Acromegaly is a rare disease, with an incidence approximated at 3–4 cases per million per year,8
and estimated prevalence of 8.6 per 100,000 or higher.9
The onset is insidious with diagnosis often delayed for many years.11
Left untreated, the disease causes a significant increase in mortality, due primarily to cardiovascular and cerebrovascular disease.1
Treatment of acromegaly improves the increased risk of mortality, decreases comorbidity, and improves quality of life. Reduction in serum GH levels and normalization of serum IGF-I levels are associated with a return of mortality risk to that of a control population.13
The goals of therapy include control of GH secretion, control of the tumor mass, reduction in associated comorbidities and symptoms of acromegaly, and preservation of normal pituitary function. Treatment modalities currently employed include surgery, medical therapy, and radiation therapy. Recent advances have furthered the field of acromegaly treatment, including improvements in surgical techniques incorporating endoscopic instruments and techniques employed for stereotactic radiation, as well as novel medications and medication delivery systems.
Surgical resection of a GH secreting pituitary tumor is the primary treatment of choice for most of the patients with acromegaly.15
In experienced hands, the surgical cure rate is high for microadenomas (maximum diameter < 10 mm), but the cure rate declines when tumors are invasive or for macroadenomas (diameter > 10 mm).6
When surgery is successful, as measured by normalization of elevated IGF-I, and suppression of GH by a glucose load, patients continue to require monitoring for tumor recurrence but do not need further treatment of excess growth hormone. If surgery is not curative, further treatment is required.
There are multiple medications available to treat acromegaly. Dopamine agonist medications, bromocriptine and cabergoline, have been used to treat acromegaly and work by suppressing GH secretion from the somatotroph adenoma. Somatostatin analogs suppress GH secretion and have been shown to have effects on tumor shrinkage. The GH receptor antagonist pegvisomant is the only drug in its class,16
and effectively blocks the effects of GH at the level of the GH receptor, reducing IGF-I levels and controlling symptoms.17
Use of these medications in combination has also been published, with increased efficacy shown with combination therapy of dopamine agonists and somatostatin analogs,18
as with combined use of pegvisomant and somatostatin analogs.19
Treatment with somatostatin analogs is generally well tolerated, efficacious in approximately 60% of patients, and has effects on both biochemical parameters (GH and IGF-I secretion) as well as effects on tumor mass.21
Somatostatin analogs may be used as adjuvant therapy after pituitary surgery or as primary therapy in selected patients.15
Somatostatin analog medications have been shown to have positive effects on symptoms, GH secretion, serum IGF-I levels, tumor size, comorbidities and effects of chronic GH secretion. However, many patients treated with somatostatin analogs will not normalize their GH and IGF-I levels, and require further treatment.
In addition to medical therapy, radiation therapy – including conventional radiation, stereotactic conventional radiation therapy, gamma knife therapy, proton beam – has been used to control tumor mass and reduce GH secretion.22
Use of radiation in the treatment of patients with acromegaly has been associated with an increased rate of mortality and cerebrovascular events.23
Despite the adverse effects that limit its appeal, radiation therapy remains an integral part of treatment for challenging patients with acromegaly. Its use varies in different treatment centers, with some reserving its use for only the most difficult cases, while others use the treatment more frequently in lieu of costly, lifelong medical treatment.
Monitoring patients with acromegaly usually entails regular assessments of serum GH and IGF-I levels, MRI surveillance, and careful regular assessments and treatments of comorbidities associated with acromegaly. Chronic GH excess can have profound effects on metabolism, the cardiovascular system, and joints, making regular assessment of glucose metabolism, cardiovascular disease, and arthritis a lifelong component of acromegaly care. Furthermore, effects on sleep apnea and the increased risk of developing colon polyps requires assessment for ongoing sleep apnea and regular colonoscopy even when biochemical control or cure is attained. Safety monitoring of medical therapy requires MRI surveillance and assessment of transaminase levels for pegvisomant, but no regular safety surveillance is required specifically for somatostatin analogs. Physicians should be aware of potential side effects of cholecystitis or gallstone formation, however, and assess complaints consistent with these side effects with gall bladder ultrasound.