Gigantism (, ''gígas'', "

giant In folklore, giants (from Ancient Greek: ''wiktionary:gigas, gigas'', cognate wiktionary:giga-, giga-) are beings of humanoid appearance, but are at times prodigious in size and strength or bear an otherwise notable appearance. The word ''gia ...

", plural γίγαντες, ''gígantes''), also known as giantism, is a condition characterized by excessive growth and height significantly above

average In colloquial, ordinary language, an average is a single number or value that best represents a set of data. The type of average taken as most typically representative of a list of numbers is the arithmetic mean the sum of the numbers divided by ...

. 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. 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 The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...

. Gigantism should not be confused with

acromegaly Acromegaly is a disorder that results in excess growth of certain parts of the human body. It is caused by excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There ...

, 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 (

adenoma An adenoma is a benign tumor of epithelium, epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organ (anatomy), organs, including the adrenal glands, pituitary gland, thyroid, prosta ...

s). These adenomas are on the

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

. They can also cause overproduction of GH's hypothalamic precursor known as growth hormone releasing hormone (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, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

, 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 Adolescence () is a transitional stage of human Developmental biology, physical and psychological Human development (biology), development that generally occurs during the period from puberty to adulthood (typically corresponding to the age o ...

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) 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 hypersecretion 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.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 hypersecretion.

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, ...

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 duplication Gene duplication (or chromosomal duplication or gene amplification) is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene ...

s 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 (biology), 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 ...

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, found by

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 succ ...

, 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, 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 is one

pharmaceutical drug Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, 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 ...

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 Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by #Nomenclature, several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G ...

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 a material medium. This includes: * ''electromagnetic radiation'' consisting of photons, such as radio waves, microwaves, infr ...

. Finding the optimal level of pegvisomant is important so normal body growth is not negatively affected. In order to do this,

titration Titration (also known as titrimetry and volumetric analysis) is a common laboratory method of Quantitative research, quantitative Analytical chemistry, chemical analysis to determine the concentration of an identified analyte (a substance to be ...

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 deviation In statistics, the standard deviation is a measure of the amount of variation of the values of a variable about its Expected value, mean. A low standard Deviation (statistics), deviation indicates that the values tend to be close to the mean ( ...

s 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 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 Augustinians, Augustinian ...

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 In grammar, the genitive case ( abbreviated ) is the grammatical case that marks a word, usually a noun, as modifying another word, also usually a noun—thus indicating an attributive relationship of one noun to the other noun. A genitive can ...

''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 or

skeletal system A skeleton is the structural frame that supports the body of most animals. There are several types of skeletons, including the exoskeleton, which is a rigid outer shell that holds up an organism's shape; the endoskeleton, a rigid internal fra ...

, 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 found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

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