Multisystem Morbidity and Mortality in Cushings Syndrome: a Cohort Study

Journal of Clinical Endocrinology and Metabolism, 03/28/2013  Clinical Article

Dekkers O.M. et al.– To examine the risks for mortality, cardiovascular disease, fractures, peptic ulcers, and infections in CS patients before and after treatment.Cushing’s syndrome (CS) is associated with hypercoagulability, insulin resistance, hypertension, bone loss, and immunosuppression. To date, no adequately large cohort study has been performed to assess the multisystem effects of CS. It was concluded that despite the apparently benign character of the disease, CS is associated with clearly increased mortality and multisystem morbidity, even before diagnosis and treatment.

Methods

• The study used Cox–regression, and computed hazard ratios (HR) with 95% confidence intervals (95% CI).
• Morbidity was investigated in the three years before diagnosis; morbidity and mortality was assessed during complete follow–up after diagnosis and treatment.

Results

• 343 CS patients and 34,300 controls were included. Mortality was twice as high in CS patients (HR 2.3, 95%CI 1.8–2.9) compared with controls.
• Patients with CS were at increased risk for venous thromboembolism (HR 2.6, 95%CI 1.5–4.7), myocardial infarction (HR 3.7, 95%CI 2.4–5.5), stroke (HR 2.0, 95%CI 1.3–3.2), peptic ulcers (HR 2.0, 95%CI 1.1–3.6), fractures (HR 1.4, 95%CI 1.0–1.9), and infections (HR 4.9, 95%CI 3.7–6.4).
• This increased multi–morbidity risk was present before diagnosis. Mortality and risk of myocardial infarction remained elevated during long–term follow–up.
• Mortality and risks for AMI, VTE, stroke and infections were similarly increased in adrenal and pituitary CS.

From MDLinx

Genetic variant is linked to obesity and insulin resistance

A large study in people at risk of diabetes has found a direct association between the presence of a small genetic alteration in a hormone receptor and increased body fat and insulin resistance. The results, to be presented Tuesday at The Endocrine Society's 94th Annual Meeting in Houston, suggest an adverse role for a previously described genetic variant, the BclI polymorphism.

"Our findings support the idea that even small variations in hormone receptor sensitivity can have metabolic implications, such as obesity or diabetes," said co-author Bastiaan Havekes, MD, PhD, of Maastricht University Medical Center, Maastricht, the Netherlands.

"Endocrinologists should not just focus on hormone levels themselves. Taking into account hormone receptor sensitivity could help in better understanding hormone-mediated effects on metabolism," he said.

The inherited BclI polymorphism occurs in the gene encoding for the glucocorticoid receptor, which controls the actions of glucocorticoids, steroid hormones that affect every system in the body. This small variant makes the receptor more sensitive to glucocorticoids, resulting in greater effects with similar hormone levels, Havekes said.

The effects of this change appear to be similar to, although much smaller than, the excessive glucocorticoid exposure that can occur from certain medications or diseases, Havekes said. Such excess exposure can result in weight gain, especially around the abdomen, as well as in disturbed blood sugar metabolism. This exposure most often occurs from long-term use of prednisone or other glucocorticoid medications, which are widely used to treat inflammatory diseases or to suppress the immune system. It also can result from endocrine diseases such as Cushing's syndrome. Cushing's causes overproduction in the body of the glucocorticoid cortisol, often called the "stress hormone."

Patients in this study, however, did not have known excess exposure to glucocorticoids, according to Havekes. He and his co-investigators studied 1,228 adults who participated in one of two Dutch studies focusing on diabetes in the general population. More than half of the study participants had either prediabetes (23 percent) or Type 2 diabetes (33 percent). All subjects underwent genetic testing for the BclI polymorphism.

The researchers found that 519 subjects did not carry the alternative form of the gene, or G-allele, for the BclI polymorphism on either chromosome. Another 540 subjects were heterozygous carriers, meaning the G-allele was present on one of the two chromosomes. The remaining 169 subjects were homozygous carriers and therefore carried the G-allele on both chromosomes.

Those who had the BclI polymorphism on each chromosome had a significantly higher body mass index and larger waist and hip circumferences than did noncarriers or heterozygous carriers, the authors reported. This was reflected by greater insulin resistance, meaning that insulin is less effective at lowering blood glucose (blood sugar).

"Determining an individual's genetic risk profile for metabolic disease is of paramount importance to prevent development of cardiovascular diseases," he said. "Future studies concerning cardiovascular risk profiling should perhaps consider the BclI polymorphism."

Provided by The Endocrine Society and posted by MedicalXPress.com

Not the Usual Suspects: Animal Study Finds Surprising Clues to Obesity-Induced Infertility

Source: Johns Hopkins Medicine

FOR IMMEDIATE RELEASE

Newswise — Infertility is common among obese women, but the reasons remain poorly understood and few treatments exist. Now a team of Johns Hopkins Children's Center scientists, conducting experiments in mice, has uncovered what they consider surprising evidence that insulin resistance, long considered a prime suspect, has little to do with infertility in women with type-2 diabetes, polycystic ovary syndrome (PCOS) and metabolic syndrome, all obesity-related conditions in which the body becomes desensitized to insulin and loses the ability to regulate blood sugar.

In a report, published online Nov.10 in the journal Diabetes, the Johns Hopkins scientists say the real culprit appears to be insulin sensitivity in the ovaries and the pituitary.

The Johns Hopkins team said its findings show that these organs escape insulin resistance and, awash with high levels of circulating insulin common in obesity, develop abnormal cell signaling that disrupts ovulation and eventually leads to infertility.

"Our findings suggest that the focus should shift from treating insulin resistance in peripheral tissue to taming insulin sensitivity in the pituitary and ovaries," says lead investigator Sheng Wu, Ph.D., of the Johns Hopkins Children's Center. Scientists traditionally have treated obesity-induced infertility by lowering blood insulin to counter the effects of insulin resistance.

A 2010 study by the same team discovered that the pituitary gland, insensitive to insulin in lean mice, became sensitive to elevated levels of insulin seen in human and rodent obesity. By knocking out the insulin receptors in the pituitary glands of obese mice, the researchers were able to partially restore fertility, thus proving that abnormal insulin signaling in the pituitary was only part of the story.

"In the original study, disrupting insulin signaling in the pituitary restored 50 percent of fertility in obese mice, but the search was on for the accomplice," says senior investigator Andrew Wolfe, Ph.D., an endocrinologist at the Johns Hopkins Children's Center. "Our new findings point to the ovaries."

In the pituitary, faulty insulin signaling stimulates increased secretion of luteinizing hormone, the researchers say. In the ovary, it puts testosterone production into overdrive. Both disrupt ovulation, the researchers explain.

In the latest study, lean mice and mice made obese on a three-month high-fat diet received injections of progressively higher doses of insulin to mimic the effects of high circulating insulin seen in obesity, diabetes and PCOS. In lean mice, the ovaries and pituitaries were insensitive to the hormone at low-dose injections, and responded only when injected with higher doses of insulin. The "trigger" doses corresponded to insulin levels typically seen in obesity. Obese mice with naturally elevated insulin levels exhibited high levels of insulin signaling in their pituitary and ovarian cells. When injected with insulin, the livers and muscles of obese mice showed greatly reduced response to insulin -- or insulin resistance. Their ovaries and pituitary glands, however, responded to insulin injections, confirming that in obese mice, these reproductive organs escape the insulin resistance seen in other organs.

To determine insulin sensitivity, the researchers focused on two signaling proteins, IRS-1 and IRS-2, regulators of cell-insulin communication involved in the development of insulin resistance in liver and muscle tissue. The scientists hypothesized that in the pituitary and ovaries, these messenger proteins would remain dormant under normal insulin levels, but would get activated once exposed to high levels of insulin. Indeed, the researchers found, the pituitary glands of obese mice showed higher IRS-2 signaling activity compared with lean mice, while the ovaries of obese mice had higher signaling activity in both IRS-1 and IRS-2 proteins, compared with lean mice.

In a follow-up study now under way, the Hopkins team is trying to determine whether knocking out the insulin receptors in both the ovaries and the pituitary would fully restore fertility in obese mice with high insulin levels.

Other co-investigators on the study included Sara Divall, M.D., and Fred Wondisford, M.D., both of the Johns Hopkins Children's Center.

The research was funded by the Endocrine Fellow Foundation, by The Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health, and by the Baltimore Diabetes Research and Training Center, which is supported by the National Institute for Diabetes and Digestive and Kidney Diseases.

 

 

Founded in 1912 as the children's hospital of the Johns Hopkins Medical Institutions, the Johns Hopkins Children's Center offers one of the most comprehensive pediatric medical programs in the country, treating more than 90,000 children each year. Hopkins Children's is consistently ranked among the top children's hospitals in the nation. 
Hopkins Children's is Maryland's largest children's hospital and the only state-designated Trauma Service and Burn Unit for pediatric patients. It has recognized Centers of Excellence in dozens of pediatric subspecialties, including allergy, cardiology, cystic fibrosis, gastroenterology, nephrology, neurology, neurosurgery, oncology, pulmonary, and transplant. For more information, please visitwww.hopkinschildrens.org

From http://www.newswise.com/articles/not-the-usual-suspects-animal-study-finds-su.../articles/list&category=medicine&page=1&search%5Bstatus%5D=3&search%5Bsort%5D=date+desc&search%5Bsection%5D=10&search%5Bhas_multimedia%5D=

Have an appointment with the doctor? Tips show what to ask

Good general info for anyone of any age, no matter what symptoms or disease you may have.

 

by John Beale

Good communication between patients and their health-care practitioners is essential for good care. To help older adults better communicate with their health-care providers, the American Geriatrics Society's Foundation for Health in Aging has released a new, easily understandable tip sheet.

 

The tip sheet, "How to Talk to Your Healthcare Practitioner: Tips on Improving Patient-Practitioner Communication," outlines steps older adults and their caregivers can take before, during and after a visit to a practitioner. These steps help ensure practitioners, older patients and their caregivers get the information they need. The tip sheet is available online at: http://www.healthinaging.org/public_education/communication_tips.php.

 

Before visiting a health-care provider, the tip sheet advises older people to, among other things, make a list of any symptoms or health problems they have, as well as past health problems, any treatments they've undergone and any adverse reactions to treatments they have had.

 

Bring medications

It also encourages older adults to put the medications, supplements and other remedies they're taking in a bag and bring it to their appointment. That way, their practitioner can see what they're taking and at what doses - important information, since medications may interact and some may affect medical test results.

 

The tip sheet also advises older adults who don't speak English as a first language to consider looking for a practitioner who speaks their native tongue, bring along a bilingual buddy to translate or call the office and request a translator ahead of time.

 

The tip sheet encourages older patients and their caregivers to answer all questions frankly, to request explanations when needed and to ask follow-up questions, such as "Are there any risks associated with this treatment?" and "Are there any alternative treatments?"

 

Understanding is vital

It also suggests patients and caregivers repeat back what their providers tell them about their health and treatments to ensure they've understood correctly.

 

After an appointment, the tip sheet advises older patients to contact their practitioner's office if they don't feel better, if they have an adverse reaction to a medication or other treatment or if they realize they've forgotten to mention something important that's relevant to their health.

 

Other easy-to-read health tip sheets for older adults and their caregivers cover such topics as cold and immunizations, falls prevention, emergency planning, and joint replacement surgery for older people.

 

Anyone who does not have online capability may call the Office for the Aging at 845-486-2555 for tip sheet copies.

 

From http://www.poughkeepsiejournal.com/article/20090629/COLUMNISTS06/906290301/1005/LIFE

~~~

How to Talk to Your Healthcare Practitioner: Tips on Improving Patient-Practitioner Communication

The list mentioned in the article from http://www.healthinaging.org/public_education/communication_tips.php

 

Good communication between you and your healthcare practitioners -- the physicians, nurse practitioners, nurses, physician assistants and other healthcare professionals you see -- is essential to good care.

 

It's important that you give your practitioner the information about yourself and your health that he or she needs to provide quality care. And it's important that he or she explain what you need to do to stay as healthy as possible, in a way that you understand.

 

Here's what experts with the American Geriatrics Society's Foundation for Health in Aging (FHA), suggest:

 

Before your appointment

Make a list Visiting a healthcare professional can be stressful -- particularly if you're not feeling well -- and stress can make it harder to remember what you need to tell and ask your practitioner. So make a list and bring it to your appointment. Write down any health problems you have had or do have, and any surgery or other treatments you've undergone. Write down the names of any medications you've taken that have caused unpleasant or dangerous side effects. If you're sick, write down all of your symptoms.

 

And don't forget to write down any questions about your health that you might have. You can find comprehensive lists of questions that older adults should consider asking their healthcare practitioners - organized by subject - on "Aging in the Know" (www.healthinaging.org/agingintheknow/questions_trial.asp), the FHA's free senior health website.

 

Bring your medications, vitamins, and other remedies to your appointment Before leaving for your visit, put all of the prescription drugs, over-the-counter medications, herbs, vitamins, and other supplements you take in a bag. Take them with you and show them to your healthcare practitioner. This way, he or she will know exactly what you're taking, when, and at what doses. This is important because some drugs, herbs and supplements can interact with medications your practitioner might prescribe. They might also affect the results of certain medical tests.

 

Pack paper Bring paper or a notebook to your appointment so you can write down what your healthcare professional tells you. If you have trouble remembering later on, you can look at your notes.

 

Consider asking a buddy along A family member or close friend who goes with you when you see your healthcare professional can offer your practitioner information that you might forget or overlook. He or she can also help you remember what your healthcare practitioner says. If you want to discuss something with your practitioner alone, you can always ask your relative or friend to leave the room while you do so.

 

Call ahead to request a translator if necessary If English is not your first language, you might seek out a healthcare practitioner who speaks your native language. Other options include bringing a bilingual buddy with you to your appointment, or calling your practitioner's office ahead of time and asking if staff can supply a translator.

 

During your appointment

Answer questions honestly It's essential that you answer all of the questions your healthcare practitioner asks you, even if he or she asks about topics that might make you uncomfortable, such as mental health problems, drinking, and sex. There's nothing to be embarrassed about. Your practitioner needs complete information to provide proper care. And everything you tell him or her is confidential.

 

Ask questions If you don't understand what your healthcare professional tells you during your visit, ask him or her to explain it. You need to -- and have a right to -- understand what your practitioner says. It's particularly important that you understand any treatments he or she recommends. You should ask if there are any risks associated with treatments, and if there are any alternatives.

 

Mention any cultural or religious traditions that might affect your care If your healthcare practitioner recommends that you eat foods that your religion prohibits, for example, or if you need to fast at certain time of the year, tell him or her.

 

Repeat back After your healthcare professional explains what you should do to stay healthy, or to treat a health problem, repeat this back to him or her using your own words. You might start by saying, "So, you're telling me that I should…." If you've misunderstood his or her advice, your practitioner will realize this, and clarify.

 

Ask for written instructions If your healthcare practitioner puts his or her advice in writing, you can refer to the written instructions at any time.

 

After your appointment

Call your practitioner's office if you don't feel better, have a bad reaction to medications, or realize you forgot to mention something If you don't feel better after your visit, or seem to be having a bad reaction to medication your healthcare professional prescribed, call his or her office immediately. You should also call if you realize, after leaving the office, that you neglected to ask a question or provide information about your health, or didn't understand what your healthcare practitioner said. Ask to speak with your practitioner as soon as he or she is available or ask to speak to another healthcare professional in the office who can help you.

 

Communication between you and your healthcare practitioner is an ongoing process. The simple tips above can help improve communication. Improved communication means better understanding, diagnosis and treatment.

The Word Is Already Getting Out...

Google Alerts for today:

Is there a connection between Addisons Disease, Diabetes, and PCOS ...
My ( maternal) Grandma died of an Addison Crisis at 40. My first cousin has type 1 diabetes, and my sister and I both have Insulin Resistance, I also have.
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Cushie Blogger
By MaryO
Addison's, sort of - Parents brought home a lot of Addisons and Jaydens in 2008 - Quad Cities Online: "Addison was the most popular name for baby girls and Jayden was the mo... 7 hours ago. Cushing's Family. - The new year begins. ...
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Cushing's & Cancer
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Saturday, January 3, 2009. Based on last blog post about Addison's Disease - a new blog (again!) to promote Addison's awareness. http://ping.fm/xQAMV. Posted by MaryO at 8:28 PM ...
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