Acromegaly
Treatment Options

Treating acromegaly effectively often relies on a multi-modal strategy that includes surgery, medical therapy, and/or radiation.

Surgical Management of Acromegaly

According to the American Association of Clinical Endocrinologists (AACE) Guidelines, surgery should be considered first-line therapy for all acromegaly patients. However, research shows that remission with surgery is based on multiple factors, including whether the patient presents with a macroadenoma or a microadenoma. Patients with a microadenoma have about an 85% chance of remission with surgery, whereas for those with macroadenoma, the chances of remission are lower — about 30%.¹ Regardless of tumor type, even if the mass is removed and the patient is initially cured it's important to note that the tumor can grow back –– so ongoing monitoring of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels is vital.

Surgical intervention aims to provide the following:²

• Immediate reduction in GH levels
• Elimination of the tumor mass and reversal of associated symptoms, including headache and visual impairment
• Alleviation of comorbidities such as hypertension, sleep apnea, arthritis, etc.
• Preservation of pituitary function and restoration of endocrine deficits caused by the tumor
• Prevention of tumor recurrence
• Ability to retrieve and test tissue

Transsphenoidal surgery, which is standard treatment and causes less morbidity than transcranial procedures, can be achieved by two approaches. The two different types of transsphenoidal surgery are: ^{2, 3}

• Translabial (surgery to reach the pituitary through an incision through the upper lip) which offers the surgeon improved visibility but is more invasive
• Transnasal (surgery to reach the pituitary through the nose) which provides less discomfort for the patient but has limited visibility and may be more appropriate for smaller pituitary tumors

With all surgical approaches in acromegaly, the surgeon's expertise is critical to a successful outcome.

Medical Therapy

Medical therapy has undergone significant advances in the treatment of acromegaly. Specifically, medical treatment options include:

• Somatostatin Analogues –– Somatostatin is a naturally occurring regulatory peptide that carries out numerous functions in the human body, including the inhibition of GH secretion from the anterior pituitary gland. Somatostatin is secreted by a broad range of tissues, including the hypothalamus. From the hypothalamus, somatostatin acts on receptors in the adjacent pituitary gland, causing an inhibitory effect on the release of many pituitary hormones, including GH.⁴

As a result of the effect of naturally occurring somatostatin, scientists developed Somatostatin analogues (SSAs) to mimic the body's own natural behavior in the treatment of acromegaly. These compounds bind to one or more somatostatin receptors to suppress GH and IGF-1 hypersecretion. Both naturally occurring somatostatin and somatostatin analogues activate somatostatin receptors. However, somatostatin analogues are 45 times more potent, have a longer half-life, and lack rebound hypersecretion compared with somatostatin produced by the body.⁵

As a result of their mechanism of action, SSAs go to the root of the problem that causes acromegaly. Additionally, these agents are recommended by the AACE Guidelines as the drug of first choice in the treatment of acromegaly or if surgery is not possible.^{6, 2}

One of the main sites of secretion of somatostatin within the CNS is the hypothalamus. In healthy people, GH (growth hormone) secretion is under the regulation of both somatostatin and growth hormone-releasing hormone (GHRH). However, variations in the secretion of somatostatin are the primary mode of GH regulation. Somatostatin acts on receptors in the adjacent pituitary gland, exerting an inhibitory effect on the release of many pituitary hormones, including GH, which in turn impacts the subsequent elevation in circulating insulin-like growth factor-1 (IGF-1).

• Dopamine Agonists –– Proven occasionally effective in selected patients, including those with modestly elevated IGF-1 levels, these agents lower both GH and prolactin levels.⁶
• GH Receptor Antagonists –– Blocks peripheral IGF-1 and is indicated in patients not controlled by other agents, however therapy is not intended to treat tumor growth.⁶

Radiation Therapy

According to the AACE Guidelines, radiation is most commonly used in acromegaly as adjuvant therapy after surgical removal of a tumor.² However, the full effect of this therapy may not occur for many years.⁴