"Glucocorticoids and Mood"

Another wonderful article from our friends at the Cushing's Support & Research Foundation (www.csrf.net) for this article. It is so important to understand the emotional as well as the physical toll that Cushing's plays.

Click here to read CSRF's article entitled Glucocorticoids and Mood

Glucocorticoids and Mood

By Dr. Jennifer Kirkland, Ph.D On June 20- 21, 2008, I had the rare opportunity to attend the conference Glucocorticoids and Mood: Clinical Manifestations, Risk Factors and Molecular Mechanisms. Sponsored jointly by UC San Diego Department of Psychiatry and The Diana Foundation, this conference came about in part, in response to the death of Diana Padelford Binkley. In 2003, after getting high dose steroids for a herniated disc, Diana suffered the side effect of steroid psychosis and subsequently committed suicide. Since glucocorticoids are used in managing many diseases, the 20% rate of psychiatric impairment found in those getting high dose treatment shows the need for better understanding of the risks and impact on patients. A call for the most recent findings brought researchers from around the world together to unravel the mysteries underlying this phenomenon and to come up with answers to lessen risks on patients. Given that cortisol and its synthetic partner cortisone are used so widely, the impact of high cortisol on mood and memory was highlighted. Since excess cortisol is the cause of Cushing's related symptoms, patients with Cushing's were studied. As many who have had Cushing's already guessed, high rates of mood and memory problems were found. Two-thirds (66%) to 100% of those studied had symptoms ranging from anxiety (66%), impaired concentration (66%), night awakenings (69%), decreased sex drive (74%), impaired memory 83%, irritability (86%), decreased energy (97%), fatigue (100%). High cortisol was found to actually shrink the hippocampus brain region, which related directly to verbal memory problems in Cushing's patients. Luckily, when the high cortisol state is reversed, the brain region goes back to normal size, and memory problems are largely reversed. And with treatment, over time, mood and psychiatric symptoms returned to levels found in those without Cushing's. What a relief to hear in a scientific conference that we aren't crazy, but having Cushing's can make us that way temporarily! The implications of such difficulties have raised awareness of the risks of giving high dose steroids. The types of treatments that tend to trigger mood problems and steroid psychosis were presented. They found that single high dose administrations of corticosteroids can cause temporary irritability, restlessness or memory problems. However, when the treatment is prolonged, steroid psychosis can happen. Studies vary on the rate this happens, but the range is 1.3% to a whopping 57%, making the average across studies 6%. The disturbing part to this finding is that no one knows why one person may have no symptoms and another may commit suicide. Thus, researchers urged that the risk be communicated with a "black box" warning by pharmaceutical companies. The one upside to this problem is that a whole new area of treating psychiatric disorders with cortisol lowering drugs has evolved. Although largely experimental, in some cases, lowering cortisol with mifepristone had a therapeutic effect similar to standard antidepressants making it a potentially good alternative when standard treatment can not be given. The second half of the conference was basic research that studied glucocorticoids on the molecular level. Glucocorticoids (cortisol) exert their effects on individual cells in the body by binding to a protein called a glucocorticoid receptor. Although still in the experimental stages, such research is paving the way for exciting developments. The first of such was the finding that glucocorticoid receptors (GR) can behave differently not just among people but even within a person. Thus, depending on the tissue type, the GR can respond in a highly sensitive or even an immune way. This variability in the action of GR may explain why Cushing's can appear so different in the way it presents clinically. Some people may or may not get the same symptoms in part due to how the GRs respond at the cellular level. Once again, we are finding that Cushing's has many faces, and can not be diagnosed on the basis of having a specific set of symptoms. Researchers have also expanded on the finding that glucocorticoids are the "first-responders" when the body is stressed. The body sends out a red flag that there is a problem by showing markers of inflammation. Glucocorticoids respond by moving in to reduce the inflammation. When studying mood disorders such as depression, a link between having an exaggerated inflammatory response to stress was linked with both depression and illness. Thus, when an individual has a GR that is resistant to this red flag of inflammation, more inflammation occurs. This lack of response is implicated in both cancer risk and depression. Perhaps the most exciting part of this half of the conference was how researchers are working to improve treatments based on basic research findings. Because different GRs behave differently, finding drugs that change behavior at the receptor level could increase the quality of many people's lives. Right now, pharmaceutical researchers are working on this issue in developing a glucocorticoid that does not cause osteoporosis. Thus, for those thousands of people who are on long term, higher dose corticosteroid treatment, within a few years, the new drug could greatly reduce the risk of osteoporosis! Another promising finding will help the many people who suffer with chronically high cortisol levels because of anxiety or depression. The challenge in treating it has been to lower cortisol without completely shutting it down. Even though chronically high cortisol has unpleasant effects, losing the body's ability to respond to stress can be life threatening. Trials of the drug mifepristone have demonstrated that the drug can lower cortisol effects without shutting it down. Thus, those who have chronically high cortisol can get relief without the danger of losing this response that is necessary during stress completely. The final panel discussion revealed that, despite having the best and the brightest researchers in the world present, we were left with more questions than answers. Obviously, the research presented is scratching the surface in finding solutions to complex problems such as Cushing's. But the best part for me though, was to see how the awareness of Cushing's as both a clinical syndrome and model for study has spread worldwide. I was able to look around at the treatment providers in the audience, and say "yeah, I think they get it" when it comes to a compassionate understanding of how devastating Cushing's can be. That was the best realization of all. Editor's Note: Jennifer Kirkland is a clinical neuropsychologist in private practice in the San Francisco Bay Area, California. Dr. Kirkland has the unique combination of years of psychological experience as well as personal experience with Cushing's, which makes her extremely qualified to report on the psychological impact of glucocorticoids.. She counts her two greatest accomplishments as completing her Ph.D. while being diagnosed and treated for adrenal Cushing's and having a baby on 11/30/07.

Solu-Cortef Alert

Thank you to our friends at www.caresfoundation.org for this important reminder. As you know, many Cushies rely on Solu-Cortef in cases of adrenal insufficiency. Solu-Cortef is for Cushies what Glucagon is for Type I diabetics. It is life-saving.

From: CARES Foundation <brendan@caresfoundation.org>

Reminder: Solu-Cortef National Drug Code (NDC) Change Last year Pfizer, the manufacturer of Solu-Cortef®, in the convenient "acto-vials," removed the preservatives from their product, and issued a new NDC number by the FDA. The number is 0009001103.   This NDC number change has apparently continued to make it difficult for pharmacies to find the product in their computer systems, resulting in erroneously informing people that it is no longer available for prescription.   The product is available, but with a new code.   If your pharmacy is having trouble obtaining these products, please instruct them to call Pfizer's Customer Service at 1(800) 533-4535.   Other possible contact numbers for Pfizer are 1(800) 821-7000 or patient services at 1(888) 691-6813.   2414 Morris Ave. Union, NJ, New Jersey 07083 Toll-free: 866-227-3737 Phone: 908-364-0272 www.caresfoundation.org

Hip pain coupled with shoulder pain

 

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Crutches in Cushing's disease

Avascular necrosis of bone can be almost silent until it comes under unusual strain. We report a case in point and lessons learned.

http://jrsm.rsmjournals.com/content/94/7/348.full

Hip Pain: Another Cushing's Symptom

Cushing's Disease Presenting with Avascular Necrosis of the Hip: An Orthopedic Emergency

ABSTRACT

Nontraumatic avascular necrosis (AVN) of the hip is commonly caused by exogenous glucocorticoid administration, whereas it has rarely been associated with endogenous hypercortisolism. We report a 30-yr-old woman with Cushing's disease whose presenting manifestation was early AVN of the hip. Although plain x-ray was negative, magnetic resonance imaging (MRI) of the hip showed stage 2 AVN. Her orthopedic disease was considered an emergency, and thus, it was treated with core decompression before the diagnosis of Cushing's syndrome (CS) was pursued further. The femur recovered fully, as demonstrated by her improved clinical picture and a subsequent MRI. AVN carries a poor prognosis, if not treated early. The diagnostic procedure of choice is MRI, because plain radiographs are falsely negative in early stages. This case illustrates that AVN can be the presenting manifestation of CS; to prevent irreversible effects on the femoral head, core decompression should not be delayed for the purpose of evaluation and treatment of CS.

Read article in full here:

http://m.jcem.endojournals.org/content/84/9/3010.full#sec-1

Yup, Your Ticker Could Go, Too!!

Cushing's Patients Must Be Screened for Heart Disease

By Piriya Mahendra, MedWire Reporter

Published August 12, 2012

Individuals who use glucocorticoids and exhibit iatrogenic Cushing's syndrome should be "aggressively" targeted for early screening of cardiovascular (CV) risk factors, say researchers.

Laurence Fardet (University College London, UK) and colleagues found that individuals with iatrogenic Cushing's syndrome who were prescribed glucocorticoids had a significantly higher incidence of CV events (including coronary heart disease, heart failure, or ischemic cerebrovascular events) than individuals prescribed glucocorticoids without iatrogenic Cushing's syndrome, or those not prescribed glucocorticoids.

Indeed, Cushing's syndrome patients prescribed glucocorticoids had a CV incidence rate per 100 person-years at risk of 15.1 compared with 6.4 and 4.1 in those without Cushing's but who were prescribed glucocorticoids and those not prescribed glucocorticoids, respectively.

Multivariate analysis revealed that iatrogenic Cushing's patients had a 2.27-fold increased risk for coronary heart disease, a 3.77-fold increased risk for heart failure, and a 2.23-fold increased risk for ischemic cerebrovascular events.

Compared with individuals prescribed glucocorticoids without iatrogenic Cushing's syndrome, those with Cushing's and glucocorticoids had a 2.74-fold increased risk for CV events.

Cushing's patients prescribed glucocorticoids also had a 4.16 higher risk for CV events than individuals not prescribed glucocorticoids.

"These results raise the question of whether glucocorticoids increase the risk of CV events in all patients or only in those who develop iatrogenic Cushing's syndrome," remark the authors.

Iatrogenic Cushing's syndrome is characterized by a cushingoid adiposity, with hypertrophy of adipose tissue in the face (giving the appearance of a "moon face"), dorsocervical region ("buffalo hump," double chin), and abdomen, and thinning of the subcutaneous adipose tissue of the limbs.

The authors say that a glucocorticoid-induced cushingoid appearance must no longer be considered as a minor adverse event of glucocorticoid treatment and point out that it has been associated with some features of the metabolic syndrome.

"It is therefore essential that patients prescribed glucocorticoids who develop iatrogenic Cushing's syndrome are assessed for CV risk and monitored regularly in both primary care and secondary care for early prevention of CV disease," they conclude in the British Medical Journal.

Licensed from Medwire news with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. 

http://www.news-medical.net/news/20120807/Cushinge28099s-patients-must-be-screened-for-heart-disease.aspx

All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.

In Loving Memory: Kym Grupido

Thank you to Boise Glow for Cushing's Awareness for sharing Kym's story as part of their continued efforts to draw attention to this terrible disease.

My heart breaks for Kym, her family, and all those who knew and loved her.

For more about Kym's life and battle with Cushing's, click to read her sister's loving account.

Editor's Note:  While the Cushing's Support & Research Foundation (csrf.net) would like to print only positive stories, many Cushing's stories are very sad.  Kym's story illustrates that even with all our current technology and diagnostics, more awareness is desperately needed.  We hope Kym's story tugs at your heartstrings and will perhaps motivate you to share your own story in a local paper, if you have not done so already.   If Kym's family and doctors had been aware of Cushing's, there is a good chance Kym would not have died.  It is for this reason the CSRF feels strongly that her story needed to be shared.

Click to enlarge.

A Cushie's Life

Pituitary Patient Sues for Misdiagnosis

Pituitary tumors are not as rare as people think. Studies of autopsy reports show that up to 20% of the population -- one in five people -- have a pituitary tumor. However, doctors continue to dismiss patents with acromegaly and Cushing's, causing years of sickness and despair.  One can only hope this court ruling prompts a few MDs study up on pituitary disorders.

For the full story, click through to the BBC website. 

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From the Pituitary Network Association (www.pituitary.org):

–	Why Is Early Diagnosis Such A Problem? The confusing constellation of symptoms that can be produced by pituitary tumors and the difficult to visualize location make diagnosis very tricky. It is not uncommon for patients to have symptoms of either hormonal deficiency (caused by compression of the pituitary or its "stalk") or hormone excess (caused by unregulated production of hormones by the pituitary tumor). In a significant minority of patients diagnosis is not made until the individual has developed debilitating or life-threatening symptoms of heart disease or adrenal (uncommon), gonadal and/or thyroid insufficiency. Even in the 21st century death from a large pituitary tumor or hormonal deficiency still occurs, albeit rarely. Early diagnosis is usually a reflection of a high index of suspicion on the part of a physician. Unfortunately, many doctors have been taught that pituitary disease is rare, so it is not at the forefront of their list of possible diagnoses.
–	How Prevalent Are Pituitary Tumors/Disease? Autopsy reports and radiologic and MRI evidence from around the globe indicate that one out of every five people worldwide has a pituitary tumor. The earliest study took place in 1936, when Dr. R.T. Costello of the Mayo Foundation conducted a cadaver study and found pituitary tumors in 22.4 % of the population (Costello R.T. Subclinical adenoma of the pituitary gland. Am. J. Pathol. 1936; 12:205-214). Statistics have not changed much ever since. The clinical significance of these findings are critical to determine.
–	Why Are These Tumors So Common? We don't know because funding for benign brain tumor research is virtually nonexistent. That's about to change. In October 2002, Congress passed the Benign Brain Tumor Cancer Registries Amendment Act, which will force hospitals, clinics and doctors to report pituitary tumor incidence rates in the data collection of cancer registries. The problem remains diagnosis. No report of incidence rates is possible without it.

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Why Aren't Pituitary Tumors/Disease Common Knowledge? There are four main reasons: Pituitary tumors/disease present a vast array of symptoms, and it's often the symptoms that get treated, not the disease. As a result, pituitary patients can spend years being misdiagnosed as their tumors grow. People with undetected pituitary tumors can die of heart attacks, hypothyroidism, adrenal insufficiency or water balance problems, all of which can mask the main cause: a pituitary tumor. Dollars spent. As a result, we have failed to answer the most important question: Why are pituitary tumors so common? There is a lack of education within the medical community and among the general public. The insurance industry hasn't caught on to the untold billions of dollars that could be saved through early diagnosis and treatment. Once it becomes clear that it's in everyone's best interest, the word will spread.