Patients with ARMC5 mutations: The NIH clinical experience

Posted on May 27, 2016 by MaryO

Screenshot 2016-05-27 13.12.55

 

Adrenal Disorders

R Correa, M Zilbermint, A Demidowich, F Faucz, A Berthon, J Bertherat, M Lodish, C Stratakis

Summary: Researchers conducted this study to describe the different phenotypical characteristics of patients with armadillo repeat containing 5 (ARMC5) mutations, located in 16p11.2 and a likely tumor-suppressor gene. They determined that patients with bilateral adrenal enlargement, found on imaging tests, should be screened for ARMC5 mutations, which are associated with subclinical Cushing’s syndrome (CS) and primary hyperaldosteronism (PA).

Methods:

  • Researchers identified 20 patients with ARMC5 mutations (germline and/or somatic) who were enrolled in a National Institutes of Health (NIH) protocol.
  • They obtained sociodemographic, clinical, laboratory, and radiological data for all participants.

Results:

  • Three families (with a total of 8 patients) were identified with ARMC5 germline mutations; the rest of the patients (13/20) had sporadic mutations.
  • The male to female ratio was 1.2:1; mean age was 48 years and 60% of patients were African American.
  • Forty percent of patients were diagnosed with CS, 20% with subclinical CS, 30% with hyperaldosteronism, and 10% had no diagnosis.
  • The mean serum cortisol (8 am) and Urinary Free Cortisol were 13.1 mcg/dl and 77 mcg/24 hours, respectively.
  • Nearly all patients (95%) had bilateral adrenal enlargement found on CT or MRI.
  • Patients underwent the following treatments: Bilateral adrenalectomy (45%), unilateral adrenalectomy (25%), medical treatment (20%), and no treatment (10%).
  • ARMC5 mutations are associated with primary macronodular adrenal hyperplasia (PMAH) and are also seen in patients with PA, especially among African Americans.

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ37C4C5D3BF1A4FAE9C479A696660535B/57884/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-AACE2016&nonus=0

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Rally for Medical Research Hill Day

Posted on May 26, 2016 by MaryO

Held every September, this Capitol Hill Day event continues the momentum established in 2013, and includes nearly 300 national organizations coming together in support of the Rally for Medical Research.

The purpose of the Rally is to call on our nation’s policymakers to make funding for National Institutes of Health (NIH) a national priority and raise awareness about the importance of continued investment in medical research that leads to MORE PROGRESS, MORE HOPE and MORE LIVES SAVED.

The next Rally for Medical Research Hill Day is Sept. 22, 2016.

Sign up to receive updates, including a link to register once it becomes available.

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Delayed diagnosis, barriers to care increase morbidity in children with Cushing’s syndrome

Posted on May 6, 2016 by MaryO

Hispanic and black children diagnosed with Cushing’s syndrome are more likely to present with higher cortisol measurements and larger tumor size vs. white children, according to study findings presented at the annual Pediatric Academic Societies Meeting in Baltimore.

“Racial and socioeconomic disparities may contribute to the severity of disease presentation for children with Cushing’s [syndrome],” Alexandra Gkourogianni, MD, of the section on endocrinology and genetics at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and colleagues wrote. “Minority children from disadvantaged backgrounds present more frequently with comorbidities associated with longstanding [Cushing’s syndrome].”

Gkourogianni and colleagues analyzed data from 135 children treated for Cushing’s syndrome (transsphenoidal surgery) at the NIH between 1997 and 2015 (mean age, 13 years; 51% girls; 33% Hispanic or black). Researchers used a 10-point index for rating severity in pediatric Cushing’s syndrome based on predefined cutoffs; degree of hypercortisolemia, impaired glucose tolerance, and hypertension were graded on a 3-point scale (0-2); height, BMI z scores, duration of disease, and tumor invasion were graded on a 2-point scale (0-1).

Researchers found that midnight cortisol measurements were higher among Hispanic and black children vs. white children (23.3 µg/dL vs. 16 µg/dL; P = .019), as were tumor sizes (mean 6.3 mm vs. 3.3 mm; P = .016). Height standard deviation score was more severely affected in black and Hispanic children (–1.6 vs. –1.1; P = .038), and mean Cushing’s syndrome score for Hispanic and black children was higher vs. white children (4.5 vs. 3.8; P = .033).

Researchers found that median income had an independent correlation with Cushing’s syndrome score in univariate regression analysis for covariates of socioeconomic status and demographics (P = .025). Multivariable regression analysis using race, prevalence of obesity, estimated income, access to pediatric endocrinologist, age and sex confirmed that race, along with lower socioeconomic status and older age, were predictors of a higher Cushing’s syndrome score (P = .002).

“We speculate that delayed diagnosis, barriers to access to care and poorer quality health care for these underserved patients may contribute to presentation at a later age and increased morbidity,” the researchers wrote. “Additional research is needed to identify potential modifiable factors that may improve care for these patients.” – by Regina Schaffer

Reference:

Gkourogianni A, et al. Poster #445. Presented at: Pediatric Academic Societies Meeting; April 30- May 3, 2016; Baltimore.

Disclosure: Endocrine Today was unable to determine relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/online/%7Be79d7c84-d539-4a04-a548-882b9f4caadd%7D/delayed-diagnosis-barriers-to-care-increase-morbidity-in-children-with-cushings-syndrome

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Day 17, Cushing’s Awareness Challenge 2016

Posted on April 17, 2016 by MaryO

 

Because it’s a Sunday again, this is a semi-religious post…

After I was finished with the Cushing’s long diagnostic process, surgery and several post-op visits to NIH, I was asked to give the scripture reading at my church. The man who preached the sermon that week was the survivor of a horrific accident where he and his family were hit by a van while waiting at an airport.

I thought I had written down the scripture reading carefully. I practiced and practiced. I don’t like speaking in front of a crowd but I said I would. When I got to church, the reading was different from what I had practiced. Maybe I wrote it down wrong, maybe someone changed it. Whatever.

The real scripture turned out to be Psalm 116. I got very emotional while reading this and started crying when I got to verse 8 “For you, O LORD, have delivered my soul from death“.  Others in the congregation who knew part of my story were very moved, too.

psalm-116-1-4

Psalm 116 (New International Version)

1 I love the LORD, for he heard my voice;
he heard my cry for mercy.

2 Because he turned his ear to me,
I will call on him as long as I live.

3 The cords of death entangled me,
the anguish of the grave came upon me;
I was overcome by trouble and sorrow.

4 Then I called on the name of the LORD:
“O LORD, save me!”

5 The LORD is gracious and righteous;
our God is full of compassion.

6 The LORD protects the simplehearted;
when I was in great need, he saved me.

7 Be at rest once more, O my soul,
for the LORD has been good to you.

8 For you, O LORD, have delivered my soul from death,
my eyes from tears,
my feet from stumbling,

9 that I may walk before the LORD
in the land of the living.

10 I believed; therefore I said,
“I am greatly afflicted.”

11 And in my dismay I said,
“All men are liars.”

12 How can I repay the LORD
for all his goodness to me?

13 I will lift up the cup of salvation
and call on the name of the LORD.

14 I will fulfill my vows to the LORD
in the presence of all his people.

15 Precious in the sight of the LORD
is the death of his saints.

16 O LORD, truly I am your servant;
I am your servant, the son of your maidservant;
you have freed me from my chains.

17 I will sacrifice a thank offering to you
and call on the name of the LORD.

18 I will fulfill my vows to the LORD
in the presence of all his people,

19 in the courts of the house of the LORD—
in your midst, O Jerusalem.
Praise the LORD.

This Psalm has come to have so much meaning in my life. When I saw at a book called A Musician’s Book of Psalms each day had a different psalm. “My” psalm  was listed as the reading for my birthday, so I had to buy this book!  For a while, it was the license plate on my car.

I used to carry a print out of this everywhere I go because I find it very soothing. “when I was in great need, he saved me.” This print out is in a plastic page saver but now I have this info on my phone and iPad.

On the other side there is an article I found after my kidney cancer.  You can read that article in yesterday’s post.

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Day 14, Cushing’s Awareness Challenge 2016

Posted on April 14, 2016 by MaryO

Way back when we first got married, my husband thought we might have a big family with a lot of kids.  He was from a family of 6 siblings, so that’s what he was accustomed to.  I am an only child so I wasn’t sure about having so many.

I needn’t have worried.

In January, 1974 I had a miscarriage.  I was devastated. My father revealed that my mother had also had a miscarriage.  I had no idea.

At some point after this I tried fertility drugs.  Clomid and another drug.  One or both drugs made me very angry/depressed/bitchy (one dwarf I left off the image)  Little did I know that these meds were a waste of time.

Eventually,  I did get pregnant and our wonderful son, Michael was born.  It wasn’t until he was seven that I was finally, actually diagnosed with Cushing’s.

When I had my early Cushing’s symptoms, I thought I was pregnant again but it was not to be.

I’ll never forget the fall when he was in second grade.  He was leaving for school and I said goodbye to him.  I knew I was going into NIH that day for at least 6 weeks and my future was very iffy.  The night before, I had signed my will – just in case.  He just turned and headed off with his friends…and I felt a little betrayed.

Michael wrote this paper on Cushing’s when he was in the 7th grade. From the quality of the pages, he typed this on typing paper – no computers yet!

Click on each page to enlarge.

When Michael started having headache issues in middle school, I had him tested for Cushing’s.  I had no idea yet if it could be familial but I wasn’t taking any chances.  It turned out that my father had also had some unnamed endocrine issues.  Hmmm…

I survived my time and surgery at NIH and Michael grew up to be a wonderful young man, if an only child.  🙂

After I survived kidney cancer (Day Twelve, Cushing’s Awareness Challenge 2015) Michael and I went zip-lining – a goal of mine after surviving that surgery.  This photo was taken in a treetop restaurant in Belize.

For the mathematically inclined, this is his blog.  Xor’s Hammer.  I understand none of it.  He also has a page of Math and Music, which I also don’t understand.

I know it doesn’t fit into a Cushing’s awareness post but just because I’m a very proud mama – Michael got a PhD in math from Cornell and his thesis was Using Tree Automata to Investigate Intuitionistic Propositional Logic

 

proud-mom

 

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