What Caused the Abnormal Growth?
Byrne's skeleton (Figure) was on display for more than a century before the true cause of his gigantism was discovered. In 1909, Harvey Cushing (1869-1939), a preeminent American neurosurgeon, received permission to examine Byrne's well-preserved skull. The major finding was an enlarged pituitary fossa, measuring 21 x 24 mm and 11 mm in depth, that was undoubtedly caused by a pituitary tumor.
Figure. Skeleton of Charles Byrne, the "Irish Giant," on view in the Hunterian Museum, Royal College of Surgeons of England. From the skeleton, Byrne's height has been estimated to be about 8 feet. Courtesy of the Board of Trustees of the Hunterian Collection.
Cushing, who trained under Halsted at Johns Hopkins, had received additional training in brain surgery from the Swiss Nobel prize-winning surgeon Theodore Kocher before returning to the United States. Cushing, an innovative neurosurgeon, pioneered the development of radiography for the diagnosis of brain tumors, electrocautery (along with Bovie) for control of hemorrhage, and mapping of the human sensory cortex with electrical stimulation. Cushing's neurosurgical training led him suspect that Byrne's excessive height might have been caused by an unsuspected cerebral tumor arising within the pituitary gland.
Cushing continued to have a special interest in pituitary diseases, and in a 1932 publication, he described what we now know as Cushing' disease, which is caused by excessive secretion of adrenocorticotropic hormone by the pituitary gland.
Current research has focused on mutations in Byrne's DNA that might have led to a growth-enhancing pituitary tumor. More than 2 centuries after Byrne's death, a research team from the United Kingdom, Germany, and Sweden received permission to extract DNA from one of Byrne's teeth and to examine blood and DNA samples from potential family members who still reside in Northern Ireland.
The DNA extracted from Byrne's teeth revealed a mutation in the aryl hydrocarbon receptor-interacting protein gene (AIP) on chromosome 11q13.3. This mutation was also present in 51 family members, of whom 14 had associated pituitary abnormalities. Ten family members had growth hormone-secreting adenomas, and 7 of these 10 relatives had gigantism. The mutation represents a low-penetrance gene but is likely to explain many cases of familial gigantism.
The data suggest that the mutation carried by Byrne and his 'relative is likely to have arisen from a common ancestor, who may have lived around 500-700 AD.
John Hunter and the Preservation of Charles Byrne's Skeleton
John Hunter (1728-1793) was born in Scotland but eventually made his way to
London, where he became an assistant to his older brother, William, a well-
established surgeon. John Hunter soon became a skilled surgeon, as well as an
anatomist and teacher. His outstanding surgical ability was widely recognized,
leading to his appointment as surgeon to King George III and as Surgeon
General of the British Army. His areas of interest included the teeth, tumors,
aneurysms, and infections. (To study the transmission of syphilis, Hunter
inoculated himself with material from a syphilitic chancre.)
Hunter had an insatiable curiosity about nature and amassed a large and diverse
collection of both usual and unusual objects. He exhibited the objects in his
private museum, which still exists and is now under the auspices of the Royal
College of Surgeons of England.
Hunter, fascinated by Byrne's enormous size, became obsessed with obtaining
the giant's skeleton for his museum. He hired a special agent, John Howison, to
follow Byrne and to notify Hunter when the giant died. However, in the 18th
century, postmortem examination was generally illegal; it was therefore very
difficult to obtain a corpse, especially that of somebody as prominent as Byrne. It
is thought that after Byrne died on Sunday, June 1, 1783, Hunter bribed the
undertaker to obtain the body. Supposedly, the undertaker removed the body to
be buried at sea, per Byrne's request, but before it reached the coast Hunter's
accomplices removed the corpse .and then refilled the enormous coffin with
stones. Hunter's detailed description of the dissection is unavailable because his
brother-in-law burned nearly all of Hunter's valuable notes after Hunter died. It
was rumored that when he was sent Charles Byrne's body, Hunter hastily
chopped it up and boiled it in a copper vat until only the bones were left. Hunter
then reassembled the skeleton but waited 4 years before displaying it in his
museum. The skeleton is still on view in the Hunterian Museum at the Royal
College of Surgeon's of England.
Medscape General Surgery © 2011
Cite this: Albert B. Lowenfels. The Case of the Big Man With a Little Lesion - Medscape - Jun 27, 2011.