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Gigantism is a rare disorder resulting from increased levels of growth hormone before the fusion of the growth plate which usually occurs at some point soon after puberty. This is most often due to abnormal tumor growths on the pituitary gland.[1][2] Gigantism should not be confused with acromegaly, the adult form of the disorder, characterized by somatic enlargement specifically in the extremities and face.[3][4]

Gigantism
Classification and external resources
Specialty Endocrinology
ICD-10 E22.0, E34.4
ICD-9-CM 253.0
DiseasesDB 30730
MedlinePlus 001174
MeSH D005877

Contents

Diagnosis and causeEdit

Gigantism is characterized by an excess of growth hormone (GH). This overproduction of growth hormone that brings about gigantism is virtually always caused by pituitary growths (adenomas).[2] These adenomas are on the anterior pituitary gland. They can also cause overproduction of GH's hypothalamic precursor known as growth hormone releasing hormone (GHRH).[5]

As a result of the excessive amounts of growth hormone, children achieve heights that are well above normal ranges.[6] 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.[1] Other health complications may occur in pediatric patients with hyper-secretion of growth hormone such as hypertension. Characteristics more similar to those seen in acromegaly may occur in patients that are closer in age to adolescence since they are nearing growth plate fusion.[7]

Hormonal causeEdit

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are two different substances that have been identified as influencing growth plate formation and bone growth and, therefore, gigantism. The specific mechanisms of these are still not completely understood.[1][8]

More broadly, GH and IGF have both been identified to be involved most stages of growth: embryonic, prenatal, and postnatal.[9][10] 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.[9][11]

Growth hormone is a precursor (upstream) of IGF-I, but each have their own independent roles in hormonal pathways. Although, both seem to ultimately come together to have a joint effect on growth.[10]

Diagnostic testingEdit

Evaluation of growth hormone hyper-secretion cannot be excluded with a single normal GH level due to diurnal 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.[12]

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 hyper-secretion.[12]

Genetic causesEdit

Finding a specific genetic 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.[1]

Some common mutations (errors in DNA) 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 between gene duplications and the gigantism.[13]

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.[2] AIP is labeled as a tumor suppressor gene and a pituitary adenoma disposition gene.[2][14]

Mutations in AIP sequencing can have deleterious effects by inducing the development of pituitary adenomas which in turn can cause gigantism.[2][14]

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.[15] This is typical in gigantism.

Additionally, a large variety of other known genetic disorders have been found to influence the development of gigantism such as multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, X-linked acrogigantism (X-LAG).[2][16]

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.[1]

TreatmentEdit

Many treatments for gigantism receive criticism and are not accepted as ideal. Various treatments involving surgery and drugs have been used to treat gigantism.[17]

PharmaceuticalsEdit

Pegvisomant is one pharmaceutical drug which has received attention for being a possible treatment route for Gigantism. Reduction of the levels of IGF-I as a result of pegvisomant administration can be incredibly beneficial for the pediatric gigantism patients.[18]

After treatment with pegvisomant, high growth rates, a feature characteristic of gigantism, can be significantly decreased.[18] Pegvisomant has been seen to be a powerful alternative to other treatments such as somatostatin analogues, a common treatment method for acromegaly, if drug treatment is paired with radiation.[19]

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.[17]

See acromegaly for additional treatment possibilities.

TerminologyEdit

Gigantism, also known as giantism (from Greek γίγας gigas, "giant", plural γίγαντες gigantes), is a condition characterized by excessive growth and height significantly above average. In humans, this condition is caused by over-production of growth hormone[20] in childhood resulting in people between 7 feet (2.13 m) and 9 feet (2.72 m) in height.[21][22][23][24]

 
Giantess Anna Swan with her parents.

The term is typically applied to those whose height is not just in the upper 1% of the population but several standard 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 healthy result of normal genetics and nutrition. Gigantism is usually caused by a tumor on the pituitary gland of the brain. It causes growth of the hands, face, and feet.[25][better source needed] In some cases the condition can be passed on genetically through a mutated gene.[26]

Other names somewhat obsolete for this pathology are hypersoma (Greek: hyper over the normal level; soma body) and somatomegaly (Greek; soma body, genitive somatos 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 in Friedrich Wilhelm I's famous Potsdam Giants regiment.

Many of those who have been identified with gigantism have suffered from multiple health issues involving their circulatory or skeletal system, as the strain of maintaining a large, heavy body places abnormal demands on both the bones and the heart.

Society and cultureEdit

Reports of gigantism exist throughout history, with some nations and tribes taller than others. The giants of Crete are listed in various historic sources, beginning with Titan, a Greek mythological giant, and including Gigantus, after whom giants and gigantism are named. Rhodes is another island where giants were said to have lived, with the Colossus of Rhodes, a giant statue of a giant patron god Helios. Goliath, a giant mentioned in the Bible, was a Philistine warrior who was killed by David in a battle between the Israelites and the Philistines. A member of Goliath's family is also recorded as having six fingers on each hand and six toes on each foot.[27]

See alsoEdit

ReferencesEdit

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  2. ^ a b c d e f Rostomyan, Liliya; Potorac, Iulia; Beckers, Pablo; Daly, Adrian F.; Beckers, Albert. "AIP mutations and gigantism". Annales d'Endocrinologie. 78 (2): 123–130. doi:10.1016/j.ando.2017.04.012. 
  3. ^ Chanson, Philippe; Salenave, Sylvie (2008-06-25). "Acromegaly". Orphanet Journal of Rare Diseases. 3: 17. doi:10.1186/1750-1172-3-17. ISSN 1750-1172. 
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  5. ^ Zimmerman, D; Young, W F; Ebersold, M J; Scheithauer, B W; Kovacs, K; Horvath, E; Whitaker, M D; Eberhardt, N L; Downs, T R (1993-01-01). "Congenital gigantism due to growth hormone-releasing hormone excess and pituitary hyperplasia with adenomatous transformation". The Journal of Clinical Endocrinology & Metabolism. 76 (1): 216–222. doi:10.1210/jcem.76.1.8421089. ISSN 0021-972X. 
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  7. ^ Murray, P. G.; Clayton, P. E. (2000). De Groot, Leslie J.; Chrousos, George; Dungan, Kathleen; Feingold, Kenneth R.; Grossman, Ashley; Hershman, Jerome M.; Koch, Christian; Korbonits, Márta; McLachlan, Robert, eds. Endotext. South Dartmouth (MA): MDText.com, Inc. PMID 25905205. 
  8. ^ Shim, Kye Shik (March 2015). "Pubertal growth and epiphyseal fusion". Annals of Pediatric Endocrinology & Metabolism. 20 (1): 8–12. doi:10.6065/apem.2015.20.1.8. ISSN 2287-1012. PMC 4397276 . PMID 25883921. 
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  14. ^ a b Beckers, Albert; Aaltonen, Lauri A.; Daly, Adrian F.; Karhu, Auli (2013-04-01). "Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene". Endocrine Reviews. 34 (2): 239–277. doi:10.1210/er.2012-1013. ISSN 0163-769X. 
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  17. ^ a b Goldenberg, Naila; Racine, Michael S.; Thomas, Pamela; Degnan, Bernard; Chandler, William; Barkan, Ariel (2008-08-01). "Treatment of Pituitary Gigantism with the Growth Hormone Receptor Antagonist Pegvisomant". The Journal of Clinical Endocrinology & Metabolism. 93 (8): 2953–2956. doi:10.1210/jc.2007-2283. ISSN 0021-972X. 
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  25. ^ "Gigantism". Question.com. Retrieved 2012-03-14. 
  26. ^ In a Giant’s Story, a New Chapter Writ by His DNA - By Gina Kolata. The New York Times, January 5, 2011
  27. ^ Story of Goliath in 1Samuel 17 – 6 fingers in 1 Chronicles 20:6 cf. 2Samuel 21:20-22

External linksEdit