Acromegaly

Acromegaly is a rare hormonal condition that develops when the body produces too much growth hormone, causing bones, organs, and tissues to grow in unusual ways. While the changes happen slowly over many years and can be difficult to notice at first, early diagnosis and proper treatment can help people with this condition live normal, healthy lives.

Table of contents

• What is acromegaly?
• How common is the condition?
• Associated anatomy
• What causes acromegaly?
• Symptoms and physical changes
• Health complications
• How is acromegaly diagnosed?
• Treatment options
• Outlook and prognosis

What is acromegaly?

Acromegaly is a hormonal condition that occurs when the body makes too much growth hormone (also called GH), a natural hormone that controls physical growth and helps maintain normal body functions^[1]. In adults, excess growth hormone causes bones, cartilage, body organs, and other tissues to increase in size in irregular ways^[2].

Growth hormone signals the liver to produce another hormone called insulin-like growth factor-1 (IGF-1). This is the hormone that actually causes bones and body tissue to grow. It also affects how the body processes blood sugar and fats. When growth hormone levels are too high, IGF-1 levels also become too high, leading to the changes seen in acromegaly^[2].

Acromegaly is different from a similar condition called gigantism, which affects children. In children, too much growth hormone before the end of puberty causes them to grow very tall. Once a person reaches adulthood and the growth plates in the bones have fused, excess growth hormone no longer increases height. Instead, it causes changes in bone shape, organ size, and other health issues^[2].

How common is the condition?

Acromegaly is a rare disease. Fewer than 15 people per 100,000 are living with acromegaly. Each year, about 3 to 5 people out of every million are diagnosed with the condition^[1]. Other studies suggest that approximately 3 to 14 of every 100,000 people have been diagnosed with acromegaly^[2][3].

Because the condition develops slowly and diagnosis is often delayed, the true number of cases may be higher than these estimates. People may have symptoms for 5 to 10 years or more before receiving a diagnosis^[11]. The condition is most often diagnosed in middle age, usually during the fourth and fifth decades of life^[2], although symptoms can appear at any age after puberty^[3].

• Pituitary gland
• Brain
• Liver
• Bones
• Hands and feet
• Face (jaw, nose, lips)

What causes acromegaly?

In over 95% of cases, acromegaly is caused by a pituitary adenoma, which is a noncancerous tumor in the pituitary gland^[7]. The pituitary gland is a small, pea-sized gland located at the base of the brain. It normally produces growth hormone and several other important hormones^[2].

When a pituitary adenoma develops, it causes the pituitary gland to release excess growth hormone. These adenomas are almost always benign, meaning they are not cancerous. Most adenomas that cause acromegaly grow slowly, which is why people may not notice symptoms of excess growth hormone for many years^[2].

Depending on its size and location, the adenoma may press against other pituitary tissue and affect the production of other hormones. Some people with acromegaly may have a genetic condition that can lead to tumors developing in different parts of their bodies^[3].

Symptoms and physical changes

The symptoms of acromegaly develop slowly over many years. Because the changes happen gradually, people with acromegaly and their loved ones may not notice them right away^[1]. It may take a long time to see changes, and healthcare professionals may have difficulty finding and treating the condition early on.

Common physical changes include swollen hands and feet, with hands, feet, ears, lips, and nose becoming larger over time. The brow bone becomes more prominent, and the lower jaw juts out. The bridge of the nose increases in size, and spaces between teeth may increase^[1][11].

Other symptoms may include tiredness or difficulty sleeping, sleep apnea, excessive sweating, numbness and weakness in the hands, thicker and more oily skin, a deeper voice, and joint pain^[4]. Some people experience headaches and visual disturbances^[11]. Women may have irregular periods, and men may experience erection problems^[4].

Healthcare professionals may ask to see photographs from the past couple of years to check for any changes in appearance over time^[4].

Health complications

Without treatment, acromegaly can lead to other serious and sometimes life-threatening complications^[1]. Because symptoms come on slowly, health problems can develop before the disorder is diagnosed and treated^[3].

Health problems can include type 2 diabetes, high blood pressure, heart disease, sleep apnea, arthritis, and carpal tunnel syndrome^[3][4]. The excess growth hormone affects how the body processes blood sugar and fats, which can lead to elevated blood sugar levels and cardiovascular problems^[2].

People with acromegaly also have an increased risk for colon polyps, which may develop into colon cancer if not removed^[3]. Regular health checks are needed to monitor these conditions, including colonoscopy screenings to check for bowel polyps^[4].

Studies show that if left untreated, people with acromegaly have a reduced life expectancy compared to the normal population. However, these complications can be improved to normal after successful treatment of acromegaly^[9]. Mortality rates are closely related to the degree of growth hormone and IGF-1 excess, and reducing their levels to normal ranges can result in life expectancy similar to that of the general population^[7].

How is acromegaly diagnosed?

Diagnosis involves several steps. A healthcare professional will ask about health history and perform a physical exam. Several tests are typically needed to confirm the diagnosis^[5].

The IGF-1 blood test measures the level of insulin-like growth factor-1 in the blood. A high IGF-1 level can mean that the level of growth hormone is also high and is an important marker for diagnosing acromegaly. However, IGF-1 can also be elevated due to other conditions such as diabetes, liver or kidney disease, or pregnancy^[5].

Because of this, healthcare professionals usually confirm the diagnosis with a second test called an oral glucose tolerance test (OGTT). This test measures growth hormone levels before and after drinking a glucose solution. In people who don’t have acromegaly, the glucose drink typically causes the growth hormone level to fall. But if a person has acromegaly, the growth hormone level tends to stay high^[5].

An MRI scan of the pituitary gland is the main imaging test for acromegaly. It shows the location and size of a pituitary tumor. If no pituitary tumor is found, healthcare professionals may order other scans to look for tumors elsewhere in the body^[5]. X-rays of the hands and feet may also be used to check for changes in bone growth caused by excess growth hormone^[5].

Treatment options

Treatment usually stops the body from producing too much growth hormone and usually improves symptoms. The goals of treatment are to reduce excess growth hormone, relieve pressure that the growing tumor may be exerting, preserve normal pituitary function, and improve long-term health and quality of life^[7][9].

Most experts define adequate control of growth hormone excess as a glucose-suppressed growth hormone level of less than 2 micrograms per liter and normalization of IGF-1 levels^[8]. After treatment, people continue to have appointments with a specialist to monitor how well the pituitary gland is working and check that treatment is right for them^[4].

Surgery

For pituitary adenomas, transsphenoidal surgery is usually considered the first line of treatment^[8]. The operation is usually carried out by making a small cut above the upper teeth behind the upper lip, or through the nose. By going behind the nose, the surgeon can see the pituitary gland without having to operate on the main part of the head^[9].

The operation takes about an hour and a half, and people tend to remain in hospital for three to five days. Results are usually better if the tumor is small. For the best results, it is important to be referred to an experienced pituitary surgeon who operates on 20 or more cases per year^[9].

Surgery will normally lower growth hormone levels, but in some instances the acromegaly is not cured. In such cases, treatment may continue with drug therapy or radiotherapy^[9].

Medications

Medical therapy is administered to patients with persistent disease after surgery. There are three types of drugs for treating acromegaly, each acting by different mechanisms^[9].

Somatostatin analogues work on specialist markers to inhibit growth hormone release from the pituitary tumor. Two somatostatin analogues are available: octreotide and lanreotide. These require injections, usually given once a month. They help reduce growth hormone levels into the target range in about half of patients^[9].

Dopamine agonists, including cabergoline and bromocriptine, are taken by mouth. Cabergoline appears to be more effective in lowering growth hormone and IGF-1 levels and needs to be taken only twice weekly^[9].

Pegvisomant is a newer drug that works differently by blocking the action of growth hormone and reducing IGF-1 levels. It appears to normalize IGF-1 levels in almost all patients^[8][9].

Radiation therapy

Radiation treatment is usually reserved for cases where surgery and medication have not been successful. Radiotherapy can target the tumor and reduce growth hormone levels^[1][4].

Outlook and prognosis

Acromegaly is treatable in most people. With treatments such as surgery, medicine, and radiation therapy, many patients can achieve good disease control^[1]. An increasing number of patients can achieve normal life expectancy as well as improved quality of life with successful treatment^[7].

After treatment, regular monitoring continues to ensure the condition remains under control and to check for any complications. People will have regular health checks to monitor conditions such as type 2 diabetes, high blood pressure, and heart disease^[4].

Information about people with acromegaly may be passed to registries that help scientists find better ways to treat and prevent this condition^[4].