A syndrome due to excessive formation of growth hormone (GH) by a tumor in the pituitary gland and characterized by coarse facial features, enlargement of hands and feet, headache, sweating, neuropathy, SLEEP APNEA, and musculoskeletal symptoms. Acromegaly affects 40 to 60 people per million population.

Cause - An adenoma (a benign tumor) of the pituitary gland that produces GH is the cause of acromegaly in 99 percent of patients. Other rare causes include tumors of the gut, pancreas, and lung that produce GH.

Symptoms - Acromegaly results in gigantism if it develops in children before puberty. More commonly, however, it develops slowly between the ages of 20 and 40 years. Symptoms may be due to either excessive production of GH or pressure effects caused by the adenoma itself.

GH causes enlargement of the soft tissues, resulting in a characteristic coarse facial appearance with an enlarged jaw and tongue, separation of the teeth, and large hands and feet. Because of this, unrelated patients with acromegaly are said to look more like each other than like any of their family members.

Internal organs such as the heart, liver, and kidneys also enlarge. Hypertension (30 percent) and diabetes (20 percent) are common. If the adenoma in the pituitary enlarges, it can cause pressure effects in the brain. The optic nerves that run from the eye to the brain pass very close to the pituitary gland.

If the adenoma presses on an optic nerve, it can cause partial blindness. The tumor can also affect normal pituitary tissue and cause reduced production of some hormones, for example gonadotrophins (hormones that regulate the release of sex hormones) and increased production of others, for example prolactin, a hormone that regulates the secretion of breast milk.

Musculoskeletal symptoms - Bone and joint problems develop in at least 50 percent of patients with acromegaly. Initially the cartilage in the joints increases in amount, and the capsule of the joint and the ligaments close to it soften and thicken, resulting in hypermobility. Later degenerative changes develop in joints perhaps because of the altered biomechanics caused by the changes in cartilage and soft tissues.

The arthritis associated with acromegaly causes pain, stiffness, and reduced range of movement, as happens in OSTEOARTHRITIS of any cause. The fingers, spine, and knees are commonly involved, and the shoulders, elbows, and ankles are affected more frequently than occurs in the usual type of osteoarthritis.

OSTEOPOROSIS may develop because of reduced sex hormone production as well as increased loss of calcium in the urine. CARPAL TUNNEL SYNDROME is common because the median nerve runs through a narrow tunnel in the wrist, and if the soft tissues increase in size, as happens in acromegaly, it causes pressure on the nerve and the symptoms of carpal tunnel syndrome.

Similarly, other nerves that run through narrow channels can become trapped by soft tissue, resulting in neuropathy. Premature coronary artery disease, heart failure, and sleep apnea all contribute to the increased mortality rate in people with acromegaly. The mortality rate in untreated acromegaly is twice that of the general population.

However, if treatment is successful in reducing GH levels in the blood to less than 5 mU/L, there is no increased risk of death. The concentration of calcium in the blood is elevated (hypercalcemia) in 5 percent of patients, and the increased excretion of calcium in the urine can increase the risk of developing kidney stones.

The osteoarthritis that often accompanies acromegaly may cause considerable pain and disability, and there is an increased risk of CALCIUM PYROPHOSPHATE DIHYDRATE DEPOSITION DISEASE and pseudogout. A large pituitary tumor can cause permanent loss of vision, particularly peripheral vision.

Diagnosis - The characteristic appearance of the face and hands usually prompts the diagnosis. X rays can support the diagnosis, showing characteristic tufting of the bones at the ends of the fingers. Other X ray changes include widened joint spaces (because of the increased amount of cartilage) and typical changes of osteoarthritis.

They include the formation of osteophytes sometimes occurring in joints such as shoulders and elbows, which are not usually affected by osteoarthritis. In the spine the X rays have an appearance similar to that of DISH. Blood tests such as elevated levels of GH or somatomedin C are useful for making the diagnosis.

Abnormalities of other pituitary hormones such as prolactin or gonadotrophins may be found but are not specific. An MRI scan is useful because the pituitary adenoma can often be seen. Eye tests may show loss of peripheral vision that the patient had not noticed.

Treatment and Outcome - The aim of treatment is to relieve symptoms of acromegaly, reduce GH levels to less than 5 mU/L, treat the local pressure effects of the tumor, and maintain normal pituitary function. The treatment of choice, transsphenoidal surgery, achieves a cure rate of between 40 and 90 percent.

Radiotherapy may be used to treat the tumor in patients who are not healthy enough to undergo surgery or those who choose not to have it. After treatment with radiotherapy the GH levels decline slowly over a few years, and with time there is an increased chance that production of other pituitary hormones will also decline.

Treatment of acromegaly with drugs such as octreotide and bromocriptine decreases GH production. These drugs are used when GH levels remain raised after surgery or radiotherapy or sometimes as the only therapy in elderly patients who prefer not to undergo surgery or radiotherapy.

Joint symptoms are treated with analgesics, NSAIDs, and physical therapy as appropriate. Surgical removal of large osteophytes is sometimes helpful, and total joint replacement may become necessary if a hip or knee joint is badly affected. The symptoms caused by carpal tunnel syndrome improve with adequate control of GH levels, but those caused by arthritis do not.