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PITUITARY GLAND TUMORS

PART I: ANATOMY AND PHYSIOLOGY OF THE PITUITARY GLAND AND RELATED STRUCTURES

(A Patient Information Service)

The pituitary gland is a part of the brain as well as part of the ENDOCRINE (hormone) system. The pituitary gland is rather small, measuring approximately 1.3 centimeters (cm.) long X .8 cm. high X 1 cm. wide (1 in.=2.54 cm.; 1 cm.=4/10 in.) It occupies a critical anatomical position relative to the brain, brain centers, vital CRANIAL NERVES, as well as major blood vessels (see Figure 1). The pituitary gland is unique for several reasons. It lies within its own protective bone casing called the SELLA TURCICA. (Early anatomists believed that this bone cavity had an appearance similar to a TURKISH — "turcica" — SADDLE — sella). The sella turcica (Figures 2 and 3) lies in the forward portion of the base of the skull just behind and slightly below the eye sockets (orbits). Directly in front of the sella (turcica) is the SPHENOID SINUS. This is part of the elaborate air sinus system of the skull. The front wall of the sella (turcica) is the back wall of the sphenoid sinus. This anatomical fact is of critical importance for surgery since a ready channel through the skull (the sphenoid air sinus) can allow for a direct surgical approach to the pituitary gland without disturbing the brain.

The pituitary gland is often referred to as the "master gland" of the entire endocrine system. By this, it is meant that the pituitary gland "controls" or influences the function of all the other hormone producing glands of the body. Examples of these other glands and their hormones are the following:

  1. Thyroid gland: This gland lies in the neck in front of the trachea (windpipe). It makes and secretes a hormone called THYROXINE. This hormone has a profound effect upon our metabolism. The pituitary gland influences the thyroid gland (and therefore the amount of THYROXINE) by manufacturing and releasing another hormone called THYROID STIMULATING HORMONE (TSH). (In this way the pituitary gland influences the rate of metabolism of the body).

  2. Sex glands: The ovaries as well as the testicles manufacture and release several hormones. These are under the influence of the hormones produced by the pituitary gland.

  3. Adrenal gland: This important gland lies on top of our kidneys. It produces and releases several hormones. Among these hormones are the "steroids." Steroids are chemical substances which are a critical element in our ability to respond to physical stress. Steroids are absolutely essential to our survival. The pituitary gland manufactures and releases a substance called Adrenocorticotropic Hormone (ACTH) which stimulates the adrenal gland to produce steroids.
The pituitary gland also produces hormones which have a direct effect on particular body functions. Examples of these are the following:
  1. Growth: GROWTH HORMONE is produced by the pituitary gland. The relative lack of it or its absence results in stunted growth of bones (dwarfism). The overproduction results in one of two serious conditions. GIGANTISM (giant stature) is the result of overproduction of growth hormone before puberty. ACROMEGALY is the development of very prominent and characteristic overgrowth of the skull, face, hands and feet as a result of far too much growth hormone. However, in this case the overproduction occurs after puberty (when growth of the long bones has ceased).

  2. Breast Milk: PROLACTIN (PRL) is the hormone produced by the pituitary gland which, when released, influences the breast to produce breast milk. Obviously there are critical times when this is quite appropriate and necessary. During pregnancy and after childbirth there is a profound increase in the level of PROLACTIN in the blood stream. Alternatively the production of more than minimum prolactin in males or in higher levels in females (who are not pregnant or postpartum) is an abnormal situation. There are a number of potential causes for this. However, among the consequences there may be an increase in breast size (male or female) possibly accompanied by breast milk secretion (discharge) through the breast nipple. Additionally there are some possible effects of prolactin on the sex glands and the hormones they produce. Prolactin may reduce the testicular production of hormone. This could result in decreased sperm production and even impotence in males as well as decrease in body hair (particularly on the face and chest). In females there is a significant influence upon ovulation and a diminishment or absence of menstruation may occur.

  3. ANTI-DIURETIC HORMONE (ADH): Antidiuretic Hormone is produced by cells located in the back (posterior) lobe of the pituitary gland (Figure 4). This hormone exerts its effect upon the kidney. It is responsible, to a large degree, for the amount of urine that we produce. Each of our kidneys functions as a purification filter for our blood. The blood serves, among several purposes, to transport waste products (resulting from our metabolic functions) away from various tissues and areas such as muscles, liver, stomach and intestines, etc. These waste products are then filtered from the blood by the kidneys. Vast quantities of blood flow through the kidneys. The fluid that is filtered must, to a degree, be excreted as urine. However most of the filtered fluid must be reabsorbed in order to maintain as adequate fluid volume for the blood. Antidiuretic hormone acts upon the kidney to force it to REABSORB more fluid. The absence of ADH results in the production of very large quantities of urine. Abnormal medical conditions in which there is a relative lack or complete absence of ADH do occur. This medical condition is called DIABETES INSIPIDUS. This is NOT diabetes mellitus ("sugar diabetes") which is related to deficiency of insulin production by the pancreas. Diabetes insipidus can be a life-threatening condition, although it is usually less serious. It is treated by using a medicine whose function substitutes for the lack of the naturally available substance.
One should acknowledge that the pituitary gland serves a wide range of functions and is particularly impressive when one considers its small size. The gland is generally divided into three distinct parts (Figure 4).

The ANTERIOR (FRONT) LOBE is the largest portion. It consists of a number of different cell types. Each cell type serves a specific purpose. Thus, some of the hormones previously described, such as PROLACTIN, THYROID-STIMULATING HORMONE, GONADOTROPIC HORMONE, ADRENOCORTICOTROPIC HORMONE AND GROWTH HORMONE (and there are others), are produced by individual cell types. In other words, one cell (or similar cells) produces only one kind of hormone. The cell type that is most numerous of any of the different kinds of cells is the "ordinary pituitary gland cell" (known as the "true chromophobe"cell). It does not appear to serve any hormone-related function at all.

The POSTERIOR (BACK) LOBE is the smaller of the two lobes of the pituitary gland. Its primary function is to produce Antidiuretic Hormone (ADH). Between the two lobes of the pituitary gland is a narrow, dividing band called the PARS INTERMEDIA.

While the PITUITARY GLAND is generally regarded as the Master Gland, in actual fact it is strongly under the influence (and in some instances the control) of the HYPOTHALAMUS. The hypothalamus is directly in the center of the brain. It is the general region where many vital life functions are monitored. It responds to changes of the body's internal environment and function by directing the pituitary gland to release selected types and quantities of hormones in order to influence other organs to perform specific functions or alternatively to influence those organs or glands to, themselves, produce and release other hormones. All of this is done in an effort to MAINTAIN INTERNAL STABILITY OF THE BODY AND ITS MANY FUNCTIONS.

As an important example (but by no means the most important), let us examine the body's ability to maintain a relatively constant, narrowly ranging, concentration of a substance called Sodium. (Most of us are more familiar with its common name, Salt. Actually table salt is a purified version of a compound made up of two substances, sodium and chloride). Sodium is vital to many chemical functions of the body. However, too much or too little could have disastrous results. One of the most fundamental requirements for life is to maintain a "normal" concentration of sodium in our cells, tissues and serum (the fluid component of blood). In order to maintain the correct relative concentration of sodium in our serum, there is a highly integrated system that monitors the concentration (monitors exist in the hypothalamus) of sodium in our serum and reacts to the actual serum levels. It directs the POSTERIOR LOBE of the pituitary gland to release more (or less) Antidiuretic Hormone (ADH) in order to influence the kidneys to reabsorb more (or less) filtered blood. This results in less (or more) urine production. If more urine is produced then less fluid (water) is present in the serum; therefore, the concentration of sodium will rise. In the event that sodium concentration is too high, then the special sensing area of the hypothalamus will direct the posterior lobe of the pituitary gland to release MORE antidiuretic hormone. The kidney responds to the increase in ADH by reabsorbing more filtered serum. (Obviously LESS urine will be produced). The increase in reabsorbed water in the serum results in the desired lowering of the relative concentration of sodium.

The hypothalamus has "centers" dedicated to the regulation of body temperature as well as the amount of food that we eat (food satiation). The hypothalamus exerts a strong influence upon the pituitary gland in another way. Examples of this are in the way the anterior lobe of the pituitary gland manufactures and releases some of its hormones. The HYPOTHALAMUS produces releasing-factor hormones which have the solitary function to control the pituitary gland's production of a particular hormone. You are now familiar with the production of PROLACTIN by a particular cell type in the anterior lobe of the pituitary gland. (The release of abnormally high levels of this hormone usually results in an increase in breast size, breast milk production and lack of ovulation in females. A decrease in sex hormones in males may occur depending on several factors). Prolactin production and release is under the influence of the HYPOTHALAMUS. Obviously this is a highly complicated biochemical, anatomical and physiological system. It is remarkable how well the whole thing functions over our life span and how infrequently the systems fail despite the many extremes visited upon our bodies from many different sources and directions.

PART 2: TUMOR TYPES, CLINICAL PROBLEMS AND THEIR INVESTIGATION

Tumors of the brain are, in relative terms, uncommon in the general population. Nevertheless, they certainly do occur. Among all brain tumors, fifteen (15%) percent are classified as PITUITARY GLAND TUMORS. The vast majority (99%) of all pituitary gland tumors are BENIGN. That is to say, they are NOT cancerous (malignant). However, they are very clearly tumors (new growths) which continue to grow in size. As a general principle, the tumors can, and frequently do, grow to sufficiently large size to press upon and possibly injure vital adjacent structures such as the optic nerves, pituitary gland, cranial nerves which control the muscles that move the globe of the eye and the blood vessels supplying blood to the brain. (See Figures 5 and 6.)

The most frequently occurring type of pituitary gland tumor is one that comprises the "ordinary pituitary gland cell" (chromophobe cell). Most pituitary tumors are relatively slow growing. The brain and its nerves can accommodate to the progressive compressing force of a slowly expanding tumor. However, there comes a point where the brain, nerves and the blood supply to the nerves can no longer tolerate the progressive expansion and function is progressively lost. This is true for the pituitary gland itself as well as the adjacent structures. The loss of function, both hormonal and/or related to adjacent structures, can be quite insidious. Because the tumor grows slowly, the patient may not recognize any change. In some cases the degree of pituitary gland function impairment and/or visual disturbance may be far advanced before the diagnosis is made.

Tumors of the pituitary gland may arise from any of the different kinds of cells. In the case where the tumor consists of cells which produce a hormone, then there will be, in addition to any effects of pressure injury, the additional consequence of the over production of the particular hormone that the specific cell type produces. If the cell type involved in the tumor is the one which produces prolactin, then the serious consequences of the over abundance of prolactin will result. Alternatively, in the event that the cell type producing the tumor is the one which produces ACTH or GROWTH HORMONE then the patient will exhibit the manifestations of these hypersecretions of hormone. It should be obvious that there are many variations and spectrum of gradations of involvement of any of these abnormalities which can exist.

Tumors which produce a hormone may become obvious to the patient and the physician when the tumor is quite small. The hormonal effects of the tumor may be sufficiently profound to bring the matter to attention long before the tumor becomes large enough to produce a pressure injury. Levels of hormone concentration can be measured in the blood. This is among the important ways by which a correct diagnosis can be achieved as well as an important tool in measuring the success of treatment. Long-term follow-up for these patients includes the monitoring of the appropriate blood hormone concentration in order to determine the possible early recurrence of the tumor or help direct any further treatment efforts.

The problem of visual impairment and its relationship to pituitary tumors is worthy of some additional comments. As the tumor grows, it presses against the walls of the bony confines of the sella turcica. It frequently erodes the bone sufficiently to become obvious on x-rays of the skull. Further growth of the tumor results in the expansion of the tumor beyond the sella turcica. The continued tumor growth follows the line of least resistance. This is in an upward direction, out of the sella, and produces pressure on the underneath surface of the brain. In addition to pressure upon the hypothalamus, it also progressively stretches the optic (eye) nerves over the top of the tumor. Of equal significance is the concomitant stretching of the small blood vessels which supply blood and nourishment to the optic nerves. All of these structures can tolerate remarkable degrees of stretching provided the tumor growth is slow. Ultimately the optic nerve will no longer tolerate the actual stretching nor the diminished blood supply and the function begins to deteriorate. It is important to recognize that the progressive loss of vision, in these circumstances, is a LATE EVENT IN THE NATURAL HISTORY OF THESE TUMORS. It is a late event because the tumor usually must grow to a substantial size before it stretches the optic nerves and their blood supply.

There are tumors in the region of the pituitary gland which may arise from other structures. Their clinical presentations may be indistinguishable from those of pituitary tumors. Some of these other tumors actually arise inside or extend into the sella turcica. Frequently the investigations (blood tests, special eye examinations, x-rays, etc.) will help to determine the probable tumor type. A firm diagnosis is possible only with a surgical biopsy.

The investigation of a patient who may have a pituitary tumor usually begins when some particular problem has been noted by the patient. Headaches, unexplained visual impairment, double vision and hormonal difficulties (including infertility) are among the more common complaints that ultimately lead to the suspicion of the presence of a pituitary tumor. On occasion the diagnosis is made on the basis of a routine skull x-ray) or other neuro-imaging techniques such as Computerized Axial Tomography — CAT SCAN — or Magnetic Resonance Imaging l; MRI Scan) which was made for some reason other than the suspicion of a brain tumor (such as x-rays for investigation of a minor head injury).

Among the early steps in the evaluation of any patient with these problems is a detailed history and physical examination. Areas to be explored in the history of the illness, as it affects each particular patient, include historical hormonal aspects of life. It should be apparent that these matters are complicated and their clinical manifestations can be quite variable. Most major medical centers with experience in these matters have a TEAM OF EXPERTS who investigate and treat these conditions. The knowledge and techniques required for all of this extends into a number of related but different, medical and surgical disciplines.

The medical specialty of ENDOCRINOLOGY is a branch of Internal Medicine which specifically involves itself with the diagnosis and medical treatment of all abnormalities of the ENDOCRINE (HORMONAL) SYSTEM. In the case of a patient with a pituitary tumor certain initial blood tests help to determine the status of basic hormonal and pituitary gland function as well as levels of the various hormones which are produced by the pituitary gland. Further tests are usually done to "challenge" the function of the body's ability to tolerate stress. These are biochemical evaluations involving taking some tablets by mouth and having blood samples drawn at certain times over the next day or two. More elaborate urine analysis for hormone by-products is also done on occasion. The interpretation of these results can be readily apparent to many physicians; however, more frequently an accurate interpretation requires the expertise of the endocrinologist. A more ideal situation results when the endocrinologist is involved in the early stages of the evaluation. In the event of the possible use of medications to attempt to control the problem, in the preparation of the patient's endocrine system for surgery, or in the early and late post-operative medical management, the endocrinologist's expertise is frequently of vital importance.

The eye manifestations of tumors of the pituitary gland constitute an important aspect of these diseases. Frequently it is only the symptom of a "visual problem" that brings the matter of a pituitary tumor to the patient's and the physician's attention. The medical specialty of NEURO-OPHTHALMOLOGY involves itself with the diagnosis (and frequently treatment) of those many neurological conditions which manifest themselves through impairment of eye function. Special tests for vision and eye movement function are carried out by these specialists. In addition, certain electronic (neurophysiologic) tests may also be carried out or supervised and interpreted by the Neuro-ophthalmologist. Visual Evoked Responses (VER's) are among the techniques available to examine for subtle impairments of visual function by "measuring" (with the aid of advanced computer technology) changes in the miniature electrical brain waves which result when a light is flashed in front of the eye. The examination is painless and virtually without risk. This test may become very important in the surgical treatment of certain patients with pituitary and pituitary region tumors since it can help to gauge the tolerance of the visual system to surgical removal of the tumor while surgery is in progress.

The NEURORADIOLOGIST is the physician who will supervise, conduct and interpret all of the "IMAGING" tests that are done. These tests will help the physician team to "visualize" the tumor as well as its affect upon anatomical structures in the area, including the hypothalamus, pituitary gland, optic nerves, bone of the sella turcica and major cerebral blood vessels. The anatomical area of the skull that is involved in these cases is regarded as part of the SKULL BASE, and as such represents a unique set of technical problems and considerations as well as a very special and focused interest for a special group of surgeons. The most basic x-ray test is the skull x-ray which gives some details concerning the bone anatomy of the sella turcica and important adjacent bone structures. The extent of erosion caused by an expanding tumor in the sella can be evaluated better using other techniques. CAT scans as well as MRI scans give us new, advanced techniques to "see" inside the head. Unfortunately, although indispensable to modern diagnosis and treatment of these diseases, they are not without their technical limitations. Special advanced expertise is required in order for the Neuroradiologist to direct the technical aspects of the "picture taking" as well as interpreting the results.

Cerebral angiography is a special test which evaluates the blood supply to the brain and pituitary tumor as well as examining the effect of the tumor on the blood supply to the brain. Anatomical variations of the cerebral (brain) blood vessels are common; however, they only infrequently are of major consequence for the treatment of the tumor. Unfortunately, we are occasionally unable to predict these very serious problems without some form of angiogram. As an example, the major blood supply to the brain is through two large blood vessels (the Internal Carotid Arteries) which lie on either side immediately adjacent to and in front of the pituitary gland, separated from it by a thin layer of bone (see Figure 6). In four (4%) percent of humans, the two carotid arteries lie sufficiently close together (less than one inch) so as to limit the neurosurgeon from safe considerations of pituitary surgery through a transphenoidal approach (figures 7). Injuries to the carotid arteries (resulting in catastrophic exsanguinating hemorrhage or impairment of blood supply to brain and a possible stroke) are, to the largest extent, avoidable by determining (prior to surgery) if there is a safe distance between these vital blood vessels. Additionally, certain very serious blood vessel problems (known as aneurysms) can masquerade as pituitary tumors. Another potential surgical disaster is avoidable when the angiogram and/or MRI forewarns of the presence of the aneurysm. These are but two (albeit more important) of the indications of cerebral angiography.

There are choices in techniques of angiography. Some advanced computerized techniques permit the neuroradiologist to obtain the same information without some of the discomfort and risks of more traditional, but modern, techniques. The newer, high-resolution MRI and/or CT scans frequently give us most of the information that we need in checking vital blood vessel anatomy that is sufficient for us to avoid angiography. Your Neuroscience physician team will explain their recommendations for the most appropriate test for you. Oftentimes only one of these examinations is required to fulfill the anatomical information needs for your surgeon.

In summary, not all of these techniques are necessary for each patient. In all cases, either a CAT scan or an MRI scan will be required. In addition, some form of visualization of the vascular (blood supply) system (i.e. angiogram) may also be necessary. We are frequently referred patients who have had some form of scan performed elsewhere under less optimum conditions. In these situations it is often necessary to repeat at least part, if not the entire, scan. Additionally, even if the scan has been conducted in an expert fashion, we may need further anatomical information which can only be obtained using scanning techniques which are not routine. In some patient situations all of these techniques will be called upon to gain the information that the team needs in order to satisfactorily evaluate the situation and make the appropriate recommendations. The Neuroradiologist will discuss all of the Neuro-imaging aspects with the patient and is always pleased to take time to answer any questions concerning the performance and interpretation of the tests.

PART 3: SURGICAL TECHNIQUES AND OTHER TREATMENTS FOR PITUITARY AND PITUITARY REGION TUMORS

Surgical treatment of pituitary and pituitary region tumors enjoys a prominent and long history in Neurological Surgery. Modern microsurgical techniques have progressively evolved to the present day circumstances in which the patient and their families can be comforted by the fact that surgery has proven to be reliable, quite safe (considering we are dealing with a brain tumor) and effective on a long-term basis. This does not mean that surgery is indicated or necessary in every case nor that it is entirely free of risk for potentially serious complications. What it does very clearly mean, is that given (a) modern Neuro-imaging techniques that allow for pinpoint, accurate neuroanatomical "maps," (b) modern Neuro-anesthetic techniques, (c) modern, effective endocrinological management (d) advanced micro-neurosurgical instrumentation and techniques (including visual evoked responses conducted during surgery when this is appropriate), and (e) an experienced neurological surgeon (and a team of dedicated skull base tumour surgeons), the risks to the patient of surgery are decidedly less than the expected natural history of the disease (in the case of larger tumors) and more reliable than the long-term medical treatment of most of these tumors.

In the cases of very small tumors of the pituitary gland, medical treatment may be the most appropriate therapy. This is particularly true for small, prolactin-secreting tumors. These patients may ultimately be referred to neurosurgeons, specifically for the purpose of tumor removal, after medical treatment has either failed or been abandoned because of intolerable side effects. In other selected cases, medical treatment is used initially in an attempt to reduce the large size of a tumor to a more reasonable one, thereby making surgery easier on everyone. Medical treatment is most effective (at the present time) for tumors which produce prolactin. It is very much less effective for tumors which produce growth hormone although medical treatment is available and can be effective in some patients. It is probably ineffective for any other pituitary tumors (whether or not they produce hormones). For prolactin-secreting tumors which have not been or cannot be entirely removed surgically (or which recur), medical treatment may become an important part of their long-term management.

Radiation (super voltage/cobalt) therapy can be very effective in the treatment of pituitary tumors. One ordinarily believes that radiation treatment is used for cancerous tumors, and we have already noted that most pituitary tumors are entirely BENIGN. Pituitary tumors can and often do respond very favorably to radiation therapy. However, this technique is used only when absolutely necessary. It is rarely ever used as a primary form of therapy. It carries with it some risk to serious side effects, particularly with larger tumors (in which cases it is also less effective), and is ineffective for certain kinds of tumors. The only way to be absolutely certain of the precise kind of tumor that is present, is by examining the tissue by various pathology techniques (microscopic analysis, special tissue-staining techniques, immunochemical analysis, etc.). This can only be done with a surgical biopsy. The process of "surgical biopsy" may also allow for the selective removal of the entire tumor thus obviating the need, in most cases, for any further treatment. In those patients where, for whatever reasons, a complete tumor removal cannot be accomplished then surgery not only permits an accurate diagnosis, but usually also allows for the removal of the largest bulk of the tumor. This accomplishes two important treatment objectives. First, in the case of large tumors which are involving the optic nerves and possibly their blood supply, the pressure upon the optic nerves can be reduced, if not totally relieved. This is very important since radiation therapy results in, among other effects, a swelling of the tissues being radiated. As a general rule radiation therapy will not be offered unless the optic nerves have been relieved of the pressure in order to reduce the risk of producing blindness as a result of the radiation. Secondly, radiation treatment is appropriate for certain tumors only. An accurate tissue diagnosis is a prerequisite, in almost all instances, for accurate effective treatment.

The most modern form of radiation therapy incorporates a concept called stereotactic or "focused beam" radiation therapy. There are several commercial types currently available. The latest technique is called "Cyberknife" or "Accuray" while another is known as "Gamma Knife". These exceptional methodologies have limited indications and applications. Nevertheless, when appropriate they represent a major advance in the treatment of some of these problems. A full discussion of this is beyond the scope of this review. They will be discussed if you ask or if it is a reasonable alternative form of therapy.

For most pituitary tumor patients the treatment of choice is surgery. Among the surgical alternatives, there is one technique that is more desirable, for several significant reasons, than any other type of surgery. This Microsurgical method of tumor removal is performed through a relatively small opening in the front wall of the sella turcica (see Figures 7 and 8). The operation is actually done with an incision in either one nostril (or rarely just beneath the inside of the upper lip) and uses a surgical avenue through the sphenoid sinus to gain access to the sella. This technique allows the surgeon to view the compressed remnant of the pituitary gland, thus permitting a more reliable way to attempt to save the damaged gland and its function. This technique frequently allows for the opportunity for a selective total removal of the pituitary tumor while preserving the remaining, compressed pituitary gland (which usually lies to the back and side of the expanded sella turcica).

Unlike the other surgical techniques which require a craniotomy (window-like opening in the skull) and retraction (lifting up) of the front part of the brain to gain access to the top of the pituitary tumor (which has the stretched optic nerves lying over it), the Transphenoidal approach avoids all of this. The tumor is seen directly through a tiny bone opening (frequently smaller than the fingernail of the fifth finger) and is removed piecemeal with special microsurgical instruments and occasionally with an advanced micro-neurosurgical laser. The tumor is removed from below the eye nerves without touching them. The surgery usually takes less time, is less stressful upon the patient and is usually associated with considerably less blood loss than any other surgical technique available for these problems.

A modification of the Transphenoidal technique involves the use of Endoscopic surgical instruments. This can be done either in conjunction with the Microsurgical procedure or as part of a Minimally Invasive Microendoscopic technique. An Endoscope is a long slender instrument which incorporates modern optics as well as a high intensity light source to permit operations to be done through "tiny keyhole-like" openings in the skull. The surgeon is able to "see" anatomical structures quite well due to the clarity of the optics, intense light, high resolution miniaturized video cameras along with specially designed instrumentation. One of the additional advantages for Endoscopic Transphenoidal Surgery is the fact that post-operative "packing" of the nasal cavity is rarely required. This usually also shortens the patient's length of stay in the hospital post-operatively.

Occasionally transphenoidal surgery cannot or should not be used. In those patients in whom the internal carotid arteries are closer than one (1) inch, it is best to avoid this operation because of the serious risk of injury to these vital arteries. It is usually advisable to use a craniotomy approach in those cases where the tumor has extended to either or both sides above the sella. Tumor above the sella is usually accessible using transphenoidal surgery (actually that is one of its major advantages). However, tumor above the sella that has gone beyond the range of the side walls of the sella usually cannot be safely approached or removed from below because of the risk of injury to the internal carotid arteries inside the skull cavity. A craniotomy technique allows the surgeon to directly view the carotid arteries inside the head and reduces the chance of injuring them.

There are some tumor types which cannot or should not be removed using the transphenoidal technique and are best managed using a craniotomy. These limiting factors to transphenoidal surgery are fortunately relatively uncommon, permitting its use in most cases. Occasionally we encounter a tumor which has either a very firm texture which will not respond to available resection methods or has a very firm tough surrounding capsule which will not collapse as tumor is removed. In this case the transphenoidal technique may fail to adequately decompress the visual sensory system. This unusual circumstance may then require a second surgical procedure via craniotomy to resect that firm capsule.

In our practice, a surgical team comprising experts from different surgical specialty areas is involved in the care of the patient. (Each patient will be informed as to which specific doctors will be involved in their care.) An Otorhinolaryngologist — Head and Neck surgeon (formerly ENT) - usually performs the surgical approach through the nose to the sphenoid sinus. On occasion, when a more extensive opening is required, a Craniofacial Plastic Surgeon may join the surgical team. In the event that this special expertise is needed, it will be discussed with you. After the Neurosurgical team removes the tumor and has completed the repair of the sella turcica, the ENT (or Craniofacial Plastic) surgeon returns to complete the repair of the nose and/or face.

The Neurosurgical team consists of a neurological surgeon and an assistant, which may be a surgical Neuro-ophthalmologist or another Neurosurgeon. The neurosurgeon opens the sphenoid sinus and selects the area in the front of the sella turcica that he will open. This choice is made by directly viewing the front of the sella (through the sphenoid sinuses) using the Neurosurgical Microscope, as well as by x-ray imaging of the skull and this region. X-rays are taken at intervals throughout the procedure in order to help guide certain important aspects of the operation (See Figure 7). Another technique utilizes an endoscopic approach through a similar route. In this case the surgeon is using a different type of visualization system compared to the operating microscope. The endoscope may be used instead of the microscope or as an adjunct depending on the anatomical requirements for the particular tumor and patient problem.

Once the sella is opened, the underlying covering (the dura mater — which is a tough, leather-like covering of the brain) is opened. The pituitary tumor lies directly in view in most cases. The tumor is removed in a piecemeal fashion with special microsurgical instruments. Frequently, a neurosurgical laser is used as well. Every effort is made to attempt to remove the entire tumor or, if this is not possible, then as much tumor as can be resected. A similar effort is made to try to save the already seriously compressed pituitary gland. It is important to know that, despite these efforts, even if the pituitary gland is left anatomically intact, it may never function properly, or at all, again Alternatively it may stop all of part of its functioning for an indefinite (usually short) time after surgery and subsequently resume its activity in part or completely.

One of the very important aspects of the removal of these rumors, particularly where vision has been impaired or is at serious risk, is to protect and try to improve upon the damaged visual system. We have the capability to monitor visual function using advanced neurophysiology techniques (a technique called Intraoperative Visual Evoked Response [VER] monitoring while the operation is being done (the patient is asleep under general anesthesia). In the event that these tests indicate that vision is being impaired by the removal of the tumor, then the procedure will be modified to try to change this. Although this is uncommon, it is a possible limiting factor since we prefer to save vision first even at the expense of leaving some tumor behind. We can usually use radiation therapy postoperatively to try to deal with the rest of the tumor.

At the completion of the neurosurgical procedure, it is necessary to seal the hole in the front of the sella (Figure 8). This is of critical importance for several reasons. Cerebrospinal fluid (the fluid which bathes and cushions the brain inside the skull) could leak out through the hole in the sella. A leak, postoperatively, of cerebrospinal fluid is a very serious complication. If fluid can get out, then bacteria can also enter (from outside) to the brain area and cause a serious infection (meningitis). Every effort is made to prevent this. A piece of muscle (which will be taken from the thigh muscle of the patient through a short skin incision earlier during the operation) and/or a piece of fat will be placed in the sella turcica to fill part of the void left by the tumor removal. This is the first of several layers that will complete the seal. The muscle also helps to prevent bleeding by pressing gently against the "walls" where the tumor was. Additionally it helps to prevent the optic (eye) nerves from herniating down into the sella turcica. Where the optic nerves were stretched over the top of the tumor, they have become elongated. Now that the tumor is out, there would be nothing to prevent them from falling into the empty pit in the sella. This could stretch them and their blood supply resulting in the same kind of problem that the tumor caused, except in the reverse direction. The muscle/fat helps to keep this from happening.

After the muscle/fat is placed, then a piece or pieces of nasal cartilage and bone are usually used to tightly seal the small bone opening in the front of the sella turcica. A final seal is made with the use of a rapidly setting, special glue. This technique has helped to reduce to a minimum the risk of cerebrospinal fluid leak in our patients. However, it is very important postoperatively to avoid sneezing, nose blowing or activities that require straining. These activities result in increased intracranial pressure. This pressure could be transmitted to the repair site and cause a leak.

As a general rule, the risks to this operation are statistically small; the results are quite reliable and favorable. However, as in any operation, there are risks. The operation is conducted under general anesthesia by an Anesthesiologist. The anesthesiologist will talk with you about the anesthetic and answer any questions which you might have. The risk to life has been reduced to a small fraction largely because of the advances in modern anesthesia.

There is a risk to recurrence of the tumor even if we believe we have removed all of it. In all cases, long-term follow-up is essential. Radiation therapy may be necessary postoperatively where we know tumor remains or if tumor recurs at some later date.

The likelihood of producing any injury during surgery is very small. The risk to injury to the carotid arteries and causing hemorrhage or stroke is very unlikely. Similarly, the risk to further injury to vision, even to loss of vision, is small. However, vision that has already been lost may not recover or may not completely recover.

There are vital structures adjacent to the tumor and the operative region. There is a very small risk that they could be injured. The nerves which control the movement of the globe of the eye, if injured, may never recover. This could result in double vision or trouble opening the eyelids. Injury to the hypothalamus is very unlikely, however it could cause difficulty with body temperature regulation, hormone control and body fluid and electrolyte (sodium, potassium, etc.) control.

Most patients use a supplemental steroid hormone postoperatively (taken as pills). Other hormones, depending on the needs of the individual patient, may also be required. These may be necessary on a permanent or long-term basis or just for a short time. The endocrinologist will help to decide and monitor these matters.

One cannot emphasize strongly enough the absolute necessity for long term follow-up on a regular basis. Even though the vast majority of these tumors are of a benign cytological (cellular) nature, there is a significant risk to the recurrence of some of these. The surgeon may well believe that he has removed the entire tumor. Nevertheless, the surgeon cannot be expected to "see" at a cellular level and some miniscule remaining tumor may not be apparent. More often than not if the surgeon believes that a complete resection has occurred then recurrence is very unlikely. I am still unwilling to pronounce a surgical "cure" in these patients. In each instance the surgeon will fully share his impressions and recommend a follow-up schedule which will include MRI scan at some interval.

We realize that it is impossible to answer every question that might arise through this group of "papers". We would like to encourage the reader to read and re-read these sections and consult the diagrams. Members of our staff will be happy to answer whatever questions you may have concerning these or any other matters.



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This page last edited on 2/20

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Author, Martin L. Lazar, MD, FACS
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