Acromegaly (from Greek akros "high" and megas "large" - extremities enlargement) is a hormonal disorder that results when the pituitary gland produces excess growth hormone (hGH). Most commonly it is a benign hGH producing tumor derived from a distinct type of cells (somatotrophs) and called pituitary adenoma. The International Statistical Classification of Diseases and Related Health Problems (commonly known by the abbreviation ICD) is a detailed description of known diseases and injuries. ... The following codes are used with International Statistical Classification of Diseases and Related Health Problems. ... // E00-E35 - Endocrine diseases (E00-E07) Disorders of thyroid gland (E00) Congenital iodine-deficiency syndrome (E01) Iodine-deficiency-related thyroid disorders and allied conditions (E02) Subclinical iodine-deficiency hypothyroidism (E03) Other hypothyroidism (E030) Congenital hypothyroidism with diffuse goitre (E031) Congenital hypothyroidism without goitre (E032) Hypothyroidism due to medicaments and other... The International Statistical Classification of Diseases and Related Health Problems (commonly known by the abbreviation ICD) is a detailed description of known diseases and injuries. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... A hormone (from Greek horman - to set in motion) is a chemical messenger from one cell (or group of cells) to another. ... Located at the base of the skull, the pituitary gland is protected by a bony structure called the sella turcica. ... For physiology of human growth hormone, see growth hormone. ...

Acromegaly most commonly affects middle-aged adults and can result in serious illness and premature death. Because of its insidious onset and slow progression, the disease is hard to diagnose in the early stages and is frequently missed for many years.

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
• Heart failure
• Compression of the optic chiasm leading to loss of vision in the outer visual fields
• 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.

Arthritis (from Greek arthro-, joint + -itis, inflammation; plural: arthritides) is a group of conditions where there is damage caused to the joints of the body. ... Carpal tunnel syndrome (CTS) is a medical condition in which the median nerve is compressed at the wrist. ... Visual pathway with optic chiasm circled The optic chiasm (from the Greek χλαζειν to mark with an X, after the letter Χ chi) is the part of the brain where the optic nerves partially cross, those parts of the right eye which see things on the right side being connected to the... For the disease characterized by excretion of large amounts of severely diluted urine, see diabetes insipidus. ... For other forms of hypertension see hypertension (disambiguation). ... The sebaceous glands are glands found in the skin of mammals. ... // General Description and Etiology Seborrhoeic dermatitis is a skin disorder affecting the scalp, face and trunk causing scaly, flaky, itchy, red skin. ...

Causes

Pituitary adenoma

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. Pituitary adenomas are tumors that occur in the pituitary gland, and account for about 10% of intracranial neoplasms. ... Impotence or, more clinically, erectile dysfunction is the inability to develop or maintain an erection of the penis for satisfactory sexual intercourse regardless of the capability of ejaculation. ...

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. In biology, mutations are changes to the genetic material (either DNA or RNA). ... The term cell growth is used in two different ways in biology. ...

Other 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. Tumor (American English) or tumour (British English) originally means swelling, and is sometimes still used with that meaning. ... The pancreas is an organ in the digestive system that serves two major functions: exocrine - producing pancreatic juice containing digestive enzymes. ... The lungs flank the heart and great vessels in the chest cavity. ... Grays Fig. ...

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.

Diagnosis

If acromegaly is suspected, medical imaging and medical laboratory investigations are generally used together to confirm or rule out the presence of this condition. It has been suggested that this article or section be merged into Radiology. ... A medical laboratory or clinical laboratory is a laboratory where tests are done on biological specimens in order to get information about the health of a patient. ...

Hormonal

IGF1 provides the most sensitive and useful lab test for the diagnosis of acromegaly. A single value of the Growth hormone (GH) is not useful in view of its pulsatality (levels in the blood vary greatly even in healthy individuals). GH levels taken 2 hours after a 75 gram glucose tolerance test are helpful in the diagnosis: GH levels are suppressed below 1 μg/L in normal people, and levels higher than this cutoff are confirmatory of acromegaly. A glucose tolerance test in medical practice is the administration of glucose to determine how quickly it is cleared from the blood. ...

Other pituitary hormones have to be assessed to address the secretory effects of the tumour as well as the mass effect of the tumor on the normal pituitary gland. They include TSH (thyroid stimulating hormone), gonadotropic hormones (FSH,LH), ACTH (adrenocorticotropic hormone), prolactin. Thyroid-stimulating hormone (also known as TSH or thyrotropin) is a hormone produced by thyrotrope cells in the anterior pituitary gland which regulates the endocrine function of the thyroid gland. ... Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. ... Adrenocorticotropic hormone (ACTH or corticotropin) is a polypeptide hormone synthesised (from POMC, pre-opiomelanocortin) and secreted from corticotropes in the anterior lobe of the pituitary gland in response to the hormone corticotropin-releasing hormone (CRH) released by the hypothalamus. ... Prolactin is a peptide hormone synthesised and secreted by lactotrope cells in the adenohypophysis (anterior pituitary gland). ...

Radiological

A MRI of the brain focussing on the sella after gadolinium administration allows for clear delineation of the pituitary and the hypothalamus and the location of the tumour. This article or section does not cite its references or sources. ... General Name, Symbol, Number gadolinium, Gd, 64 Chemical series lanthanides Group, Period, Block n/a, 6, f Appearance silvery white Atomic mass 157. ...

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. Clinac 2100 C100 accelerator Radiation therapy (or radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). ...

Surgery

Surgery is a rapid and effective treatment. The surgeon reaches the pituitary through an incision in the nose and, with special tools, removes the tumor tissue in a procedure called transsphenoidal surgery. This procedure promptly relieves the pressure on the surrounding brain regions and leads 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. Cerebrospinal fluid (CSF), Liquor cerebrospinalis, is a clear bodily fluid that occupies the subarachnoid space in the brain (the space between the skull and the cerebral cortex—more specifically, between the arachnoid and pia layers of the meninges). ... Meningitis is the inflammation of the membranes (meninges) covering the brain, usually due to bacterial or viral infections elsewhere in the body that has spread into the blood and into the cerebrospinal fluid (CSF). ...

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. Bromocriptine is an ergoline derivative dopamine agonist that is used in the treatment of pituitary tumors and Parkinsons disease. ... The insulin-like growth factors (IGFs) are polypeptides with high sequence similarity to insulin. ...

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. Somatostatin is a hormone. ...

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. This article or section does not cite its references or sources. ... This article is about the disease that features high blood sugar. ... It has been suggested that Oral insulin be merged into this article or section. ...

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. Anna Haining Bates with her parents Gigantism or giantism, (from Greek gigas, gigantos giant) is a condition characterized by excessive height growth. ... For other uses, see Bone (disambiguation), including Bones which redirects here. ...

Notable sufferers

Famous patients, all standing in excess of 2.00 metres:

• Actor Richard Kiel ('Jaws' in the James Bond movies), 7'2" tall
• Actor Carel Struycken (known e.g as Lurch in the Addams Family -movies, and for his other giant roles), 7' tall
• Actor Matthew McGrory (is listed in the Guinness Book of World Records for having the largest feet - size 29 1/2), 7'6" tall
• Wrestler and actor André the Giant, 7'2" tall
• Wrestler Paul Wight (The Big Show), had surgery on his pituitary gland in the 1990s to fix the condition, his height peaking at 7'1" tall
• Former NBA player Gheorghe Mureşan (star of My Giant), 7'7" tall
• Aspiring basketball player Sun Ming Ming, 7'9" tall

It has been suggested that the character 'Punch' from Punch and Judy was originally a caricature of an Acromegaly sufferer.^[1] Richard Kiel as Jaws from two James Bond movies, showing the characters eponymous metal teeth. ... The James Bond 007 gun logo James Bond 007 is a fictional British agent (the Bond character is usually referred to as a spy, but was actually a counter-agent and professional killer) created by writer Ian Fleming in 1952. ... Carel Struycken (born July 30, 1948 in The Hague, Zuid-Holland, Netherlands) is a character actor in film, television, and stage. ... Lurch is the fictional manservant to The Addams Family created by cartoonist Charles Addams. ... Four major characters from the original television adaptation: Thing (foreground) with Uncle Fester, Morticia and Gomez Addams The Addams Family is the creation of American cartoonist Charles Addams. ... Matthew McGrory Matthew McGrory (May 17, 1973 – August 9, 2005) was an American actor, known for his massive height. ... The Guinness Book of Records (or in recent editions Guinness World Records, and in previous US editions Guinness Book of World Records) is a book published annually, containing an internationally recognized collection of superlatives: both in terms of human achievement and the extrema of the natural world. ... André the Giant (June 19, 1946 – January 27, 1993) was a professional wrestler and actor, born André René Roussimoff in Grenoble, France. ... Paul Wight (born February 8, 1972), better known by the ring names (The) Big Show and (The) Giant, is an American professional wrestler. ... See also 1990s, the band Germans dancing on the Berlin Wall in late 1989, the symbol of the cold war divide falls down as the world unites in the 1990s. ... Gheorghe Mureşan standing behind six-foot (1. ... My Giant is a 1996 Comedy/Drama film starring Billy Crystal. ... Sun Ming Ming (孫明明) is a Chinese basketball player. ... A stained glass illustration of Punch by Professor Ignorant Punch and Judy is a popular glove-puppet show for children (although the earliest shows used marionettes), featuring Punch and his wife Judy. ...

See also

• Gigantism

Anna Haining Bates with her parents Gigantism or giantism, (from Greek gigas, gigantos giant) is a condition characterized by excessive height growth. ...

External links

• Acromegaly - Geneva Foundation for Medical Education and Research
• This article was largely derived from http://www.niddk.nih.gov/health/endo/pubs/acro/acro.htm
• Endotext.org, an "online Endocrine textbook"
• An article on Acromegaly and gigantism
• eMedicine med/27

1. ^ BBC News report on Punh and Acromegaly