Acromegaly (from Greek akros "extreme" or "extremities" and
megalos "large" - extremities enlargement) is a hormonal disorder that results when the
pituitary gland produces excess growth
hormone (hGH). Most commonly it begins when a GH producing tumor derived from a distinct type of cells (somatotrophs) and called pituitary adenoma.
Acromegaly most commonly affects middle-aged adults and can result in serious illness and premature death. Because of its
insidious pathogenesis 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:
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 because of reduced testosterone
production.
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.
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.
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.
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 or 100 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.
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.
Radiological
An MRI of the brain focussing on the sella
turcica after gadolinium administration allows for clear delineation of the pituitary
and the hypothalamus and the location of the tumour.
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
Endonasal Transphenoidal
surgery, involves the surgeon reaching the pituitary through an incision in the nasal cavity wall. The wall is reached by
passing through the nostrils with microsurgical instruments. The second method is Transphenoidal surgery during which an incision
is made into the gum beneath the upper lip. Further incisions are made to cut through the septum to reach the nasal cavity, where
the pituitary is located. Endonasal Transphenoidal surgery is a less invasive procedure with a shorter recovery time than the
older method of Transphenoidal surgery, and the likelihood of removing the entire tumor is greater with reduced side-effects.
Consequently, Endosnasal Transphenoidal surgery is often used as a first option, with Transphenoidal and other treatments, such
as, medicinal therapy or radiostatic neurosurgery being used to reduce the remaining adverse effects of the remaining tumor.
These procedures normally 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.
Notable sufferers
Famous patients, all but two (Tony Robbins, Maurice
Tillet) standing in excess of 2.00 metres:
- Actor Richard Kiel ('Jaws' in the James Bond
movies), 7'2" tall
- Actor Carel Struycken (known for playing Lurch in the
Addams Family movies, and for his other giant roles), 7' tall. Had successful
pituitary surgery in 1993.
- 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)
- Actor Rondo Hatton
- Wrestler and actor André the Giant, 7' tall after back surgery; his original
wrestling stats listed him at 7'4". He died at the age of 46, when most sufferers weren't expected to live past the age of 40.
(He chose not to be treated and died from disease)
- 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
- Wrestler Maurice Tillet ( 1903?- August 4, 1954 ), 5'10", 276 Ibs.
- * Wrestler and mixed martial artist Paulo César da Silva (Giant Silva), 7'5"
tall
- Wrestler Jorge Gonzalez (El Gigante), 7'6" tall
- Former NBA player Gheorghe Mureşan (star of My
Giant), 7'7" tall
- Aspiring basketball player Sun Ming Ming, 7'9" tall
- Makeup artist Kevyn Aucoin
- Composer Sergei Rachmaninoff [citation needed]
- Life coach, writer, and professional speaker Tony Robbins, 6'7" tall
- Kickboxer Choi Hong Man, 7'2" tall
It has been suggested that the character 'Punch' from Punch and Judy was originally a
caricature of an Acromegaly sufferer.[1]
The actor Paul Benedict had an arrested case of acromegaly. After his performance in a
stage production, a member of the audience came backstage and introduced himself as an endocrinologist; he had diagnosed
Benedict's condition during the performance and was ultimately able to cure him before the disease reached its later
stages.[citation needed]
The film The Monster Maker erroneously presents the concept of "acromegaly
germs."
See also
External links
References
- ^ BBC News report on Punch and Acromegaly
|
Endocrine pathology:
endocrine diseases (E00-35, 240-259) |
| Thyroid |
Hypothyroidism
(Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre, Myxedema) - Hyperthyroidism (Graves
disease, Toxic multinodular goitre, Teratoma with thyroid tissue or Struma ovarii) - Thyroiditis (De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's thyroiditis) -
Euthyroid sick syndrome |
| Pancreas |
Diabetes
mellitus (type 1, type
2, coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy) - Hypoglycemia - Hyperinsulinism - Zollinger-Ellison syndrome |
| Parathyroid |
Hypoparathyroidism
(Pseudohypoparathyroidism) - Hyperparathyroidism (Primary, Secondary, Tertiary) |
| Pituitary |
Hyperpituitarism (Acromegaly, Hyperprolactinaemia, SIADH)
- Hypopituitarism (Simmonds'
disease/Sheehan's syndrome, Kallmann
syndrome, Growth hormone deficiency, Diabetes insipidus) |
| Adrenal |
Cushing's syndrome
(Nelson's syndrome, Pseudo-Cushing's
syndrome) - CAH (due to 21-hydroxylase deficiency) - Hyperaldosteronism (Conn syndrome, Bartter syndrome) - Adrenal insufficiency
(Addison's disease) - Hypoaldosteronism |
| Gonads |
Polycystic ovary syndrome - 5-alpha-reductase
deficiency - Hypogonadism - Delayed puberty
- Precocious puberty |
| Other |
Autoimmune
polyendocrine syndrome - Carcinoid syndrome - Laron syndrome - Multiple endocrine neoplasia
(1, 2)
- Psychogenic dwarfism - Androgen
insensitivity syndrome - Progeria |
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