Day 6: Cushing’s Awareness Challenge 2015

Posted on April 6, 2015 by MaryO

People sometimes ask me how I found out I had Cushing’s Disease.  Theoretically, it was easy.  In practice, it was very difficult.

Ladies Home Journal, 1983In 1983 I came across a little article in the Ladies Home Journal which said “If you have these symptoms…”

I found the row with my symptoms and the answer read “…ask your doctor about Cushing’s”.

After that article, I started reading everything I could on Cushing’s, I bought books that mentioned Cushing’s. I asked and asked my doctors for many years and all of them said that I couldn’t have it.  It was too rare.  I was rejected each time.

 

 

Due to all my reading at the library, I was sure I had Cushing’s but no one would believe me. My doctors would say that Cushing’s Disease is too rare, that I was making this up and that I couldn’t have it.

In med school, student doctors are told “When you hear hoofbeats, think horses, not zebras“.

According to Wikipedia: “Zebra is a medical slang term for a surprising diagnosis. Although rare diseases are, in general, surprising when they are encountered, other diseases can be surprising in a particular person and time, and so “zebra” is the broader concept.

The term derives from the aphorism “When you hear hoofbeats behind you, don’t expect to see a zebra”, which was coined in a slightly modified form in the late 1940s by Dr. Theodore Woodward, a former professor at the University of Maryland School of Medicine in Baltimore.  Since horses are the most commonly encountered hoofed animal and zebras are very rare, logically you could confidently guess that the animal making the hoofbeats is probably a horse. By 1960, the aphorism was widely known in medical circles.”

So doctors typically go for the easily diagnosed, common diseases.  Just because something is rare doesn’t mean that no one gets it.  We shouldn’t be dismissed because we’re too hard to diagnose.

When I was finally diagnosed in 1987, 4 years later, it was only because I started bleeding under the skin. My husband made circles around the outside perimeter each hour with a marker so my leg looked like a cut log with rings.

When I went to my Internist the next day he was shocked at the size of the rings. He now thought I had a blood disorder so he sent me to a Hematologist/Oncologist.

Fortunately, he ran a twenty-four hour urine test and really looked at me and listened to me.  Both he and his partner recognized that I had Cushing’s but, of course, couldn’t do anything further with me.  They packed me off to an endo where the process started again.

My final diagnosis was in October, 1987.  Quite a long time to simply  “…ask your doctor about Cushing’s”.

Looking back, I can see Cushing’s symptoms much earlier than 1983.  But, that ‘s for a different post.

 

Filed under: Cushing's, pituitary, Rare Diseases | Tagged: , , , , , , , , , , , , , | 7 Comments »

What Causes Cushing’s Disease?

Posted on March 12, 2015 by MaryO

0276f-pituitary-gland

 

A condition in which the body produces too much cortisol, Cushing’s disease occurs when a tumor on the pituitary gland makes the gland create too much ACTH, the hormone that stimulates the production and release of cortisol (also known as “the stress hormone”). It may also occur with excess growth of the pituitary gland, known as hyperplasia. For most patients, Cushing’s disease will show itself through symptoms like red lines on the abdomen, abdominal weight gain and roundness to the face. And while the condition only affects 10 to 15 people per million per year, patients who suffer with it understandably wonder why. What are the causes? Where would a pituitary gland tumor come from? What leads to excess growth of that gland? To help answer these questions, here’s a look at Cushing’s disease causes:

Causes of Cushing’s Disease

The most common cause for Cushing’s disease is adenoma, a usually benign tumor on the pituitary gland. Because the tumors are normally pretty small, they can be hard to diagnose. For this reason, many patients who have Cushing’s disease don’t find out right away. Meeting with an endocrinologist can help the diagnosis process, improving your chances for a fast, successful recognition of the disease.

Risk Factors for Cushing’s Disease

Even though it’s a rare condition, Cushing’s disease occurs more commonly in women, particularly those between the ages of 20 and 50. Other factors that may increase the risk of Cushing’s disease include obesity, type 2 diabetes, poorly controlled blood sugar levels and high blood pressure. While none of these factors are a direct cause of the condition, they are associated with higher prevalence of it.

Cushing’s Disease vs. Cushing’s Syndrome

Often mistaken for one another, Cushing’s disease and Cushing’s syndrome are actually not the same condition. What they have in common is that they both involve the body’s producing too much cortisol. Cushing’s disease is a medical condition, however, while Cushing’s syndrome is a symptom of it. Cushing’s syndrome will often occur when a patient is taking corticosteroid medication.

Why You Should See an Endocrinologist

If you believe you or someone you love may have Cushing’s disease, it is best to see a specialist. Symptoms develop slowly and sometimes in cycles, so without proper testing it can be hard to identify what’s happening. A skilled endocrinologist can conduct hormone blood tests to measure blood cortisol levels at different times. He or she can also schedule an MRI for an individual who is not taking cortisol medications, in order to isolate the location of any tumors.

Have you been dealing with the symptoms of elevated cortisol levels, such as unexplained weight gain, particularly in the abdominal area and/or back of the neck? Is your skin or vision changing? These symptoms could be indicating a deeper problem in your body — so schedule an appointment to have your condition evaluated by a professional as soon as you can. Through proper treatment, you may be able to reduce or even eliminate your symptoms and be restored to full health again.

From http://www.hormone.org/diseases-and-conditions/pituitary/secretory-tumors/cushings-disease/cushings-disease-causes

Filed under: Cushing's, FAQ, pituitary | Tagged: , , , , , , | 1 Comment »

OR17-Novel Aspects of Adrenal Tumors and the HPA Axis

Posted on March 6, 2015 by MaryO

ENDO_2015

 

March 06, 2015

OR17-Novel Aspects of Adrenal Tumors and the HPA Axis

Epigenetic modulation of DNA Is associated with fatigue, depression and anxiety in patients with Cushing’s syndrome in remission: A genome-wide methylation study

CAM Glad, JC Andersson-Assarsson, P Berglund, R Bergthorsdottir, O Ragnarsson, G Johannsson

Summary: Researchers conducted this study to determine whether patients with Cushing’s syndrome (CS) that is in remission have specific epigenetic alterations that are associated with persistent cognitive impairments, anxiety, fatigue, and depression. Patients with CS in remission were shows to have specific DNA methylation that differed from that of healthy controls and was strongly correlated with clinical traits of anxiety, depression and fatigue, they concluded, adding that their results may suggest that an interaction between the glucocorticoid and the retinoic acid receptor is implicated in the long-term outcome of patients with CS in remission. The persistent cognitive impairment observed in patients with CS in remission, therefore, may be due to epigenetic modulation of DNA, they concluded.

Methods:

  • For this cross-sectional, case-controlled, single center study, researchers included 48 women with CS in remission (mean age±SD: 52.9±14 years) and 16 controls (mean age±SD: 53.6±16 years) matched for age, gender and educational level.
  • The mean age at diagnosis of CS was 37±14 years and the median (interquartile range) duration of remission was 13 (5-19) years.
  • In all, 37 patients had Cushing’s disease (CD) and 11 had a cortisol producing adrenal adenoma.
  • Researchers used the fatigue impact scale (FIS) to evaluate fatigue, and the comprehensive psychopathological rating scale to evaluate depression and anxiety; they assessed cognitive function by standardized neuropsychological tests.
  • DNA was isolated from whole blood, and DNA methylation was analyzed on the Illumina Infinium HumanMethylation450K BeadChip, which simultaneously interrogates >465,000 methylation sites per sample.
  • Researchers performed data quality control and analysis using the ChAMP methylation analysis package in R, and used Spearmen’s rho to perform correlation analyses.

Results:

  • Researchers found that patients had higher median score for FIS, depression and anxiety.
  • Methylation analysis identified 3,903 probes (in 340 genes) in regions that were differently methylated between CS patients and controls, and they found that 28% of these were significantly correlated to at least one of the clinical traits.
  • Fatigue, depression and anxiety were the most commonly correlated traits, and two of the most highly correlated genes were RXRB and COL11A2.
  • Gene ontology analysis revealed that these belong to the same GO-terms and are involved in retinoic acid receptor activity.
  • Finally, researchers found that both genes were specifically hypomethylated in cases as compared to controls.

 

This project has received financial support from the Swedish federal government under the LUA/ALF agreement, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, The Swedish Society of Medicine and The Swedish Society of Endocrinology.

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ5BA369FDE9DE4CED82CB6A7CD5BFD1BE/42321/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-ENDO2015&nonus=0

Filed under: adrenal, Clinical trials, Cushing's, Meetings and Conferences, pituitary | Tagged: , , , , , , , , , , , , | Leave a comment »

After massive weight gain, Cushing’s disease diagnosis saves man’s life – Health – TODAY.com

Posted on March 4, 2015 by MaryO

Donelle Trotman was only in his 30s when his health suddenly took a strange and frightening turn.

He was rapidly gaining weight — more than 100 pounds in one year. His upper torso was getting bigger, but not his legs. And he felt overwhelmingly tired.

“My body just started changing,” the Staten Island, New York, native told TODAY as part of a three-day series, “Medical Mysteries,” looking at people who have recovered from rare diseases.

It was especially puzzling because Trotman had never had weight issues before.

In school, Trotman was never a skinny kid, but he wasn’t overweight. He loved sports, playing both basketball and baseball.

So as he entered adulthood, he was active and in good shape. Then, three years ago, he suddenly began to gain weight.

“It was just specific places: My stomach, under my arms, my back of my neck, my face, the bottom of my back,” Trotman said. “My legs stayed the same for a long time.”

To lose the extra pounds, Trotman began running, working out and lifting weights. Nothing worked.

In the span of one year, Trotman gained more than 120 pounds, topping the scale at 366 pounds, twice the amount he weighed at 18.

“I doubled, like, I got a whole person on me,” he said.

There were other alarming changes. Trotman became so easily tired that he’d get out of breath just by chewing food. When he woke up seeing double three months ago, he knew it was time to go to the hospital.

Doctors ran a flurry of tests, but the results offered few clues, leaving everyone puzzled. Then one day, an intern noticed stretch marks all over Trotman’s body, a telltale sign that solved the mystery. Trotman had Cushing’s disease, a rare condition that affects fewer than 50,000 people in the U.S. every year.

Trotman’s weight gain was being caused by a tiny tumor at the base of his brain, prompting his body to produce too much of the hormone cortisol. He had some of the classic symptoms: major weight gain in his upper body, skin problems and acne, plus fatigue.

Dr. John Boockvar and Dr. Peter Costantino at New York’s Lenox Hill Hospital discovered Trotman had steroid levels ten times higher than normal.

“In Cushing’s disease, the pituitary gland has a small growth that releases a single hormone that causes the body to live with very high levels of steroids. The skin becomes very thin. You get increased acne. You can grow hair. You start sweating. You gain a lot of fat,” Boockvar said.

There was no time to lose: Untreated, Cushing’s is a fatal disease. Trotman was getting close to the point where doctors would not be able to reverse the changes, Costantino noted. He underwent surgery two weeks ago and had the growth successfully removed.

“The tumor was no bigger than the size of the tip of my pen,” Boockvar said. “And that something so small can cause a man to grow to 350 pounds and absolutely destroy his life is rather remarkable.”

These days, Trotman is feeling much better. His main focus now is to lose the weight he gained and regain an active lifestyle. He hopes to play basketball with his son soon.

“It’s wonderful. Every day it’s just like I feel a little stronger,” he said.

Doctors say Trotman will continue to lose weight and can shoot hoops with his son in about three months. There is an 8-10 percent chance the disease could come back, but Trotman said he knows what to look for now.

One of the reasons Trotman wanted to share his story is so others might recognize the symptoms of Cushing’s, although doctors stress it is a very rare illness.

 

Watch the video here: After massive weight gain, Cushing’s disease diagnosis saves man’s life – Health – TODAY.com.

Filed under: Cushing's, pituitary, Rare Diseases | Tagged: , , , , , , , | Leave a comment »

Scientists Find Potential Therapeutic Target for Cushing’s Disease

Posted on March 2, 2015 by MaryO

Scientists at the Salk Institute for Biological Studies have identified a protein that drives the formation of pituitary tumors in Cushing’s disease, a development that may give clinicians a therapeutic target to treat this potentially life-threatening disorder.

The protein, called TR4 (testicular orphan nuclear receptor 4), is one of the human body’s 48 nuclear receptors, a class of proteins found in cells that are responsible for sensing hormones and, in response, regulating the expression of specific genes. Using a genome scan, the Salk team discovered that TR4 regulates a gene that produces adrenocorticotropic hormone (ACTH), which is overproduced by pituitary tumors in Cushing’s disease (CD). The findings were published in the May 6, 2013 early online edition of Proceedings of the National Academy of Sciences.

The diagram shows how adrenocorticotropin hormone is secreted in Cushing's disease.

“We were surprised by the scan, as TR4 and ACTH were not known to be functionally linked,” says senior author Ronald M. Evans, a professor in Salk’s Gene Expression Laboratory and a lead researcher in the Institute’s Helmsley Center for Genomic Medicine. “TR4 is driving the growth and overexpression of ACTH. Targeting this pathway could therapeutically benefit treatment of CD.”

In their study, Evans and his colleagues discovered that forced overexpression of TR4 in both human and mouse cells increased production of ACTH, cellular proliferation and tumor invasion rates. All of these events were reversed when TR4 expression was reduced.

First described more than 80 years ago, Cushing’s disease is a rare disorder that is caused by pituitary tumors or excess growth of the pituitary gland located at the base of the brain. People with CD have too much ACTH, which stimulates the production and release of cortisol, a hormone that is normally produced during stressful situations.

While these pituitary tumors are almost always benign, they result in excess ACTH and cortisol secretion, which can result in various disabling symptoms, including diabetes, hypertension, osteoporosis, obesity and psychological disturbances. Surgical removal of the tumors is the first-line therapy, with remission rates of approximately 80 percent; however, the disease recurs in up to 25 percent of cases.

Drugs such as cabergoline, which is used to treat certain pituitary tumors, alone or in combination with ketoconazole, a drug normally used to treat fungal infections, have been shown to be effective in some patients with Cushing’s disease. More recently, mefipristone-best known as the abortion pill RU-486-was approved by the FDA to treat CD. Despite these advances in medical therapy, the Salk scientists say additional therapeutic approaches are needed for CD.

“Pituitary tumors are extremely difficult to control,” says Michael Downes, a senior staff scientist in the Gene Expression Laboratory and a co-author of the study. “To control them, you have to kill cells in the pituitary gland that are proliferating, which could prevent the production of a vital hormone.”

Previous studies have found that, by itself, TR4 is a natural target for other signaling molecules in the pituitary. Small-molecule inhibitors that have been developed for other cancers could be potentially applied to disrupt this signaling cascade. “Our discovery,” says Evans, a Howard Hughes Medical Institute investigator and holder of the March of Dimes Chair in Molecular and Developmental Biology, “might lead clinicians to an existing drug that could be used to treat Cushing’s disease.

Notes about this neurogenetics and Cushing’s disease research

Other researchers on the study were Li Du, Marvin Bergsneider, Leili Mirsadraei, Stephen H. Young, William H. Yong and Anthony P. Heaney of the David A. Geffen School of Medicine at the University of California, Los Angeles, and Johan W. Jonker of the University of Groningen.

The study was supported by the National Institutes of Health, the Leona M. and Harry B. Helmsley Charitable Trust, the Samuel Waxman Cancer Research Foundation, the Jonsson Comprehensive Cancer Center at UCLA, and Ipsen/Biomeasure.

Contact: Andy Hoang – Salk Institute
Source: Salk Institute press release
Image Source: The ACTH Cushing’s disease diagram is credited to NIDDK/NIH and is available in the public domain.
Original Research: Abstract for “Evidence for orphan nuclear receptor TR4 in the etiology of Cushing disease” by Li Du, Marvin Bergsneider, Leili Mirsadraei, Steven H. Young, Johan W. Jonker, Michael Downes, William H. Yong, Ronald M. Evans, and Anthony P. Heaney in Proceedings of the National Academy of Sciences. Published May 6 2013 doi: 10.1073/pnas.1306182110

From http://neurosciencenews.com/tr4-cushings-disease-acth-neurogenetics-120/

Filed under: Cushing's, pituitary | Tagged: , , , , , , , , , , , , , , , , , | Leave a comment »

« Previous Page — Next Page »