Journal of Neurology, Neurosurgery, and Psychiatry, 1973, 36, 1063-1068

Hydrocephalus complicating pituitary adenomaH. A. SHENKIN AND J. N. CROWLEY

From the Department of Neurosurgery, Episcopal Hospital,Philadelphia, Peinnsylvaniia, U.S.A.

SUMMARY Hydrocephalus complicated the clinical course of four patients with pituitary adenoma.In three it was noted late, long after surgical intervention and radiotherapy had been carried out. Inone patient, hydrocephalus was part of the presenting syndrome. The differential diagnosis ofhypopituitarism and occult hydrocephalus is difficult. The possibility of hydrocephalus complicatinga pituitary adenoma constitutes another indication for arteriography before carrying out definitivetreatment, or should the clinical course be unsatisfactory at any time.

Hydrocephalus in adults as a complication ofneurological entities, such as subarachnoidhaemorrhage, has been increasingly remarkedupon in recent years. Its occurrence even withoutincreased intracranial pressure or a clearlyunderstood aetiology has provided us with a newneurological syndrome, so-called occult or lowpressure hydrocephalus. Undoubtedly, theavailability of an effective treatment, the variousshunting procedures utilizing a unidirectional

valve, has spurred its recognition in these variouscircumstances.The occasional occurrence of hydrocephalus

in the presence of a pituitary tumour has beenmentioned in the past (Pancoast et al., 1940;Davidoff and Epstein, 1955; Dandy, 1969).However, in the recent literature it has beenalluded to only infrequently and only passingmention of its specific therapeutic implicationshas been made (Stern and Batzdorf, 1970). Four

FIG. 1. Case I (J.K.) Ventriculogram. A-P and lateral views demonstrating enlarged ventricles and lack ofvisualization of third ventricle. Pericallosal antgle is relatively acute (A-P view), further suggesting obstructivehydrocephalus.

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such patients have been encountered in the pastseven years and are the subject of this report.

CASE 1

J.K., a 50 year old woman, was examined in 1956,with a progressive history of tiring easily andsomnolence over a period of two months. She had aright homonymous hemianopia with normal visualacuity and a generally enlarged sella turcica with theanterior clinoid processes preserved and the dorsumdestroyed. Her serum protein-bound iodine (PBI)was 6 mg/100 ml. and the 24 hour urinary 17-ketosteroid excretion was 24-4 mg. Ventriculographyrevealed no increase of intracranial pressure andnormal ventricles except for some distortion of theleft temporal horn. Exploration of the optic chiasmand beneath the left temporal lobe failed to disclosetumour. Radio therapy was given and 3,500 r weredelivered to the pituitary fossa and the region justposterior to it. The visual fields showed no improve-ment, but other symptoms remitted.

In 1963 she had a recurrence of complaints of tiringeasily, somnolence, and forgetfulness. She was alert,oriented, and cooperative but had some unsteadinessof gait and a right homonymous hemianopia wasagain noted. Pneumoencephalography demonstratedmoderately dilated lateral ventricles but the thirdventricle was poorly visualized. The aqueduct andfourth ventricle were normal. PBI was 7-1 mg/l00 ml.,24 hour urinary corticosteroid excretion 8 3 mg, and17-ketosteroid excretion 5-1 mg. ACTH stimulation

test was normal as was the metapyrone test. Becauseshe was depressed, methylphenidate, 5 mg t.i.d. wasstarted, in addition to prednisone, 10 mg daily.She improved for a time and then began ex-

periencing progressive difficulty with her gait and hermemory became even poorer. In 1964 a secondcourse of radiotherapy was administered, a tumourdose of 3,500 r being delivered to the region of thesella turcica. Within two weeks she was considered tobe brighter, with some improvement of gait andmemory, but this improvement was not maintainedand she was readmitted to the hospital in March1964 with the added symptom of urinary in-continence. A Torkildsen's procedure was carriedout and she became brighter and her memoryimproved.

Early in 1965 she began to have syncopal episodesand by April she was mentally obtunded, incontinent,and bedfast. Endocrine studies now showed noevidence of hypopituitarism. Ventriculographydemonstrated lateral ventricles larger than noted in1963 without visualization of the third ventricle(Fig. 1). The Torkildsen's shunt was functioning, asdemonstrated by injecting dye into a lateral ventricleand recovering it in the lumbar sac. A right trans-frontal craniotomy was performed and biopsy ofnecrotic tissue from the sella turcica was reported tobe compatible with chromophobe adenoma. Thirdventriculostomy was performed. Shc did not improveand was discharged to a nursing home.

In September 1965 she was seen again because of asudden onset of right hemiplegia and aphasia.

FIG. 2. Case 2 (P.B.) Pneumoencephalogram. A-P and lateral views showing dilated lateral ventricles.

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Hydrocephalus complicating pituitary adenoma

FIG. 3. Case 3 (M.K.) Pneumoencephalogram. A-P and lateral views showing dilated lateral ventricles and hugesuprasellar extension of pituitary tumour (lower arrows in each view). Upper arrows point out extension oftunmours to area offoramen of Monro.

FIG. 4. Case 4 (P.K.) Arteriogram. A-P and lateral views demonstrating presence of hydrocephalus.

Brain scan was normal and a left carotid arteriogramrevealed large lateral ventricles. Lumbar puncturedemonstrated an opening pressure of 240 mm ofwater and the protein was 203 mg/l00 ml. Becauseshe had remained stuporous and the lateral ventricleswere large, it was felt that her ventriculostomy andTorkildsen's shunt were not functioning. A ven-

triculojugular shunt was performed. She brightened,the hemiplegia improved, and she was able to speakagain.

In June 1967 she developed a sudden, recurrentright hemiplegia and aphasia. Left carotid arterio-gram demonstrated a complete block of the internalcarotid artery. She subsequently developed epilepsy

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but survived until May 1969. Necropsy revealed thefloor and dorsum of the sella turcica to be erodedand filled with brownish, semi-liquid necroticmaterial which did have small areas of viable neo-plastic tissue typical of a chromophobe adenoma.The cause of death was bronchopneumonia and apulmonary embolus.

CASE 2

P.B., a 73 year old right-handed woman, wasadmitted to Episcopal Hospital in 1966 with pro-gressive mental obtundity and change of personalityover the course of the previous year. Her familyreported that she had had progressive unsteadiness ofgait for at least two years. In 1959 she had beenoperated upon at another hospital for a chromophobeadenoma of the pituitary gland and had receivedpostoperative radiation therapy. The patient had adry, smooth skin, a coarse, raspy voice and she wasdull, disoriented, and confused. There was nodefinite visual field cut, but she was unable tocooperate for a detailed examination. The rightoptic nerve head appeared pale. She had generalizedhyperreflexia and was unable to walk. Radiographsof the skull demonstrated destructive changes of thedorsum sella with deepening of the pituitary fossaand erosion ofthe floor. Blood PBI was 5 jig/100 ml.;urinary excretion of pituitary gonadotropins wereless than 12 u. in 24 hours; the T-3 index was 23(normal, 27 to 35). Plasma cortisol was 18 ,ug/100 ml.in the morning and in the evening 3. Cortisol pro-duction was 3-4 mg over 24 hours (normal values 15to 25). ACTH stimulation test yielded a plasmacortisol content of 12 ,ig/100 ml. as a baseline andpost-stimulation was 27 ,ug/100 ml. A trial of re-placement therapy with hydrocortisone failed toproduce a significant improvement. A fractionalpneumoencephalogram showed generalized dilata-tion of the ventricular system (Fig. 2). A ventriculo-atrial shunt was performed which almostimmediately resulted in a brightening of her mentalstatus. She was discharged on hydrocortisone, 10 mgq.i.d. and thyroid extract, 0-12 g daily. She was ableto return to doing her own housework and cookingfor two years.

After an acute episode of nausea and vomiting shewas again readmitted to the hospital on 17 February1969. The shunt was performing satisfactorily but itwas discovered that she had not been taking hermedications. She was again placed on hydrocortisoneand thyroid extract and improved to the point whereshe once again could look after herself.She subsequently died at home in May 1971 at the

age of 78 years, but the circumstance of her deathcould not be ascertained.

CASE 3

A woman, M.K., was first admitted to the EpiscopalHospital in 1951 because of progressive blurring ofvision and headaches. Examination at that timedemonstrated a suggestion of right central facialweakness and partial bitemporal hemianopsia withnormal visual acuity. She had a markedly expandedpituitary fossa with an eroded floor and barelydiscernible clinoid processes. The diagnosis ofpituitary adenoma was made, and radiotherapy wasgiven, which relieved her headaches. Her visionimproved but the patient did not complete the entireprojected course of treatment.

In 1960, after recurrence of symptoms, craniotomywas carried out in another hospital. A partiallynecrotic right temporal lobe was removed togetherwith a large cystic pituitary chromophobe adenoma.

In December 1969 she was readmitted to EpiscopalHospital dehydrated, confused, disoriented, andincontinent. She was blind and both optic discs werevery pale. There were no focal neurological signs.Radiography revealed complete destruction of hersella turcica. Plasma PBI was 7-7 ,ig/100 ml., T-42-9 ,ug/100 ml., and her growth hormone 3 ng/100 ml.Cortisol production was 12 mg/24 hours. Plasmacortisol content in the morning and before ACTHstimulation was 3-1 [Lg/100 ml.; after ACTHstimulation it was 29. A pneumoencephalogramutilizing a limited amount ofair (25 ml.) demonstrateda huge pituitary tumour with widespread suprasellarextension, particularly encroaching upon the inferiorportions of the third ventricle up to the foramen ofMonro (Fig. 3). The lateral ventricles were grosslydilated. She was prepared with intravenous hydro-cortisone and a ventriculojugular shunt performed.She became oriented and continent within 48 hours.Two weeks later a left transfrontal craniotomy wasperformed with almost total removal of a hugechromophobe adenoma. She awoke after surgery andappeared to be in good condition for 48 hours, butthen developed a series of generalized grand malseizures. Despite reasonably prompt control withanticonvulsant medications, she remained stuporous.She improved slowly but never became competent.She died in November 1970 at the age of 66 years.

CASE 4

P.K., a 45 year old man, was admitted to EpiscopalHospital in March 1970, with a four month historyof progressive mental and personality deterioration.The family had noted that the patient had difficultywith vision but details were lacking. During the sameperiod he had progressive difficulty with his gait. Thepatient was conscious, but dull and disoriented.Funduscopic examination revealed pallor of both

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optic discs, and a bitemporal hemianopsia waspresent. Visual acuity could not be determined. Thesella turcica was enlarged with erosion of the floorand infralateral wall of the optic foramina on theleft. His pituitary and thyroid functions were normal.Arteriography demonstrated a pituitary tumourwith hydrocephalus (Fig. 4). He was placed on100 mg hydrocortisone daily and a ventriculojugularshunt was performed on 31 March 1970. On can-nulization of the lateral ventricles, the hydrocephaluswas confirmed. After the shunting procedure, he wasdefinitely brighter and more oriented. He wascontinued on hydrocortisone. On 2 April 1970 alarge chromophobe adenoma of the pituitary glandwas removed in toto. Postoperatively, the patient didwell and, though he was fully alert after the first fewdays, he remained disoriented for time and place andoccasionally for person. He was discharged on30 mg hydrocortisone and 200 mg phenytoin daily. InMay 1970, he had fully recovered intellectually andthe valve was functioning well. By December 1970his visual acuity could be corrected on the left to20/20 but not beyond 20/200 on the right. He hadreturned to operating a service station. When last seenin March 1972 he was continuing to do well, onsubstitution endocrine therapy and his valve wasfunctioning.

DISCUSSION

So-called occult or normal pressure hydro-cephalus in the adult generally presents as adisturbance of gait and mentation. Apathy,irritability, incontinence, and severe disorienta-tion can develop in these patients. Hypo-pituitarism frequently produces similar changesand therefore in the presence of a known tumourof the pituitary gland it is difficult, if not im-possible, to differentiate between these twopossible complications on a clinical basis alone.The initial opinion on cases 1-3 was that theirclinical picture was the result of an endocrineaberration. They had previously been operatedupon for pituitary tumour and given radiationtherapy postoperatively. All three were givenendocrine replacement therapy and only whenthere was no significant improvement was hydro-cephalus considered as the cause of the clinicalpicture. Treatment of the latter by shuntingproduced prompt if not always completeimprovement. Patient P.B. (case 2) was able to gohome and do her own cooking and houseworkand generally look after herself; patient J.K.(case 1) brightened to the point where she could

walk and talk but required nursing homeassistance. M.K. (case 3) became oriented andcontinent after shunting; however, after sub-sequent suraery on her pituitary gland she had aseries of postoperative convulsions and becamedeeply stuporous. She never fully recovered andwas confined to bed in a nursing home for oneyear before she died. The improvement in eachcase was reasonably prompt and not dependentupon change in endocrine substitution therapy.In one patient, P.B. (case 2), hypopituitarism andhydrocephalus were both clearly present, andwhile some improvement occurred with replace-ment therapy her improvement was dramaticonly after her hydrocephalus had been shunted.We were fully alerted to this problem when thelast patient (P.K.) was encountered and, on thebasis of the arteriogram, proceeded with shunt-ing immediately. It can be speculated that, ifshunting had been resorted to sooner in the firstthree patients, the improvement might have beenmore complete.

There are several mechanisms involved inproduction of hydrocephalus with pituitarytumours (Taveras and Wood, 1964; Schmitzet al., 1967). Approximately 25% of all pituitaryadenomas, and the majority of large adenomas,grow upward and forward, producing a deformityof the inferior aspect of the anterior horns oflateral ventricles. These tumours rarely becomelarge enough to cause an obstruction at theforamen of Monro. The principal directionalgrowth in the other cases is upward and back-ward. In these instances the tumour may invadethe suprasellar area at an early stage and largetumours may also invaginate the floor of thethird ventricle and cause an obstruction of theaqueduct of Sylvius. A third possibility is thatthe cisterna chiasmatica and cisterna inter-peduncularis can be encroached upon sufficientlyor even obliterated and in this manner produce ahydrocephalus. In this series, three of thetumours had become large enough to involve thethird ventricle. In the other case there was noevidence of suprasellar extension of the tumour.As three of the four cases had been previouslyoperated upon and irradiated, scarring fromsurgery and irradiation obliterating the cisternamust also be considered as a possible contributoryfactor. The process in all instances was obviouslyslow enough to permit adjustments to occur,

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thereby avoiding any obvious increase in intra-cranial pressure accompanying the hydro-cephalus.

This series of patients identified another cause

of occult hydrocephalus. It further emphasizesthe desirability of using cerebral contrast mediastudies in the evaluation ofpatients with suspectedor proven pituitary tumours either beforedefinitive treatment or in those patients whoseprogress after treatment is poor. Indeed,arteriography before surgery on a suspectedpituitary tumour has been generally recom-

mended to exclude an aneurysm. If patients are

judged to be suffering from hypopituitarism andtheir response to substitution therapy is notcomplete, it is necessary to exclude hydro-cephalus also. Patient P.K. presents the unusual

picture of hydrocephalus complicating thepresenting clinical picture of pituitary adenoma.The relief of the former by shunting permitted a

technically less complicated surgical attack on

the latter, with an exceptionally fine end result.

REFERENCES

Dandy, W. E. (1969). The Brain. Harper and Row: New York.Davidoff, L. M., and Epstein, B. S. (1955). The AbnormalPneumoencephalogram. Lea and Febiger: Philadelphia.

Pancoast, H. K., Pendergrass, E. P., and Schaeffer, J. P.(1940). The Head and Neck is Roentgen Diagnosis. Thomas:Springfield, Ill.

Schmitz, A. L., Haveson, S. B., and Hanna, D. (1967).Illustrative Cranial Neuroradiology. Thomas: Springfield,Ill.

Stern, W. E., and Batzdorf, U. (1970). Intracranial removal ofpituitary adenomas. Journal of Neurosutrgery, 33, 564-573.

Taveras, J. M., and Wood, E. H. (1964). Diagnostic Neuro-radiology. William and Wilkins: Baltimore.

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