Acromegaly

Acromegaly (from Greek akros "high" and megalos "large" - extremities enlargement) 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.

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.

~ ~ ~ ~ ~ ~ ~ ~ ~ ~