Richard Kiel as Jaws

Photo: Richard Kiel, as “Jaws”, from James Bond. He suffered acromegaly
Acromegaly is an uncommon hormonal disorder that develops when your pituitary gland produces too much growth hormone during adulthood. When this happens, your bones increase in size, including those of your hands, feet and face. The term “acromegaly” is derived from the Greek words akros: “extreme” or “extremities” and megas: “large” – extremities enlargement. Acromegaly usually affects middle-aged adults and can result in serious illness and premature death.
Because acromegaly is so uncommon and the physical changes occur so gradually, doctors often don’t recognize it immediately. If not treated promptly, acromegaly can lead to serious illness and even become life-threatening. Treatment of acromegaly involves approaches to lower your production of growth hormone.

Signs and symptoms

Features that result from high level of hGH or expanding tumor include:

  • Soft tissue swelling of the hands and feet
  • Brow and lower jaw protrusion
  • Enlarging hands
  • Enlarging feet
  • Arthritis and carpal tunnel syndrome
  • Teeth spacing increase
  • Macroglossia [enlarged tongue]
  • Heart failure
  • Compression of the optic chiasm leading to loss of vision in the outer visual fields (typically bitemporal hemianopia)
  • Headache
  • Diabetes mellitus
  • Hypertension
  • Increased palmar sweating and sebum production over the face (seborrhea) are clinical indicators of active growth hormone (GH) producing pituitary tumours.

These symptoms can also be used to monitor the activity of the tumour after surgery although biochemical monitoring is confirmatory.

What causes acromegaly?

Acromegaly is caused by prolonged overproduction of GH by the pituitary gland. The pituitary is a small gland at the base of the brain that produces several important hormones to control body functions such as growth and development, reproduction, and metabolism. GH is part of a cascade of hormones that, as the name implies, regulates the physical growth of the body. This cascade begins in a part of the brain called the hypothalamus, which makes hormones that regulate the pituitary. One of these, growth hormone-releasing hormone (GHRH), stimulates the pituitary gland to produce GH. Another hypothalamic hormone, somatostatin, inhibits GH production and release. Secretion of GH by the pituitary into the bloodstream causes the production of another hormone, called insulin-like growth factor 1 (IGF-1), in the liver. IGF-1 is the factor that actually causes the growth of bones and other tissues of the body. IGF-1, in turn, signals the pituitary to reduce GH production. GHRH, somatostatin, GH, and IGF-1 levels in the body are tightly regulated by each other and by sleep, exercise, stress, food intake and blood sugar levels. If the pituitary continues to make GH independent of the normal regulatory mechanisms, the level of IGF-1 continues to rise, leading to bone growth and organ enlargement. The excess GH also causes changes in sugar and lipid metabolism and can cause diabetes.

Pituitary Tumors

In over 90 percent of acromegaly patients, the overproduction of GH is caused by a benign tumor of the pituitary gland, called an adenoma. These tumors produce excess GH and, as they expand, compress surrounding brain tissues, such as the optic nerves. This expansion causes the headaches and visual disturbances that are often symptoms of acromegaly. In addition, compression of the surrounding normal pituitary tissue can alter production of other hormones, leading to changes in menstruation and breast discharge in women and impotence in men.
There is a marked variation in rates of GH production and the aggressiveness of the tumor. Some adenomas grow slowly and symptoms of GH excess are often not noticed for many years. Other adenomas grow rapidly and invade surrounding brain areas or the sinuses, which are located near the pituitary. In general, younger patients tend to have more aggressive tumors.
Most pituitary tumors arise spontaneously and are not genetically inherited. Many pituitary tumors arise from a genetic alteration in a single pituitary cell which leads to increased cell division and tumor formation. This genetic change, or mutation, is not present at birth, but is acquired during life. The mutation occurs in a gene that regulates the transmission of chemical signals within pituitary cells; it permanently switches on the signal that tells the cell to divide and secrete GH. The events within the cell that cause disordered pituitary cell growth and GH oversecretion currently are the subject of intensive research.

Non-pituitary Tumors

In a few patients, acromegaly is caused not by pituitary tumors but by tumors of the pancreas, lungs, and adrenal glands. These tumors also lead to an excess of GH, either because they produce GH themselves or, more frequently, because they produce GHRH, the hormone that stimulates the pituitary to make GH. In these patients, the excess GHRH can be measured in the blood and establishes that the cause of the acromegaly is not due to a pituitary defect. When these non-pituitary tumors are surgically removed, GH levels fall and the symptoms of acromegaly improve.
In patients with GHRH-producing, non-pituitary tumors, the pituitary still may be enlarged and may be mistaken for a tumor. Therefore, it is important that physicians carefully analyze all “pituitary tumors” removed from patients with acromegaly in order not to overlook the possibility that a tumor elsewhere in the body is causing the disorder.

Screening and diagnosis of Acromegaly

To begin the diagnostic process, your doctor will take a complete medical history and conduct a physical exam. Then he or she may recommend the following steps:

  • GH and IGF-I measurement. After you’ve fasted overnight, your doctor will take a blood sample to measure your levels of GH and IGF-I. Elevated levels of these hormones suggest acromegaly.
  • Growth hormone suppression test. This is the definitive method for verifying acromegaly. In this test, your blood levels of GH are measured before and after you drink a preparation of glucose (sugar). Normally, glucose ingestion depresses levels of GH. If you have acromegaly, your GH level will tend to stay high.
  • Imaging. Your doctor may recommend that you undergo imaging procedures — such as a computerized tomography (CT) scan or magnetic resonance imaging (MRI) scan — to help pinpoint the location and size of a tumor of your pituitary gland. If radiologists, who usually perform the procedures, see no tumor of your pituitary, they may look for nonpituitary tumors that might be responsible for high levels of GH.

Incidence of acromegaly

Small pituitary adenomas are common. During autopsies, they are found in up to 25 percent of the U.S. population. However, these tumors rarely cause symptoms or produce excessive GH or other pituitary hormones. Scientists estimate that about 3 out of every million people develop acromegaly each year and that 40 to 60 out of every million people suffer from the disease at any time. However, because the clinical diagnosis of acromegaly often is missed, these numbers probably underestimate the frequency of the disease

Complications

Progression of acromegaly can result in major health problems. Complications may include:

  • High blood pressure (hypertension)
  • Cardiovascular disease, particularly enlargement of the heart muscle (cardiomyopathy)
  • Osteoarthritis
  • Diabetes mellitus
    Precancerous growths (polyps) on the lining of your colon
  • Sleep apnea, a condition in which breathing repeatedly stops and starts during sleep
  • Carpal tunnel syndrome
    Reduced secretion of other pituitary hormones (hypopituitarism)
  • Uterine fibroids, benign tumors in the uterus
  • Spinal cord compression
  • Vision loss
  • Early treatment of acromegaly can prevent these complications from developing or becoming worse. If untreated, acromegaly and its complications can lead to premature death.

Treatment

The goals of treatment are to reduce GH production to normal levels, to relieve the pressure that the growing pituitary tumor exerts on the surrounding brain areas, to preserve normal pituitary function, and to reverse or ameliorate the symptoms of acromegaly. Currently, treatment options include surgical removal of the tumor, drug therapy, and radiation therapy of the pituitary.

Surgery

Surgery is a rapid and effective treatment, of which there are two alternative methods. The first method, a procedure known as transsphenoidal surgery, involves the surgeon reaching the pituitary through an incision in the nose and, with special tools, removing the tumor tissue. The second method is the removal of the tumor via a craniotomy, during which a bone flap is removed from the patient’s skull to allow access to the tumor from the front and side. Once the tumor has been removed, the section of bone is replaced. Transsphenoidal surgery is a less invasive procedure with a shorter recovery time than a craniotomy, yet the likelihood of successfully removing the entire tumor is lower. Consequently, transsphenoidal surgery is often used as a first option, with craniotomy and other treatments being used to remove any remaining tumor.
These procedures promptly relieve the pressure on the surrounding brain regions and lead to a lowering of GH levels. If the surgery is successful, facial appearance and soft tissue swelling improve within a few days. Surgery is most successful in patients with blood GH levels below 40 ng/ml before the operation and with pituitary tumors no larger than 10 mm in diameter. Success depends on the skill and experience of the surgeon. The success rate also depends on what level of GH is defined as a cure. The best measure of surgical success is normalization of GH and IGF-1 levels. Ideally, GH should be less than 2 ng/ml after an oral glucose load. A review of GH levels in 1,360 patients worldwide immediately after surgery revealed that 60 percent had random GH levels below 5 ng/ml. Complications of surgery may include cerebrospinal fluid leaks, meningitis, or damage to the surrounding normal pituitary tissue, requiring lifelong pituitary hormone replacement.
Even when surgery is successful and hormone levels return to normal, patients must be carefully monitored for years for possible recurrence. More commonly, hormone levels may improve, but not return completely to normal. These patients may then require additional treatment, usually with medications.

Drug therapy

Two medications currently are used to treat acromegaly. These drugs reduce both GH secretion and tumor size. Medical therapy is sometimes used to shrink large tumors before surgery. Bromocriptine (Parlodel) in divided doses of about 20 mg daily reduces GH secretion from some pituitary tumors. Side effects include gastrointestinal upset, nausea, vomiting, light-headedness when standing, and nasal congestion. These side effects can be reduced or eliminated if medication is started at a very low dose at bedtime, taken with food, and gradually increased to the full therapeutic dose. Because bromocriptine can be taken orally, it is an attractive choice as primary drug or in combination with other treatments. However, bromocriptine lowers GH and IGF-1 levels and reduces tumor size in less than half of patients with acromegaly. Some patients report improvement in their symptoms although their GH and IGF-1 levels still are elevated.
The second medication used to treat acromegaly is octreotide (Sandostatin) and lanreotide (Somatulin). Both are synthetic forms of a brain hormone, somatostatin, that stops GH production. The long-acting forms of these drugs must be injected every 2 to 4 weeks for effective treatment. Most patients with acromegaly respond to this medication. In many patients, GH levels fall within one hour and headaches improve within minutes after the injection. Several studies have shown that octreotide and lanreotide are effective for long-term treatment. Octreotide and lanreotide have also been used successfully to treat patients with acromegaly caused by non-pituitary tumors.
Because octreotide inhibits gastrointestinal and pancreatic function, long-term use causes digestive problems such as loose stools, nausea, and gas in one third of patients. In addition, approximately 25 percent of patients develop gallstones, which are usually asymptomatic. In rare cases, octreotide treatment can cause diabetes. On the other hand, scientists have found that in some acromegaly patients who already have diabetes, octreotide can reduce the need for insulin and improve blood sugar control.
The latest development in the medical treatment of acromegaly is the use of growth hormone receptor antagonists. The only available member of this family is pegvisomant (Somavert). By blocking the action of the endogenous growth hormone molecules, this compound is able to control disease activity of acromegaly in virtually all patients. Pegvisomant has to be administered subcutaneously by daily injections. Combinations of long-acting somatostatin analogues and weekly injections of pegvisomant seem to be equally effective as daily injections of pegvisomant.

Radiation therapy

Radiation therapy has been used both as a primary treatment and combined with surgery or drugs. It is usually reserved for patients who have tumor remaining after surgery. These patients often also receive medication to lower GH levels. Radiation therapy is given in divided doses over four to six weeks. This treatment lowers GH levels by about 50 percent over 2 to 5 years. Patients monitored for more than 5 years show significant further improvement. Radiation therapy causes a gradual loss of production of other pituitary hormones with time. Loss of vision and brain injury, which have been reported, are very rare complications of radiation treatments.
No single treatment is effective for all patients. Treatment should be individualized depending on patient characteristics, such as age and tumor size. If the tumor has not yet invaded surrounding brain tissues, removal of the pituitary adenoma by an experienced neurosurgeon is usually the first choice. After surgery, a patient must be monitored for a long time for increasing GH levels. If surgery does not normalize hormone levels or a relapse occurs, a doctor will usually begin additional drug therapy. The first choice should be bromocriptine because it is easy to administer; octreotide is the second alternative. With both medications, long-term therapy is necessary because their withdrawal can lead to rising GH levels and tumor re-expansion. Radiation therapy is generally used for patients whose tumors are not completely removed by surgery; for patients who are not good candidates for surgery because of other health problems; and for patients who do not respond adequately to surgery and medication.

Pituitary gigantism in children

This condition of growth hormone excess is rare in children and is referred to as pituitary gigantism, because the excessive growth hormone produces excessive growth of bones and the child can achieve excessive height. As an affected child becomes an adult, many of the adult problems can gradually develop. The distinction between gigantism (occurring in children) and acromegaly (occurring in adults) can be made by the occurrence of the adenoma in relation to the closure of the epiphyses. If elevated growth hormone levels occur before the closure of the epiphyses (i.e. in prepubertal children), then gigantism ensues. If it occurs after the closure of the epiphyses (i.e., in adults) then acromegaly ensues.

Famous sufferers

Famous patients, all standing in excess of 2.00 metres:

  1. Actor Richard Kiel (’Jaws’ in the James Bond movies), 7′2″ tall
  2. Actor Carel Struycken (known e.g as Lurch in the Addams Family -movies, and for his other giant roles), 7′ tall
  3. Actor Matthew McGrory (listed in the Guinness Book of World Records for having the largest feet – size 29 1/2), 7′6″ tall (died at the age of 32)
  4. Actor Rondo Hatton
  5. Wrestler and actor André the Giant, 6′9″ tall after he had a back surgery that made him a couple inches shorter than he originially was, which was closer to 7 feet tall. He died at the age of 46, when most sufferers weren’t expected to live past the age of 40. (chose not to be treated and died from disease)

Source: wikipedia, mayo clinic, endocrine and metabolic diseases home

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