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History of Pituitary Tumors
and Microneurosurgery

Jules Hardy, OC, CQ, MD, FRCS
Jules Hardy, OC, CQ, MD, FRCS
Professeur Titulaire
Université of Montrealé
Adjunct Professor
McGill University
AANS Member Since 1964

Historically, the first recorded use of transsphenoidal approach with successful removal of a pituitary tumor was that of Schioffer of Vienna on March 16, 1907, through a superior nasal operation. Oscar Hirsch, also from Vienna, suggested in 1909 an endonasal operation by the ethmoid. But he modified this procedure to an endonasal sub-mucosal rhino-septal approach which he performed on dune 4, 1910, the same day that Cushing, unknowingly, did his first case through a sublabial incision and sub-mucosal resection of the septum. Cushing used this route in more than 75% of a series of 339 pituitary tumor cases. Despite the low incidence of serious complications, the operation left much to be desired in dealing with pituitary tumors. For one thing, it did not adequately cope with all types of tumors, especially those which extended beyond the sella. Cushing observed that "in the average favorable cases probably 1/3 or even 2/3 of the tumor was removed". Norman Dott of Edinburgh, a pupil of Cushing, remained faithful to his master and performed this operation in more than 120 patients throughout his career. The main drawback of this approach was that it was a "blind" procedure.

Credit for taking this operation out of the "blind" and reviving it goes to Gerard Guiot of Paris who introduced the use of radiofluoroscopic control and cisternal pneumography during surgical removal of the tumor which allowed visualization of the supra-sellar contour and more extensive removal.

After spending a year of training with Guiot in 1961-62, I was impressed by the benignity and rapidity of the procedure with swift recovery from visual disturbances. At that time, the only indication for transsphenoidal surgery was the debulking of large pituitary tumors in order to relieve pressure on the optic nerves. Upon my return to Montreal in 1962, I introduced transsphenoidal surgery at the Notre-Dame Hospital of the University of Montreal. My very first patient had a very large tumor with a supra-sellar expansion; he was blind from one eye and had hemianopsia on the other. I therefore performed a sub-total debulking as Guiot taught me and the patient's vision improved rapidly. During the same period, the treatment for advanced metastatic cancer of the breast encompassed sequential hormones depleted by oophorectomy and hypophysectomy. Because of the very narrow operative field deep at the base of the skull and of poor illumination, I introduced the surgical microscope, the Zeiss OPM1. It improved considerably the technique with better definition and more precise surgical manipulation in the sella allowing pituitary ablation in one piece. This has led me to considerable exposure to the surgical dissection of both normal and tumoral pituitary gland. Alternatively, I was operating on patients with large pituitary tumors in whom the standard practice so far was only debulking of the tumor. A major problem however remained at that time which was clearly stated by Guiot: "Although the complete removal of a pituitary adenoma might restore the previous hormonal deficit, one should agree this is rather exceptional. From this point of view one must say that the patient is rather endangered since the adenomatous tissue is not separable from the normal hypophyseal tissue and the attempt to perform a complete radical excision brings in the curettes the glandular tissue still functionally active. Therefore, this increases the hormonal deficit which can lead to a complete pituitary insufficiency following surgery."

This statement was upsetting to me so that when I decided to use the surgical microscope, I soon became aware of a new fact: at higher magnification I was able to distinguish in some cases the residual normal pituitary gland quite separate from the tumoral tissue. As a result I decided to make all effort to preserve the pituitary to prevent new deficits. This was successful and even more we observed restoration of functions after tumor removal due to relief of pressure upon the normal gland.

In 1966 I therefore rejected the current concept of diffuse hyperplasia or hypertrophy of the pituitary gland in hypersecreting disorders and I became convinced that these were caused by development of an autonomous pituitary adenoma quite separate from the surrounding hypophyseal tissue. This is when occurred in my mind the concept of "microadenoma", a micronodule embedded within the pituitary gland just like the pimento in an olive, so small that it could not be detected by available radiologic methods of that time. Having in mind that concept was a provocation to search for its reality. I decided to convince my colleague endocrinologists to let me surgically explore patients who had hypersecreting disorders like acromegaly and Cushing's Disease and whose sella turcica was considered radiologically normal. To my greatest satisfaction, but of no surprise, I discovered the reality of this concept: the presence of microadenomas. From this moment, I began developing microinstruments: curettes, enucleators, dissectors. According to the depth and the size of these lesions in the sella, the instruments were mounted on bayonet handles thus allowing good visibility in a deep field without obliterating the surgeon's view in front of the co-axial light.

The concept of microadenoma was not readily accepted in the beginning by my colleagues who did not believe in the presence of such tiny lesions not radiologically visible. My first paper on this subject was presented in 1968 at the Congress of Neurological Surgeons in Toronto, but these findings were met with much skepticism and controversy for many years until the reality of microadenoma and its topographical localisation was confirmed by CT demonstration. It was finally accepted ten years later, in 1978, at a symposium in Milan on "Pituitary Microadenoma". Selective microadenomectomy has become the standardized therapeutic approach in the management of Cushing's Disease and acromegaly as well as the micro-prolactinoma removal in the syndrome amenorrhea-galactorrhea infertility. Restoration of fertility in sterile women resulted as a major achievement in functional neuro-endocrinological surgery of the modern era.

After 30 years of practice of neurosurgery and the performance of over 2300 transsphenoidal operations, it is with great satisfaction that I see that this therapeutic method has reached a consensus. The privilege to have been an early seeker who was fortunate to have found the reality of the microadenoma gives me a relief from controversies and challenges of the past. It is with equanimity that I can apply this endeavor to the sentence of Jonathan Livingston Seagull:

"It's good to be a seeker
But sooner or later
You have to be a finder.
And then it is well
To give what you have found
A Gift into the world
For whoever will accept it."

An abstract of the oral history of Dr. Hardy is available.

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