| Gigantism | |
|---|---|
| Other names | Giantism |
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| Robert Wadlow stood at 8 ft 11 in (2.72 m). He is pictured here with his father, who was 5 ft 11.5 in (1.82 m) tall. | |
| Pronunciation | |
| Specialty | Endocrinology |
| Symptoms | Abnormal growth in height or size, weakness andinsomnia |
| Complications | Excessive sweating,delayed puberty, weakness and severe or recurrent headaches, strokes, vomiting or nausea, high fevers, daytime sleepiness or narcolepsy, dry mouth, frequent diarrheas, stomachaches, ear pains, memory loss, back pains, excessive muscle cramps, chest pains |
| Causes | Hyperplasia in thepituitary gland |
| Treatment | Surgically remove the enlargedpituitary gland |
| Medication | Octreotide,lanreotide orpegvisomant |
Gigantism (/dʒaɪˈɡæntɪzəm/jy-GAN-tiz-əm; fromAncient Greek:γίγας,romanized: gígās,lit. 'giant', plural:γίγαντες,gígantes), also known asgiantism, is a condition characterized by excessive growth and height significantly aboveaverage. Technically, it includes humans with height at least threestandard deviations above the mean, i.e., 198 cm (6'6") for men and 183 cm (6'0") for women. This condition is caused by over-production ofgrowth hormone in childhood.[1][2][3][4][5]
It is a rare disorder resulting from increased levels of growth hormone before the fusion of thegrowth plate which usually occurs at some point soon after puberty. This increase is most often due to abnormal tumor growths on thepituitary gland.[6][7] Gigantism should not be confused withacromegaly, the adult form of the disorder, characterized bysomatic enlargement specifically in the extremities and face.[8][9]
Many of those who have been identified with gigantism have had multiple health problems involving thecirculatory orskeletal system, as the strain of maintaining a large, heavy body places abnormal demands on both thebones and theheart.
Gigantism is characterized by an excess ofgrowth hormone (GH). The excess of growth hormone that brings about gigantism is virtually always caused by pituitary growths (adenomas).[7] These adenomas are on theanterior pituitary gland. They can also cause overproduction of GH's hypothalamic precursor known asgrowth hormone releasing hormone (GHRH).[10]
As a result of the excessive amounts of growth hormone, children achieve heights that are well above normal ranges.[11] The specific age of onset for gigantism varies between patients and gender, but the common age that excessive growth symptoms start to appear has been found to be around 13 years.[6] Other health complications, such ashypertension, may occur inpediatric patients withhyper-secretion of growth hormone. Characteristics more similar to those seen inacromegaly may occur in patients that are closer in age toadolescence since they are nearing growth plate fusion.[12]
Growth hormone (GH) andinsulin-like growth factor-I (IGF-I) are two substances that have been identified as influencing growth plate formation and bone growth and, therefore, gigantism. Their specific mechanisms are still not well understood.[6][13]
More broadly, GH and IGF have both been identified to be involved in most stages of growth: embryonic, prenatal, and postnatal.[14][15] Moreover, the receptor gene for IGF has been shown to be particularly influential throughout various stages of development, especially prenatally. This is the same for GH receptor genes which have been known to drive overall growth throughout various pathways.[14][16]
Growth hormone is a precursor (upstream) of IGF-I, but each has its independent role in hormonal pathways. Yet both seem to ultimately come together to have a joint effect on growth.[15]
Evaluation of growth hormone hypersecretion cannot be excluded with a single normal GH level due todiurnal variation. However, a random blood sample showing markedly elevated GH is adequate for diagnosis of GH hyper-secretion. Additionally, a high-normal GH level that fails to suppress with administration of glucose is also sufficient for a diagnosis of GH hyper-secretion.[17]
Insulin-like growth factor-1 (IGF-1) is an excellent test for evaluation of GH hyper-secretion. It does not undergo diurnal variation and will thus be consistently elevated in GH hyper-secretion and therefore patients with gigantism. A single normal IGF-1 value will reliably exclude GH hypersecretion.[17]
Finding a specificgenetic cause for gigantism has proven to be difficult. Gigantism is the primary example of growth hormone hyper-secretion disorders, a group of illnesses that are not yet deeply understood.[6]
Some commonmutations have been associated with gigantism. Pediatric gigantism patients have shown to have duplications of genes on a specific chromosome, Xq26. Typically, these patients also experienced an onset of typical gigantism symptoms before reaching the age of 5. This indicates a possible linkage betweengene duplications and the gigantism.[18]
Additionally, DNA mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are common in gigantism patients. They have been found to be present in about 29 percent of patients with gigantism.[7] AIP is labeled as atumor suppressor gene and apituitary adenoma disposition gene.[7][19]
Mutations in AIP, found bysequencing, can have deleterious effects by inducing the development of pituitary adenomas which in turn can cause gigantism.[7][19]
Two specific mutations in the AIP gene have been identified as possible causes of pituitary adenomas. These mutations also have the ability to cause adenoma growth to occur early in life.[20] This is typical in gigantism.
Additionally, a large variety of other known genetic disorders have been found to influence the development of gigantism such asmultiple endocrine neoplasia type 1 and 4,McCune–Albright syndrome,Carney complex, familial isolated pituitary adenoma, X-linked acrogigantism (X-LAG).[7][21]
Although various gene mutations have been associated with gigantism, over 50 percent of cases cannot be linked to genetic causes, showing the complex nature of the disorder. However, in some cases it was observed that the condition had been passed on genetically through a mutated gene.[6][22]
Many treatments for gigantism receive criticism and are not accepted as ideal. Various treatments involving surgery and drugs have been used to treat gigantism.[23]
Pegvisomant is onepharmaceutical drug which has received attention for being a possible treatment route for gigantism. Reduction of the levels ofIGF-I as a result of pegvisomant administration can be effective for the pediatric gigantism patients.[23]
After treatment with pegvisomant, high growth rates, a feature characteristic of gigantism, can be significantly decreased.[23] Pegvisomant has been seen to be a powerful alternative to other treatments such assomatostatin analogues, a common treatment method for acromegaly, if drug treatment is paired withradiation.[24]
Finding the optimal level of pegvisomant is important so normal body growth is not negatively affected. In order to do this,titration of the medication can be used as a way to find the proper administration level.[23]
Seeacromegaly for additional treatment possibilities.
The term is typically applied to those whose height is not just in the upper 1% of the population but severalstandard deviations above mean for persons of the same sex, age, and ethnic ancestry. The term is seldom applied to those who are simply "tall" or "above average" whose heights appear to be the result of normalgenetics and nutrition. Gigantism is usually caused by atumor on the pituitary gland of the brain.
Other names somewhat obsolete for this pathology are hypersoma (Greek:hyper over the normal level;soma body) and somatomegaly (Greek;soma body,genitivesomatos of the body;megas, gen.megalou great). In the past, while many of them were social outcasts because of their height, some (usually unintentionally) found employment inFriedrich Wilhelm I's famousPotsdam Giants regiment.
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