ACROMEGALY – Causes, Clinical Manifestation, Diagnostic Evaluations Management and Medication
The term acromegaly comes from Greek words meaning “extremites” and “enlargement”. Enlargement of the hands and feet is one of the most common signs of the disease. Acromegaly is a chronic metabolic disorder in which there is too much growth hormone and the body tissues gradually enlarge. Acromegaly occurs in about 6 of every 100,000 adults. Acromegaly occurs in adulthood, usually during middle age. It is caused by abnormal production of growth hormone after the skeleton and other organs finish growing.
CAUSES OF ACROMEGALY
Acromegaly occurs when body produces too much growth hormone. In adults, a tumor is the most common cause of excess growth hormone.
- Pituitary Tumors: Most cases of acromegaly are caused by a noncancerous (benign) tumor, or adenoma, of the pituitary gland. In addition to producing excess growth hormone, these tumors can press on nearby tissues as they grow. This pressure can cause some of the symptoms of acromegaly, such as headaches and impaired vision.
- Nonpituitary Tumors: In a few people, acromegaly is caused by benign or cancerous tumors in other parts of the body, such as the lungs, pancreas or adrenal glands. Some of these tumors actually secrete growth hormone. In other cases, they produce a hormone called growth hormone-releasing hormone (GH-RH), which stimulates the pituitary gland to make more growth hormone
Growth hormone plays an important role in growth and regeneration of bones and other tissues by stimulating liver to produce another hormone called insulin-like growth factor-I (IGF-I). Excess growth hormone and IGF-1 in the blood cause most of the physical problems in acromegaly. Too much IGF-1 causes the bone growth that leads to changes in physical appearance and function.
CLINICAL MANIFESTATIONS
Some adenomas are aggressive, growing quickly. In these cases, the signs and symptoms of acromegaly tend to develop fairly quickly. Others grow more slowly, causing very gradual onset of symptoms.
Symptoms can be divided into 2 group: those that are effects of the tumor pressing on surrounding tissues and those caused by excess growth hormone and IGF-1 in the blood.
Symptoms due to pressure on surrounding tissues depend on the size of the tumor.
- Headaches and partial loss of vision are the most common symptoms
- Partial loss of vision may occur in one or both eyes
- Pituitary tumors also can damage the pituitary gland itself, disrupting hormone production. The resulting hormone imbalances are responsible for symptoms such as impotence, low sex drive, and changes in the menstrual cycle.
Symptoms due to excess growth hormone or IGF-1 vary widely.
- Increase in ring size or tightness of rings (due to hand swelling, “sausage-like” fingers)
- Increase in shoe size (due to foot swelling)
- Increased sweating
- Coarsening or thickening of facial features, especially the nose
- Increased prominence of jaw and/or forehead
- Thickened skin, especially on palms of hands or soles of feet
- Swelling of tongue
- Thickening or swelling of the neck (due to goiter)
- Arthritis (pain, swelling, or stiffness in any joint)
- Difficulty breathing during sleep (sleep apnea), causing poor sleep and excessive sleepiness
- Pain, numbness, tingling, or weakness in hands and wrists (carpal tunnel syndrome)
- Large numbers of skin tags
- Increased thirst or urination
- Shortness of breath
- Chest pain
- Palpitations or rapid heart beat
- Heart failure
DIAGNOSTIC EVALUATIONS
IGF-1 and growth hormone levels together usually are used to confirm the diagnosis of acromegaly. Health care provider may decide to measure levels of IGF-binding protein-3 (IGFBP-3), a protein that interacts with IGF-1. Sometimes this can help confirm the diagnosis of acromegaly. Spine x-ray shows abnormal bone growth.
After acromegaly has been confirmed by growth hormone and IGF-1 levels, patient will probably undergo a CT scan or MRI of the head to confirm adenoma in pituitary gland. CT scans of the abdomen and pelvis look for tumors of the pancreas, adrenal glands or ovaries that might secrete growth hormone or GHRH. CT scan of the chest looks for lung cancer, which also can secrete growth hormone or GHRH.
MANAGEMENT
The goals of therapy are to relieve and reverse the symptoms of acromegaly. This is done by normalizing production of growth hormone and IGF-1 and reducing the effects of the pituitary tumor on the surrounding tissues. A secondary goal is avoid damaging normal pituitary tissue.
The choice of treatments in acromegaly depends on its cause. For the large majority of cases caused by pituitary adenomas, treatments include surgery, drug therapy and radiation therapy.
SURGERY
Surgery is the first treatment used for most people with excess growth hormone, regardless of the cause. Surgery brings about remission in some people, but not in all. People who are in remission after surgery usually need no further treatment
The operation of choice for pituitary adenoma is transsphenoidal hypophysectomy. The tumor is removed via one of the nasal sinuses through an incision inside the nose.
If it is successful, this operation has 2 advantages. It rapidly improves symptoms caused by the tumor pressing on adjacent tissue, and it normalizes levels of growth hormone and IGF-1.
MEDICATION
Medication can be used if surgery is not possible, or not wanted. It is also used whilst waiting for surgery or radiotherapy. It can also be used in cases where surgery fails to remove the tumor totally and the level of growth hormone remains high.
The following medications may be used to treat acromegaly:
- Somatostatin analogues (octreotide and lanreotide) reduce the level of growth hormone to normal in over half of cases, and reduce the size of the tumor in about 8 in 10 cases. However, these medicines need to be given as an injection.
- Dopamine agonists (such as cabergoline, bromocriptine and quinagolide) can be taken as tablets. They work by preventing the releasing of growth hormone from tumor cells. However, they only work well in about 1 in 5 cases. Side-effects such as feeling sick and dizzy are also quite common
- Growth hormone receptor antagonists Pegvisomant (somavert) are taken as a daily injection. However, unlike the other medicines listed above, it does not act directly at the pituitary. Pegvisomant works by blocking the action of growth hormone on your body’s cells. Therefore, although many of the symptoms of growth hormone excess will be eased, it does not reduce the size of the tumor and headaches are not eased.
RADIOTHERAPY
Radiotherapy is an option to reduce the size of the tumor and hence reduce the production of growth hormone. Radiotherapy focuses high-intensity radiation at pituitary tumor to destroy the abnormal cells. Radiation treatments are given in 2 forms, external beam and stereotactic. It may be used if patient are not able to have surgery, or if surgery was only partially successful. However, it can take months or years after the radiotherapy is given for the level of growth hormone to reduce to normal.
ACROMEGALY – Causes, Clinical Manifestation, Diagnostic Evaluations Management and Medication