Acromegaly is a chronic condition characterized by the body producing too much growth hormone (GH). This overproduction typically stems from a noncancerous tumor, known as an adenoma, located on the pituitary gland, a small gland at the base of the brain. The excess GH leads to elevated levels of insulin-like growth factor 1 (IGF-1), which in turn causes abnormal growth of bones and soft tissues throughout the body. Untreated, acromegaly can lead to serious long-term complications, including cardiovascular disease, diabetes, and joint problems. Treatment aims to normalize hormone levels, reduce tumor size, and alleviate symptoms.
Surgical Removal of the Tumor
Surgical removal of the pituitary tumor is often the initial approach for acromegaly. The most common method is transsphenoidal surgery, accessing the pituitary gland through the nasal cavity or, less commonly, an incision under the upper lip. This minimally invasive technique aims to remove the tumor while preserving surrounding healthy pituitary tissue.
The primary goals of surgery are to eliminate the source of excess GH, normalize GH and IGF-1 levels, and relieve any pressure the tumor might be exerting on nearby structures, such as the optic nerves. Patients often experience immediate improvement in symptoms like headaches and visual disturbances following successful tumor removal. Success rates for normalizing hormone levels are higher for smaller tumors (microadenomas, less than 1 cm), with reported cure rates around 76.9% to 91%. For larger tumors (macroadenomas, greater than 1 cm), success rates range from 48% to 72.3%.
While transsphenoidal surgery is considered safe, potential risks include cerebrospinal fluid leaks, infection, or damage to normal pituitary tissue, which could necessitate lifelong hormone replacement therapy. The experience of the neurosurgeon plays a significant role in the outcome and the likelihood of achieving a cure. Even if surgery doesn’t achieve complete remission, it can significantly reduce tumor size and hormone levels, making subsequent medical or radiation therapies more effective.
Medical Therapies
Medical therapies are used when surgery is not feasible, fails to normalize hormone levels, or as an additional treatment after surgery. These medications work through different mechanisms to control growth hormone and IGF-1 levels.
Somatostatin Receptor Ligands (SRLs)
Somatostatin Receptor Ligands (SRLs) are often a first-line medical treatment for acromegaly. These medications, such as octreotide and lanreotide, mimic the natural hormone somatostatin, binding to specific receptors on pituitary tumor cells. This action inhibits growth hormone secretion and reduces IGF-1 levels. SRLs are administered as long-acting injections, either intramuscularly or subcutaneously, once a month. Side effects can include gastrointestinal discomfort, such as nausea, diarrhea, or abdominal pain, and gallstone formation. Tumor shrinkage of 20% or more is observed in many patients, with mean reductions ranging from 27% to 51%.
A newer SRL, pasireotide, has a broader receptor binding profile. It has demonstrated greater efficacy in achieving biochemical control and tumor shrinkage, even in patients who did not respond adequately to other SRLs. However, it carries an increased risk of affecting glucose metabolism, leading to elevated blood sugar levels or diabetes, which can be managed with standard anti-diabetic medications. Oral formulations of SRLs are also being developed, offering a potential alternative to injections.
Dopamine Agonists
Dopamine agonists, such as cabergoline and bromocriptine, are also used in acromegaly, particularly for patients with mild IGF-1 elevations or tumors co-secreting prolactin. These medications work by stimulating dopamine D2 receptors on pituitary tumor cells, inhibiting growth hormone secretion. Cabergoline is preferred over bromocriptine due to its greater effectiveness in lowering GH and IGF-1 levels and its less frequent dosing, twice weekly.
While dopamine agonists are less potent than SRLs in normalizing hormone levels, they are orally administered and less expensive. Side effects can include nausea, headache, fatigue, and dizziness, especially when starting treatment. Cabergoline has been shown to normalize IGF-1 levels in one-third of patients. Tumor size reduction is less common with these agents, seen in 10% to 20% of patients treated with bromocriptine, and about one-third of patients with cabergoline.
Growth Hormone Receptor Antagonists
Growth Hormone Receptor Antagonists block the action of GH at its receptors in the body’s tissues, rather than reducing GH production by the pituitary gland. Pegvisomant is the only approved medication in this class. It effectively lowers circulating IGF-1 levels, the primary mediator of GH’s effects, and can improve symptoms associated with excess GH.
Pegvisomant is administered as a daily subcutaneous injection. This medication is used when other treatments, such as surgery and SRLs, have not normalized IGF-1 levels. Since pegvisomant directly blocks GH action, monitoring effectiveness relies on normalizing IGF-1 levels, as GH levels may remain elevated or even increase. Side effects include injection site reactions, diarrhea, nausea, and transient elevations in liver enzymes. Pegvisomant also has beneficial effects on glucose metabolism and insulin sensitivity.
Radiation Options
Radiation therapy is used when surgery and medical therapies are not fully effective or suitable for controlling hormone levels or tumor growth. The aim of radiation is to slowly reduce GH levels and prevent further tumor growth. The full therapeutic effects often take months to years to become apparent.
Conventional/Fractionated Radiotherapy
Conventional, or fractionated, radiotherapy involves delivering radiation to the tumor in multiple small doses over an extended period, 4 to 6 weeks. This approach allows healthy surrounding tissues to recover between treatments. While effective in controlling tumor growth and gradually lowering GH levels, biochemical remission rates range from 35% to 75% over several years, taking up to 10 years for maximum effect. A potential long-term side effect is hypopituitarism, a decline in the production of other pituitary hormones, which can develop over time in 50% to 80% of patients.
Stereotactic Radiosurgery (SRS)
Stereotactic radiosurgery (SRS) is a precise radiation delivery method using highly focused beams to target the tumor directly, minimizing exposure to healthy brain tissue. This method involves a single, high dose of radiation or a few sessions, and requires the patient to wear a rigid head frame for accuracy. Technologies such as Gamma Knife, CyberKnife, and linear accelerators (LINAC) are used for SRS.
SRS is preferred for treating residual tumor after surgery due to its precision and more rapid hormonal remission compared to conventional radiotherapy, within three years. Reported rates of endocrine remission with SRS range from 40% to 60% at five years, and 56.9% to 69% at 10 years. The risk of new hypopituitarism with SRS is lower than conventional radiotherapy, ranging from 10% to 38%. Rare complications include new visual deficits or damage to cranial nerves.
Ongoing Care and Monitoring
Long-term management of acromegaly requires ongoing care and monitoring to ensure hormone balance and address any persistent symptoms or complications. Regular follow-up appointments with an endocrinologist are standard practice. These appointments involve periodic blood tests to measure growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, primary indicators of disease activity and treatment effectiveness.
Imaging studies, such as MRI scans of the pituitary gland, are also performed regularly to assess tumor size, detect any recurrence, and monitor for changes in surrounding brain structures. The frequency of these tests depends on the individual’s treatment response, tumor characteristics, and overall health. Even after successful tumor control and hormone normalization, some individuals may still experience residual symptoms or complications that developed before or during treatment.
These complications can include cardiovascular issues like hypertension or cardiomyopathy, metabolic problems such as diabetes, joint pain, or sleep apnea. Managing these conditions often involves collaboration with other specialists and may require additional medications or therapies. Due to its chronic nature, acromegaly necessitates lifelong monitoring and, for many, ongoing therapy to maintain stable hormone levels and optimize quality of life.