Endocrine Myopathies

Endocrine myopathies are caused by underlying conditions caused by the

over- or underproduction of hormones. These conditions can develop in
children and adults and usually respond well to treatment.
Steroid myopathy is the most common endocrine muscle disease.
Steroid excess, whether caused by an adrenal gland disorder (e.g., Addison
disease) or chronic administration of glucocorticoid drugs, causes muscle
weakness and wasting.
Hyperthyroid myopathy is caused by the thyroid gland producing too
much thyroxine. Its symptoms include weakening and wasting of the
muscles, especially in the shoulders and hips, and sometimes the eyes.
Hypothyroid myopathy is caused by the underproduction of thyroxine
and results in muscle weakening in the legs and arms. The muscles may
become enlarged.
Cushing's disease, characterized by overproduction of hormones
produced by the pituitary and adrenal glands, cause myopathy.
Excess parathyroid hormone results in hypercalcemia, which causes
proximal muscle pain and weakness.
Hormone-secreting tumors (e.g., growth-hormone secreting
pituitary adenoma) can cause endocrine disorders that produce myopathy.

Inflammatory Myopathies
Inflammatory myopathies are autoimmune disorders. An autoimmune
disorder is caused by the body's immune system mistakenly attacking
healthy tissue. In this case, it attacks healthy muscle fibers and causes
inflammation, which in turn damages the muscle. It is not known what
triggers this autoimmune response.
The severity and progression of these myopathies vary considerably. Some
people develop other disorders, such as abnormal heart rhythms, lung
disease, gastrointestinal problems, arthritis, or cancer.
Polymyositis (PM) can occur at any age in either gender, but is more
common in children and in women between 40 and 60 years old. Most people
with PM suffer muscle aches, cramping, and tenderness. The muscle
weakness is, however, quite intense and may fluctuate over weeks to
months. It is often worse in the neck, arms, and thighs, making it difficult to
 stand up from a sitting position. Many patients also experience fever, general
discomfort (malaise), and loss of appetite.
Dermatomyositis (DM) is characterized by a skin rash and all of the
muscle symptoms of PM. The rash is a purple discoloration around the eyes
and on the cheeks but may also appear on other parts of the body.
Eventually the skin becomes thin and fragile. DM most commonly develops
in children between the ages of 5 and 14 years. People who have DM have
an increased risk for developing cancer.

Toxic Myopathies
Exposure to certain medications, chemicals, and excessive alcohol intake can
damage skeletal muscle. Drugs and types of chemicals that can cause
myopathy include the following:
Anesthetics (e.g., lidocaine, mepivacaine, ethyl chloride)
Cholesterol-lowering agents (e.g., clofibrate, genfibrozil, lovastatin,
simivastatin, niacin)
Glucocorticoids (e.g., triamcinolone, dexamethasone, betamethasone)
Narcotics (e.g., cocaine, heroin, meperidine)
Other drugs (e.g., zidovudine, D-penicillamine, procainamide,
chloroquine, gallamine)
Herbicides, insecticides, flame retardants
Myopathies
Definition
Myopathies are diseases of skeletal muscle that are not caused by nerve disorders. These
diseases cause the skeletal or voluntary muscles to become weak or shrunken (atrophied).

Description
There are many different types of myopathies. Some are inherited, some inflammatory, and
some caused by endocrine or metabolic problems. Myopathies usually are not fatal. Typically
they cause muscle weakness and movement problems. The shoulders and thigh muscles are
usually, but not always, affected earlier than the muscles of the hands and feet. Most
myopathies are degenerative, meaning they become more pronounced over time. Some
weaknesses are transitory. Only rarely do individuals become dependent on a wheelchair.
However, muscular dystrophy (technically a myopathy) is far more severe. Some types of
muscular dystrophy are fatal in early adulthood.

Causes and symptoms

There is great variety among myopathies, but what they all share are effects on the skeletal
muscles. The main causes of myopathies are genetic, inflammatory (caused by infection),
endocrine (hormonal), and metabolic (errors in how cells function). Often the cause of the
myopathy is not known (idiopathic disease).

Genetic myopathies
Among their many functions, genes are responsible for overseeing the production of proteins
important in maintaining healthy cells. Muscle cells produce thousands of proteins. With each of
the inherited myopathies, a genetic defect is linked to a lack of, or defect in, one of the proteins
needed for normal muscle cell function.

There are several different kinds of myopathy caused by defective genes:

central core disease

centronuclear (myotubular) myopathy

myotonia congenita

nemaline myopathy

paramyotonia congenita

periodic paralysis (hypokalemic and hyperkalemic forms)

mitochondrial myopathies

Most, but not all, of these genetic myopathies are inherited through an autosomal
dominant pattern of inheritance. In this pattern of inheritance, one copy of each gene comes
from each parent. Only one of these two copies needs to have the mutation (change) or defect
in order for the child to have the disease. The parent with the defective gene has the disease,
and each of this parent's children has a 50 percent chance of inheriting the disease. This
percentage is not changed by results of other pregnancies. With this pattern of inheritance, male
and female children are equally at risk of developing the disease.

However, for a child to have one type of myotonia congenita and some forms of nemaline
myopathy, two defective genes must be inheritedone from each parents. This is called an
autosomal recessive pattern of inheritance. Neither parent may have symptoms of the disease,
but each carries a recessive defective gene for it. Each child of such parents has a 25 percent
chance of inheriting both genes and showing signs of the disease, and a 50 percent chance of
inheriting one defective gene from only one parent. If the child has inherited just one defective
gene, he or she will be a carrier of the disease and can pass the gene on to his or her offspring,
while showing no signs of the disease himself.

A few forms of centronuclear myopathy develop primarily in males. Females who inherit the
defective gene are usually carriers without symptoms, like their mothers, but they can pass on
the disease to their sons. Mitochondrial myopathies are inherited only through the mother, since
sperm do not contain mitochondria.

The major symptoms associated with the genetic myopathies are:

 Central core disease: mild weakness of voluntary muscles, especially in the hips and
legs; hip displacement; delays in reaching developmental motor milestones; problems
with running, jumping, and climbing stairs develop in childhood.

Centronuclear myopathy: weakness of voluntary muscles, including those on the face,

arms, legs, and trunk; drooping upper eyelids; facial weakness; foot drop; affected
muscles almost always lack reflexes.

Myotonia congenita: voluntary muscles of the arms, legs, and face stiff or slow to relax
after contracting (myotonia); stiffness triggered by fatigue, stress, cold, or long rest
periods, such as a night's sleep ; stiffness can be relieved by repeated movement of the
affected muscles.

Nemaline myopathy: moderate weakness of voluntary muscles in the arms, legs, and
trunk; mild weakness of facial muscles; delays in reaching developmental motor
milestones; decreased or absent reflexes in affected muscles; long, narrow face; high-
arched palate; jaw projects beyond upper part of the face.

Paramyotonia congenita: stiffness of voluntary muscles in the face, hands, and forearms;
attacks spontaneous or triggered by cold temperatures; stiffness made worse by
repeated movement; episodes of stiffness last longer than those seen in myotonia
congenita.

Periodic paralysis: attacks of temporary muscle weakness (muscles work normally

between attacks); in the hypokalemic (low potassium) form, attacks triggered by
vigorous exercise , heavy meals high in carbohydrates, insulin, stress, alcohol, infection,
pregnancy; in the hyperkalemic (high potassium) form, attacks triggered by vigorous
exercise, stress, pregnancy, missing a meal, steroid drugs, high potassium intake.

Mitochondrial myopathies: symptoms vary quite widely with the form of the disease and
may include progressive weakness of the eye muscles (ocular myopathy), weakness of
the arms and legs, or multisystem problems primarily involving the brain and muscles.

Endocrine-related myopathies
In some cases, myopathies can be caused by a malfunctioning endocrine gland that produces
either too much or too little of the chemical messengers called hormones. Hormones travel
through the bloodstream. One of their many functions is to help regulate muscle activity.
Problems in producing hormones can lead to muscle weakness.

Hyperthyroid myopathy and hypothyroid myopathy affect different muscles in different ways.
Hyperthyroid myopathy occurs when the thyroid gland produces too much of the hormone
thyroxine, leading to muscle weakness, some muscle wasting in hips and shoulders, and,
sometimes, problems with eye muscles. The hypothyroid type of myopathy occurs when too little
hormone is produced, leading to stiffness, cramps, and weakness of arm and leg muscles.

Inflammatory myopathies
Some myopathies are caused by inflammation. Inflammation is a protective response of injured
tissues characterized by redness, increased heat, swelling, and/or pain in the affected area.
Examples of this type of myopathy include dermatomyositis , polymyositis, and myositis
ossificans.

Dermatomyositis is a disease of the connective tissue that also involves weak, tender, inflamed
muscles. Muscle tissue loss may be so severe that the individual may be unable to walk. Skin
inflammation is also present. The cause of dermatomyositis is as of 2004 unknown, but viral
infection and antibiotic use are associated with the condition. In some cases, dermatomyositis is
associated with rheumatologic disease or cancer . Polymyositis involves inflammation of many
muscles, usually accompanied by deformity, swelling, sleeplessness, pain, sweating, and
tension. It, too, may be associated with cancer. Myositis ossificans is a rare inherited disease in
which muscle tissue is replaced by bone, beginning in childhood.

Muscular dystrophies
While considered a separate group of diseases, the muscular dystrophies also involve muscle
wasting and can be described as myopathies. Symptoms of muscular dystrophy (MD) diseases
usually appear during childhood and adolescence . These are genetic disorders that result in
defects in the production of specific proteins. The forms of muscular dystrophy differ according
to the way they are inherited, the age at which symptoms begin, the muscles they affect, and
how fast they progress.

Demographics
Myopathies are not common. About 14 percent of myopathies are inherited. Worldwide the rate
of inflammatory myopathies is about five to ten individuals per 100,000. These myopathies are
more often seen in women. MD is found in about 63 of every 1 million individuals, but the rates
vary widely depending on the type of MD. The most common type is Duchenne MD, affecting
one in every 3,300 boys. Other more common types of MD are Becker's, myotonic dystrophy ,
limb-girdle MD, and facioscapulohumeral MD. MD is more common in boys. The rate of
metabolic and endocrine myopathies was, as of 2004, not known.

When to call the doctor

Parents should let the doctor know as soon as possible if there is a family history of muscle
weakness or muscle wasting disease. Otherwise, they should contact their pediatrician if the
child is showing any signs of delayed or abnormal growth or unexplained muscle weakness.

Diagnosis
Early diagnosis of myopathy is important in order to provide the best care possible. An
experienced physician can diagnose a myopathy by evaluating a child's medical history and by
performing a thorough physical examination. Diagnostic tests can help differentiate among the
different types of myopathies, as well as between myopathy and other neuromuscular disorders.
If the doctor suspects a genetic myopathy, a thorough family history will also be taken. Genetic
tests are available for a few myopathies.

Diagnostic tests the doctor may order include: measurements of potassium, (K) creatine kinase,
(CK) lactic dehydrogenase (LDH) and pyruvate kinase (PK) and certain antibodies in the blood;
muscle tissue biopsy; and electromyogram (EMG).

Treatment
As of 2004, there was no cure for many myopathies. Treatment depends on the specific type of
myopathy the person has and is aimed at controlling symptoms. Specific treatment approaches
for specific forms of myopathies are as follows:

periodic paralysis: medication and dietary changes

hyperthyroid or hypothyroid myopathy: treatment of the underlying thyroid abnormality

myositis ossificans: medication to help prevent abnormal bone formation, but there is no
cure following onset

central core disease: no treatment

nemaline myopathy: no treatment

centronuclear (myotubular) myopathy: no treatment

paramyotonia congenita: treatment often unnecessary

myotonia congenita: drug treatment (if necessary), but drugs do not affect the underlying
disease, and attacks may still occur
General treatments aim at supporting the individual's functioning and independence. Physical
therapy can help preserve or increase strength and flexibility in muscles. Ankle and wrist braces
can support weakened limbs. Occupational therapy is used to develop tools and techniques to
compensate for loss of strength and dexterity. A speech-language pathologist can provide
retraining for weakness in the muscles controlling speech and swallowing.

Prognosis
The prognosis for patients with myopathy depends on the type and severity of the individual's
disease. In most cases, the myopathy symptoms can be successfully treated, but in others, the
disease can be fatal in childhood or adolescence.

KEY TERMS
Electrooculography (EOG) A diagnostic test that records the electrical activity of the
muscles that control eye movement.

Hyperkalemia An abnormally high level of potassium in the blood.

Hypokalemia A condition characterized by a deficiency of potassium in the blood.

Inflammation Pain, redness, swelling, and heat that develop in response to tissue irritation or
injury. It usually is caused by the immune system's response to the body's contact with a foreign
substance, such as an allergen or pathogen.

Mitochondria Spherical or rod-shaped structures of the cell. Mitochondria contain genetic

material (DNA and RNA) and are responsible for converting food to energy.

Voluntary muscles Muscles that can be moved by conscious thought.

Muscular dystrophy is generally a more serious disease than many other types of myopathies.
Duchenne's MD is usually fatal by the late teens; Becker's MD is less serious and may not be
fatal until the 50s.

Prevention
As of 2004 there is no way to prevent the genetic mutations that cause myopathies, nor are
there ways to prevent metabolic and endocrine failures that result in myopathies. Inflammatory
myopathies often occur as a result of exposure to viruses or drugs, but it is almost impossible to
predict their development.

Parental concerns
Individuals with known myopathies who wish to become parents may want to seek genetic
counseling before attempting to have children.