Symptoms of Acromegaly

Symptoms of acromegaly vary in severity and may develop slowly over several years. Common signs include:

• Physical Changes: Enlarged hands and feet, widened fingers and toes, coarse facial features (such as an enlarged nose, jaw, or brow), and spacing between the teeth due to jaw growth.
• Skin Changes: Thickened, oily, or coarse skin.
• Joint and Muscle Pain: Stiffness and discomfort in the joints due to excess tissue growth.
• Swelling: Enlarged soft tissues, particularly in the hands and face.
• Other Symptoms: Fatigue, weakness, snoring due to enlarged airway tissues, or deeper voice from thickened vocal cords.

Without treatment, acromegaly can lead to serious complications, including heart disease, diabetes, high blood pressure, sleep apnea, and arthritis.

Causes of Acromegaly

Acromegaly is primarily caused by excessive growth hormone (GH) production, which leads to abnormal tissue and bone growth. In most cases, this overproduction is triggered by a benign (noncancerous) tumor in the pituitary gland, known as a pituitary adenoma.

Pituitary Adenomas (Benign Tumors)

The pituitary gland, located at the base of the brain, plays a critical role in regulating hormones throughout the body. When an abnormal pituitary tumor grows, it can disrupt the normal balance of hormone secretion, causing the gland to release excess GH. Most of these tumors grow slowly and are not cancerous, but their effects on the surrounding tissues and hormone levels can be significant.

• Macroadenomas (large tumors) can also compress nearby structures, such as the optic nerves, potentially causing vision problems, headaches, or other neurological symptoms in addition to hormonal imbalances.
• Microadenomas (small tumors) are less likely to cause physical compression but can still produce excessive GH and lead to acromegaly.

Rare Causes of Acromegaly

In a small percentage of cases, acromegaly is caused by factors outside the pituitary gland. These include:

• Ectopic Tumors: Rarely, tumors located in other parts of the body, such as the lungs, pancreas, or adrenal glands, can produce growth hormone-releasing hormone (GHRH). This hormone stimulates the pituitary gland to release excessive GH.
• Non-Pituitary GH-Secreting Tumors: Even more rarely, tumors in other areas of the body may directly produce GH, bypassing the pituitary gland altogether.

Genetic Causes

Although most cases of acromegaly are not inherited, certain genetic conditions may predispose individuals to develop pituitary adenomas. These include:

• Multiple Endocrine Neoplasia Type 1 (MEN1): A hereditary condition that causes tumors in various endocrine glands, including the pituitary.
• Familial Isolated Pituitary Adenomas (FIPA): A genetic syndrome associated with pituitary adenomas, often presenting at a younger age.

Hormonal Cascade Leading to Symptoms

Regardless of the underlying cause, the overproduction of GH results in elevated levels of insulin-like growth factor 1 (IGF-1), a hormone produced in the liver. IGF-1 is responsible for many growth-related changes in acromegaly, such as abnormal tissue enlargement, bone overgrowth, and organ changes.

Understanding the root cause of acromegaly is crucial for effective treatment. While pituitary adenomas are the most common culprit, addressing rarer causes requires specialized diagnostic approaches and tailored treatments.

Risk Factors for Acromegaly

While acromegaly can develop in anyone, certain factors may elevate the likelihood of developing the condition:

• Pituitary Tumors: Most acromegaly cases stem from benign (non-cancerous) pituitary gland tumors, known as pituitary adenomas. These tumors lead to the excessive production of growth hormone, which drives the characteristic symptoms of the condition.
• Family History and Genetic Conditions: A family history of specific genetic disorders, such as multiple endocrine neoplasia type 1 (MEN1), may increase the risk. MEN1 is a hereditary condition that causes tumors to develop in endocrine glands, including the pituitary gland, and predisposes individuals to hormonal imbalances. Another potential genetic link is familial isolated pituitary adenomas (FIPA), which may cluster within families.
• Age: Acromegaly is most commonly diagnosed in middle-aged adults, typically between the ages of 30 and 50. While the condition can occur at any age, it is less common in children, where it can result in a related condition called gigantism due to the impact on developing bones.

Identifying these risk factors can help in early detection, especially for individuals with a genetic predisposition or those experiencing symptoms suggestive of abnormal growth hormone activity.

Diagnosing Acromegaly

Because acromegaly develops slowly, it is often not diagnosed until noticeable symptoms occur. Diagnosis typically involves:

• Medical History and Physical Exam: A healthcare provider will look for characteristic signs, such as enlarged hands and feet or facial changes.
• Hormone Tests: Blood tests measure levels of growth hormone (GH) levels and insulin-like growth factor 1 (IGF-1), which are elevated in individuals with acromegaly.
• Imaging: An MRI or CT scan may be used to identify pituitary tumors or other abnormalities.

Treatment Options for Acromegaly

The primary goal of treatment for acromegaly is to reduce GH production, alleviate symptoms, and prevent complications. Treatment options include:

Surgery

The first-line treatment for pituitary tumors is often surgical removal. The most common approach is transsphenoidal surgery, which removes the tumor through the nasal cavity. When successful, this procedure can quickly normalize GH and IGF-1 levels.

Medications

If surgery is not an option or does not fully resolve the condition, medications may help control hormone levels. These include:

• Somatostatin Analogs: Octreotide, Lanreotide
• GH Receptor Antagonists: Pegvisomant
• Dopamine Agonists: Cabergoline

Radiation Therapy

For patients who cannot undergo surgery or do not respond to medication, radiation therapy may be used to shrink the tumor and lower hormone levels. This approach may take several years to achieve its full effect.