Acromegaly and gigantism

Douglas J Lanska MD FAAN MS MSPH (

Dr. Lanska of the University of Wisconsin School of Medicine and Public Health, the Medical College of Wisconsin, and IM Sechenov First Moscow State Medical University has no relevant financial relationships to disclose.

)
Originally released April 1, 1995; last updated December 14, 2020; expires December 14, 2023

Overview

Acromegaly is a disease characterized by the gradual enlargement of the peaked (acral) parts of the body, including the nose, lips, tongue, lower jaw, hands, and feet and by hyperplastic alterations in the entire osseous system. Gigantism occurs before epiphyseal closure. AIP gene mutations (AIPmut) often predispose to familial isolated pituitary adenomas with clinical features that may negatively impact treatment efficacy. The clinical picture of acromegaly is influenced by many factors, including the levels of growth hormone and insulin-like growth factor, age, tumor size, and delay in diagnosis. Surgical excision of the adenoma by transnasal transsphenoidal approach or by endoscopic endonasal transsphenoidal surgery is recommended. Pegvisomant is a medical therapy that blocks growth hormone action at peripheral receptors, normalizes insulin-like growth factor-1 levels, reduces signs and symptoms, and corrects metabolic defects.

Key points

 

• Acromegaly is characterized by the gradual enlargement of the acral parts of the body, with hyperplastic alterations in the entire osseous system due to growth hormone excess after epiphyseal closure.

 

• Gigantism occurs with growth hormone excess before epiphyseal closure.

 

• Acromegaly is usually diagnosed by increased insulin-like growth factor and growth hormone after an oral glucose tolerance test.

 

• For the treatment of acromegaly, surgical excision of the responsible pituitary adenoma by the transnasal transsphenoidal approach or by endoscopic endonasal transsphenoidal surgery is recommended. Alternatively, gamma knife therapy is an option.

 

• Pegvisomant, a growth-hormone-receptor antagonist, reduces signs and symptoms of acromegaly and corrects metabolic defects.

Historical note and terminology

Acromegaly, the first recognized pituitary syndrome, was described by the French neurologist Pierre Marie (1853-1940) working under Jean-Martin Charcot (1825-1893) at the Salpêtrière Hospital in Paris (Marie 1886).

Image: French neurologist Pierre Marie (1853-1940) circa 1900
Marie realized that many of the arthritic patients had an unusual enlargement of the hands and feet, which inspired the name he gave to this disorder (acromegaly literally means large extremities) (Robbins and Melmed 1987).

Acromegaly is a disease characterized by the gradual enlargement of the peripheral (acral) parts of the body including the nose, lips, tongue, lower jaw, hands, and feet and by hyperplastic alterations, particularly in the osseous system.

Image: Clinical features of acromegaly
Image: Man showing the characteristic appearances of acromegaly

In 1909, American neurosurgeon Harvey Cushing (1869-1939) deduced that the associated eosinophilic pituitary tumors are associated with states of hormonal overproduction and that the hypopituitarism that occurs concomitantly with some eosinophilic and chromophobe adenomas is due to compression of the remaining normal portion of the gland (Cushing 1909).

Image: American neurosurgeon Harvey Cushing (1869-1939)

In the 1920s at the University of California at Berkeley, American anatomist and embryologist Herbert Mclean Evans (1882-1971), in collaboration with zoologist Joseph A Long, found that the injection of anterior pituitary extract caused gigantism in rats (Evans and Long 1921).

Image: American anatomist and embryologist Herbert Mclean Evans (1882-1971)
The impact of species specificity of growth hormone was clarified in 1957, and treatment with human growth hormone proved effective (Lindholm 2006).

Gigantism refers to the increased linear growth in affected children when growth hormone levels are increased before epiphyseal closure. Historically, those affected by gigantism often wound up as sideshow performers in circuses. Some with gigantism and acromegaly were renowned for their superhuman strength and found work as cowboys and professional wrestlers.

In 1900, French internist Émile Charles Achard (1860-1944) reported a man with gigantism, acromegaly, and diabetes; he stood approximately 6 feet 9 inches tall.

Image: Man with gigantism, acromegaly, and diabetes

Another man with gigantism was (Joseph) Édouard Beaupré (1881-1904), Canada's tallest man. His height increased rapidly from age 3 to around age 21. His final height was variously given as from 2.40 meters (7 feet 10.5 inches) to 2.52 meters (8 feet 3 inches) with a weight of 166 to 170 kg (365-375 pounds). He was exceptionally strong and worked as a cowboy and as a sideshow performer. From age 17 (1897), he toured as “The Willow Bunch Giant” in circus side shows and at fairs throughout Canada and the United States. He was able to lift a horse weighing 363 kg (800 pounds) to shoulder height by crouching under it and extending his legs but he injured his back in an attempt to lift 408 kg (900 pounds). He died in 1904 at age 23 while he was performing at the “World's Fair” held in St Louis, Missouri. The cause of death was pulmonary hemorrhage as a result of tuberculosis. After death, his body was displayed for money by a funeral parlor and then a museum before inclusion in the collection of the department of anatomy at the University of Montreal. A skull x-ray in 1967 showed an enlarged sella tursica (measuring 1.6 × 1.2 cm, or 0.6 × 0.5 inches) and overgrowth of the frontal bones (Blais 1967; Blais 1973). Following a legal action, his body was returned to his relatives in 1989 and then cremated to prevent further exploitation and exposition.

Image: Édouard Beaupré and a normal-sized man
Image: Growth chart for Édouard Beaupré

John Aasen (1890-1938), also known as the “Minneapolis giant”, was an American silent film actor and sideshow performer who was one of the tallest actors in history. By 1917, he began his career as a circus sideshow performer who was known as “Johnny the Gent.” He started his acting career in 1922 and acquired a new nickname of “Harold Lloyd Giant”. Aasen is shown in this photograph standing next to a normal sized man. Aasen's height has variously been reported from 2.68 meters to 2.74 meters (8 feet 9.7 inches to 8 feet 11.5 inches). Aasen never underwent pituitary surgery nor was he treated with pituitary radiotherapy. Just before his death, at age 46, he was measured during a medical evaluation at 7 feet 0.9 inches, but by this time he had lost some height due to aging and could not stand completely straight anymore. He died at age 48 from pneumonia. In June 2008, Loma Linda University confirmed that the 7-foot-2.4-inch (219 cm) skeleton they had in their collection was his.

Image: American actor John Aasen suffered from gigantism

The tallest man who ever lived for whom there is irrefutable evidence was the American giant Robert Pershing Wadlow (1918-1940), also known as the Alton Giant and the Giant of Illinois. Wadlow reached 2.72 meters (8 feet 11.1 inches) in height, weighed 199 kg (439 pounds), and had a U.S. shoe size of 37 AA at the time of his death at age 22. His great size and his continued growth in adulthood were due to hyperplasia of his pituitary gland. He required leg braces to walk and had little feeling in his legs and feet. He became a celebrity after his 1936 U.S. tour, at age 18, with the Ringling Brothers Circus, with appearances at Madison Square Garden and the Boston Garden. During his circus appearances, he always appeared in the center ring (never in the sideshow), always wearing his regular clothes, and consistently refusing the circus's request that he wear a top hat and tails. In 1938, he began a promotional tour with the International Shoe Company, which provided him with free shoes. Wadlow considered himself as a celebrity who worked in advertising, not as a freak who was being exhibited. He possessed great physical strength until shortly before his death. He died of sepsis that resulted from an infection of his ankle brought on by chafing from a faulty brace.

Image: American giant Robert Wadlow, the tallest man who ever lived

Perhaps the most famous acromegalic giant was André René Roussimoff (1946-1993), better known as André the Giant. Roussimoff worked as a professional wrestler and actor. He was diagnosed with gigantism and acromegaly when he was in his mid-20s and wrestling professionally in Japan. By the late 1980s, Roussimoff was 7 foot 4 inches tall (224 cm) and then weighed 520 pounds, a result of gigantism caused by excess growth hormone, which later resulted in acromegaly. By this point the features of acromegaly had become much more apparent. In 1988, he defeated Hulk Hogan (Terry Eugene Bollea) to win the World Wrestling Federation's World Heavyweight Championship. Outside of wrestling, he was best known for appearing as Fezzik the Giant in The Princess Bride, a 1987 American fantasy adventure comedy film. He declined medical treatment for his acromegaly that may have prolonged his life because he was worried it would adversely affect his professional wrestling career. He died of congestive heart failure at age 46. At that time, he wore a size 24 shoe and weighed 555 pounds.

Image: Professional wrestler André the Giant in 1973
Image: Professional wrestler André the Giant walking to the ring in the late 1980s

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