Genetic Mutation Causes Pituitary Tumor Gigantism, The Interesting Case Of Charles Byrne The Irish Giant

Somehow while I as doing research for the site I stumbled upon a site and article that made me question a few of my own assumptions on the way growth works. The article talks about the interesting case of Charles Bryne who was called The Irish Giant. Apparently the propensity for the development of pituitary gigantism may have a genetic and hereditary cause, at least for some people. I have always thought that gigantism was a disorder that was random and hit people indiscriminantly.

If you want to take a look at the article your self, the site I found it from can be reached by clicking HERE.

I’m going to copy and paste the full article right below and do a VERY extensive analysis and critique of this article because I believe that this giant will definitely further at least me understanding of growth possibilities and how height works. I will highlight all the parts that are important


In a Giant’s Story, a New Chapter Writ by His DNA

By GINA KOLATA (Published January 5, 2011)

He was a giant of a man, 7 feet 7 inches tall, who left his home in Ireland when he was 19 and traveled to London to make his fortune as a freak. There Charles Byrne, known as the Irish Giant, garnered wealth and fame. But, suffering from tuberculosis and an excessive love of gin, he died a few years later, in 1783. A surgeon — John Hunter — bought Mr. Byrne’s corpse, boiled it in acid to remove the flesh, and exhibited the skeleton in his museum in London.

And there the bones remained, studied in 1909 by the renowned American surgeon Harvey Cushing, who removed the top of the skull and pronounced that Mr. Byrne had had a pituitary tumor. Other than that, Mr. Byrne remained a curiosity, a famous giant, the subject of a 1998 novel by the British writer Hilary Mantel, yet, with only a skeleton remaining, of little interest to science.

Until now: researchers in Britain and Germany have extracted DNA from Mr. Byrne’s teeth and solved the mystery of his excessive height.

It turned out to be a rare and mysterious gene mutation, discovered only in 2006. The researchers then found the mutation in four families from Northern Ireland, near where Mr. Byrne was born. Following a hunch, they decided to ask whether Mr. Byrne had had the mutation, too, and whether the mutation indicated that the four families were related to him. Their hunch was right.

The group, led by Dr. Marta Korbonits, professor of endocrinology and metabolism at Barts and the London School of Medicine and Dentistry, reports its finding in Thursday’s issue of The New England Journal of Medicine.

Symptom-producing pituitary tumors are rare, and those caused by an inherited mutated gene are rarer still. At most only 5 percent of people with pituitary tumors have them in their families.

The tumors can lead to disfigurement — patients develop bulging foreheads and large jaws, hands and feet — and chronic severe headaches. They can also cause visual problems, because the tumor presses on the optic nerve. They may even cause milk secretion, because the tumor can secrete prolactin, a hormone that is needed for fertility and to produce milk in the breasts.

Usually, tumors that secrete growth hormone start to grow in adulthood, after people have reached their full height. But when tumors start growing in children or adolescents — as they do with many patients with the mutated gene — they can result in gigantism because they make the gland churn out growth hormone, prodding bones to keep growing. Pituitary tumors are of great interest to researchers because they grow very slowly and almost never spread elsewhere in the body.

Dr. Shlomo Melmed, a pituitary tumor researcher at Cedars-Sinai Medical Center in Los Angeles, explained that the tumor cells undergo premature aging. “We think it might be protective,” Dr. Melmed said, a reason the tumor does not spread.

The involvement of the gene, known as AIP, in pituitary tumors is a surprise, researchers say. Mutations in the gene are associated with about 20 percent of inherited pituitary tumors when no other organ is involved. But it is not clear why mutations in this gene, which seems to be involved in metabolism — possibly to detoxify chemicals — can cause tumors or how these tumors form.

“There is nothing solid scientifically,” said Dr. Constantine Stratakis, a geneticist and pituitary tumor researcher who is the acting scientific director for the Division of Intramural Research at the National Institute of Child Health and Human Development.

And for unknown reasons, only about 30 percent of people with the mutated gene develop tumors.

In London, Dr. Korbonits said she had been aware of the Irish Giant because of her work on pituitary tumors. She suspected he might have had the AIP mutation when she saw a drawing of him standing with twin brothers who also were giants, who came from a nearby village, and who were said to be related to Mr. Byrne. That, she said, “suggested it was a genetic disease.”  (Me: So the Irish Giant had lived close to TWO brothers who were relative who were also giants!!)

And she had found the gene in members of four families from the same region of Ireland.

Dr. Korbonits wrote to the Hunterian Museum, where Mr. Byrne’s skeleton is still displayed, and asked to test the giant’s DNA, and then she and her colleagues removed two of his molars. She enlisted the help of an expert on ancient DNA, Joachim Burger of Gutenberg University in Mainz, Germany, to extract DNA from the giant’s teeth. She was worried that the DNA might be too degraded to analyze — after all, the giant’s corpse had been boiled in acid and then displayed in a museum for a couple of centuries.

“It was not clear at all that we would have suitable DNA,” Dr. Korbonits said. The DNA turned out to be broken in many pieces, but it could still be analyzed.

The investigators calculated that the giant and the four contemporary Irish families had a common ancestor who lived about 1,500 years ago. And, they report, there are probably 200 to 300 people living today who have inherited that same mutation.

One is Brendan Holland, a 58-year-old Irishman who sells mining equipment. Mr. Holland started growing excessively when he was 13, he said in a telephone interview.

“I kept growing and growing,” he said, eventually reaching a height of 6 feet 9 inches. As he grew, he said, he became less coordinated, developed frequent violent headaches and had sporadic episodes when he could not see. He had no idea what was wrong, but left school when he was 19, on the theory, he said, “that all that studying was giving me headaches.”

Finally, when Mr. Holland was 20 and living in London, an endocrinologist, Dr. G. Michael Besser at Barts and the London School of Medicine, figured out that Mr. Holland had a pituitary tumor. As soon as the tumor was destroyed with radiotherapy, Mr. Holland’s headaches disappeared and his growth hormone levels dropped to normal.

After the AIP gene mutation was discovered in 2006, Dr. Korbonits asked to test Mr. Holland to see if he had it. He did. Then, Mr. Holland said, she started suggesting he might be related to the giant.

“She was asking me pointed questions about where he lived and where I lived,” Mr. Holland said. “Then she said, ‘I think it is possible that you and this chap are related.’ ”

With the giant’s DNA analysis, it turned out that Dr. Korbonits was right.

Mr. Holland says he was touched thinking about the giant’s life, knowing how hard it is to be so tall and the subject of barbs and jeers.

The genetic analysis also had another effect, he said.

“I remember having a conversation with Dr. Besser when I was first diagnosed,” Mr. Holland said. “I said, ‘With eight children, why was I suffering from it and none of the others?’ He was very honest with me: He said they did not have a medical explanation.”

Now, at least, Mr. Holland has an explanation for his physical problems. And that helps, he said.

“I can only speak for myself,” he said, “but having a logical explanation helps me to come to terms with my condition.”

This article has been revised to reflect the following correction:

Correction: January 7, 2011

An article on Thursday about a genetic mutation in the case of Charles Byrne, known as the Irish Giant, misstated the year of publication of a novel by Hilary Mantel based on him. It was 1998, not 2007.


Here is the 2nd resource I wanted to use and that is from TheTallestMan.Com website. The webpage for Charles Byrne is found HERE.

This is the few parts on the page that really got me puzzled.

Charles Byrne (1761 – 1783) also known as Charles O’Brien or “The Irish Giant”, was a human curiosity or freak in London in the 1780s….His exact height is of some conjecture, but most accounts refer to him as from 8 feet 2 inches (248 cm) to 8 feet 4 inches (254 cm) tall, however true and undeniable skeletal evidence pitches him at just over 7 feet 7 inches….Although Charles Byrne was 22 years old when he died, radiographic images of his wrist bones showed that the epiphyses were not yet fused. His “bone age” was estimated to be only about 17, indicating that he was still growing at the time of death.”

The last resource I wanted to use HeightQuest.Com Again because Tyler does talk in a few articles about the fact that Gigantism and Pituitary tumors are not as simple as made to believe to the public.

FULL CRITICAL ANALYSIS: Like most of the general public my view point for gigantism was always very simple. The way gigantism and suspiciously tall humans happen is very logical and sequential.

1. The gigantism is from a benign or malignant tumor that has grown to a certain size to push against he pituitary gland at a region to cause excess release of HGH.

2. The HGH gets released to the liver which creates IGF-1 which runs gets distributed by the blood stream and causes any areas of the body like cartilage to start accelerated cell divions thus the bones and body of the person gets bigger in all dimension.

3. It does NOT matter whether the person was past puberty or before puberty. As long as the pituitary gland can release excess HGH, the human body will find a way to grow even by height. My old theory on how a post-puberty adult person with completely fused growth plates grew was that the IGF-1 reached the cartilage on the ends of their synovial joints and caused chondrocyte proliferation there. You can read up on that theory/ idea in my previous post found HERE.

4. The condition people have before growth plate closure is called Gigantism. The condition people have after growth plate closure is Acromegaly. It does not matter whether a person has Gigantism or Acromegaly, they will increase in height in both cases. So growth plate closure does not inhibit continual height increase.

5. As long as person has a pituitary gland that can release excess HGH, their body will find a way to grow in size, and height.

The issue now is that the case of Charles Byrne puts some of my deepest beliefs and ideas on how height work into question. The first problem I had with it was when the article stated the phrase “researchers have now figured out the reason for his excessive height” . For me, I didn’t think that scientist needed another reason to explain his height because his height can already be explain by the fact that he had a pituitary tumor problem, so he was just another pituitary giant. End of story. I didn’t understand why scientists and geneticists felt the need to look for another reason for his height. Didn’t the fact that an old surgeon state that he suffered a pituitary gland problem be good enough to explain his gigantism??

That was where I was coming from. Well it turns out that the situation is not that simple.

First, Bryne apparently has a genetic propensity to develop a pituitary condition causing gigantism. The researchers had found two twin brothers who were related to Byrne who also developed into giants, from gigantism. There is actually a genetic mutation in the AIP gene to cause this condition of pituitary gland disorder and gigantism to be far more prevalent. Byrne had it and his blood relatives throughout  the centuries also have it and a modern distant relative developed acromegaly. This is the first complication.

Second, on the Tallest Man’s Website, they showed that Byrne was reported in height upwards of 8′ 4″ but his skeleton measures 7′ 7″ , still a very amazing height. He died when he was 22 but X-Rays show that his growth plates were still there and that his plates indicated he was growing like a 17 year old. This excerpt challenged two beliefs I had always had.

Belief 1 – Pituitary giants even though they have the pituitary gland problem should not be able to also influence their growth plates and the rate at which the growth plates go through senescence.

Belief 2- Pituitary giants have the same age range for growth plate evolutions as the rest of us.

It seems that Byrne not only had a pituitary gland problem and had ALSO a genetic mutation to cause him to be more likely to develop gigantism, His growth plates were also very different from the average person. Could it be that either the genetic mutation or the fact that he has a putuitary condition cause his growth plates to go through with senescence a lot slower than the average human? That would be definitely something that I have never considered, but Tyler did.

I had tried to show that with cases like Sultan Kosen and Tanya Angus that they had closed growth plate because they were in their 20s or late teens when they started to go through their growth spurt. Tanya grew from 5′ 8″ to 6′ 11″ from age 18-30. Kosen grew from 8′ 1″ to 8′ 3″ from 27-29.

This just shows that Pituitary giants like Byrne , Kosen, and Angus may be even more unique than the ordinary pituitary giant (or the other possibility is that all or most pituitary giants have this skill and potential). I do note that Byrne did not start go through his massive growth spurt when he was in his adult years, but that he suffered from gigantism so he went through his massive growth spurt as a child with growth plates still open.

If this new case proves that having either the genetic mutation or pituitary condition can actually have an affect on the  rate of senescence of the growth plates in the individual, then my previous theory is wrong and that humans may NOT actually be able to grow taller naturally after puberty after all. My idea was that with enough HGH released into the body, the articular cartilage was what took over the height increase growth.

I decided not to write about the findings found by Tyler since this article post is getting quite long so I will save the discussion of the relationship between gigantism , pituitary giants, and gene mutations from the articles I found on HeightQuest for another time. That post will be very interesting so I can compare old and new theories to see which one makes more sense.

 

 

2 thoughts on “Genetic Mutation Causes Pituitary Tumor Gigantism, The Interesting Case Of Charles Byrne The Irish Giant

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