Gigantism ( el, γίγας, ''gígas'', " giant", plural γίγαντες, ''gígantes''), also known as giantism, is a condition characterized by excessive growth and height significantly above

average In ordinary language, an average is a single number taken as representative of a list of numbers, usually the sum of the numbers divided by how many numbers are in the list (the arithmetic mean). For example, the average of the numbers 2, 3, 4, 7 ...

. In humans, this condition is caused by over-production of

growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...

in childhood, resulting in people up to in height. It 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 increase is most often due to abnormal tumor growths on the

pituitary gland In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The h ...

. Gigantism should not be confused with

acromegaly Acromegaly is a disorder that results from excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be an enlargement of the forehead, jaw, and nose. Othe ...

, the adult form of the disorder, characterized by somatic enlargement specifically in the extremities and face.

Cause

Gigantism is characterized by an excess of

(GH). The excess of growth hormone that brings about gigantism is virtually always caused by pituitary growths (adenomas). These adenomas are on the

anterior pituitary gland A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...

. They can also cause overproduction of GH's hypothalamic precursor known as

growth hormone releasing hormone Growth may refer to: Biology * Auxology, the study of all aspects of human physical growth * Bacterial growth * Cell growth * Growth hormone, a peptide hormone that stimulates growth * Human development (biology) * Plant growth * Secondary growth ...

(GHRH). As a result of the excessive amounts of growth hormone, children achieve heights that are well above normal ranges. 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. Other health complications, such as

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...

, may occur in pediatric patients with hyper-secretion of growth hormone. Characteristics more similar to those seen in

may occur in patients that are closer in age to adolescence since they are nearing growth plate fusion.

Hormonal cause

Growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...

(GH) and insulin-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. More broadly, GH and IGF have both been identified to be involved in most stages of growth: embryonic, prenatal, and postnatal. 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. Growth hormone is a precursor (

upstream Upstream may refer to: * Upstream (bioprocess) * ''Upstream'' (film), a 1927 film by John Ford * Upstream (networking) * ''Upstream'' (newspaper), a newspaper covering the oil and gas industry * Upstream (petroleum industry) * Upstream (software ...

) 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.

Diagnostic testing

Evaluation of growth hormone hyper-secretion cannot be excluded with a single normal GH level due to

diurnal variation A chronotype is the behavioral manifestation of underlying circadian rhythm's myriad of physical processes. A person's chronotype is the propensity for the individual to sleep at a particular time during a 24-hour period. ''Eveningness'' (delayed ...

. 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.De Mais, Daniel. ASCP Quick Compendium of Clinical Pathology, 2nd Ed. ASCP Press, Chicago, 2009. 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.

Genetics

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. Some common

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...

s 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. 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. AIP is labeled as a

tumor suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or re ...

and a

pituitary adenoma Pituitary adenomas are tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas. Mutations in AIP

sequencing In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which suc ...

can have deleterious effects by inducing the development of pituitary adenomas which in turn can cause gigantism. 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. 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 Carney complex and its subsets LAMB syndrome and NAME syndrome are autosomal dominant conditions comprising myxomas of the heart and skin, hyperpigmentation of the skin ( lentiginosis), and endocrine overactivity. It is distinct from Carney's tria ...

, familial isolated pituitary adenoma, X-linked acrogigantism (X-LAG). 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.

Treatment

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

Pharmaceuticals

Pegvisomant Pegvisomant, sold under the brand name Somavert, is a growth hormone receptor antagonist used in the treatment of acromegaly. It is primarily used if the pituitary gland tumor causing the acromegaly cannot be controlled with surgery or radiation ...

is one

pharmaceutical drug A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...

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. After treatment with pegvisomant, high growth rates, a feature characteristic of gigantism, can be significantly decreased. 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 In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes: * ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visi ...

. 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. See

for additional treatment possibilities.

Terminology

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 Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar work ...

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. In some cases the condition can be passed on genetically through a mutated gene.In a Giant's Story, a New Chapter Writ by His DNA – By Gina Kolata. The New York Times, January 5, 2011
/ref> 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 had multiple health problems involving the

circulatory The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, t ...

skeletal system A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...

, as the strain of maintaining a large, heavy body places abnormal demands on both the

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

s and the

heart The heart is a muscular Organ (biology), organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as ca ...

References

Bibliography

External links

*
Gigantism Clinical Trials from U.S. National Institutes of Health

* ttps://www.ncbi.nlm.nih.gov/pubmed/11081170 Epidemiology of acromegaly from Pubmed.gov US National Library of Medicine & National Institutes of Health {{Authority control Growth disorders Human height Growth hormones Neuroendocrinology Rare diseases