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Diagnosis and Surgical Treatment of Pituitary Tumors
Diagnosis and Surgical Treatment of Pituitary Tumors J. GRAFTON LOVE
TUMORS of the pituitary body constitute about 10 per cent of all intracranial neoplasms that come to operation at the Clinic; obviously, therefore, they occur rather often. In 1886 Marie described 2 cases of what he called "acromegaly" which, at that time, was a new disease, or at least it was recognized as such. It was, as is well known today, characterized by an enlargement of the hands and feet and an abnormally prominent lower jaw. Frohlich in 1901 described a case of tumor of the pituitary gland without acromegaly. In fact, in his case there was arrested development, particularly of the organs of reproduction. Figure 306 illustrates such arrested development. His case represented, ,as is known today, deficient function of the pituitary body or a state of hypopituitarism, as contrasted with the hyperpituitarism of acromegaly. The commonest tumor or disease process affecting the pituitary gland for which the neurosurgeon is called upon to operate is chromophobe adenoma. This tumor likewise produces endocrine disturbances, usually of a hypopituitary type. In addition to adenomatous tumors of the pituitary gland, there is a group of congenital tumors of pituitary origin, namely, pituitary adamantinomas. These are the most frequently encountered tumors of the supratentorial cavity in childhood. They are also known as craniopharyngiomas, hypophysial duct tumors, and Rathke's pouch tumors. Krause probably was the first to. employ successfully a transcranial operative procedure for the removal of a pituitary tumor. But since his time, surgical treatment of pituitary tumors has been developed tremendously and today transcranial removal of pituitary tumors is an accepted procedure and is a frequently performed operation in all neurosurgical clinics. SYMPTOMATOLOGY OF PITUITARY TUMORS
As stated previously with respect to the pituitary body, there are hyperfunctioning tumors, namely, eosinophilic adenomas and basophilic 1005
1006
J. Grafton Love
adenomas, and nonfunctioning tumors, namely chromophobe adenomas. Then there are the so-called suprasellar cystic tumors or pituitary adamantinomas which are most frequently seen in childhood. The
Fig. 306. A woman 26 years old who had not menstruated for eight years and who complained of headaches and visual loss. For one year there had been "blurring of vision" in the left eye and this had progressed to complete blindness in that eye. The vision in the right eye was normal. Roentgenograms of the head revealed enlargement and erosion of the sella turcica due to an epidermoid cyst which involved the pituitary gland. The cyst was successfully removed but owing to atrophy and loss of substance of the left optic nerve, no visual improvement occurred. The photograph shows the lack of normal development of the breasts, the absence of axillary hair and scantiness of pubic hair due to pituitary insufficiency.
Diagrwsis and Treatment of Pituitary Tumors
1007
neurosurgeon is called upon to operate for a pituitary tumor when, because of the size of the tumor, interference with vision has occurred or there has been blockage of the third ventricle with the production of increased intracranial pressure, with resultant headache and vomiting and choked disks. Eosinophilic adenomas characteristically produce the syndrome of acromegaly. There is enlargement of the hands and feet, the head increases in size and a larger hat size is required, the lower jaw becomes prominent, there is some separation of the teeth, and in the female the appearance of the body approaches that of the male. Menstruation in the female mayor may not cease, and there mayor may not be loss of libido and potentia in the male suffering from an eosinophilic adenoma. These tumors have a tendency to expand the sella turcica downward into the sphenoid air sinus and thus to grow away from the optic nerves and chiasm; hence, only in a small percentage of cases, probably 5 per cent, do patients suffering from eosinophilic adenoma require surgical treatment of their tumor. Basophilic adenomas, which according to Cushing are in some cases responsible for the syndrome of hirsutism, the development of the buffalo type of obesity, hypertension, amenorrhea, and atrophic purplish striae of the skin in the female, rarely if ever require surgical attack. Therefore, it is the chromophobe adenoma of the pituitary body which most often requires surgical treatment. Chromophobe adenoma, because of its increase in size, tends to destroy the normally functioning pituitary gland and thus to produce endocrine disturbances characterized by rather waxy pallor, diminution or loss of sexual function, and loss of beard, axillary hair and other secondary sex characteristics in the male. In the female there is usually loss of menstruation and ability to conceive. Chromophobe adenoma may require surgical treatment because of pressure effects. These pressure effects are local or general, the more common being the former in which, because of the continued growth of the adenoma, local pressure is exerted on the visual apparatus with resultant visual disturbance. Occasionally a pituitary adenoma will present itself above the sella and encroach on the domain of the third ventricle and produce increased intracranial pressure before signs of visual loss occur. The classic visual disturbance in the case of chromophobe adenoma of the pituitary body is a bitemporal visual disturbance or bitemporal hemianopsia. This defect is produced by the tumor breaking through the diaphragm of the sella, rising anterior to the optic chiasm and between the optic nerves, and displacing the chiasm posteriorly and the optic nerves laterally. Thus the nasal fibers and the crossing fibers in the chiasm are compressed with the resultant loss of vision to the outer or temporal side of the field of vision. The bitemporal, as stated, is the
J. Grafton Love
1008
classic type of field defect. However, innumerable variations may occur. Occasionally the adenoma will break out from the sella laterally, below the internal carotid artery underneath the lateral half of the optic chiasm, and produce a homonymous visual defect to the opposite side. Occasionally the tumor will interrupt the central fibers and produce a central scotoma in one eye with or without a bitemporal defect. Early in the development of a pituitary tumor the optic disks appear normal. If pressure is not relieved at this stage, pallor of the disks occurs and later there is loss of substance of the disks; when pronounced loss of substance has occurred there is little or no hope that the visual Table 1 OCULAR MANIFESTATIONS IN A SERIES OF 314 PITUITARY TUMORS OF THE ADENOMA TYPE SURGICALLY VERIFIED AT THE CLINIC CASES VISlTAL FIELDS
I Chromo- Malig-
Total N
~e~-I
Bitemporal defects .... Blind ...... One eye. . . . . . . . . . . Both eyes .. Scotomas .. Homonymous defects. Normal fields. Choked diskst . Contraction of lid, fissure type .. ............
.
233 37 33 4 16 17 8 2
phobe Per cent adenoma 74.3 11.8 5.1 5.4 2.5 0.6
203 31 28 3 14 13 7 2
0.3
nant adenoma 12 2 2 0 2 3 1
0 0
Adenoma, mixed type
Acidophilic adenoma
14 4
4 0
3 1* 0 1 0 0
0 0 0 0
0
0
---
Total .................
314
100.0
271
20
19
4
* Bilateral choked disks. t One patient had normal fields with bilateral choked disks; the other had temporal contraction in one eye and choked disk in the other eye.
loss may be restored even though successful removal of the tumor is accomplished (table 1). Roentgenologic examination of the head in case of suspected pituitary tumor is one of the most important examinations which can be carried out. In the majority of cases of pituitary adenoma, there is either enlargement of the sella turcica or enlargement and erosion. In many cases there is in addition to the enlargement and erosion evidence of extrasellar extension of the tumor. However, occasionally one will encounter a pituitary tumor with a perfectly normal sella as shown by the roentgenogram. In a study of 314 surgically verified pituitary adenomas at the Clinic, it was found that the sella turcica, by roentgenray examination, was normal in 12 of the cases; so, one would be forced
..
' " Diagnosis and Treatment of Pituitary Tumors
1009
to conclude from this that in a given patient showing symptoms and signs of dyspituitarism with a bitemporal visual defect one should not hesitate to make a diagnosis of a tumor involving the pituitary gland. In the case of pituitary adamantinomas, in addition to erosion or enlargement of the sella turcica there is often calcification either within the sella turcica or most often above and behind the posterior clinoid processes. In a review of 108 cases of craniopharyngioma, Mar-
Fig. 307. Brow-up ventriculogram in the case of a 30-year-old woman who was semistuporous with bilateral edema of the optic disks of 2 to 3 diopters and relative bitemporal hemianopsia. Her chief complaint was headache of two months' duration. There is symmetrical hydrocephalus with only a crescent of the upper portion of the third ventricle visible owing to a large chromophobe adenoma of the pituitary body which extends up into the third ventricle and is blocking the escape of cerebrospinal fluid.
shall and I found that calcification was observed in only 50 per cent of the cases, an incidence which is much lower than that usually recorded. Again, it was of interest that in 26 cases the roentgenograms of the skull revealed no calcification about, nor erosion or enlargement of, the sella turcica. Other aids to be considered in the diagnosis of pituitary tumors include the electro-encephalogram. In my experience this diagnostic instrument is of little or no value in the diagnosis of a pituitary tumor and probably rarely is indicated when this condition is suspected.Pneumoencephalography likewise. in my experience, is of little or no value in
1010
J. Grafton Love
the diagnosis of the ordinary pituitary tumor. In an occasional bizarre case, particularly if there is a homonymous field defect, pneumo-encephalography may be employed to exclude a lesion of the temporal lobe. or a lesion interfering with the visual apparatus because of pressure on the optic radiations posterior to the optic tract. In an occasional case of pituitary tumor in which there are choked. disks but absence of endocrine, ophthalmologic-that is, bitemporal hemianopsia-and roentgenologic changes, ventriculography may be required to show the presence of an adenoma encroaching upon the floor of the third ventricle and producing internal hydrocephalus and choked disks (fig. 307). Carotid angiography may be of value in an occasional case of pituitary tumor. The type of case in which it is apt to be of benefit is that of pituitary tumor in which the adenoma has broken out of the sella laterally and produced a homonymous or other more or less atypical field defect plus palsy of the third cranial nerve. In such a case angiography would serve to distinguish a pituitary tumor from an aneurysm of the circle of Willis or of the internal carotid artery. Radioisotopes are being extensively investigated for their use in the diagnosis and localization of intracranial neoplasms. Whether or not they will increase the accuracy of diagnosis of pituitary tumors and serve to distinguish pituitary tumors from other chiasmal lesions remains to be seen. The record of . a typical case of pituitary tumor has been abstracted to indicate the methods used in the diagnosis and surgical treatment of a pituitary tumor. A man 43 years of age came to the Clinic with a history of visual difficulties of only three or four weeks' duration. At the onset he noted that 3-digit numbers would appear as 5 or 6-digit numbers. One week before the patient came to the Clinic, an ophthalmologist charted his visual fields and recommended a neurologic examination. The patient denied difficulty in seeing to either side, but in retrospect he recalled that on several occasions in the past year he had driven his car onto the curb when turning to the right (fig. 308). He had also had vague headaches off and on for a year. During the preceding three weeks, the headaches had increased in frequency. The patient was 5 feet 6 inches tall and weighed 169~ pounds stripped. His blood pressure was 148 mm. of mercury systolic and 92 mm. diastolic. His appearance was somewhat waxy. His thyroid gland was barely palpable. There was normal axillary and pubic hair. His testes were small and soft. The results of neurologic examination were normal except for the findings referable to the eyes. Examination of the eyes revealed the central vision to be 6/60 in the right eye and 2/60 in the left eye with correction. There was pallor, grade 1, of the temporal sector of both disks (graded on a basis of 1 to 4). The patient was myopic by about 5 diopters. Narrowing of the retinal arterioles was graded 1 plus to 2, and there was hypertensive sclerosis, grade 1. There was a small hemorrhage below the left disk. On plotting the visual fields it was found that the patient had bitemporal hemianopsia (fig. 308) indicative of compression
Diagnosis and Treatment of Pituitary Tumors
1011
Pre-operative Nov. 7,1951
Date:
w.e. O. S.:
v.
~
60
14 178
Woe.
v.
O. D·:
6 14 60 3S
Post-ope~a.tive Date:
12.-1-51
w.e.
v.
O. S.:
~
7
14
eo1
w.e.
'6
V. O.D.:?
Fig. 308. Preoperative and postoperative fields of vision in the case reported, showing the rapid and excellent recovery of vision following the removal of a pituitary tumor. of the optic chiasm. Roentgenographic examination of the head disclosed marked enlargement and erosion of the sella turcica (fig. 309). The laboratory findings prior to operation follow: The urine had a specific
101f2
J. Grafton Love
gravity of 1.017, the reaction was acid, there was grade 1 albuminuria, sugar was absent, and there was grade 3 erythruria (graded on a basis of 1 to 5). The presence of red cells in the urine was due to the fact that there was a ureteral calculus in the lower of duplicated ureters on the right side. The concentration of blood urea was 34 mg. and of blood sugar, 86 mg. per 100 cc. The value for chlorides was 98.8 mEq. and for carbon dioxide 28 mEq. per liter. The Kolmer, Kline, Hinton and Kahn reactions were all negative. The sedimentation rate was 45 mm. in one hour (Westergren method). This elevation of rate probably was due to an incipient head cold, which necessitated the postponement of surgical removal of the pituitary tumor for one week. The value for hemo-
Fig. 309. Lateral roentgenogram of head of patient in the case reported, showing marked enlargement and erosion of the sella turcica by a chromophobe adenoma of the pituitary gland. globin was 12.8 gm. per 100 cc. of blood and the leukocyte count was 7,600 per cubic millimeter. Other values were as follows: blood calcium 9.8 mg. and phosphates 4.2 mg. per 100 cc., sodium 130 mEq. and potassium 4.0 mEq. per liter, 17-ketosteroids 3.9 mg. in twenty-four hours, and corticosteroids 0.61 mg. in twenty-four hours. The urine was negative for estrogen and the value for pituitary gonadotropin was normal. The cell volume was 42 per cent. The basal metabolic rate was - 6. A diagnosis of pituitary tumor was made and surgical removal of the tumor was advised. The patient was admitted to the hospital for preoperative preparation with cortisone. On November 24, 1951, with the patient under open drop ether given over the end of an intratracheal tube, a right transfrontal craniotomy was performed with intracapsular removal of a pituitary tumor and extensive resection of the capsule. During the course of the operation 500 cc. of blood was given by transfusion. This is a routine procedure on my service. The tumor was a large
Diagnosis and Treatment of Pituitary Tumors
lOiS
blue-domed mass which presented between the optic nerves anterior to the optic chiasm. There was no cystic fluid within the tumor. The capsule was opened in a cruciate fashion and a large amount of adenomatous tissue was removed. After removal of all the adenomatous tissue within the capsule, the capsule itself was resected to the floor of the sella turcica thus removing all pressure from the optic nerves and chiasm. The tissue removed was reported by the pathologist as being that of a chromophobe adenoma, the pieces aggregating 2 cm. in diameter. A good portion of the tumor was removed with the sucker and was therefore not available to the pathologist. The day following operation the patient was alert and he was able to read the name and address written with an ordinary typewriter on an envelope. Immediately following operation the patient's temperature went to 101.50 F., then gradually declined and his convalescence was uneventful except for symptoms of diabetes insipidus. . The day of operation the intake of fluid was 1,240 ce., with the urinary output at 650 cc. The next day the urinary output was 4,500 cc. and the intake of fluid was 2,500 cc. The next day 2,000 cc. of urine was voided, the intake of fluid being 3,750 cc. The increased intake and output gradually decreased so that by the ninth postoperative day the intake and output were normal without the administration of posterior pituitary powder. During the period of clinical diabetes insipidus, the specific gravity of the urine was 1.001; when the symptoms of diabetes insipidus had subsided the specific gravity of the urine increased to 1.008. During the period of diabetes insipidus the values for blood sodium, chlorides and carbon dioxide remained normal. This patient received 100 mg. of cortisone intramuscularly the day before operation and the morning of the day of operation. He then received cortisone intramuscularly in a dose of 50 mg. a day for three days and in a dose of 25 mg. a day for an additional four days. It is our practice at present to use cortisone for all patients who. are to undergo an operation for a pituitary tumor. It is hoped that its use will fortify the patient for the operation and support him during the immediate postoperative period. Our experience at the Clinic has not been great enough nor has it extended over a long enough period to permit us to state just exactly how beneficial cortisone is in the therapy of patients operated on for a pituitary tumor. At the time of dismissal, the patient had shown marked improvement in vision (fig. 308) and generally his condition was excellent. SURGICAL PROCEDURE FOR REMOVAL OF A PITUITARY TUMOR
Early in the history of removal of pituitary tumors the transsphenoidal route was often employed. Later the transcranial or intracranial approach gained favor and was the method of choice. More recently some surgeons have adopted the transsphenoidal route for those lesions producing a large sella turcca and not appearing to have extended upward beyond the confines of the sella. It is considered particularly applicable for cystic lesions. (Unfortunately there is no sure way short of exposure of the lesion to determine when an adenoma of the pituitary is cystic, and probably no more than 10 to 20 per cent are cystic.) The intracranial approach is preferred at the Clinic. Classically we employ a right transfrontal type of craniotomy (fig. 310) and proceed extradurally to the wing of the sphenoid; then we open the dura mater
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J. Grafton Love
along the sphenoid ridge and proceed to the midline anteriorly and upward parallel to the falx cerebri. This provides a flap of dura mater for protection of the frontal pole of the cerebral hemisphere which must, be elevated to expose the sella turcica and adjacent structures, namely, the optic"nerves, chiasm, internal carotid arteries and the tumor. Some surgeons -prefer the intradural approach. They reflect a flap of dura
Fig. 310. Artist's drawing of the classic transfrontal flap used for removal of pituitary tumors and other lesions about the optic chiasm. The scalp is reflected forward and the bone attached to the temporal muscle and periosteum is reflected laterally. The five holes are made with an Adson or McKenzie perforator (burr is not used) and thus when the flap is healed there are no unsightly depressions even though the holes are not filled with anything such as tantalum or bone dust.
mater along the limits of the craniotomy and proceed over the exposed cerebral hemisphere to the chiasmal region. My experience with the intradural approach was not as satisfactory as with the extradural subfrontal route. When the fluid at the base of the brain has been removed with the sucker, exposure of the visual apparatus usually is easy. The pituitary tumor, as stated previously, usually presents anterior to the optic chiasm and between the optic nerves. The capsule of the tumor should be perforated with a small spinal puncture needle attached to a syringe by means of a flexible rubber tube. This is done (1) to determine whether
Diagrwsis and Treatment of Pituitary Tumors
1015
the tumor is cystic and if so to collect the fluid for study and to prevent its irritating effect on the brain should it escape, and (2) to exclude an aneurysm. The next step is to coagulate the capsular vessels with the electrosurgical unit. The capsule is then opened in a cruciate fashion with a sharp ureteral knife. The contents of the capsule are then removed by means of punches, pituitary forceps, gallbladder scoop and sucker. It is essential to remove any adenomatous tissue that may be beneath the optic nerves and chiasm or that· may extend posteriorly toward the cerebral peduncles. To remove the midline suprasellar and intrasellar tissue alone is insufficient. After the adenomatous tissue has been removed, the capsule should be gently teased free and resected to the floor of the sella turcica. It is essential to avoid trauma to the optic nerves and chiasm. When hemostasis is cemplete, the wound should be closed in layers. A drain mayor may not be used. It is my feeling that a Penrose cigarette drain placed beneath the frontal lobe and brought out the posterior limb of the flap and left for 24 to 48 hours prevents excess swelling of the eyelids on the side of the flap and allows the bloody cerebrospinal fluid to escape, thus preventing the chemical meningismus from broken-down blood which is .apt to occur postoperatively. The postoperative course is usually smooth and uneventful if the operation has not been delayed too long. With a large tumor that has extended beyond the sella turcica and with a tumor that involves the third ventricle the postoperative course may be very stormy and the nursing problem may be difficult. For temperatures of 103°F. or higher, the oxygen tent with its temperature held at 70°F. is very useful. Ice bags to the axillae and groips are also used. Aspirin, grains 10, and aminopyrine (pyramidon), grains 7!, may be given by mouth if the patient is able to take them in this manner; otherwise they may be given by rectum. These may be repeated every four hours for several doses but should not be given over a period of days. It is essential to keep up the intake of fluid and to maintain the electrolyte balance. Some patients have diabetes insipidus in the immediate postoperative period, as in the case reported herein (some, of course, have the disease prior to operation) and it is my practice to let them consume as much fluid as they desire provided there is adequate urinary output. The condition usually rights itself within a period of several days. If it should be unduly prolonged or if the patient is getting inadequate rest because of the ingestion of fluids or the passing of urine, then nasal insufHation of posterior pituitary powder is indicated. The patients are allowed to be ambulatory as soon as they feel like it. The time at which ambulation starts varies from a few hours to several days after operation. It has been reported by some authors that the routine postoperative
J. Grafton Love
1016
use of roentgen-ray therapy to the region of the sella turcica gives an improved long-term result and decreases the· chances of recurrence of the pituitary tumor. My colleagues and I follow the policy of advising radiation therapy only when we have been unable to do as thorough removal of the tumor as we desire or when the pathologist reports the tumor as being unusually active or malignant. Patients harboring such tumors must be followed closely for the appearance of symptoms or signs of recurrence. Periodic determination of the fields of vision will usually indicate progressive reduction of the patient's vision if there is recurrence of the tumor. If recurrence is going to take place, it usually will manifest itself within the first five years following surgical removal of the tumor. REFERENCES 1. Cushing, Harvey: Papers Relating to the Pituitary Body, Hypothalamus and Parasympathetic Nervous System. Springfield, Illinois, Charles C Thomas, 1932, 234 pp. 2. Frohlich, A.: Ein Fall von Tumor der Hypophysis cerebri ohne Akromegalie. Wien. klin. Rundschau. 15: 883-886; 906-908, 1901. 3. Krause, F.: Hirnchirurgie. Deutsche Klin. 8: 953-1024,1904. 4. Love, J. G. and Marshall, T. M.: Craniopharyngiomas (Pituitary Adamantinomas). Surg., Gynec. & Obst. 90: 591-601 (May) 1950. 5. Marie, Pierre: Sur deux cas d'acromegalie; hypertrophie singuliere noncongenitale des extremites superieures, inferieures et cephalique. Rev. de med., Paris. 6: 297~333, 1886.
TUMORS of the pituitary body constitute about 10 per cent of all intracranial neoplasms that come to operation at the Clinic; obviously, therefore, they occur rather often. In 1886 Marie described 2 cases of what he called "acromegaly" which, at that time, was a new disease, or at least it was recognized as such. It was, as is well known today, characterized by an enlargement of the hands and feet and an abnormally prominent lower jaw. Frohlich in 1901 described a case of tumor of the pituitary gland without acromegaly. In fact, in his case there was arrested development, particularly of the organs of reproduction. Figure 306 illustrates such arrested development. His case represented, ,as is known today, deficient function of the pituitary body or a state of hypopituitarism, as contrasted with the hyperpituitarism of acromegaly. The commonest tumor or disease process affecting the pituitary gland for which the neurosurgeon is called upon to operate is chromophobe adenoma. This tumor likewise produces endocrine disturbances, usually of a hypopituitary type. In addition to adenomatous tumors of the pituitary gland, there is a group of congenital tumors of pituitary origin, namely, pituitary adamantinomas. These are the most frequently encountered tumors of the supratentorial cavity in childhood. They are also known as craniopharyngiomas, hypophysial duct tumors, and Rathke's pouch tumors. Krause probably was the first to. employ successfully a transcranial operative procedure for the removal of a pituitary tumor. But since his time, surgical treatment of pituitary tumors has been developed tremendously and today transcranial removal of pituitary tumors is an accepted procedure and is a frequently performed operation in all neurosurgical clinics. SYMPTOMATOLOGY OF PITUITARY TUMORS
As stated previously with respect to the pituitary body, there are hyperfunctioning tumors, namely, eosinophilic adenomas and basophilic 1005
1006
J. Grafton Love
adenomas, and nonfunctioning tumors, namely chromophobe adenomas. Then there are the so-called suprasellar cystic tumors or pituitary adamantinomas which are most frequently seen in childhood. The
Fig. 306. A woman 26 years old who had not menstruated for eight years and who complained of headaches and visual loss. For one year there had been "blurring of vision" in the left eye and this had progressed to complete blindness in that eye. The vision in the right eye was normal. Roentgenograms of the head revealed enlargement and erosion of the sella turcica due to an epidermoid cyst which involved the pituitary gland. The cyst was successfully removed but owing to atrophy and loss of substance of the left optic nerve, no visual improvement occurred. The photograph shows the lack of normal development of the breasts, the absence of axillary hair and scantiness of pubic hair due to pituitary insufficiency.
Diagrwsis and Treatment of Pituitary Tumors
1007
neurosurgeon is called upon to operate for a pituitary tumor when, because of the size of the tumor, interference with vision has occurred or there has been blockage of the third ventricle with the production of increased intracranial pressure, with resultant headache and vomiting and choked disks. Eosinophilic adenomas characteristically produce the syndrome of acromegaly. There is enlargement of the hands and feet, the head increases in size and a larger hat size is required, the lower jaw becomes prominent, there is some separation of the teeth, and in the female the appearance of the body approaches that of the male. Menstruation in the female mayor may not cease, and there mayor may not be loss of libido and potentia in the male suffering from an eosinophilic adenoma. These tumors have a tendency to expand the sella turcica downward into the sphenoid air sinus and thus to grow away from the optic nerves and chiasm; hence, only in a small percentage of cases, probably 5 per cent, do patients suffering from eosinophilic adenoma require surgical treatment of their tumor. Basophilic adenomas, which according to Cushing are in some cases responsible for the syndrome of hirsutism, the development of the buffalo type of obesity, hypertension, amenorrhea, and atrophic purplish striae of the skin in the female, rarely if ever require surgical attack. Therefore, it is the chromophobe adenoma of the pituitary body which most often requires surgical treatment. Chromophobe adenoma, because of its increase in size, tends to destroy the normally functioning pituitary gland and thus to produce endocrine disturbances characterized by rather waxy pallor, diminution or loss of sexual function, and loss of beard, axillary hair and other secondary sex characteristics in the male. In the female there is usually loss of menstruation and ability to conceive. Chromophobe adenoma may require surgical treatment because of pressure effects. These pressure effects are local or general, the more common being the former in which, because of the continued growth of the adenoma, local pressure is exerted on the visual apparatus with resultant visual disturbance. Occasionally a pituitary adenoma will present itself above the sella and encroach on the domain of the third ventricle and produce increased intracranial pressure before signs of visual loss occur. The classic visual disturbance in the case of chromophobe adenoma of the pituitary body is a bitemporal visual disturbance or bitemporal hemianopsia. This defect is produced by the tumor breaking through the diaphragm of the sella, rising anterior to the optic chiasm and between the optic nerves, and displacing the chiasm posteriorly and the optic nerves laterally. Thus the nasal fibers and the crossing fibers in the chiasm are compressed with the resultant loss of vision to the outer or temporal side of the field of vision. The bitemporal, as stated, is the
J. Grafton Love
1008
classic type of field defect. However, innumerable variations may occur. Occasionally the adenoma will break out from the sella laterally, below the internal carotid artery underneath the lateral half of the optic chiasm, and produce a homonymous visual defect to the opposite side. Occasionally the tumor will interrupt the central fibers and produce a central scotoma in one eye with or without a bitemporal defect. Early in the development of a pituitary tumor the optic disks appear normal. If pressure is not relieved at this stage, pallor of the disks occurs and later there is loss of substance of the disks; when pronounced loss of substance has occurred there is little or no hope that the visual Table 1 OCULAR MANIFESTATIONS IN A SERIES OF 314 PITUITARY TUMORS OF THE ADENOMA TYPE SURGICALLY VERIFIED AT THE CLINIC CASES VISlTAL FIELDS
I Chromo- Malig-
Total N
~e~-I
Bitemporal defects .... Blind ...... One eye. . . . . . . . . . . Both eyes .. Scotomas .. Homonymous defects. Normal fields. Choked diskst . Contraction of lid, fissure type .. ............
.
233 37 33 4 16 17 8 2
phobe Per cent adenoma 74.3 11.8 5.1 5.4 2.5 0.6
203 31 28 3 14 13 7 2
0.3
nant adenoma 12 2 2 0 2 3 1
0 0
Adenoma, mixed type
Acidophilic adenoma
14 4
4 0
3 1* 0 1 0 0
0 0 0 0
0
0
---
Total .................
314
100.0
271
20
19
4
* Bilateral choked disks. t One patient had normal fields with bilateral choked disks; the other had temporal contraction in one eye and choked disk in the other eye.
loss may be restored even though successful removal of the tumor is accomplished (table 1). Roentgenologic examination of the head in case of suspected pituitary tumor is one of the most important examinations which can be carried out. In the majority of cases of pituitary adenoma, there is either enlargement of the sella turcica or enlargement and erosion. In many cases there is in addition to the enlargement and erosion evidence of extrasellar extension of the tumor. However, occasionally one will encounter a pituitary tumor with a perfectly normal sella as shown by the roentgenogram. In a study of 314 surgically verified pituitary adenomas at the Clinic, it was found that the sella turcica, by roentgenray examination, was normal in 12 of the cases; so, one would be forced
..
' " Diagnosis and Treatment of Pituitary Tumors
1009
to conclude from this that in a given patient showing symptoms and signs of dyspituitarism with a bitemporal visual defect one should not hesitate to make a diagnosis of a tumor involving the pituitary gland. In the case of pituitary adamantinomas, in addition to erosion or enlargement of the sella turcica there is often calcification either within the sella turcica or most often above and behind the posterior clinoid processes. In a review of 108 cases of craniopharyngioma, Mar-
Fig. 307. Brow-up ventriculogram in the case of a 30-year-old woman who was semistuporous with bilateral edema of the optic disks of 2 to 3 diopters and relative bitemporal hemianopsia. Her chief complaint was headache of two months' duration. There is symmetrical hydrocephalus with only a crescent of the upper portion of the third ventricle visible owing to a large chromophobe adenoma of the pituitary body which extends up into the third ventricle and is blocking the escape of cerebrospinal fluid.
shall and I found that calcification was observed in only 50 per cent of the cases, an incidence which is much lower than that usually recorded. Again, it was of interest that in 26 cases the roentgenograms of the skull revealed no calcification about, nor erosion or enlargement of, the sella turcica. Other aids to be considered in the diagnosis of pituitary tumors include the electro-encephalogram. In my experience this diagnostic instrument is of little or no value in the diagnosis of a pituitary tumor and probably rarely is indicated when this condition is suspected.Pneumoencephalography likewise. in my experience, is of little or no value in
1010
J. Grafton Love
the diagnosis of the ordinary pituitary tumor. In an occasional bizarre case, particularly if there is a homonymous field defect, pneumo-encephalography may be employed to exclude a lesion of the temporal lobe. or a lesion interfering with the visual apparatus because of pressure on the optic radiations posterior to the optic tract. In an occasional case of pituitary tumor in which there are choked. disks but absence of endocrine, ophthalmologic-that is, bitemporal hemianopsia-and roentgenologic changes, ventriculography may be required to show the presence of an adenoma encroaching upon the floor of the third ventricle and producing internal hydrocephalus and choked disks (fig. 307). Carotid angiography may be of value in an occasional case of pituitary tumor. The type of case in which it is apt to be of benefit is that of pituitary tumor in which the adenoma has broken out of the sella laterally and produced a homonymous or other more or less atypical field defect plus palsy of the third cranial nerve. In such a case angiography would serve to distinguish a pituitary tumor from an aneurysm of the circle of Willis or of the internal carotid artery. Radioisotopes are being extensively investigated for their use in the diagnosis and localization of intracranial neoplasms. Whether or not they will increase the accuracy of diagnosis of pituitary tumors and serve to distinguish pituitary tumors from other chiasmal lesions remains to be seen. The record of . a typical case of pituitary tumor has been abstracted to indicate the methods used in the diagnosis and surgical treatment of a pituitary tumor. A man 43 years of age came to the Clinic with a history of visual difficulties of only three or four weeks' duration. At the onset he noted that 3-digit numbers would appear as 5 or 6-digit numbers. One week before the patient came to the Clinic, an ophthalmologist charted his visual fields and recommended a neurologic examination. The patient denied difficulty in seeing to either side, but in retrospect he recalled that on several occasions in the past year he had driven his car onto the curb when turning to the right (fig. 308). He had also had vague headaches off and on for a year. During the preceding three weeks, the headaches had increased in frequency. The patient was 5 feet 6 inches tall and weighed 169~ pounds stripped. His blood pressure was 148 mm. of mercury systolic and 92 mm. diastolic. His appearance was somewhat waxy. His thyroid gland was barely palpable. There was normal axillary and pubic hair. His testes were small and soft. The results of neurologic examination were normal except for the findings referable to the eyes. Examination of the eyes revealed the central vision to be 6/60 in the right eye and 2/60 in the left eye with correction. There was pallor, grade 1, of the temporal sector of both disks (graded on a basis of 1 to 4). The patient was myopic by about 5 diopters. Narrowing of the retinal arterioles was graded 1 plus to 2, and there was hypertensive sclerosis, grade 1. There was a small hemorrhage below the left disk. On plotting the visual fields it was found that the patient had bitemporal hemianopsia (fig. 308) indicative of compression
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Pre-operative Nov. 7,1951
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Post-ope~a.tive Date:
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Fig. 308. Preoperative and postoperative fields of vision in the case reported, showing the rapid and excellent recovery of vision following the removal of a pituitary tumor. of the optic chiasm. Roentgenographic examination of the head disclosed marked enlargement and erosion of the sella turcica (fig. 309). The laboratory findings prior to operation follow: The urine had a specific
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gravity of 1.017, the reaction was acid, there was grade 1 albuminuria, sugar was absent, and there was grade 3 erythruria (graded on a basis of 1 to 5). The presence of red cells in the urine was due to the fact that there was a ureteral calculus in the lower of duplicated ureters on the right side. The concentration of blood urea was 34 mg. and of blood sugar, 86 mg. per 100 cc. The value for chlorides was 98.8 mEq. and for carbon dioxide 28 mEq. per liter. The Kolmer, Kline, Hinton and Kahn reactions were all negative. The sedimentation rate was 45 mm. in one hour (Westergren method). This elevation of rate probably was due to an incipient head cold, which necessitated the postponement of surgical removal of the pituitary tumor for one week. The value for hemo-
Fig. 309. Lateral roentgenogram of head of patient in the case reported, showing marked enlargement and erosion of the sella turcica by a chromophobe adenoma of the pituitary gland. globin was 12.8 gm. per 100 cc. of blood and the leukocyte count was 7,600 per cubic millimeter. Other values were as follows: blood calcium 9.8 mg. and phosphates 4.2 mg. per 100 cc., sodium 130 mEq. and potassium 4.0 mEq. per liter, 17-ketosteroids 3.9 mg. in twenty-four hours, and corticosteroids 0.61 mg. in twenty-four hours. The urine was negative for estrogen and the value for pituitary gonadotropin was normal. The cell volume was 42 per cent. The basal metabolic rate was - 6. A diagnosis of pituitary tumor was made and surgical removal of the tumor was advised. The patient was admitted to the hospital for preoperative preparation with cortisone. On November 24, 1951, with the patient under open drop ether given over the end of an intratracheal tube, a right transfrontal craniotomy was performed with intracapsular removal of a pituitary tumor and extensive resection of the capsule. During the course of the operation 500 cc. of blood was given by transfusion. This is a routine procedure on my service. The tumor was a large
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blue-domed mass which presented between the optic nerves anterior to the optic chiasm. There was no cystic fluid within the tumor. The capsule was opened in a cruciate fashion and a large amount of adenomatous tissue was removed. After removal of all the adenomatous tissue within the capsule, the capsule itself was resected to the floor of the sella turcica thus removing all pressure from the optic nerves and chiasm. The tissue removed was reported by the pathologist as being that of a chromophobe adenoma, the pieces aggregating 2 cm. in diameter. A good portion of the tumor was removed with the sucker and was therefore not available to the pathologist. The day following operation the patient was alert and he was able to read the name and address written with an ordinary typewriter on an envelope. Immediately following operation the patient's temperature went to 101.50 F., then gradually declined and his convalescence was uneventful except for symptoms of diabetes insipidus. . The day of operation the intake of fluid was 1,240 ce., with the urinary output at 650 cc. The next day the urinary output was 4,500 cc. and the intake of fluid was 2,500 cc. The next day 2,000 cc. of urine was voided, the intake of fluid being 3,750 cc. The increased intake and output gradually decreased so that by the ninth postoperative day the intake and output were normal without the administration of posterior pituitary powder. During the period of clinical diabetes insipidus, the specific gravity of the urine was 1.001; when the symptoms of diabetes insipidus had subsided the specific gravity of the urine increased to 1.008. During the period of diabetes insipidus the values for blood sodium, chlorides and carbon dioxide remained normal. This patient received 100 mg. of cortisone intramuscularly the day before operation and the morning of the day of operation. He then received cortisone intramuscularly in a dose of 50 mg. a day for three days and in a dose of 25 mg. a day for an additional four days. It is our practice at present to use cortisone for all patients who. are to undergo an operation for a pituitary tumor. It is hoped that its use will fortify the patient for the operation and support him during the immediate postoperative period. Our experience at the Clinic has not been great enough nor has it extended over a long enough period to permit us to state just exactly how beneficial cortisone is in the therapy of patients operated on for a pituitary tumor. At the time of dismissal, the patient had shown marked improvement in vision (fig. 308) and generally his condition was excellent. SURGICAL PROCEDURE FOR REMOVAL OF A PITUITARY TUMOR
Early in the history of removal of pituitary tumors the transsphenoidal route was often employed. Later the transcranial or intracranial approach gained favor and was the method of choice. More recently some surgeons have adopted the transsphenoidal route for those lesions producing a large sella turcca and not appearing to have extended upward beyond the confines of the sella. It is considered particularly applicable for cystic lesions. (Unfortunately there is no sure way short of exposure of the lesion to determine when an adenoma of the pituitary is cystic, and probably no more than 10 to 20 per cent are cystic.) The intracranial approach is preferred at the Clinic. Classically we employ a right transfrontal type of craniotomy (fig. 310) and proceed extradurally to the wing of the sphenoid; then we open the dura mater
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along the sphenoid ridge and proceed to the midline anteriorly and upward parallel to the falx cerebri. This provides a flap of dura mater for protection of the frontal pole of the cerebral hemisphere which must, be elevated to expose the sella turcica and adjacent structures, namely, the optic"nerves, chiasm, internal carotid arteries and the tumor. Some surgeons -prefer the intradural approach. They reflect a flap of dura
Fig. 310. Artist's drawing of the classic transfrontal flap used for removal of pituitary tumors and other lesions about the optic chiasm. The scalp is reflected forward and the bone attached to the temporal muscle and periosteum is reflected laterally. The five holes are made with an Adson or McKenzie perforator (burr is not used) and thus when the flap is healed there are no unsightly depressions even though the holes are not filled with anything such as tantalum or bone dust.
mater along the limits of the craniotomy and proceed over the exposed cerebral hemisphere to the chiasmal region. My experience with the intradural approach was not as satisfactory as with the extradural subfrontal route. When the fluid at the base of the brain has been removed with the sucker, exposure of the visual apparatus usually is easy. The pituitary tumor, as stated previously, usually presents anterior to the optic chiasm and between the optic nerves. The capsule of the tumor should be perforated with a small spinal puncture needle attached to a syringe by means of a flexible rubber tube. This is done (1) to determine whether
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the tumor is cystic and if so to collect the fluid for study and to prevent its irritating effect on the brain should it escape, and (2) to exclude an aneurysm. The next step is to coagulate the capsular vessels with the electrosurgical unit. The capsule is then opened in a cruciate fashion with a sharp ureteral knife. The contents of the capsule are then removed by means of punches, pituitary forceps, gallbladder scoop and sucker. It is essential to remove any adenomatous tissue that may be beneath the optic nerves and chiasm or that· may extend posteriorly toward the cerebral peduncles. To remove the midline suprasellar and intrasellar tissue alone is insufficient. After the adenomatous tissue has been removed, the capsule should be gently teased free and resected to the floor of the sella turcica. It is essential to avoid trauma to the optic nerves and chiasm. When hemostasis is cemplete, the wound should be closed in layers. A drain mayor may not be used. It is my feeling that a Penrose cigarette drain placed beneath the frontal lobe and brought out the posterior limb of the flap and left for 24 to 48 hours prevents excess swelling of the eyelids on the side of the flap and allows the bloody cerebrospinal fluid to escape, thus preventing the chemical meningismus from broken-down blood which is .apt to occur postoperatively. The postoperative course is usually smooth and uneventful if the operation has not been delayed too long. With a large tumor that has extended beyond the sella turcica and with a tumor that involves the third ventricle the postoperative course may be very stormy and the nursing problem may be difficult. For temperatures of 103°F. or higher, the oxygen tent with its temperature held at 70°F. is very useful. Ice bags to the axillae and groips are also used. Aspirin, grains 10, and aminopyrine (pyramidon), grains 7!, may be given by mouth if the patient is able to take them in this manner; otherwise they may be given by rectum. These may be repeated every four hours for several doses but should not be given over a period of days. It is essential to keep up the intake of fluid and to maintain the electrolyte balance. Some patients have diabetes insipidus in the immediate postoperative period, as in the case reported herein (some, of course, have the disease prior to operation) and it is my practice to let them consume as much fluid as they desire provided there is adequate urinary output. The condition usually rights itself within a period of several days. If it should be unduly prolonged or if the patient is getting inadequate rest because of the ingestion of fluids or the passing of urine, then nasal insufHation of posterior pituitary powder is indicated. The patients are allowed to be ambulatory as soon as they feel like it. The time at which ambulation starts varies from a few hours to several days after operation. It has been reported by some authors that the routine postoperative
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use of roentgen-ray therapy to the region of the sella turcica gives an improved long-term result and decreases the· chances of recurrence of the pituitary tumor. My colleagues and I follow the policy of advising radiation therapy only when we have been unable to do as thorough removal of the tumor as we desire or when the pathologist reports the tumor as being unusually active or malignant. Patients harboring such tumors must be followed closely for the appearance of symptoms or signs of recurrence. Periodic determination of the fields of vision will usually indicate progressive reduction of the patient's vision if there is recurrence of the tumor. If recurrence is going to take place, it usually will manifest itself within the first five years following surgical removal of the tumor. REFERENCES 1. Cushing, Harvey: Papers Relating to the Pituitary Body, Hypothalamus and Parasympathetic Nervous System. Springfield, Illinois, Charles C Thomas, 1932, 234 pp. 2. Frohlich, A.: Ein Fall von Tumor der Hypophysis cerebri ohne Akromegalie. Wien. klin. Rundschau. 15: 883-886; 906-908, 1901. 3. Krause, F.: Hirnchirurgie. Deutsche Klin. 8: 953-1024,1904. 4. Love, J. G. and Marshall, T. M.: Craniopharyngiomas (Pituitary Adamantinomas). Surg., Gynec. & Obst. 90: 591-601 (May) 1950. 5. Marie, Pierre: Sur deux cas d'acromegalie; hypertrophie singuliere noncongenitale des extremites superieures, inferieures et cephalique. Rev. de med., Paris. 6: 297~333, 1886.