Journal of Neuro-Ophthalmology, September 1985, Volume 5, Issue 3

Third nerve palsy: the presenting sign of a pituitary adenoma in five patients and the only neurological sign in four patients.

Five male patients sought medical attention for diplopia and were found to have third nerve palsies secondary to pituitary adenomas. In four cases this was the only neurologic abnormality. In the fifth there was an additional, asymptomatic, temporal visual field defect in one eye. Partial third nerve involvement was seen in all but one patient. Four patients underwent successful surgery and were found to have chromophobe adenomas. One patient had clinical and laboratory evidence of Cushing's syndrome. An initial diagnosis of cerebral aneurysm was made in three cases when the third nerve palsy followed a severe, acute headache. Later it became evident that pituitary apoplexy was the correct diagnosis. The mechanisms by which a pituitary adenoma causes a third nerve palsy are discussed. The importance of recognizing a pituitary tumor as the etiology of an isolated third nerve palsy is emphasized.

f. Clipl. NCllrll-opiltilalll/ol. 5: 1R5-193, 1985 (1) 1985 Raven Press, New York Third Nerve Palsy: The Presenting Sign of a Pituitary Adenoma in Five Patients and the Only Neurological Sign in Four Patients ROBERT F. SAUL, M.D. JAN K. HILLIKER, M.D. Abstract Five male patients sought medical attention for di­plopia and were found to have third nerve palsies secondary to pituitary adenomas. In four cases this was the only neurologic abnormality. In the fifth there was an additional, asymptomatic, temporal visual field defect in one eye. Partial third nerve involvement was seen in all but one patient. Four patients underwent successful surgery and were found to have chromophobe adenomas. One pa­tient had clinical and laboratory evidence of Cush­ing's syndrome. An initial diagnosis of cerebral aneurysm was made in three cases when the third nerve palsy followed a severe, acute headache. Later it became evident that pituitary apoplexy was the correct diagnosis. The mechanisms by which a pituitary adenoma causes a third nerve palsy are discussed. The importance of recognizing a pitu­itary tumor as the etiology of an isolated third nerve palsy is emphasized. Neurologically, pituitary tumors most com­monly produce visual field defects initially and cause ophthalmoplegia only late in their courSe. It was onCe assumed that if a patient with a pituitary tumor developed ocular nerve palsies, then the tumor was an aggressive one invading the cavernous sinus and thus the prognosis poor. Also, a sudden ophthalmoplegia in a pa­tient having a pituitary tumor usually implied an acute hemorrhage, which carried an equally poor prognosis. Francois and Neetens l felt that an early ophthalmoplegia with no visual defect implied a good prognosis. But if the reverse oc- From the Neuro-Ophthalmology Section, Departments of Neurology and Ophthalmology, Geisinger Ml'dical Center, Danville, Pennsylvania. . . Write for reprints to: R. F. Saul, M.D., 14-U5 Geisinger Medical Center, Danville, PA 17822, U.S.A. September 1985 curred, i.e., the ophthalmoplegia following the visual field defect, the prognosis was worse. The latter situation is more common; the former theory has become accepted. We examined five patients who presented with third nerve palsies and who have done well; we agree with the assumptions of Francois and Neetens. Case 1 A 78-year-old man developed acute, severe, right superior orbital pain that was followed in 48 h by diplopia and complete ptosis of the right eyelid. The pain resolved, and he \·vas admitted to the hospital 1 week after the incident. A myo­cardial infarction 13 years previously and a left cerebral infarction 8 years after that constituted his past medical history. He was neither dia~ betic nor hypertensive. There was no history ot head trauma or endocrine dysfunction. He de­nied visual loss. Neuro-ophthalmic examination showed normal funduscopy, visual fields, and color vi­sion. Visual acuity was 20/30 in the right e~'e and 20/25 in the left eye. The pupils measured 4 mm on the right, with a sluggish reaction to direct light, and 3 mm on the left, with a normal reaction to light. There was complete ptosis and paralysis of all the other muscles innervated by the right third nerve. All other oculomotor nerves functioned normally. Corneal sensitivity and facial sensation were normal bilaterallv. An aneurysm was the initial suspected diagnosis, but skull roentgenograms showed an enlarged, eroded sella turcica (Fig. 1). A computerized to­mographic (CT) scan showed a contrast-en­hancing mass in the sella extending into the right cavernous sinus (Fig. 2). Cerebral arteri­ography confirmed an avascular, intrasellar mass with right lateral extension. Endocrine studies revealed evidence of anterior pituitary dysfunction. Prolactin level was normal. Sur- 185 Third Nerve Palsy Figure 1. Lateral skull roentgenogram showing enlarged, eroded sella turcica in case 1. Figure 2. CT scan showin~ a contrast-enhancing mass in the sella extending into the right cavernous sinus in case 1. gery was not done, and the patient was placed on bromocriptine and monitored. In 2 months, the third nerve palsy cleared. Sixteen months later, the patient was asymptomatic, although the CT scan was unchanged. Case 2 A 28-year-old male truck driver experienced an acute, excruciating, bifrontal headache, di- 186 plopia, and complete ptosis of the right eyelid within the following 24 h. He drove cross­country from New Mexico to our hospital in Pennsvlvania where he was admitted with the presumptive diagnosis of cerebral aneurysm. The patient was an obese man with adult-onset diabetes mellitus and hypertension for which he was taking Orinase and Dyazide, respectively. He smoked and drank heavily. He denied any visual loss, symptl)ms of endocrine dysfunc­tion, or head trauma. Neuro-ophthalmic examination showed a vi­sual acuity of 20'20-1 in each eve, with normal color visi'on, funduscopy, and visual fields. There was a complete right third nerve palsy with a 7-mm unreactive pupil (Fig. 3). Other­wise, ocular motility and trigeminal function were normal. The CT scan confirmed an intra­sellar mass with some extension into the right cavernous sinus area. Cerebral arteriography was normal. A cerebrospinal tluid examination showed no cells, a protein of 70 mg%, and a hlucose level of 108 mg'7c. The patient initially refused surgery, and the third nerve palsy resolved in 1 month. Two months after the initial presentation, through a transsphenoidal approach, a chromophobe ad­enoma was removed. No hemorrhage or ne­crosis was seen pathologically in the tumor sec­tions. Initial preoperative endocrine studies Journal of Clinical Neuro-ophthalmology Figure 3. Pati,'nt ((.l~" ~) with right third nerve pals\'. Saul, Hilliker suggested decreased thyroid and gonadal func­tion. These studies had returned to normal the day before surgerv. The patient has remained asymptomatic. Case 3 A 58-year-old man complained of 8 months of horizontal double vision in right gaze. His wife noted occasional drooping of the left eyelid. Myasthenia gravis was the initial diag­nosis by another physician. A second examiner felt that he had a partial left third nerve palsy that was caused by fibrous dysplasia of the left superior orbital fissure as seen on skull roent­genography and CT scan. There had been no improvement in his diplopia and he sought fur­ther consultation. There was no history of accompanying pain or visual loss. Head trauma was denied. Hy­pertension had been present for 15 years. He noted some increasing redness to his facial com­plexion in the last year, but there were no clear symptoms of endocrine dysfunction. Neuro-ophthalmic examination now showed a visual acuity of 20/20 in each eye, and normal color vision and visual fields. There was no fifth nerve dysfunction. A partial left third nerve palsy was manifest by decreased elevation, depression, and adduction of the left eye. There was no ptosis and the pupils were equal, with normal reaction to light and accommodation. The remainder of the ocular motility was normal. A CT scan of the brain showed a con­trast- enhancing lesion in the sella with left lat­eral extension (Fig. 4). Tomography of the sella confirmed thinning of the floor and the left an­terior clinoid. Cerebral arteriography showed September 1985 atherosclerotic narrowing of the left carotid si­phon only. A left frontal craniotomy was per­formed to explore the superior orbital fissure and cavernous sinus. No fibrous dysplasia was found in the superior orbital fissure, and no tumor was seen in the suprasellar area. The third nerve was identified just proximal to the superior orbital fissure, and was noted to be gray and atrophic in appearance. It was decided to close and consider trans-sphenoidal surgery later. The patient was monitored for 2 months. An impaired dexamethasone suppression test and an elevated 24-h urine cortisol leveL followed by a full endocrinological evaluation, led to a diagnosis of Cushing's syndrome. Trans-sphen­oidal surgery was performed and a large chrom­ophobe adenoma removed. There has been some improvement of the third nerve palsy 3 months after surgery. Case 4 A 41-year-old man was admitted to another hospital with acute onset of fever, headache, and vomiting. Several days later, he awakened with diplopia and ptosis of his left eyelid. An ophthalmologist diagnosed a left third nerve palsy and suspected a cerebral aneurysm. The CT scan, however, showed a large intrasellar mass. The patient denied any visual loss. He felt that his body hair had become sparse, but de­nied any other endocrine symptoms. Examina­tion showed an alert patient with marfanoid fea­tures. Visual acuity was 20/200 in the right eye and 20/40 in the left eye with significant poste­rior, subcapsular cataract. There were posterior 187 Third Nerve Palsy (a) (b) Figure 4. CT scans showing contrast-enhancing lesion in the sella with left lateral extension in case 3. (a): Axial view showing tumor extending into left cavernous sinus. (bi Cor­onal view of same. synechiae in the right eye and keratic precipi­tates in the left eye, indicating previous uveitis of unknown etiology. The pupils measured 2.5 mm on the right and 3.5 mm on the left, with decreased direct light reaction in the left eye. No afferent defect was present. Visual fields were full. Funduscopic examination showed no optic nerve pallor but significant inferior cres­cents bilaterally. There was no fifth nerve dys­function. Complete paralysis of adduction, ele­vation, and depression was noted in the left eye, along with 3 mm of ptosis on that side. The remainder of the ocular motility was normal bi­laterally. The CT scan and subsequent cerebral arteri­ography showed an intrasellar, avascular mass with left lateral extension. Endocrine studies re­vealed evidence of panhypopituitarism without diabetes insipidus. A chromophobe adenoma was found at surgery with microscopic evidence of ischemic infarction of the tumor (Fig. 5). The patient's ocular motility returned to normal 2112 months after surgery. Case 5 A 35-year-old man developed sudden hori­zontal diplopia one day v."hile driving his au­tomobile. His wife noted that the right eyelid drooped. The patient had been involved in a minor rear-end automobile accident 2 weeks earlier with no apparent head or neck injury. He had noted some mild, right-sided, throbbing headaches for 1 year. There was no history of endocrine dysfunction. The diplopia gradually worsened, causing him to seek medical advice 0' ... , , '0 ,.. t},. ~.': .... 'It. . ­• 0 :.~ .. :., ~.,. .~~!.~; .. -.....: : f· " • Figure 5. Pathological specimen in case 4 showing infarction of the pituitary tumor. a: Low magnification (x 106). b: HIgh magnIficatIOn (x 266). Note pale, poorly staInIng cells indicative of ischemic infarction. lal 188 Journal of Clinical Neuro-ophthalmology 4 months into his illness. Visual loss was de­nied. Neuro-ophthalmic examination shl)wed a vi­sual acuity of 20/20-2 in the right eye and 20/15­1 in the left eve, with normal l'olor vision bil,lt­erally. There 'was qUt'stionablt' temporal pallor of the right optil' nerve with a 1+ afferent pu­pillary defect. A subtle right temporal visual field defect was found on pt'rimetrv. The ldt visual field was normal. Fifth nerve function was intact bilaterall~'. The patient had an ob­vious partial right third nerw palsv with paresis of adduction, elevation, and depression. A mild ptosis of the right eyelid was noted. The pupils measured 3 mm on the right and 2.5 mm on the left. The remainder of the l1ClIlar motility was normal bilaterally. Skull roentgenograms 'and a CT scan confirmed a huge intrasellar mass ex­tending superiorl~', inferiorly, and laterally to the right (Figs. 6 and 7). Cerebral arteriography confirmed the mass and the absence of an an­eurvsm. All endocrine studies were normal. Trans-sphenoidal surgery revealed a large chromophobe adenoma with no evidence of hemorrhage or necrosis. Within 1 month, the patient's ocular motility returned to normal and there was no visual field defect to be found on examination. Saul, Hilliker Summary All five of our patients sought initial medical advice for diplopia. Four had isolated third nerve palsies. The fifth (case 5) had a minimal asymptomatic temporal visual field defect in one eye in addition to the partial oculomotor palsy. Four had partial paralysis of the third nerve, while only case 2 had involvement of the entire nerve. All five were men between the ages of 28 and 78 years. Three presented with probable pituitary apoplexy, complaining of se­vere headaches followed shortly by diplopia, which was initially diagnosed as an aneurysm. Interestingly, two patients' diplopia resolved without or before surgery (cases 1 and 2, re­spectively). Two patients' diplopia resolved fol­lowing surgery, and one patient's diplopia is still improving. Chromophobe adenoma was found at surgery in four patients, although one adenoma caused Cushing's syndrome. In the fifth case (case 1) there was substantial radio­logic and endocrinologic evidence to indicate the same pathology. In the four who underwent surgery, no pathological evidence of hemor­rhage was found. Computed tomography in all five cases failed to reveal any evidence of hem­orrhage in the acute stage. Ischemic infarction Figure 6. Lateral skull roentgen­ogram showing large, eroded sella extending into the sphenoid sinus in case 5. September 1985 189 Third Nerw Paby Figure 7. CT scan showing huge intrasellar mass extending superiorly, inferiorly, and laterally to the right (R) in case 5. was diagnosed pathologically in case 4, but there was no evidence of ischemic infarction in any of the others examined surgically. How­ever, the clinical presentation clearly favors pi­tuitary apoplexy in two cases (cases 1 and 2), and the entire surgical pathology was not ex­amined microscopically in them. Miller and Moses2 reported the case of a hy­pertensive patient with a complete third nerve palsy who was taking thiazide diuretics that caused glucose intolerance. Though osmotic shifts may have helped cause the acute syn­drome in our one patient who was a poorly con­trolled diabetic taking thiazides (case 1), we do not feel this was the etiology of his third nerve palsy. Discussion Pituitary adenomas comprise approximately 8% of all intracranial neoplasms. This figure is probably too low if we account for the asymp­tomatic microadenomas found at autopsy. Loss of vision is often the earliest and most common 190 neurologic manifestation of the macroa?en­omas. It is reported that nearly 100% of patients treated for chromophobe adenomas WIll have visual loss.3 In Cushing's series, tumor-related visual loss was found in 243 of 247 patients with chromophobe adenoma. 4 • Ocular nerve palsy is less common but IS re­ported in 5-17('k of patients with pituitary tu­mors. 3 Even less common are the patients who present with an isolated ocular nerve palsy. In the last 4 years, we have examined 40 patients with pituitary macroadeno~as,and only one. of them, in addition to the ftve reported he~em, had an ocular palsy (a sixth nerve palsy WIth a concomitant visual field defect). _ Though reported in 1940 by Weinberger et aP and re-emphasized by others, 1,6-15 we f~el one should include pituitary tumor 10 the dlffer~n­tial diagnosis for any patient who pre.sents WIth a third nerve palsy. We also feel that It does not necessarily carry a grave prognosi~. . Foix is given credit for first calhng attention to paralysis of the oculomotor ~erves as an early sign of a pituitary adenoma." Most cases re­ported in the literature are chromophobe ad­enomas and most involve more than one ocular nerve. Review of these papers reveals about 20 cases of isolated third nerve palsy, but the_ Vi: sual fields are not alwavs included. 1,~-1J Rucker, If>. I7 in two isolated studies, each of 1,000 patients with extraocular muscle pa~sies, found a total of 28 patients with a pItUItary tumor and an isolated third nerve palsy. How­ever, he did not mention the \'isual fields. The third nerve pals~' was complete in only one of our cases. This is a distinguishing fea­ture, as compared with the usually complete pa­ralvsis seen with an aneurysm. A complete palsy generall~' was accepted 'as evidence of pe­ripheral paralysis until Cogan called atten~on to the incomplete involvement of the thud nerve in cavernous sinus lesions. 18 This is dem­onstrated in our patients. The mechanism causing such paralysis has long been debated. Trumble19 has provided a most eloquent and interesting description of his observations on large tumors spreadin§ beyond the confines of the sella turcica. Walshl felt that the oculomotor palsy was due to an expanding tumor transmitting pressure on the wall of the cavernous sinus. Symonds,6 Cairns,? and Jefferson'l believed that the oculomotor nerve was damaged at its point of entry into the cav­ernous sinus, being compressed between the tumor and the interclinoid ligament. Jefferson9 felt that a finger of tumor would break through the wall of the cavernous sinus and primarily compress the nerve. He also stated that a cranial JO"Jrnal of Clinical Neuro-ophthalmology nerve is capable of great stretching and deflec­tion, before clinical symptoms til-wlop. Cushing211 noted that the fifth and the sl'vl'nth ~ranial nerves could be stretched approximately tour times their normal length around ,1il acoustic tumor and still maintain function. Thus, tlattening and Itmgthening of the nerve, until function suddenly falters, explains thl:' acute diplopia from a slowly growing lesion but still does not explain the acute headache and why the third nerve alone was affected in three of our cases. These three patients p[l'bablv developed an acute ischemic infarctitm of their tumors. With acute ischemic infarction, rapid swelling caused compression of the cavernous sinus, resulting in the acute headache and third nerve palsies. Because the pain and ophthalmoplegia were so similar to that seen in patients with posterior communicating arter~' aneurysms, this was the initial diagnosis in each case. Diabetic oculo­motor palsy may also be clinically indistinguish­able from the above. Coincidental infarction of the vasa nervorum supplying the oculomotor nerve and the trigeminal fibers in the cavernous sinus is the mechanism involved in diabetic ophthalmoplegia. 21.22 Spontaneous resolu tion of the pain and ophthalmoplegia in cases 1 and 2 make compression of the vasa nervorum, and subsequent infarction of the third nerve, plau­sible. On the other hand, the sudden enlarge­ment of the mass may simply have compressed the third nerve against the interclinoid liga­ment, or against the wall of the cavernous sinus, as noted previously.6.7.9 Once the edema resolved, the oculomotor nerve decompressed spontaneously, and again functioned normally. Because the trans-sphenoidal approach was used in all of our patients who underwent sur­gery, it was impossible to tell if the cavernous sinus was compressed or invaded. The CT scans showed lateral extensions toward the cavernous area but do not clearly show if the third nerves were compressed or enveloped. Because there was spontaneous and postoperative resolution of the third nerve palsies in four patients, pri­mary compression of the nerves or of their blood supply is the most likely mechanism. The third nerve is at the same horizontal level as the pituitary gland anatomically, and it may catch most of the laterally transmitted pressure from pituitary tumors abutting the cavernous sinus. We therefore assume that slow compression is the mechanism causing the ophthalmoplegia in cases 3 and 5, although primary intracaver­nous invasion is still possible in the former. And, rapid expansion, with compression or neural infarction, caused the acute oculomotor September 1985 Saul, Hilliker paralysis in cases I, 2, and 4. Although ischemic infarction of the tumor was only pathologically proven in case 4, we feel that the clinical picture in cases I and 2 implies the same mechanism, or what is commonly referred to as pituitary apopit'xy. Pituitary apoplexy most commonly occurs be­cause of sudden hemorrhilge into an adenoma, but ischemic infarction is not infrequent and seems to be the etiology of the apoplexy in our three patients. There was no radiological or pathological evidence of hemorrhage in any of our cases. It is postulated that a tumor will out­grow its blood supply, infarct, and swell, due to rapidly developing edema 23 If the patient survives, and the edema resolves, the neurolog­ical signs and endocrine abnormalities may revert to normal. Factors predisposing patients to pituitary apoplexy include irradiation, alteration of pres­sure gradients (i.e., changes in blood pressure, or lumbar punctures), trauma, estrogens, bro­mocriptine therapy, diabetic ketoacidosis, and anticoagulants. 23 - 27 None of these factors seem to playa role in our patients. Recently, abscess, developing in primary pi­tuitary adenomas, has been shown to cause chiasmaI compression. 28 This could theoretically cause a third nerve palsy due to rapid swelling with apoplexy, or by slow expansion and com­pression. Post et al. 29,30 showed that pituitary apoplexy, either hemorrhagic or ischemic in nature, may be diagnosed by high-resolution CT scanning with and without contrast. Therefore, it is im­portant to recognize an acute isolated third nerve palsy as a sign of pituitary apoplexy and to not assume that the patient has an aneurysm. In summary, an isolated third nerve palsy may be the presenting sign of a pituitary ade­noma. It may occur slowly, secondary to me­chanical compression against the interclinoid ligament, or by compression and/or invasion of the cavernous sinus by the tumor. It rna\, occur rapidly, associated with headache, again' due to compression against the wall of the cavernous sinus and/or against the interclinoid ligament, or by compromise of the vascular supply to the nerve itself. This rapidly developing syndrome seems to be caused by a sudden edematous in­farction (as in our patients), or by a primary hemorrhage of the tumor itself, producing sec­ondary compression of the nerve or its vascular supply. Patients with pituitary tumors may therefore develop a third nerve palsy by several mechan­isms. They may also be predisposed to pitu­itary apoplexy by a number of conditions that 191 Third Nerve Palsy TABLE 1. Possible Mechanisms and Conditions Causing or Predisposing One to a Third Nerve Palsy in the Presence of a Pituitary Adenoma Ml'ch,lIlisms (',Im pression Tr,1I1smitted prl'ssure from tumor expdnsion ,lgdinst the Idtl'rdl wdllof the Cdvernous sinus 10 NerVl' compressed bt'tween interdinoid ligdment ,1I1d tumor"·7." Direct tumor inVl.1Sionlj Hemorrhdge Ischemic infarction of the tumor with secondary edemdtous expansion Abscess Ischemic infdrction of the nerve itself, due to compression of the vasa nervorum Predisposing conditions Trauma Lumbar puncture Bromocriptine Estrogens Hypertensive diabetics receiving thiazides and oral hypoglycemic agents (?) Radiation Anticoagulation ultimately lead to third nerve compromise sec­ondary to acute expansion of the tumor mass by edema or hemorrhage. These mechanisms and conditions by which one may develop or be predisposed to an oculomotor palsy in the presence of a pituitary tumor, are summarized in Table l. The clinician should be aware that an isolated third nerve palsy may be due to a pituitary ad­enoma, recognize the predisposing conditions, and identify the mechanisms that may have caused it. References 1. Francois, J., and Neetens, A.: Oculomotor paral­ysis and tumors of the pituitary gland. Conti/fia Neural, 30: 239-252, 1968. 2. Miller, N. Ro, and Moses, H.: Transient oculo­motor palsy: association with thiazide-induced glucose intolerance. I.A.M.A. 240: 1887-1888, 1978. 3. Martins, A. N.: Pituitary tumors and intrasellar cysts. In Handbook ot Clinical Neurology, Vol. 17. North Holland Publishing Company, New York, 1974, pp. 375-439. 4. German, W. J., and Flanigan, S.: Pituitary ad­enomas: a follow-up study of the Cush'ing's series. Clin. Neurosurg. 10: 72-81, 1962. 192 5. Weinberger, L. M., Adler, F. H., and Grant, F. c.: Primary pituitary adenoma and the syn­drome of the cavernous sinus: a clinical and an­atomic study. Arch. Ophthalmol. 24: 1197-1236, 1940. 6. Symonds, C. P.: Ocular palsy as the presenting symptom of pituitary adenoma. Bull. Johns Hop­kins Hasp. 111: 72-82, 1962. 7. Cairns, H. W. B.: Peripheral ocular palsies from the neurosurgical point of view. Trans. Ophthalmol. Soc. U.K. 58: 464, 1938. 8. Robert, C. M., Jr., Feigenbaum, J. A., and Stern, W. E.: Ocular palsy occurring with pituitary tu­mors. f. Neurosurg, 38: 17-19, 1973. 9. Jefferson, G.: Extrasellar extensions of pituitary adenomas. Proc R. Soc. Med. 33: 433-458, 1940. 10. Walsh, F. S.: Bilateral total ophthalmoplegia with adenoma of the pituitary gland: report of two cases; an anatomic study. Arch. Ophthalmol. 42: 646-654, 1949. 11. Neetens, A., and Selosse, P.: Oculomotor anom­alies in sellar and parasellar pathology. Ophthal­molo.;; ica 175: 80-104,1977. 12. Cha'mlin, M., Davidoff, L. M., and Feiring, E. H.: Ophthalmological changes producing pi­tuitary tumors. Am. f. Ophthalmol. 40: 353-368, 1955. 13. Meadows, S. P.: L'nusual clinical features and modes of presentation in pituitary adenoma, in­cluding pituitary apoplexy. In Neuro-ophthal­mology, J. L. Smith, Ed. C.V. Mosby Co., SI. Louis, 1968, pp. 178-189. 14. Lvle, T. K., and Clover, P.: Ocular symptoms and signs in pituitary tumours. Proc. R. 'Soc. Med. 54: 611-619, 1961. 15. Kearns, T. P., Salassa, K M., Kernohan, J. W., and MacCartv, C. S.: Ocular manifestations of pituitary tumor in Cushing's syndrome. Arch. Opilthallllol. 62: 2-12-2-17, 1959. 16. Rucker, C. W: Paralysis of the third, fourth and sixth cranial nerves. '..1111. f. Ophthallllol. 46: 787­79- 1, 1958. 17. Rucker, C. W.: The causes of paralysis of the third, fourth and sixth cranial nerves. Am. f. 0l'htl1<llllll11. 61: 1293-1298, 1966. 18. Cogan, D. G.: Neurolog~1 ot the Ocular Muscles (2nd ed.). Charles C Thomas, Springfield, IL, 1977, pp.5-1-73. 19. Trumble, H. c.: Observations on large tumours which have spread widely beyond the confines of the sella turcica. Br. 1. Surg. 39: 7-24,1951. 20. Cushing, H.: Tumours of the Nen'us Acusticus and the Syndrollle ot the Cerebellopontine Angle. W.B. Saunders Co., Philadelphia, 1917, p. 190. 21. Goldstein, J. E., and Cogan, D. G.: Diabetic oph­thalmoplegia with special reference to the pupil. Arch. OphthalHlLl1. 64: 592-600, 1960. 22. Asbury, A. K., Aldredge, H., Hershburg, K, and Fisher, C. M.: Oculomotor palsy in diabetes mel­litus: a clinical pathological study. Brain 93: 555­566, 1970. 23. Cardoso, E. R., and Peterson, E. W.: Pituitary apoplexy: a review. Neurosurgery 14: 363-373, 1984. 24. Rovit, R. L., and Fein, J. M.: Pituitary apoplexy: Journal of Clinical NeuTo-ophthalmology a review and reappraisal. I. NCI/I'tl~/I"S. 37: :?HO­282, 1972. 25. Weisberg, L. A.: Pituitarv ,1poplexy: ,1ssoci,ltillll of degenerativl' l'hange in pituit.HV ,1 d l'tW III ,1 with radiotherapv ,1nd detl'l'tion bv l'erl'br,ll Clllll­puted tOlllography. Alii. I. Ivied. 63: llllJ- lIS, 1977. :?6. Rengal'h,u\', S. S., Tlllllit,l, T.,ldfrks, H. r., ,1Ild Watanabe, I.: Strul'tur,ll l'hangl's in Illllll,1I1 pi­tuitar\' tumors <liter brnllllll"riptil1l' tl1l'r,lpv. NCI/­rosllr" t'n/ 10: :?-l:?-:?51, 19H:?. 27. Nou~izadeh, A. R., and Pitts. F. W.: Hemor- September 1985 Saul, Hilliker rhagl' into pituitary adenoma during anticoagu­lant therapy. lAMA 193: 623-625, 1965. :?H. Domingue, J. N., and Wilson, C. B.: Pituitary ab­Sl'l'SSeS: report of seven cases and review of the IiteraturL'. /. NCI/rosurg. 46: 601-608, 1977. :?9. Post, M. J. D., David, N. J., Glaser, J. S., and Safran, A.: Pituitary apoplexy: diagnosis by com­puted tomography. I<adiology 134: 665-670,1980. 30. Post, M. J. D., Jnd David, N. J.: Pituitary apo­plexy: radiographic-clinical correlation. In Nel/ro­Ophtlwllllology Focus, 1982, J. L. Smith, Ed., Masson, New York, 1982, pp. 177-221. 193