biomedical research is essential to improve human health and save lives," said Eve Marder, Ph.D., Society for Neuroscience President. "At a time when reasoned debate has turned into illegal harassment, trespass, and threat of violence, universities have an obligation to provide an appropriate and safe environment for their researchers." (The SfN document can be found at: www.sfn.org/animals)
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Endocrine Practice |
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TopEndocrine DiscoveryEndocrine PolicyNew Guidelines Established for...Endocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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It was a costly mistake. In October 2007, the parents of a 3-year-old Florida boy who was born small for his age took him in for a routine diagnostic test to assess his pituitary function at an outpatient pediatric clinic. One of the tests was an arginine stimulation test for growth hormone (GH) deficiency. During the test, the boy became distressed. The mother said that she questioned the dose and the father asked for the procedure to be stopped; but the infusion of arginine was continued. The next day, the child was hospitalized and later died.
Through a tragic series of errors, the boy had received a 10-fold overdose of arginine (R-GENE 10, 10% hydrochloride injection). Although the child’s pediatrician had specified 5.75 g of arginine (500 mg/kg/dose for the 11.5 kg child) to be administered intravenously over 30 minutes, the child ended up receiving 60 g. The only brand of arginine available in the US (R-GENE 10, Pfizer) is supplied only in 300 mL bottles containing 30 g each—the recommended dose for an adult undergoing testing. Containers with smaller doses are not available for pediatric patients.
The first mistake took place at the outpatient pharmacy that dispensed the drug. In order to remind herself to order more medication for the next patient, the pharmacist wrote down on the prescription "2 bottles." The second pharmacist who entered the prescription into the computer mistakenly thought that both bottles were for the same patient to be given on one day and repeated on the next. She proceeded to fill out the prescription and gave the parents both bottles.
The next pattern of mistakes occurred at the outpatient clinic. Although the bottles were labeled to infuse to 5.75 g, the clinic staff thought they were to infuse both bottles. Specifically, the nurse who administered the drug read the front labels and thought that together, the dose would equal 5.75 g. The drug’s labeling on the front prominently displays the brand and generic names and concentration of 10%, but the actual quantity of arginine (10g/100mL) only appears in very small print on the back of the bottle, which the nurse didn’t see—failing to appreciate that each bottle contained 30 g of arginine.
The child started to develop a headache upon administration of the drug. Despite the parents’ concern, the procedure was continued. Later that night, the child became disoriented and began vomiting, and was admitted to hospital, where he suffered a seizure, became comatose, and was ultimately declared brain dead.
Pfizer labeling already includes the following warning: "Extreme caution must be exercised when infusing R-GENE 10 into pediatric patients. Overdosage of R-GENE 10 in pediatric patients can result in hyperchloremic metabolic acidosis, cerebral edema, or possibly death."
The vital lesson for endocrinologists using the arginine test, says Mary Parks, M.D., director of the Division of Metabolism and Endocrinology at the Food and Drug Administration, is that they "should check the dosing before administering the test."
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Milestones in Endocrinology |
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TopEndocrine DiscoveryEndocrine PolicyNew Guidelines Established for...Endocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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In the Journal 25 Years Ago |
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TopEndocrine DiscoveryEndocrine PolicyNew Guidelines Established for...Endocrine PracticeMilestones in EndocrinologyIn the Journal 25... |
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Synthetic human pancreas growth-hormone-releasing factor (hpGRF 1–44-NH2) stimulates growth hormone secretion in normal men. Rosenthal SM, Schriock EA, Kaplan SL, Guillemin R, Grumbach MM. J Clin Endocrinol Metab 1983;57:677–679. "The results of these studies support the potential usefulness of hpGRF44 for the assessment of GH secretion and reserve...."
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