making muscle wasting history

By Meilan Rutter, MB, BCh, FRACP

What is an endocrinologist?

Yet another specialist with an unpronounceable name!” families with Duchenne may say. In addition, an endocrinologist is a doctor who specializes in the endocrine system. Endocrine glands produce hormones (chemical messengers) which stimulate parts of our body to carry out specific functions. For example, the pituitary gland secretes growth hormone which regulates growth. The pancreas produces the hormone, insulin, which controls the body’s blood sugar levels. A boy’s testicles make the male hormone, testosterone, which causes him to develop during puberty. Hormones like testosterone and vitamin D are important for bone health. An endocrinologist sees patients who produce too little or too much of a particular hormone, leading to problems such as abnormal growth or weight gain, delayed puberty or osteoporosis (thinning of bones).

How does the endocrine system relate to Duchenne?

Boys with Duchenne who are treated with long-term steroids (such as prednisone or deflazacort) may experience endocrine problems. It is important to note that these problems can occur in any child receiving long-term steroids, and Duchenne boys do not inherently have an underlying endocrine disorder. Steroids significantly improve the outcome in Duchenne: they prolong the time a boy is able to continue walking, and benefit muscle strength, lung and heart function. However, steroids may have adverse effects on the endocrine system, including slowing of height growth, excessive weight gain, increased insulin or blood sugar levels, prevention of normal puberty, and thinning of bones. In addition, treatment with steroids shuts down the body’s own ability to produce a similar hormone, cortisol, which helps the body cope with illness or injury – this is usually not a problem as long as steroids continue to be given in its place.

What are typical endocrine problems that boys with Duchenne face?

Some steroid-treated boys with Duchenne may experience slowing of height growth and excessive weight gain. The growth chart (figure) shows an extreme example of a boy with Duchenne on steroids whose weight continued to increase despite his height staying the same. Wheelchair dependency without due attention to calorie intake may exacerbate weight gain, regardless of steroids. Being overweight may cause the hormone, insulin, to become less effective (“insulin resistance”), occasionally resulting in increased blood sugar levels or even diabetes. Excessive weight may also impede mobility, lung and heart function. Long-term steroids may prevent puberty from occurring, as well as preventing other benefits of puberty hormones such as building strong bones. The corollary of weakened bones is an increased risk of fractures, which can affect mobility. Each of these endocrine issues has the potential to impact quality of life in Duchenne.

Is there anything we can do?

In general, endocrine therapies involve replacing deficient hormones or countering the effects of hormone (e.g. steroid) excess. The table summarizes potential endocrine therapies for the typical problems in Duchenne. Awareness on the part of the family and monitoring by the medical team may identify endocrine issues warranting concern, prompting referral to an endocrinologist if indicated.

Following growth over time with a growth chart will reveal slowing of height growth or excessive weight gain. If there is severe growth failure, endocrine evaluation should be undertaken and growth hormone may be considered if criteria are met. A healthy diet is critical in preventing excessive weight gain, and advice from a dietician may be invaluable. When significant weight gain persists despite a family’s best efforts, and if “insulin resistance” is found on further testing, an endocrinologist could consider a medicine which counters insulin resistance and helps control weight, such as metformin.

A physical examination will show whether a boy has started puberty. If puberty is absent in a teenage boy on steroids, testosterone (the male hormone which brings about puberty changes) could be given. A related aspect of care is bone health, and a “DXA” scan is often used to measure bone density. Optimizing vitamin D and calcium intake is important at an early stage, testosterone replacement is an option for older boys, and medicines used to treat osteoporosis in adults (“bisphosphonates”) are sometimes considered in severe cases.

Are there any caveats?

Some endocrine therapies have not been specifically tried and tested in Duchenne, and long-term data from large scientific studies is lacking. An example which has generated recent interest is growth hormone. Growth hormone is typically used to treat people who lack growth hormone, and may improve height in children with chronic arthritis on steroids (although the latter would be considered an investigational use). At Cincinnati Children’s Hospital in the USA, 20 boys with Duchenne and severe steroid-induced growth failure were treated with growth hormone, of which the first 8 boys followed up for over a year showed an improvement in growth rate, muscle strength and lung function. However, growth hormone is an extremely expensive medication, and rigorous criteria must be met for treatment to be approved.

Where does this leave me?

“Yet another specialist…” – but we now have a choice. We can remain inactive, or reactive, addressing the endocrine problems should they arise, or even proactive, seeking to prevent problems before they set in. The latter approach raises the need for more research in this area. In the meantime, seeing an endocrinologist is an option to be considered. However, should endocrine care be undertaken, it needs to be individualized and ideally monitored in a multidisciplinary setting, to optimize health and quality of life in boys with Duchenne.