Neurosurgery

Diagnosis and Treatment of Acromegaly

 

Overview

Acromegaly is a rare disorder resulting from a pituitary tumor that overproduces growth hormone (GH). The physical changes may be disfiguring (enlarged nose, lips, hands, feet) and uncomfortable (excess sweating, headaches, dizziness, arthritis). Acromegaly can also cause:

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.

Treatment at Stanford

Patients can receive an evaluation and treatment for acromegaly at the Stanford Pituitary Center.

Diagnosis

Once acromegaly is suspected, diagnosis is straightforward.

Therapy

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.  The goal is to remove or debulk the tumor.  Success of surgery depends on the size and location of the tumor, and the experience 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). Overall, 60% of patients have normal GH and IGF-1 levels following surgery. With an experienced surgeon, complication rates following surgery are very low.

Medical Therapy

For residual disease following surgery, the options include medical therapy or radiation therapy. There are 3 classes of medical therapies:

Somatostatin analogs are administered as monthly injections. There are two available analogs: octreotide (Sandostatin®) LAR (long-acting release) is administered as a monthly intramuscular injection and lanreotide autogel (Somatuline®) depot is administered as a monthly deep subcutaneous injection. Both analogs control GH and IGF-1 levels in approximately 2/3 of patients. Somatostatin analogs lead to improvement in symptoms in the majority. In selected patients, 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 (Parlodel®) 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 (Dostinex®), may be more effective in controlling GH levels, in up to 39% of patients in one study. The dopamine agonists are oral preparations. In recent studies of patients with Parkinson’s disease who were taking high doses of cabergoline, cardiac valve problems were noted. It is unclear whether these findings are relevant in subjects with acromegaly who take cabergoline.

A Growth Hormone Receptor Antagonist (GH), pegvisomant (Somavert®), 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, biweely, or weekly 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.

Combination Therapy

In patients who are partially responsive to somatostatin analogs, further benefit can be achieved by adding either a dopamine agonist, such as cabergoline, or pegvisomant.

Radiation Therapy

Radiation therapy for acromegaly is usually reserved for patients who have tumor remaining after surgery, and are often incompletely responsive to medical therapy. Radiation therapy may be given in divided doses over four to six weeks. This treatment lowers GH levels by about 50 percent over 2 to 5 years, and may lead to normal growth hormone and IGF-1 levels in patients.

In selected patients, radiation therapy may be given as highly focused, single treatments.  CyberKnife, proton beam, or gamma knife radiosurgery may be used for such treatment.  Radiosurgery may lead to more rapid decreases in GH levels.  Radiation therapy causes 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.

 

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