Acromegaly

Overview

Acromegaly is a hormonal disorder in which the pituitary gland produces too much growth hormone. This disorder causes abnormal enlargement of bones and tissues, noticeably in the hands and feet, which occurs gradually over several years.

Enlarged bones in the nose and mouth may cause a large tongue and widely spaced teeth and may lead to sleep apnea. Bone and cartilage growth may lead to arthritis. People with acromegaly can also develop diabetes, high blood pressure, and other problems.

The excess production of growth hormone usually is caused by a tumor of the pituitary gland. Acromegaly is usually treated with medicine, surgery, or radiation treatment to the tumor.

Our neuroendocrinology experts at the Stanford Pituitary Center are widely recognized for their expertise in diagnosing and treating Acromegaly, and our pituitary-expert neurosurgeons are highly specialized in the endoscopic endonasal approach for Acromegaly and have developed innovative techniques aiming to improve surgical results.

Symptoms

The onset of acromegaly is insidious and seemingly benign, so the signs and symptoms are often ignored or are associated with other more common causes.

By the time an acromegaly patient sees an endocrinologist for diagnosis and treatment, the signs and symptoms have already become very distressing and in some cases permanent. Acromegaly may also lead to a risk of premature mortality.

Early diagnosis and appropriate therapy may lead to reversal and/or prevention of these long-term consequences.

Diagnosis

Once acromegaly is suspected, diagnosis is straightforward.

An elevated serum insulin-like growth factor -1 (IGF-1), in the appropriate clinical setting, is adequate for the diagnosis of acromegaly. This blood test can be drawn anytime during the day, and does not need to be fasting.

A glucose tolerance test is another test, and, following ingestion of the glucose drink (75 gm glucola), GH levels in normals should fall to below 1 ng/mL. If they do not fall to that level, acromegaly is strongly suggested.

A brain MRI should be performed to locate the tumor and confirm the diagnosis. In most cases of acromegaly, a pituitary macroadenoma (greater than 10 mm) is found. Often, adenomas causing Acromegaly are large and invasive representing a real challenge for treatment.

Treatment

Surgery is the preferred treatment for Acromegaly.

In the past, microscopic transsphenoidal surgery was the most common operation. At Stanford, we use the more advanced endoscopic endonasal approach, which uses the latest technological advances, such as 4K endoscopic visualization technology and very fine instruments, to approach the pituitary gland through the nostrils in combination with the ENT endoscopic experts. This is an extremely delicate procedure, which should only be performed by highly specialized surgeons at multidisciplinary Pituitary centers.

Success of surgery depends on the size and location of the tumor, and the experience and skills of the neurosurgeon. For example, surgery is more successful with a microadenoma (a tumor less than 10 mm in size) compared with a macroadenoma (tumor greater than 10 mm in size). In our experience about 70% of patients have normal GH and IGF-1 levels following surgery. The expertise of the surgical team is a key factor in achieving best possible results with very low complication rates. Recent surgical innovations introduced by Dr. Fernandez-Miranda, such has removal of the medial wall of the cavernous sinus and removal of cavernous sinus tumors, have significantly improved surgical outcomes in acromegalic patients.

Medical treatment

For residual or active disease following surgery, the options include medical therapy or radiation therapy. Given the novel medical therapies available, growth hormone control should be achieved in most patients.

There are several medical therapies available:

Somatostatin analogs are administered as intramuscular injections once a month. In the U.S., the analogs octreotide LAR (long-acting release) and lanreotide depot are available and control GH and IGF-1 levels in approximately 2/3 of patients. Octreotide and lanreotide lead to improvement in symptoms in the majority. In about 40% of patients, the tumor can shrink modestly as well. In selected patients, when the tumor is not completely removable and is not causing visual loss, somatostatin analogs may be used as initial therapy in lieu of surgery. Side effects include 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.

Dopamine agonists have been used largely as second-line medial therapy. Bromocriptine in divided doses of up to 20 mg daily reduces GH secretion from a small number of pituitary tumors. Side effects include gastrointestinal upset, nausea, vomiting, light-headedness when standing, and nasal congestion. Another dopamine agonist, cabergoline, may be more effective in controlling GH levels, in up to 39% of patients in one study. The dopamine agonists are oral preparations.

A growth hormone receptor antagonist, pegvisomant, is a novel approach to acromegaly treatment by blocking all peripheral effects of GH, resulting in decreased production of IGF-1, both locally and at the liver. Pegvisomant, administered as a daily subcutaneous injection, can be used in patients who do not respond to somatostatin analogs or other types of treatment or may be considered as first line therapy in selected patients. Pegvisomant is highly effective, and may normalize IGF-1 levels in up to 97% of patients. Potential complications include an increase in tumor size (uncommon) and changes in liver function tests. MRI scans and liver tests need to be monitored.

A relatively new medication, pasireotide, that works like somatostatin to lower tumor production of GH. It works better than either ocreotide or lanreotide, but has a higher risk of raising glucose or causing diabetes mellitus.

Radiation treatment

Radiation therapy for acromegaly is usually reserved for patients who have tumor remaining after surgery. These patients often also receive medication to lower GH levels. Radiation therapy may be given in divided doses over four to six weeks. This treatment lowers GH levels by about 50 percent over two to five years.

In selected patients, radiation therapy may be given as highly focused, single or multiple treatments. CyberKnife, proton beam, or gamma knife radiosurgery may be used for such treatment. Radiation therapy may cause a gradual loss of pituitary hormone levels over time, resulting in hypopituitarism. Loss of vision and brain injury, which have been reported, are very rare complications of radiation treatments.