Based on a consensus of over 60 of the top experts in acromegaly, there are 4 goals in the treatment of acromegaly:

1. Reduce concentration of growth hormone (GH) and insulin-like growth factor-I (IGF-I) to a normal level
2. Relieve pressure from the pituitary tumour on the optic nerves and surrounding areas of the brain
3. Preserve normal pituitary function
4. Reverse or improve the symptoms of acromegaly.

Treatment options recommended by the Expert Consensus Guidline for acromegaly include:

• Surgery to remove the tumour
• Drug therapy
• Radiation therapy of the pituitary

Surgery

Transsphenoidal surgery is an invasive procedure performed to remove pituitary tumours. With this surgery, pressure on the brain regions surrounding the tumour is relieved and growth hormone levels are reduced. If the surgery is successful, the patient's facial appearance and soft tissue swelling improve within a few days. Surgery is most successful in patients who have pituitary tumours no larger than 10 mm in diameter. The best measures of surgical success are normal levels of growth hormone and insulin-like growth factor-I (IGF-I). A GH level of less than 1 µg/L after an oral glucose load is ideal.

Complications of transsphenoidal surgery may include:

• Damage to surrounding normal pituitary tissue, requiring lifelong pituitary hormone replacement
• Cerebrospinal fluid leaks
• Meningitis

Even after successful surgery and normalization of hormone levels, patients should be monitored closely for possible recurrence, even years after the surgery. More commonly, hormone levels will improve, but they may not return to normal. Additional treatment, usually with drug therapy, may be required.

 

Drug Therapy

Medication for acromegaly may decrease the secretion of GH and the subsequent production of IGF-I, reduce the size of the tumour, and control symptoms. Drug therapy has been used to shrink large tumours before surgery.

Somatostatin is a brain hormone that inhibits GH release. Octreotide is a synthetic form of somatostatin used in the treatment of acromegaly. Sandostatin® LAR® (octreotide/IM injection, Novartis), a longer-acting slow-release form of octreotide, is available for the treatment of acromegaly. It is administered intramuscularly once montly (compared with 3 times a day for the standard formulation of octreotide). Efficacy of the slow-release form of octreotide-in the control of GH, IGF-I, and clinical symptoms-is similar to that of the standard formulation, which has been used as a safe and effective treatment for acromegaly for over 15 years.

Another somatostatin analogue, lanreotide, is available as an extended-release aqueous gel and as a long-acting microparticle formulation.5 A variety of dopamine agonists, the most common being bromocriptine (eg, Parlodel®, originally used effectively for prolactin-secreting tumours of the pituitary), are used to treat acromegaly. Pegvisomant, a GH receptor antagonist, selectively binds to growth hormone (GH) receptors on cell surfaces, blocking the binding of GH and interfering with GH signal transduction.

 

Radiation Therapy

According to Expert Consensus Guideline, external pituitary radiotherapy should not be used as the primary therapy except under extraordinary circumstances. The effects of radiotherapy on GH and IGF-I levels are slow-in 50 percent of cases, GH and IGF-I levels are less than 2.5 µg/L at 10 years. An almost constant decline in pituitary function occurs, and replacement therapy with sex steroids, thyroxine, hydrocortisone, or a combination of these is necessary in 70 percent of patients after 10 years of radiotherapy.

The effect of radiotherapy on the pulsatility of GH may result in GH deficiency. Less frequent side effects of radiotherapy include visual problems, a second malignancy in the field of radiotherapy (rate of 2 percent in 20 years), and psychological or memory deficit.

Gamma-knife radiotherapy has also been used in the treatment of acromegaly and is administered as a single dose. It has been shown that the decrease in GH levels occurs more quickly than with ordinary external beam radiotherapy. However, long-term studies have not been published, and there are a limited number of machines worldwide.

 

Mortality

Patients with acromegaly have a reduced life expectancy, with an increased mortality rate of two-to-four-fold. The main determinant is the most recent serum GH concentration measured over a 24-hour period, and increased mortality is also associated with elevated insulin-like growth factor-I (IGF-I). Analysis of acromegalic patients has shown that post-treatment GH levels in excess of 5 to 10 µg/L predict increased mortality. The duration of symptoms before diagnosis, older age at diagnosis, duration of disease, and the presence of diabetes, hypertension, and cardiovascular disease are other factors associated with increased mortality. A decrease in the level of GH to <2.5 µg/L improves mortality.