Throughout history, folklore, and every culture, stories about giants have persisted. The mythos surrounding them elicits memories of simpler times. Growing up, most children are made aware of Jack’s giant (Jack and the Beanstalk) or how Paul Bunyan carved the Grand Canyon by dragging his ax behind him. Giants have been portrayed as grotesque brutes and less than human, as is the case with Jack’s giant or the Cyclops from Greek mythology. Sometimes, giants are extremely agreeable and pleasant, such as the lovable gentle giant Fezzik in The Princess Bride. Giants may also represent monolithic feats or something that must be conquered, as is the case with the story of David and Goliath. Virtually every religion references giants, typically as creatures in the early days of mankind. In fact, giants have such a connection to religion that in recent years there have been several hoaxes involving giants that attempt to confirm biblical accounts. One of the more famous giant hoaxes occurred in Cardiff, New York, in 1869. The Cardiff giantwas deliberately sculpted and buried at a farm in New York State by George Hull, a self-proclaimed atheist. The fake fossil was carved out of gypsum and measured over 10 feet long. Immediately upon its discovery, it was deemed a fake. However, that didn’t deter swarms of people from flocking to New York and shelling out 50 cents to see the real-life Goliath. As the rumor mill ramped up, declaring that the Cardiff giant was evidence of the Bible’s accuracy, P.T. Barnum wanted to cash in too. Barnum tried to rent the giant for his traveling circus but was turned down. Undeterred, Barnum created his own fake Cardiff giant and, interestingly enough, Barnum’s fake fossil was more popular than the original.

To date, Robert Wadlow was the tallest man ever recorded. Wadlow measured almost 9 feet at the time of his death in 1940; he was only 22 years old. The tallest fossilized record belongs to the Giant of Castelnau. In 1890, scientists uncovered a humerus, tibia, and femoral mid-shaft from a cemetery in Castelnau, France. Based on bone dimensions, they estimated its height to be about 11.5 feet. It is noteworthy that at the time, several scientists declared the remains to be undeniably human, but since 1895, no further examinations have been made. Because of that fact and in the absence of any supporting evidence, many consider the Giant of Castelnau to be a mistake or just another hoax.

At what height is someone classified as a giant? The answer is not so straightforward. Gigantism is typically associated with acromegaly. Height is a prerequisite for gigantism, although not everyone diagnosed with acromegaly is also a giant. That said, some people are genetically predisposed to be tall, or they may have another underlying medical condition, such as Marfan syndrome, XYY syndrome, neurofibromatosis, tuberous sclerosis, McCune-Albright syndrome (MAS), Carney complex (CNC1), or multiple endocrine neoplasia type I (MAS, CNC1 and MEN 1 are associated with familial acromegaly). Even using the simplest definition allows for a tremendous amount of variation and it is dependent upon when and where you are born. However, generally speaking, in terms of height, anyone who is above 2 standard deviations of the mean is considered a giant.

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What is acromegaly?

Acromegaly is a rare condition in which a person releases an overabundance of growth hormones (GHs) and, more specifically, insulin-like growth factor 1 (IGF-1). Causes include either pathological or morphological changes to the pituitary (pituitary hyperplasia), and adenomas. Hypothetically, hypothalamic dysregulation resulting in an increase of GH-releasing hormone (GHRH) could also result in acromegaly but it is uncommon. It is also postulated that an excess of IGF-binding proteins can prolong the half-life of circulating IGF-I and result in increased GH exposure. The causes may vary but, generally speaking, the pituitary secretes an overabundance of IGF-1.

The most common cause is an adenoma or pituitary hyperplasia. Pituitary adenomas are typically benign tumors, although, depending on their location and rate of growth, they can become clinically significant. One study found that pituitary adenomas are more common than previously thought, with a prevalence rate of 16.7%. However, the vast majority are nonfunctional (based on relatively normal hormonal activity). This is not to say non-functional adenomas do not present problems. Typically, nonfunctional adenomas are more aggressive and tend to be invasive. Some can cause visual field disturbances or invade the sinuses, and there is a concern that even clinically silent adenomas may affect hormone regulation enough to increase mortality. However, with regard to gigantism, the focus is on how pituitary adenomas release an excess of GH.

Acromegaly and gigantism as a result of a pituitary adenoma or hyperplasia require either an adenoma composed of specialized hormone-secreting cells or, in cases of hyperplasia, a proliferation of specialized cells. These cells include GH-producing cells called somatotrophs, or in extremely rare cases, mammosomatotropic cells that produce both GH and prolactin. The latter is also associated with MAS. Symptoms of acromegaly vary based on age of onset. With adult onset, symptoms include:

  • Progressive enlargement of hands and feet (often individuals need to get larger wedding bands and shoes)
  • Coarsening of facial features (an enlarging/widening nose, a more prominent lower lip that turns slightly out)
  • Carpal tunnel syndrome
  • Snoring and/or sleep apnea
  • Progressive enlargement of jaw (lower jaw protrusion, separation and misalignment of teeth, and pain in the temporomandibular joint)
  • Arthralgia and premature osteoarthritis
  • Headaches (in about 50% of cases; headaches can mimic classic migraines, they can be lateralized or global headaches, or they can be tension headaches)
  • Excessive sweating
  • Dysmorphophobia (however, this aspect is more of a direct result of real and noticeable physical changes)

Gigantism can be inherited or sporadic. Loss of heterozygosity on chromosomes 11q13 and 13q14 is associated with sporadic hormone-secreting adenomas.Approximately 20% of gigantism cases are a result of MAS, with additional symptoms that include precocious puberty, café au lait spots, and fibrousdysplasia.

Gigantism occurs as a direct result of an adenoma or pituitary hyperplasia manifesting during childhood. It can present with similar symptoms as the adult form; however, it is distinguished by a runaway growth process. Essentially, the affected individual doesn’t stop growing because of an overabundance of IGF-1 before the epiphyseal growth plates fuse. Typically, these growth plates fuse by age 18 in males and sooner in females, although this is not always true. The case of Tanya Angus exemplifies this. Tanya Angus was a beautiful young woman who dreamed of becoming a model. At 5 ft, 8 in and 130 lbs, her dream may have been realized, but as a young adult everything changed. At age 21, an adenoma was discovered that had wrapped itself around her pituitary gland. She developed an extreme form of acromegaly and gigantism. As her condition worsened, she was fired from a Michigan Wal-Mart where she worked as a supervisor. Her boyfriend broke up with her and, adding insult to injury, his parent’s questioned whether Tanya was a man. At age 34, she died fromcomplications associated with her condition. At that time, she weighed nearly 400 lbs and was almost 7 feet tall. Ironically, about a year before herdeath, she and her family were hopeful due to the fact that, for the first time, her hormone levels fell to a normal range.

Tanya Angus, Doctors Hope To Find Cure For Giant Woman

Other clinical features include hypertension (present in 43% of patients), and an increase in left ventricular mass, stroke volume, cardiac output, and isovolumic relaxation time. In gigantism, there are reports of high resting ejection fraction rates with lower rates during exercise. Increased diastolic peak velocity and increased intima-media thickness have also been reported. Simply speaking, this condition is correlated with poor cardiovascularoutcomes.

Reference

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Topics:

Immune System Development Rare Conditions Rare Disease