Experts in the field of endocrinology, neurology, pediatrics, and rehabilitative medicine met at Kennedy Kreiger to discuss endocrine issues in Duchenne. Alan Rogol, M.D., Ph.D. chaired the first session. In the endocrine community, Alan is considered one of the world’s best. The meeting included 40 individuals representing endocrinology, neurology, cardiology, rheumatology, rehabilitation, and orthopedics. Craig McDonald discussed the effect of steroid on the natural history of Duchenne. Manual Muscle Testing (MMT) and Quantitative Muscle Testing (QMT) demonstrate the difference in functional loss: With steroids 0.2 motor units/year. Without: 0.4 u/year.

In medicine, there is always controversy, always opposing opinions. This is because we are all individuals and each person has his or her own pattern of development. It is never “one size fits all” and never will be. And we have to remember, there is no correlation between size of muscle and the function that results.

Walter Lippmann said: “When we all think alike, no one is thinking.”.

Discussions centered around delayed growth, puberty, bone health, and weight control. As is typical in meetings, presenters presented data on specific topics, as well as, their clinical opinion.

Not one of these issues is simple and there is considerable controversy around each topic: How to treat, when to treat, what type of tests should be done, and how to interpret those tests. With several clinics represented, it was pretty clear that each clinic has their own particular approach, each performing different tests. One of the issues that became quite apparent was the need to drive to a consensus on common data elements – what data to collect, what tests to perform. Carsten Bonnemann suggested checking the website http://www.commondataelements.ninds.nih.gov. This will be included in our advocacy agenda!

Session 1: Growth and Self-Esteem

Drs. Adrian Dobs, Alan Rogol, and Meilan Rutter discussed the Gonadal Axis in Duchenne: growth and growth hormone (GH), and puberty. Hormones regulate processes. They may have a factor of up to one million fold in terms of speeding up or slowing down processes. Adrian Dobs discussed the gonadal axis of testosterone with the circadian curve (varying levels throughout the day). Dr. Dobs suggested that it is critical to treat individuals with delayed puberty with testosterone. There is NO data on testosterone in the Duchenne population. The discussion was lively about the potential risk and benefit of GH, testosterone, and its effect on bone health and maturity, as well as self-esteem. Discussions centered around the concept of ‘shorter is better’, clinical trials, and combination therapies, as well as the necessity of organizing a working group to drive consensus. While there have been small/pilot trials on GH (no change in skeletal muscle function), Maxindol and anabolic steroids, there were concerns about the trial design, statistics, and results. Leanne Ward, M.D. from Ottawa will be chairing working groups on puberty and bone health.

Session 2: Metabolic Issues and Obesity

Katie Ness (Seattle), Kathy Matthews (Iowa), and Doug Biggar discussed steroid induced obesity in children and observations in weight, over and under. They agreed there are three body types in Duchenne, describing very thin boys who are able to eat whatever they want and never seem to gain weight. He mentioned the boys who seem to gain significant weight, in spite of every effort to limit calories. Of course, there are a lot of boys in the middle. Clearly nutrition counts – high protein diets are critical with limited carbs. Metformin was discussed with considerable concern from some of the participants. One question that was posed – should we be routinely checking for type 2 diabetes in Duchenne? Other questions included when and why to use Metformin.

Session 3: Bone Heath

Two perspectives were included in this session – endocrinology and neurology. Boys with Duchenne are typically normal in height and weight at birth. There is normal subsequent growth along the curve, crossing percentiles in the first year with the median height less than the 50th percentile by age 10. The cause is unknown. The myths were discussed “shorter is better,” “growth spurt causes increased weakness and contractures,” “shorter Duchenne children are stronger than taller ones at the same age,” and “short stature is detrimental to self-image and self-confidence.” The working group will work on understanding whether there is a genetic basis for short stature. Diana Escolar recommended that the working group consider testing for the SHOX mutation as this gene is also located on the X-chromosome.

The bisphosphonates were discussed at length, some centers recommending IV or oral at certain ages or with results of specific testing. The group agreed to drive consensus for a protocol to address bone health, testing, and interventions.

Clearly there is more work to be done. Working groups will meet to deal with specific issues generated from this meeting. The goal is to keep the excitement and momentum going so that the work can continue. With this dedicated group, we can only be excited for new research and results to come.

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Comment by Ofelia Marin on December 3, 2010 at 8:48am
Can you please provide a reference for this pre-steroids data?

It is just so difficult for me to see what is due to DMD and what is due to chronic steroid use. Are non-steroid treated boys insuline resistent as well? Do they have delayed puberty? We are talking about short stature, delayed growth, puberty, bone health, weight control and their implication on self-esteem after a certain age, on the other hand we are pushing steroids starting around age 3 when we know that this means short stature, delayed growth, puberty, bone health, weight control problems etc. It would be good to know that chronic steroid use is not what triggers all these in the majority of boys.

Staff
Comment by Pat Furlong on December 3, 2010 at 7:12am
Hi, yes, they are using natural history data (pre-steroids) to describe short stature. Craig McDonald's natural history study is post steroids, outcomes from the meeting include:
1. document for families - we are working on this, will outline rationale for endo. referral, tests that may be recommended and why, pros and cons of specific interventions. There have been no studies, therefore there is no consensus at this time
2. working groups on puberty and bone health
3. paper submitted for publication -will let you know when paper is submitted for publication and will post when published
4. follow-up meeting scheduled within 6-9 mo.
All of these issues are extraordinarily complex, but the good news is that referrals to endocrinology will increase across the US and the world, expanding inter-disciplinary care and hopefully increased knowledge about what to measure, when to intervene and with what medicactions, improved outcomes.
pat
Comment by Char Burke on December 2, 2010 at 10:28pm
HI Pat - thanks for the update. I am curious as to whether the metabolic issues and obesity group talked about things parents and doctors can do. Is there going to be any thing published on this and if so, where could I read it?
Thanks.
Char Burke
Comment by Susan Rathfelder on December 2, 2010 at 9:48pm
Ofelia, my son has never taken steroids and he is always been on the normal, slightly below normal side for his height. At 19 he might be 5'9". By contrast his sisters have always been in the 95%+ mark on the growth charts. My 25 y/o is 5'10" or 5'11" and my 21 y/o is 6 feet (she will only admit to 5'11").
Comment by Ofelia Marin on December 2, 2010 at 4:56pm
With the majority of boys now on steroids starting early, do they have enough data to accurately describe "normal/abnormal" height and weight of DMD boys 3+years of age? Looking at my 3 year old son (sample size = 1 I know...) I cannot say that his height/weight was affected by DMD so far. However, starting steroids will certainly change that (at the very minimum his height). So how can we extrapolate to age 10 under these conditions? Do they use historical data in non-steroid treated boys?

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