History of Acromegaly

As a reminder, in Europe, a disease is considered rare when it affects one person in 2,000. In the United States, a disease is considered rare when it affects less than 200,000 people throughout the country. As far as Acromegaly is concerned, it is estimated that it affects between one person in 15,000 and one person in 25,000. Although it occurs most often between the ages of 30 and 40, the disease can develop at any age. Acromegaly is therefore characterized in patients in two different ways: an exaggerated growth of the face and extremities when it occurs after puberty, and a very large waist when it occurs before puberty. In this second case, it has often been called “gigantism” throughout history. As we shall see in this regard, it took centuries for scientists to understand that Acromegaly and gigantism were in fact the same condition. Today, we know that this disease is linked to an excessive production of growth hormone, called GH. According to the French portal for rare diseases and orphan drugs Orphanet :

“This hormone is a kind of messenger that circulates in the bloodstream and thus acts on the whole body. As its name suggests, it plays a major role in the growth of children and adolescents. However, it is also essential for adults, since it maintains the thickness of the skin and muscles and helps to reduce fat mass […]. Growth hormone is produced by the pituitary gland, a small gland the size of a chickpea, located in the brain. Acromegaly is most often linked to the “enlargement” of the pituitary gland, whose cells multiply and produce too much growth hormone. In fact, this enlargement is due to the appearance of a benign tumor, i.e. a non-cancerous mass in the pituitary gland. This tumor is called pituitary adenoma.”

 The physical changes associated with Acromegaly are slow and progressive, which often explains why patients often wait up to ten years before going to see a doctor and being diagnosed. The consequences of the disease can include back and joint pain, bone deformities such as scoliosis or protrusion of the sternum. In 40-50% of patients, a carpal tunnel syndrome also occurs, resulting in a loss of volume in the muscles of the hand. There are many other symptoms such as the development of the hair system, the increase in volume of certain muscles and organs such as the liver, thyroid and especially the heart.  Diabetes and high blood pressure are also among other symptoms. As we will see in this episode, it is possible to find and imagine traces of acromegaly during antiquity. From the modern period onwards, the disease began to be described precisely until the Frenchman Pierre Marie gave it the name Acromegaly in 1886.



  1. Traces of Acromegaly in ancient texts and in antiquity?


We begin the History of acromegaly between myth and reality. We all know the famous story of David against Goliath, a story that characterizes the triumph of an underdog. Although the historicity of these two biblical characters is, quite rightly, subject to debate, it is possible to imagine that Goliath may have suffered from acromegaly. In chapter 17 of the First Book of Samuel, we are told that the Philistines are at war with the people of Israel. The two armies are facing each other, each occupying the heights of a mountain facing the other. Only a valley separates them. As it was common at the time, since this avoided a pitched battle between two armies and thus a bloodbath, the Philistines sent their best warrior, Goliath, to fight a Jewish warrior. The outcome of this duel would decide who would win the war. For 40 days, Goliath presented himself twice a day, in the morning and in the evening, in front of the opposing army, without anyone daring to go and challenge him on a one on one combat. The text tells us that “at the sight of this man, all the Israelites fled and were filled with fear.” It must be said that the Philistine warrior was very intimidating. He was tall, very tall… He was also massive, strong, and had an incredibly robust appearance. According to the biblical text, he would have a height of “six cubits and a span”, or about 2.70 m. He worn copper chain mail weighing around 50 kilos, and the iron blade of his spear weighed 7 kilos. Interestingly, he was also always accompanied by someone who carried his shield. In short, Goliath is a giant, incredibly powerful, and one can understand why no Jewish warrior had ever ventured to go and confront him. These physical characteristics, this “gigantism”, can already put us on the track of acromegaly. But, a second detail, to be found in what will perhaps cause the loss of the colossus, also brings us closer to acromegaly. Finally, it was a young Shepherd, David, who decided to face Goliath. Equipped with a stick and a slingshot, he advanced into the valley without forgetting to pick up a few stones. When Goliath saw him coming, he shouted to him: “Am I a dog, so that you come to me with sticks?” This is a somewhat a strange remark, since David had only one stick in his possession. After a few more invectives, the two men charge, David then grabs his sling and a stone, throws the projectile with dreadful precision towards his opponent, who takes it in the middle of his forehead. Goliath couldn’t dodge this stone, which arrived very quickly, and so the giant was defeated. David then only had to finish off his fearsome opponent, to the surprise of all.

But what I didn’t tell you in the introduction, and which is interesting in this story of David against Goliath, is that in many people suffering from acromegaly, there is a decrease in vision, or even a narrowing of the field of vision on the sides. Some of the details of this story are then to be seen in a new light. Remember, Goliath was always accompanied by a person wearing his shield. Would it be possible that, because of Goliath’s poor eyesight, this person was actually there to show Goliath the way and thus help him down the mountain from where the Philistine camp was based? Another detail: Goliath told David when he saw him coming: “Am I a dog, so that you come to me with sticks?” Yet David only comes to him with one stick. Finally, how is it possible that such a powerful warrior cannot dodge a stone, certainly thrown at him with great speed and precision, on open ground where his opponent is alone and in front of him? With these symptoms of acromegaly in mind, how can one not imagine that Goliath suffered from this condition, and had diminished vision, which put him at a great disadvantage in his duel with David. The historicity of these two characters, whether true or not, cannot prevent us from thinking that this philistine giant would have suffered from acromegaly. In the end, this duel was perhaps not as unbalanced as it seemed…

Another example, this one a little easier to prove from a historical point of view, is that of Pharaoh Sa-Nakht. In 1901, a skeleton was indeed found in the sumptuous Mastaba K2 tomb near Beit Khallaf, Egypt. It is estimated that these remains date from the 3rd dynasty, approximately 2700 BC. The remains are those of a very tall man for the time as he would have measured 1m87. 1m87 might not seem tall for us who live in the 21st century, but it is important to point out that the size of the different human populations has varied over the millennia. At the time, the average size of the Egyptians was between 1m60 and 1m70. These remains were therefore attributed to King Sa-Nakht, who was a king/pharaoh of the third dynasty. This case is of great value as it could be the oldest known case of acromegaly. By comparing research papers, databases and photographs of Sa-Nakht’s skull, five scientists concluded in 2017, in a study published in The Lancet, that:

“Sa-Nakht probably had gigantism and is thus the oldest known paleopathological case in the world. Evaluation of the facial structure suggests a slight acromegaly, which could indicate a regression of hyperpituitarism. In ancient times, no surgical or medicinal treatment was available; therefore, regression could only result from degeneration of the pituitary gland”.

It seems important to specify that the remains of this man might not be those of Pharaoh Sa-Nakht. They could have been those of one of the members of his entourage. In any case, the splendor of the tomb indicates that in ancient Egypt, gigantism was not a factor of exclusion or social marginalization, which will not always be the case, as you will see, during these last centuries. If you are a regular listener of our podcast channel, many of the cases that we are going to talk about will perhaps make you think of a certain form of scientific racism.



  1. Towards the understanding of the disease: the first descriptions

Let’s take a huge leap forward in time and go directly to the 16th century in the Duchy of Brabant, which at that time was part of the Spanish Netherlands. It was the home of a brilliant doctor, Johannes Wier. It is to him that we owe one of the first medical reports on the disease. In the course of the centuries, these descriptions were of course based on the patients themselves. In the case of diseases such as acromegaly, the physical peculiarities that accompany the condition were the subject of curiosity, often misplaced by the public and the scientific community. In the case of Johannes Wier, it was his encounter with a woman of “gigantic” stature, who earned her living by travelling through many regions to exhibit her physique, that prompted him to seek out more details about her. In his treatise Medicarum Observationum, published in 1567, Wier explained:

“I inquired with specific questions and learned from her answers and those of her mother that she was born of parents who were both small and that neither of her ancestors was taller than the average man. From birth to her twelfth year she was small: but by the time she had reached her fourteenth year and had been menstruating for some time, it suddenly stopped, and she began to increase in size, all her limbs formed proportionally so that nothing seemed unusual. Unless I am mistaken, when I saw her, she was in her twenty-fifth year from the time she noticed the cessation of her menstruation.”

Without knowing exactly what the disease was, and without even knowing whether it was actually an illness, Johannes Wier was putting his finger on something fundamental. For acromegaly sufferers, a reduction in the level of sex hormones can be responsible for the absence of menstruation or amenorrhea in women.

Two hundred years later, it was the French physician and surgeon Nicolas Saucerotte who described the case of a 39-year-old man who most likely suffered from acromegaly. In 1772, in a communication to the French Academy of Surgery entitled Singular increase in bone size of a 39-year-old man, he reported a progressive increase in bone and cranial circumference, prognathism, hypertrophy of the hands and feet and significant and generalized joint pain. It is difficult not to think of acromegaly, with the hindsight that is ours. In this communication, Saucerotte noted, but did not attempt to determine the cause of this “singular increase”. At the turn of the 18th and 19th centuries, this disease began to be recognized, without knowing what caused it. Several names were then attributed to it. In 1822, the French dermatologist Jean-Louis-Marc Alibert gave it the name “Scrofula Giant Syndrome”. In 1864, the Italian neurologist Andrea Verga gave it the name “Prosopo-ectasia”, which translates as enlargement of the face.  A little like Johannes Wier, almost 300 years before him, Verga met a woman, somewhat by chance, suffering from acromegaly. He described this encounter in a publication entitled Singular case of prosopoectasi, published in 1864:

“Since 1860, visiting the chronically ill admitted to the church of Santa Maria ai Nuovi Sepolcri […], I had been impressed by the sight of a patient [Maria B., born in Milan], whose waxy pallor and disproportionate size of the face were almost frightening. The staff who worked in this hospital must have been equally impressed, because they had nicknamed this woman “Big Face”. Seeing me looking at her, she told me that she had not always been ugly and that she used to look like other girls.”

Beyond these misplaced comments on the physical appearance of this woman, unfortunately typical of the time, Verga’s meeting with Maria B, was preponderant in the understanding of the disease. Verga continued to hear from the patient until her death two years later from the causes of typhus. He then asked for a post-mortem examination. During this examination, he found a walnut-sized tumor, which had caused a displacement of the optic nerves. He did not find the pituitary gland, however, and wondered whether it had disappeared or whether the tumor itself was a degeneration of this gland. Andrea Verga was not able to provide answers to his questions, but he did find something fundamental. 15 years later, in 1877, the French physician Henri Henrot made the same observation. While performing an autopsy on a patient with what was then still called “gigantism”, he found a tumor in the same place as Verga. In the same year, 1877, the Italian doctor Vincenzo Brigidi made exactly the same observation when he performed an autopsy on an actor suffering from gigantism. He was also the first to examine this tumor of the pituitary gland under a microscope.




  1. Pierre Marie and the clinical description of the disease


All these discoveries and findings paved the way for the French physician Pierre Marie. A pupil, disciple and protégé of the famous Jean-Martin Charcot, Pierre Marie met two patients suffering from acromegaly at the Pitié-Salpêtrière, at the request of his mentor. The year was 1886 and this is how Pierre Marie described the first patient, aged 37:

“It was at the age of twenty-four, when her period suddenly stopped, that she noticed the sudden increase in her hands. At that time, her face also underwent changes … so that when the patient went home, none of her relatives could recognize her. The whole feet are large, including the toes. Although the toes have increased in size, they have retained their shape, there is no real deformity, their appearance is simply that of a very tall person … The tongue is enlarged … The sight is also defective … The top of the skull is almost the same size as the end of the chin. The lower jaw is well developed.”

With regard to the second patient, aged 54, Pierre Marie noted that: “the edges of the eye sockets are very thick, as well as the frontal eminences […] The nose is large. The lower jaw is very thick. He went on to suggest that this condition be called “acromegaly”. He explained:

“A state characterized by hypertrophy of the hands, feet and face which we propose to call “acromegaly” which means hypertrophy of the extremities. In reality, the extremities are swollen during the course of the disease and their increase in volume is the most characteristic feature of this disease.”


Having examined these two patients while they were still alive, Pierre Marie did not refer to the pituitary gland. In that year 1886, our French doctor was unaware of the discoveries of his predecessors on this specific point. It was finally the Lithuanian physician Oskar Minkowski who confirmed, in 1887, that enlargement of the pituitary gland appears in all post-mortem studies of acromegaly patients. At that time, however, a major question remained unanswered. Are acromegaly and gigantism two different conditions, or are they two forms of the same disease? For Pierre Marie and his collaborators, it was the first option. As Wouter de Herder tells us in a publication entitled History of Acromegaly, published in 2014, “gigantism was considered an exaggerated variant of normal development, while acromegaly was considered a pathological condition”. But this assumption would not hold for long. Only a few years later, in 1891, the Scottish physician Daniel John Cunningham, leaned in favor of two forms of the same disease. To arrive at this conclusion, he studied the skeleton of an Irish man who lived in the 19th century, called Cornelius Magrath, who was 2.26 meters tall. In the years that followed, many other scientists reached the same conclusions as Cunningham, such as the American neurologist Charles Dana, the English physician Woods Hutchinson and the Frenchmen Edouard Brissaud and Henry Meige. As the discoveries were made, it became clear that both disorders had the same pathogenesis but that the disease was different depending on the age at which it occurred.


  1. Treatment approaches

As scientists began to understand the disease better and better, the time for treatment finally arrived, at the turn of the 19th and 20th centuries. At that time, the first attempts at pituitary surgery took place. In 1892, Ercole Sacchi and Guilio Vassale, two Italian surgeons, succeeded in removing the pituitary gland in cats. Unfortunately, two years later, they declared that “the pituitary gland… is vital to the body. Its function consists in the elaboration and endocrine secretion of a special product, necessary for the organism”. Even if their attempt finally turned out to be a failure, the experiences of our two Italian surgeons allowed us to understand the role of the pituitary gland/hypophysis in metabolic functions and growth. At the same time, the first surgeries on people with acromegaly were performed. In 1893, British neurosurgeons Richard Caton and Frank Thomas Paul operated on a patient with acromegaly who was suffering from terrible headaches. Unfortunately, they were unable to reach the tumor. However, they did manage to relieve the sub temporal pressure, allowing the patient to have a better quality of life and greatly reduce the headaches. It was a semi-success that paved the way for about twenty years to this type of operation. Back then, it was not possible to cure the patients, but from the beginning of the 20th century, it was possible to give them a little more comfort.

In 1906, a major advance was made. It came from the Austrian surgeon Hermann Schloffer, who successfully removed a tumor of the pituitary gland via the transnasal-trans-sphenoidal route. The following year, his compatriot and colleague, Julius von Hochenegg, carried out the first trans-sphenoidal approach to acromegaly. A major breakthrough, which made the headlines in international newspapers. In its edition of 10 May 1908, The New York Times headlined, with a backdrop of rivalry between American and European scientists:

“Acromegaly cured; operation successfully carried out by Professor Hochenegg of Vienna.

American surgeons, who by the reluctant consent of their European colleagues are now ranked at the top of their profession, will be interested in the brilliant achievement reported last week at the Berlin Congress of Surgery by Professor Hochenegg of Vienna. Professor Hochenegg told how he successfully operated on a case of acromegaly, a disease that causes strange and enormous enlargements of the bones of the hands, feet and face. The patient on whom the operation was performed was a young girl. She showed the usual symptoms of brain tumors and a marked disturbance of her vision. The diagnosis having been confirmed by X-rays, Professor Hochenegg moved the girl’s nose to one side, cut the thin floor of the skull and then removed the tumor from the pituitary gland, which was shaped like a gland hanging like a cherry, from the base of the brain. The difficulty in reaching the acromegalic tumor was such that the surgeons were rather reluctant to operate on it. It is said that none of the operations reported before last week had been successful; but the girl from Vienna left the hospital six weeks after Professor Hochenegg’s operation, her health having completely recovered. Acromegaly is not uncommon in the United States, but as a result, the Germans say, it has baffled American surgical skills.”

In the decades to come, two routes were favored for operating on people with acromegaly. The trans-sphenoidal route, therefore, and the trans-cranial route, which will gain in popularity from the 1920s onwards. The development of endoscopic techniques and microscopic surgery from the 1930s onwards enabled a new direction to be taken, particularly thanks to Canadian neurosurgeon Jules Hardy.

Despite this progress, pituitary surgery unfortunately remained very complicated and often led to complications during and after the operation. Many patients died on the operating table and in the days that followed. Although the successes of pituitary surgery were spectacular at the time, they were rare, and this fact helped another treatment approach to develop itself: radiotherapy. You should remember this if you have listened to our podcasts on the History of Cancer, the principles of radiotherapy were discovered at the end of the 19th century, and its practice spread widely and very quickly, from the beginning of the 20th century.  In 1909, the French radiotherapist Antoine Béclère succeeded in weakening a tumor of the pituitary gland in a young woman suffering from acromegaly by the repeated use of radiotherapy. Radiotherapy was used for the most part in the decades that followed. Numerous advances in radiotherapy enameled this period of time, including better dosage and better knowledge about the frequency of sessions.

In 1945, the Growth Hormone (GH) was finally isolated by the Chinese-born American scientist Cho Hao Li. It had been discovered 25 years earlier, in 1920, by Herbert McLean Evans and Joseph Long. Cho was also able to determine its molecular structure. This was a major discovery that led to many advances. Shortly afterwards, Geoffrey W. Harris, a British neuroendocrinologist, succeeded in demonstrating that pituitary secretion is controlled by the hypothalamus. This process took place through release factors transported from the hypothalamus to the pituitary gland via the pituitary stem. As the role of the hypothalamus came to light, progress was made, and research during the 1950s, 60s and 70s accelerated. In 1977, the Nobel Prize for Medicine was awarded, in part, to Andrew V. Schally and Roger Guillemin for the identification of several hypothalamic factors including growth hormone-releasing hormone and somatostatin. Today, somatostatin plays an important role in the treatment of patients with acromegaly. Analogues of this protein hormone, which inhibits the secretion of growth hormone, are now commonly used, such as octreotide and lanreotide. These drugs used to be given several times a day by injection but advances in technology and research have now made it possible to use a single injection per month. According to Orphanet, these analogues “normalize growth hormone levels in about two thirds of those treated; after 6 months of treatment, they also lead to a reduction in the volume of the adenoma.”   

In the end, the history of acromegaly is quite similar to the patients’ journey. Just like the patients, it took an enormous amount of time to identify the disease. This identification, which can be attributed to Pierre Marie, was also made possible thanks to the work of many other scientists such as Johannes Wier, Nicolas Saucerotte or Vincenzo Brigidi. It was often confused with other diseases and the slow progression of the disease did not help to understand it more quickly. Today, the two preferred types of treatment are surgery, which has obviously improved considerably since the end of the 19th century, and drug treatments. Radiotherapy, on the other hand, is now only used very occasionally. It is also important to remember that the objective of acromegaly treatment is twofold: it is necessary to stop the progression of the tumor and thus reduce the symptoms, and to normalize the rate of growth hormone in order to halt the evolution of the disease. According to the French Rare Diseases Portal, today:

“Acromegaly research focuses on four key areas:

  1. The search for increasingly effective and better tolerated drugs.
  2. Assessment of the long-term evolution of treated and cured acromegaly compared to acromegaly with only partially reduced growth hormone levels.
  3. The study of the role of excess growth hormone in the development of tumors, especially in the colon, and in the development and evolution of heart problems and high blood pressure.
  4. Research into the causes and mechanisms of the disease.”

In France, acromegaly can be recognized as a “serious condition characterized by a progressive or disabling form, requiring continuous care for a foreseeable duration of more than 6 months, but not appearing on the list of 30 conditions defined by the Social Security Code”. Patients suffering from acromegaly may be exempted from the co-payment system, i.e. 100% of the medical expenses inherent to their illness (drugs, laboratory tests, X-rays or scans, etc.) may be reimbursed. The file must be drawn up by the attending physician with the support of specialists. However, to reach this stage, it is still necessary to have been diagnosed. This is the major challenge for this disease, like many other rare diseases. As Marie Hélène Boucand points out in Une approche éthique des maladies rares génétiques (An Ethical Approach to Genetic Rare Diseases), “The patient affected by a rare disease experiences the distressing singularity of being ill without corresponding to the usual representations of other patients.”

Sources :

  1. Portail Orphanet, Acromégalie, avec la collaboration du Professeur Philippe Chanson, 2007


  1. Victoire de David contre Goliath, Premier livre de Samuel, Chapitre 17, 1-18.4


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