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Gigantism or giantism, (from Greek gigas, gigantos "giant") is a condition characterized by excessive height growth. As a medical term, gigantism is rarely used except to refer to the rare condition of pituitary gigantism due to prepubertal growth hormone excess. There is no precise definition of the degree of tallness that qualifies a person to be termed a "giant." The term has been 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. more...

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Typical adult heights of Americans and Europeans to whom the term might be applied are 210 - 240 cm (7 - 8 feet) though it may be possible for a person to grow up to 270 cm (9 feet) or taller. The term is rarely applied to basketball players and those whose heights appear to be the healthy result of normal genetics and nutrition.

Pituitary gigantism

Pituitary gigantism due to growth hormone excess is the single condition that accounts for nearly all cases of pathologic extreme height. The excess growth hormone usually results from oversecretion by a group of somatotrope cells of the anterior pituitary gland (termed a "somatotrope adenoma"). These cells do not respond to normal controls of growth or function. They grow very slowly, so that for many years the only effects of such an adenoma are the effects of excessive growth hormone.

The primary effect of growth hormone excess in childhood is excessive growth, but the tallness is accompanied by a characteristic physique recognizable to an endocrinologist. The typical physique involves heavy, thick bones, with large hands and feet and a heavy jaw. Once puberty is complete and adult height is achieved, continued thickening of the skin and growth of the jaw results in a combination of features referred to as acromegaly. Over decades, such an adenoma may reach a large enough size (2 cm or more in diameter) to cause headaches, impair vision, or damage other pituitary functions. Many years of growth-hormone excess can cause other problems as well.

If pituitary gigantism or acromegaly is suspected by a physician, the simplest diagnostic screening test is measurement of insulin-growth factor 1 in the blood. This is usually quite elevated but levels must be interpreted in relation to age and pubertal status. Additional confirmatory testing may include magnetic resonance imaging (MRI) of the pituitary to look for a visible adenoma, and suppressibility of growth hormone levels by glucose. Treatment depends on the size of the adenoma and may involve removal by a neurosurgeon, drugs such as octreotide or bromocriptine, or radiation. Treatment is discussed in more detail in the acromegaly article.

Childhood pituitary gigantism is a rare condition, and those affected are often unusual enough to attain a degree of celebrity status (e.g., André the Giant) Acromegaly is the term used for the condition of growth hormone excess when it occurs in adults. Acromegaly is a far more common disease in adults than pituitary gigantism is in children.

Other conditions of overgrowth or excessive tallness in childhood

Children who are excessively tall are often referred to pediatric endocrinologists for evaluation. The majority of children who seem excessively tall or large to their parents usually have a combination of simple familial tallness and childhood obesity.


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Mutants: on Genetic Variety and the Human Body
From Natural History, 11/1/03 by Laurence A. Marschall

by Armand Marie Leroi Viking Press, 2003; $25.95

Don't let the bearded lady on the dust jacket fool you: this book is not a smarmy gallery of freaks and monsters. Armand Marie Leroi, a developmental biologist at Imperial College, London, has written an elegant study, filled with narratives from early medical literature and insights from the latest biomolecular research, on the subject of genetic variability and its manifestations in the developing human organism.

Not that the book isn't bulging with such oddities as flies born without eyes and babies born without irises--not to mention the person born with five nipples on one side and four on the other (a record). Leroi is also a gifted raconteur, and he's assembled a cast of fascinating and exotic characters. Josef Boruwlaski, an eighteenth-century Polish courtier whose memoirs introduce a chapter on human stature, stood just over three feet tall. He was a fixture at the courts of Europe, however, married well, raised a family, and died at the respectable age of 98. Carl Herman Unthan, born without arms in 1848, appears in a chapter on limb development. By age 20 Unthan was an established violin virtuoso, performing in Viennese concert halls with the great classical musicians of his time. In 1928, by then a naturalized citizen of the United States, he produced an autobiographical "pediscript" (so named because he had typed it out with his toes) that was published under the title The armless fiddler.

For every uplifting story, of course, there are many tales far more disturbing: conjoined twins sharing a single pair of legs; a man virtually frozen in place when his flesh turned to bone; people with single eyes, or with no eyes at all.

But Leroi's aim is to illuminate, not to titillate. Variability in the human species can be trivial, heroic, or tragic, but in all cases it is evidence of the coded blueprint in our genes, and of the way that blueprint is expressed in the developing organism. Although it is ethically impossible to experiment with the blueprint in the laboratory--turning genes on and off to see what happens--the outcome can be studied if nature does the experiment. Each mutation thus offers a glimpse of how one set of instructions, written in our genes, ends up forming a body.

Sometimes a mutant form arises from one alteration in a single gene. Leroi cites the descendants of an "exceptionally philoprogenitive" Chinese sailor, who in 1896 came ashore at Cape Town, South Africa, and settled in the Cape Malay quarter. All of his numerous progeny carry a mutation, on a gene called CBFA1, that affects cells that produce bone. And many of his descendants have inherited the mutation's traits, which include soft skulls, missing clavicles, and missing teeth--a fact that does not seem to affect their vitality: a 1996 survey turned up about a thousand people around Cape Town with the mutation, and they all speak with pride of their cartilaginous ancestor.

Other mutations involve multiple genes and work in ways far subtler than do single-point mutations. Such characteristics as skin color, stature, longevity, and propensities for particular types of cancers often require several mutations to express themselves. Many variations in the human form, such as dwarfism or gigantism, can arise from such combined mutations. To make matters even more complicated, the DNA blueprint can be modified during the "construction" phase, and changing conditions in the embryonic environment can have far-reaching effects on later development. The thalidomide disaster of the 1960s, for instance, was caused by a drug prescribed to alleviate morning sickness. Inadvertently, though, it affected the growth of limb buds, and thousands of infants worldwide were born without the long bones of their arms or legs.

Although the entire human genome has been officially mapped since 2001, most of the ways it expresses itself are still unexplored. Leroi has written a guidebook to the territory, in which mutations are the landmarks that give an overview of the terrain. But it is clear that geneticists are only beginning to understand the connection between the dull sequences of C's, A's, G's, and T'S in the genome map and the "real stuff" of bodies and minds. Leroi's book is a testament to both the ingenuity of organic life and the protean nature of what it means to be human.

Laurence A. Marschall, author of The Supernova Story, is the W.K.T. Sahm professor of physics at Gettysburg College in Pennsylvania, and director of Project CLEA, which produces widely used simulation software for education in astronomy.

COPYRIGHT 2003 American Museum of Natural History
COPYRIGHT 2003 Gale Group

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