Acromegaly
Acromegaly (from Greek akros "high" and megalos "large" - extremities enlargement) is a is a hormonal disorder that results when the pituitary gland produces excess growth hormone (hGH). Most commonly it is a benign hGH producing tumor derived from a distinct type of cells (somatotrophs) and called pituitary adenoma. It most commonly affects middle-aged adults and can result in serious illness and premature death. In children the related condition is called gigantism, because long bones can still grow. The disease because of its slow and often insidious onset, is frequently not diagnosed correctly.
Features that result from high level of hGH or expanding tumor include:
- Soft tissue swelling of the hands and feet (early sign)
- Brow and lower jaw protrusion (enlarging jaw and hat size)
- Enlarging hands (ring size)
- Enlarging feet (shoe size)
- Arthritis and carpal tunnel syndrome
- Teeth spacing increase
- Heart failure (major medical problem).
- Compression of the optic chiasm leading to loss of vision in the outer visual fields.
- diabetes mellitus
- hypertension
Causes
In over 90 percent of acromegaly patients, the overproduction of GH is
caused by a benign tumor of the pituitary gland, called an adenoma.
These tumors produce excess GH and, as they expand, compress surrounding
brain tissues, such as the optic nerves. This expansion causes the
headaches and visual disturbances that are often symptoms of acromegaly.
In addition, compression of the surrounding normal pituitary tissue can
alter production of other hormones, leading to changes in menstruation
and breast discharge in women and impotence in men.
There is a marked variation in rates of GH production and the
aggressiveness of the tumor. Some adenomas grow slowly and symptoms of
GH excess are often not noticed for many years. Other adenomas grow
rapidly and invade surrounding brain areas or the sinuses, which are
located near the pituitary. In general, younger patients tend to have
more aggressive tumors.
Most pituitary tumors arise spontaneously and are not genetically
inherited. Many pituitary tumors arise from a genetic alteration in a
single pituitary cell which leads to increased cell division and tumor
formation. This genetic change, or mutation, is not present at birth,
but is acquired during life. The mutation occurs in a gene that
regulates the transmission of chemical signals within pituitary cells;
it permanently switches on the signal that tells the cell to divide and
secrete GH. The events within the cell that cause disordered pituitary
cell growth and GH oversecretion currently are the subject of intensive
research.
In a few patients, acromegaly is caused not by pituitary tumors but by
tumors of the pancreas, lungs, and adrenal glands. These tumors also
lead to an excess of GH, either because they produce GH themselves or,
more frequently, because they produce GHRH, the hormone that stimulates
the pituitary to make GH. In these patients, the excess GHRH can be
measured in the blood and establishes that the cause of the acromegaly
is not due to a pituitary defect. When these non-pituitary tumors are
surgically removed, GH levels fall and the symptoms of acromegaly improve.
In patients with GHRH-producing, non-pituitary tumors, the pituitary
still may be enlarged and may be mistaken for a tumor. Therefore, it is
important that physicians carefully analyze all "pituitary tumors"
removed from patients with acromegaly in order not to overlook the
possibility that a tumor elsewhere in the body is causing the disorder.
Treatment
The goals of treatment are to reduce GH production to normal levels, to
relieve the pressure that the growing pituitary tumor exerts on the
surrounding brain areas, to preserve normal pituitary function, and to
reverse or ameliorate the symptoms of acromegaly. Currently, treatment
options include surgical removal of the tumor, drug therapy, and
radiation therapy of the pituitary.
Surgery
Surgery is a rapid and effective treatment. The surgeon reaches the
pituitary through an incision in the nose and, with special tools,
removes the tumor tissue in a procedure called transsphenoidal surgery.
This procedure promptly relieves the pressure on the surrounding brain
regions and leads to a lowering of GH levels. If the surgery is
successful, facial appearance and soft tissue swelling improve within a
few days. Surgery is most successful in patients with blood GH levels
below 40 ng/ml before the operation and with pituitary tumors no larger
than 10 mm in diameter. Success depends on the skill and experience of
the surgeon. The success rate also depends on what level of GH is
defined as a cure. The best measure of surgical success is normalization
of GH and IGF-1 levels. Ideally, GH should be less than 2 ng/ml after an
oral glucose load. A review of GH levels in 1,360 patients worldwide
immediately after surgery revealed that 60 percent had random GH levels
below 5 ng/ml. Complications of surgery may include cerebrospinal fluid
leaks, meningitis, or damage to the surrounding normal pituitary tissue,
requiring lifelong pituitary hormone replacement.
Even when surgery is successful and hormone levels return to normal,
patients must be carefully monitored for years for possible recurrence.
More commonly, hormone levels may improve, but not return completely to
normal. These patients may then require additional treatment, usually
with medications.
Drug Therapy
Two medications currently are used to treat acromegaly. These drugs
reduce both GH secretion and tumor size. Medical therapy is sometimes
used to shrink large tumors before surgery. Bromocriptine (Parlodel)
in divided doses of about 20 mg daily reduces GH secretion from some
pituitary tumors. Side effects include gastrointestinal upset, nausea,
vomiting, light-headedness when standing, and nasal congestion. These
side effects can be reduced or eliminated if medication is started at a
very low dose at bedtime, taken with food, and gradually increased to
the full therapeutic dose.
Because bromocriptine can be taken orally, it is an attractive choice as
primary drug or in combination with other treatments. However,
bromocriptine lowers GH and IGF-1 levels and reduces tumor size in less
than half of patients with acromegaly. Some patients report improvement
in their symptoms although their GH and IGF-1 levels still are elevated.
The second medication used to treat acromegaly is octreotide
(Sandostatin). Octreotide is a synthetic form of a brain hormone,
somatostatin, that stops GH production. This drug must be injected under
the skin every 8 hours for effective treatment. Most patients with
acromegaly respond to this medication. In many patients, GH levels fall
within one hour and headaches improve within minutes after the
injection. Several studies have shown that octreotide is effective for
long-term treatment. Octreotide also has been used successfully to treat
patients with acromegaly caused by non-pituitary tumors.
Because octreotide inhibits gastrointestinal and pancreatic function,
long-term use causes digestive problems such as loose stools, nausea,
and gas in one third of patients. In addition, approximately 25 percent
of patients develop gallstones, which are usually asymptomatic. In rare
cases, octreotide treatment can cause diabetes. On the other hand,
scientists have found that in some acromegaly patients who already have
diabetes, octreotide can reduce the need for insulin and improve blood
sugar control.
Radiation Therapy
Radiation therapy has been used both as a primary treatment and combined
with surgery or drugs. It is usually reserved for patients who have
tumor remaining after surgery. These patients often also receive
medication to lower GH levels. Radiation therapy is given in divided
doses over four to six weeks. This treatment lowers GH levels by about
50 percent over 2 to 5 years. Patients monitored for more than 5 years
show significant further improvement. Radiation therapy causes a gradual
loss of production of other pituitary hormones with time. Loss of vision
and brain injury, which have been reported, are very rare complications
of radiation treatments.
No single treatment is effective for all patients. Treatment should be
individualized depending on patient characteristics, such as age and
tumor size. If the tumor has not yet invaded surrounding brain tissues,
removal of the pituitary adenoma by an experienced neurosurgeon is
usually the first choice. After surgery, a patient must be monitored for
a long time for increasing GH levels. If surgery does not normalize
hormone levels or a relapse occurs, a doctor will usually begin
additional drug therapy. The first choice should be bromocriptine
because it is easy to administer; octreotide is the second alternative.
With both medications, long-term therapy is necessary because their
withdrawal can lead to rising GH levels and tumor re-expansion.
Radiation therapy is generally used for patients whose tumors are not
completely removed by surgery; for patients who are not good candidates
for surgery because of other health problems; and for patients who do
not respond adequately to surgery and medication.
Largely adopted from http://www.niddk.nih.gov/health/endo/pubs/acro/acro.htm
Referenced By
Carpal Tunnel syndrome | Endocrinology | List of rare diseases | List of rare diseases/A | List of rare diseases starting with A
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