Journal of Neurology, Neurosurgery, and Psychiatry, 1975, 38, 919-930

Visual failure from pituitary and parasellar tumoursoccurring with favourable outcome in

pregnant women

M. A. FALCONER' AND M. A. STAFFORD-BELL2

From the Neurosurgical Unit of Guy's, Maudsley, and King's College Hospitalsand the Department of Obstetrics and Gynaecology, Guy's Hospital, London

SYNOPSIS Very few cases have been reported of a successful outcome after relief by operation ofsevere visual failure from a pituitary or other parasellar tumour during the late stages of pregnancy.Two such cases are recorded here together with the obstetric features and follow-up studies of morethan three years. Usually the deterioration of vision occurs in the latter half of the pregnancy andrecovers rapidly after delivery, whether the onset of labour has occurred spontaneously or afterinduction. In subsequent pregnancies vision deteriorates at an earlier stage and becomes even more

marked. Some cases are now occurring even in pregnancies induced by modern fertility drugs. Thetreatment of choice whenever vision is seriously threatened at any stage of pregnancy is a surgicalattack on the pituitary, followed by suitable replacement therapy to ensure that the pregnancycontinues.

CASE 1

A 25 year old woman was admitted to the Neuro-surgical Unit in March 1971 at 21 weeks' gestationwith a history of rapidly deteriorating vision of twomonths' duration and of headache sometimesassociated with vomiting. Her visual acuity fourweeks before admission had been right eye 6/18 andleft eye 6/12 with normal fundi. Straight radiographsof the skull had been reported as normal. Withintwo weeks the vision of the right eye had deterioratedto hand movements only (Dr C. Constantinides).She was placed on betamethasone 4 mg four timesdaily and this eased her headaches. Five yearsearlier she had given birth to a daughter followed bya period of lactation. There had been no visualdisturbances during that pregnancy. Her mensesthen remained normal until the present pregnancy.Examination on admission showed a well nour-

ished (72 kg) woman from the Middle East with theuterine fundus compatible with the period of gesta-tion. Her blood pressure was 110/70 mmHg. Thevisual acuities were left eye 6/24, J.10 and right eyehand movements only, with an advanced bitemporal

I Address for reprint requests: M. A. Falconer, Neurosurgical Unit,Maudsley Hospital, De Crespigny Park, London SE5 8AZ.2 Present address: Canberra Hospital, Canberra, Australia.

919

hemianopia (Fig. 1). Radiographs of the sella turcicawere normal (Fig. 2). A right carotid arteriogram dis-closed the presence of an avascular suprasellar mass(Fig. 3). A tentative diagnosis of a meningioma ofthe tuberculum sellae was made.

On 30-March, about 22 weeks after the presumedtime of conception and under a cortisone cover, aright frontal craniotomy was performed undergeneral anaesthesia (nitrous oxide, oxygen, curare,and halothane: Dr P. Hewitt) and a spherical cystictumour about 2.5 cm in diameter was found beneaththe optic chiasm compressing it and attached belowto the diaphragma sellae. After its suprasellar por-tion had been removed, an aperture 4 mm in dia-meter was seen in the middle of the diaphragm, butthere was no sign of the pituitary stalk which pre-sumably had been avulsed. It was felt that there wasstill some pituitary tissue remaining within the sellaturcica. The histological report was of a chromo-phobe pituitary tumour (Dr I. Janota) and this wasunexpected because the sella turcica seemed normalon radiological examination. Recently Clifford andEchols (1973) reported a pituitary tumour causingvisual troubles with a normal sella turcica and saidthat they had found only one other example in theliterature. The skull radiograph of the sella turcica inour patient was more normal than it was in their case.

920 M. A. Falconer and M. A. Stafford-Bell

6/24 JO an nm t

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rat. visa-.. - ; . . ~25- ;L !.-.'.oFIG;.i Cas .. .Preprtv viua fils. _

FIG. 2 Case 1. Radiograph of skull shows normalsella turcica.

FIG. 3 Case 1. Right carotid arteriogram. Lateral view (a) and anteroposterior (b) show upward displacementof the first portions of both anterior cerebral arteries indicating a suprasellar space-occupying lesion. The leftanterior and middle cerebral arteries have been filled by cross-compression of the left carotid artery in the neck.

Visual failure from pituitary and parasellar tumours occurring in pregnant women

During the first 24 hours after operation the60. patient had a urinary output of more than five56 - .- : ! litres. This diuresis was arrested by an intramuscular

54-'-: .:: :.: :: ,., .... . / jinjection of 1.0 ml pitressin tannate in oil everysecond day. By the fifth day her serum potassium

48 - --- / concentration had fallen to 2.9 mmol/l (normal 3.5-44-.-- - / f 5.0 mmol/l) and her ECG was suggestive of hypo-42+- kalaemia. This was corrected with effervescent:40 potassium drinks by mouth. Her craniotomy wound3,5-/~ | healed soundly and within a week her visual acuity34 had returned to 6/9 and Ji bilaterally, with almost

E 3-' :/ normal visual fields. The pre- and postoperativeo2 blood counts were normal. As a result of operationcc44 . .she now has bilateral anosmia.L24 .

On the ninth day she was transferred to the20 S ,- Obstetric Department of Guy's Hospital. During the6y,ensuing weeks she lived outside the hospital reporting

|4 -: --t- / at frequent intervals. The blood levels of triiodo-12 .; _ j thyronine and total thyroxine remained within

8 : = I normal limits for pregnancy. She remained normo-4 r - tensive throughout the remainder of her pregnancy.1V>::f.i¶., ] Clinical impression, satisfactory weight gain, and

o--T-----jjI. ultrasonic measurements of the fetal biparietal26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 diameter all suggested satisfactory fetal growth in

GESTATION tveeksi spite of low urinary oestriol levels (Fig. 4). How-ever, as the other indications of fetal growth were

1IG. 4 Case 1. Urinary excretion ofoestriol. The satisfactory it was felt that these levels could bePatie' v ariry o

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nignored. Her replacement therapy for the remainder

aetieent tsvleaencired. T normalrne lest of the pregnancy was cortisone acetate 25 mg everyxcretion. eight hours, pitressin snuff by inhalation morning

and night, potassium supplements, and pheno-barbitone 30 mg twice daily.An elective lower segment caesarean section was

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-~~~~m-01 FIG. 5 Case 1. Mother- and baby atj~~~~~~~three weeks.

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921

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M. A. Falconer and M. A. Stafford-Bell

performed at 39 weeks' gestation and a live maleinfant weighing 3.2 kg was delivered (Mr T. L. T.Lewis). The child was slow to respond, requiringintubation (Apgar score 3, 7, 7, 8 at 1, 5, 10, and 15minutes respectively).

Subsequently the mother and child thrived. Nopostoperative radiation was given to the patient. Shereturned to the Middle East about two months afterconfinement and was then on cortisone acetate37.5 mg and L-thyroxine 0.1 mg by mouth daily, aswell as an intramuscular injection of L-pitressintannate in oil every second day or third day. Shehad not lactated, but was otherwise well (Fig. 5)except that the anosmia remained complete.A year later she returned to Great Britain. Her

weight was then 70 kg. Recently the cortisone acetatehad been replaced by prednisolone 5 mg daily. Thiswas changed back to cortisone. Her blood pressurewas a little low at 90/50 mmHg. Her tendon jerkswere absent. Her serum electrolytes were normal, aswas her blood count and ESR. Her body hair andbreasts were normal, her vagina was moist andregular sexual intercourse was taking place. She hadhad amenorrhoea since delivery and on threeoccasions her luteinizing hormone (LH) levels were20.2, 30.6, and 21.8 IU/12 hr (within normal levels),while her follicular stimulating hormone (FSH)levels were 1.7, 2.3, and 2.0 IU/24 hr (very low) andher urinary excretion of oestrone levels were 2.1, 2.3,and 2.0 ,ug/24 hr on three successive days (very low).Three and a half years after her confinement she

again reported back to the Neurosurgical Unit. Sheappeared well except for persistent diabetes insipidusfor which she required an intramuscular injection ofpitressin tannate in oil every fourth or fifth day. Shewas also taking cortisone acetate 25 mg and L-thyroxine 0.1 mg daily. Her weight had fallen to64 kg from 72 kg because of dieting. Her visualacuity and visual fields remained normal as did heroptic discs. The blood pressure was 110/65 mmHg.She still had a complete anosmia, but retained thebasic tastes of sweet and sour, bitter, and acid.Radiographs of the skull still showed a normal sellaturcica. Her tendon jerks had returned. She also hadcomplete amenorrhoea. The cervical cytology wasclass II with no malignant cells. Her urinary excre-tion ofoestrones was 1.8 and 2.9 ,ug/24 hr on consecu-tive days. Her FSH excretion was 1.2 IU/24 hr (low)and LH excretion was 21 IU/24 hr (normal). Otherinvestigations included a normal blood count withnormal serum electrolyte levels, and a serumcholesterol of 7.7 mmol/l (normal 3.9 to 6.5 mmol/l).The protein bound iodine was 569.4 nmol/1(7.2 t±g/dl) (normal 3.3-7.8 ,ug/dl). The ECG was normal.Regular sexual intercourse was still occurring with-out difficulty.

Her 31 year old son was reported as completelynormal.

CASE 2

A 23 year old woman, also from the Middle East,was referred to this country in the seventh month ofher first pregnancy because of deterioration ofvision. She had a mildly acromegalic appearance,and five years previously had undergone a plasticprocedure to correct the enlargement of her nose.The acuity in the left eye had then been found to beslightly impaired when she underwent a test ofvision. She had only recently sought medical atten-tion for this deterioration and radiographs had dis-closed enlargement of the sella turcica.

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FIG. 6 Case 2 Preoperative visual fields.

On admission to the Neurosurgical Unit on 20August 1971 she showed slightly acromegalicfeatures. The visual acuity of the left eye was 6/24,J12 with full peripheral vision but with a largedense hemicentral scotoma in the temporal half,while the visual acuity in the right eye was normal(Fig. 6). Pulse rate was 78/mn and blood pressure115/70 mmHg. Blood count was normal. Thehydroxy- and ketosteroid excretions in the urinewere normal as was her plasma protein boundiodine (457 nmol/l; 5.8 pLg/dl). Pneumoencephalo-graphy performed on 20 August showed a supra-sellar extension of a pituitary tumour displacing theanterior part of the third ventricle upward and back-ward (Fig. 7). This was followed by a right cranio-tomy with the intracapsular removal of a pituitaryadenoma which reached up 1.0 cm above the level ofthe sella. The histological report was of a chromo-phobe pituitary tumour (Dr L. Duchen). Within a

922

Visual failure from pituitary andparasellar tumours occurring in pregnant women

FIG. 7 Case 2. Coned.4lateral view ofpneumo-encephalogram shows aslightly dilated sellaturcica with filling of theventricular system andbasal cisterns. Theanterior part of thethird ventricle (arrow) isdisplaced upwards andbackwards.

week her visual acuity in the left eye was 6/18, J6 andthe visual field had also improved. She then promptlyreturned to the Middle East. There the pregnancycontinued satisfactorily until 34 weeks' gestationwhen she was admitted to hospital with pre-eclamptictoxaemia. Labour was induced at 36 weeks by arti-ficial rupture of the membranes and an intravenousdrip of synthetic oxytocin (Syntocinon) resulting inthe normal delivery of a live male infant weighing2.2 kg. Lactation was not established but otherwisemother and child progressed well (Fig. 8). Smellsensibility was retained. After her confinement shehad amenorrhoea, except for some irregular bleedingon three occasions in the first year. Shortly after thebirth she was given radiation therapy to the pituitary,receiving a tumour dose of 4 000 rads in an overalltime of 37 days (Dr D. H. Mortazavi). Her visualfields still showed a slight defect in the left uppernasal quadrant. The right field remained normal.Three years after her operation while on a visit

to Great Britain it was found that she had takenno replacement therapy since the course of radiationtherapy, but she appeared healthy in almost every

way. Although her facial features were still acro-megalic, her heel pads now measured 18 mmwhereas before operation they were 25 mm (upperlimit of normal is 23 mm). The blood pressure was110/70 mmHg. Vision was normal in the righteye at 6/9, Jl uncorrected with a normal field ofvision and was slightly impaired in the left eye withan uncorrected visual acuity of 6/12, J4 and a fullvisual field but with an incomplete central scotomain the upper temporal quadrant to 2/2 000 but not to5/2 000. Her energy seemed normal and there was nothirst or polyuria. Her plasma protein bound iodinewas not measurable because of iodine contamina-tion. The blood thyroxine (T4) level was 56.6nmol/l (low normal). The early morning and midnightplasma cortisol levels were normal. She even re-ported occasional menstrual bleeding at intervals oftwo to three months, but there was no certain evi-dence of ovulation (Dr H. Amini). Pelvic examina-tion disclosed normal sized healthy pelvic organs.The urinary excretion of FSH was 6 IU/24 hr (low)and LH 32 IU/24 hr (normal). A cervical smearshowed more oestrogenic effect than in the first

923

M. A. Falconer and M. A. Stafford-Bell

FIG. 8 Case 2. Mother and child at 11 months.

patient, without any malignant cells. An endo-metrial biopsy showed scanty endometrium withslight proliferative change. She and her husbandwere still practising contraception.Her 3 year old son was completely normal (Dr S.

Davidson).

DISCUSSION

In 1947 Sir Steward Duke-Elder wrote:'The evidence is strong that in certain cases duringpregnancy adenomatous changes may be stimulated or

accelerated in the pituitary, that these may eventuallyinvolve complete biteinporal hemianopia and may pro-gress in subsequenit pregnancies so that eventualoperative removal of the neoplasm is necessary. In thepresent state of our knowledge the relationship hasnow been completely established and such cases

should be watched with care'.It is our intention to show from our experiencethat nowadays, in cases with serious impairmentof vision from optic nerve or chiasmal compres-

sion, the neurosurgeon is justified in operatingupon the patient at any stage of the pregnancy tosave vision, and that his obstetrical colleague

should be able to carry the patient to full-termnormal delivery or caesarian section as indicated.The literature relating to pregnancy occurring

in women with pituitary tumours or other formsof dysfunction is steadily increasing. Sommers(1958) reviewing the functions of the pituitarygland during pregnancy stated:

'It is generally appreciated that for a certain periodof pregnancy in animals normal pituitary function isessential, since hypophysectomy early in pregnancyresults in foetal death. The effects ofhypophysectomyvary considerably with the species and with the stageof gestation. The critical period for women is notknown. It appears to be before the 12th week ofpregnancy, based on one case of pituitary necrosis inwhich the foetus remained alive. The corpus luteumin women is evidently non-essential after the 10thweek of pregnancy. Chorionic gonadotrophinsecretion in urine is found almost at once after thehuman blastocyst implants and rises to a peak after8 to 10 weeks'.

From the literature it would appear that twogroups ofpatients should be considered and someof these case reports in the literature will bereviewed to show the variations of the syn-dromes: (1) patients with intrasellar or para-sellar tumours who become pregnant and thendevelop failing vision; (2) patients who have hadamenorrhoea or anovulatory menstrual cyclesand then become pregnant, either spontaneouslyor as a result of drug therapy, before the failureof vision appears. This second type is lesscommon but in future years may become sowith increasing use of ovulation-inducing agents.

PATIENTS WITH PARASELLAR TUMOURS WHOBECOME PREGNANT AND THEN DEVELOP FAILINGVISION Several authors have now reportedcases of failure of vision appearing during preg-nancy with interesting variants of the clinicalsyndromes provided by pregnancy, pituitaryinsufficiency, and failing vision.

Enoksson et al. (1961) reported a case of theirown and summarized the literature.

Their patient, a woman born in 1930, had had fromthe age of 10 years attacks characterized by paraes-thesias of the right face, a strange taste in hermouth, and a feeling of anxiety. At 15 years hervisual acuity was 1.0 in each eye with normal visualfields, while skull radiographs showed a normal sellaturcica. At the age of 24 years she came under

924

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Visual failure from pituitary and parasellar tumours occurring in pregnant women

observation at the 38th week of gestation with fail-ing vision for the past two months. Her vision thenwas right eye 0.4 and left eye 0.2, while her visualfields showed an incomplete bitemporal hemianopia.Radiographs of the skull now showed thinning ofthe posterior clinoid processes. Induction of labourby rupture of the membranes was, therefore, under-taken and next day she spontaneously bore a 3.2 kghealthy child. Two days later a pneumoencephalo-gram showed slight elevation of the chiasmal cisternbut the third ventricle appeared normal. By the thirdday her visual acuity had improved to 0.7 in theright eye and 0.2 in the left eye. Two weeks later hervision and visual fields were once more normal.

Eighteen months later she was investigated be-cause of amenorrhoea. Her vision then was normaland she had no signs of hypopituitarism apart froma basal metabolic rate of - 12%4 to - 16%. Herblood cholesterol and 1311 uptake were normal. Theoutcome as regards amenorrhoea is not stated, butin spite of advice that she should have her visiontested every six months she did not report for follow-up until she was aged 27, when she reappeared,pregnant for the second time at the twelfth week ofgestation. A pneumoencephalogram repeated at theseventeenth week showed a suprasellar extension10 mm high with a deformation of the anterior partof the third ventricle. However, she could read 1.0 ineach eye, although bitemporal defects in her visualfields had appeared. As she wanted another child,periodic checking of her vision was arranged. By the37th week her vision had fallen to right eye 0.3 andleft 0.1 with a complete loss of the temporal field ofthe left eye as well as some reduction of its nasalhalf. The right visual field had a large temporaldefect. The membranes were ruptured and the nextday she gave birth to a healthy 2.5 kg child. Hervision began to improve spontaneously by thesecond day and by the twelfth day had recovered to0.5 (right) and 0.2 (left) with expanding visual field.By the twentieth day she could see 1.0 with eithereye and had only insignificant field defects.

Six months later it was evident that she had beenhaving epileptic seizures all along and that they hadbecome more severe during the last six years. How-ever, during her pregnancies their frequency haddiminished. Further radiology showed an enlargedsella turcica with a deformation of the anterior partof the third ventricle of much the same degree as inthe seventeenth week of the second pregnancy. Atoperation the tumour proved to be a cystic chromo-phobe adenoma at least 2.5 cm behind the tuber-culum. On discharge her vision was 1.0 with fullvisual fields on the right and 0.9 with an almost fullfield on the left.

Recently, Professor Nils Lundberg who had per-formed the operation in 1960 said that she lactatedafter both deliveries, but that the quantities of milkwere not always sufficient (personal communication).After the pituitary operation she had amenorrhoea,and a temperature test in 1963 indicated no ovula-tions. Her libido was poor, she put on weight, andhad low values for her basic metabolic rates andplasma protein-bound iodine levels. She was notgiven replacement therapy. Her seizures becamemild and infrequent but she still takes phenytoin. Hergeneral condition remains good and her visionremains normal. She runs her home and has a part-time job in a bank.

Enoksson and his colleagues (1961) also re-viewed from the literature six cases of pregnantwomen all of whom at some stage in the latterhalf of pregnancy had developed visual impair-ment with visual field changes, usually withrecovery or improvement of vision after deliveryor abortion. Of the six cases, two were chromo-phobe adenomas, three were parasellar menin-giomas, and one was a craniopharyngioma. Inconsidering therapy for pregnant women with asellar or parasellar tumour, they pointed outthat it was usually in the latter half of pregnancythat visual failure appeared. They discussed fourdifferent therapies: (1) therapeutic abortion inthe early stages, for which they found littlesupport; (2) expectant treatment with prematureinduction of labour as soon as the child wasviable-this is how they managed their ownpatient; (3) operation of the tumour duringpregnancy; and (4) radiation therapy to thepituitary. They cited a patient of Rand (1957)who had bitemporal hemianopia during preg-nancy with an enlarged sella turcica and whoafter delivery had several courses of radiationtherapy, finally terminating in a pituitary opera-tion. They also cited two cases of chromophobetumour causing visual failure in the later stagesof pregnancy and operated upon during thepregnancy with favourable outcome by Guillau-mat and by Philippides respectively.Two other cases with some similarities to our

own have been reported by Kaplan (1961) andLepoire et al. (1964). The first of these developedsigns of pituitary disturbances in successivepregnancies during the first trimester and, after apituitary operation, developed diabetes insipidusand hypothyroidism. The second case after

925

M. A. Falconer and M. A. Stafford-Bell

similar visual disturbances and operation eventu-ally recovered her senses.

Kaplan's case (1961) was a 41 year old womanwho developed an abrupt onset of blurred visionand frontal headache one month after her lastmenstrual period.Four years earlier, after seven years of barrenmarriage, she had conceived and had a normal infantby caesarean section. A year later she twice mis-carried at the third month. With each pregnancy shehad noticed headaches and blurred vision from soonafter the missed menstrual period remaining un-changed until they disappeared three weeks afterdelivery. In her last pregnancy deterioration ofvision in both eyes became gross by the fourth monthwith a bitemporal hemianopia. Under a cortisonecover a chromophobe pituitary adenoma wasremoved. Diabetes insipidus, evident on the secondday after operation, required therapy with pitressinand desiccated thyroid. In the 38th week she gavebirth by an elective caesarean section to a boyweighing 3.3 kg. Scanty lactation occurred in thepuerperium. Her visual fields quickly became normalbut features of myxoedema appeared. Her case wassubsequently followed up for three months. Theauthor claimed that this was the first recorded casein which pituitary insufficiency had developed in thefirst trimester and then after a pituitary operationhad resulted in a successful pregnancy.

Lepoire and his colleagues (1964) described apatient who went through four pregnancies,three with recurrence of visual failure.Subsequently after several months an eosinophilicadenoma was removed but she did not require endo-crine replacement therapy afterwards. Her firstpregnancy at the age of 25 years had been normal,but in three succeeding pregnancies she developed anincomplete bitemporal hemianopia which in thesecond pregnancy appeared in the seventh month,disappearing rapidly after delivery, and in the thirdit appeared during the sixth month and disappearedone month after delivery. In the fourth pregnancyher field defect appeared during the fourth monthbut this time did not disappear after delivery. Shedeveloped an abundant and persistent lactationwhich did not respond to treatment and because ofthis as well as the hemianopia and amenorrhoea shewas admitted to hospital. She had no sign ofacromegaly but had signs of hypopituitarism andgalactorrhoea. A gynaecological examination showedan atrophic uterus. At operation an eosinophilicadenoma was removed. When reviewed one yearafter operation she was in good health without anysubstitution therapy. Her galactorrhoea had per-

sisted for five months after operation, followedshortly afterwards by the return of her menstrualperiods. Her vision was reported as good.PARASELLAR TUMOURS IN PREGNANCY Otherparasellar tumours besides pituitary tumourscan also produce the clinical picture of repeatedfailure of vision in the later stages of pregnancy.Hagedoorn (1937), for instance, reported thecase of a woman, mother of nine children, whountil then had no trouble with her vision.In the fifth month of her tenth pregnancy shedeveloped a central scotoma in the right eye. Visionin the right eye was 0.5 and in the left 1.0. By theseventh month she had a complete bitemporalhemianopia and her visual acuity was only 2/60 inthe right eye with a pale optic disc. Two months laterher visual acuity was right eye 1/60 and left 1/4. Amonth later at term she bore a healthy child. Afterdelivery her vision improved rapidly and after onemonth was right eye 1/4 and left 1/2. Seven monthsafter delivery her vision in each eye was 0.5 and 1.0,while the field of vision on the right still showed analmost complete temporal hemianopia with only aslight temporal constriction on the left. When seenagain a further two months later she was pregnantfor the eleventh time and was in the fourth month ofgestation. During this pregnancy her visual fieldssteadily deteriorated. By the sixth month the bi-temporal hemianopia was complete and her visualacuity was right eye 1/60 and left 1/3. Termination ofpregnancy was carried out when the patient couldhardly distinguish between daylight and darkness.The child (1.9 kg) died soon after birth. Afterdelivery, however, vision slowly improved and 10months after delivery the visual acuity had returnedto 2/60 in the right eye and 9/10 in the left eye. Shestill had a complete bitemporal hemianopia with alsosome reduction of the nasal half of the right field.Radiographs of the sella turcica throughout hadevidently shown little abnormality, but explorationof the chiasmal region revealed an encapsulatedsuprasellar meningioma. She died of haemorrhage afew hours after operation and at postmortemexamination the right optic nerve was found embed-ded in the tumour.

PATIENTS WHO HAVE BECOME PREGNANT AFTERINDUCED OVULATION FOLLOWING A LONG PERIODOF AMENORRHOEA AND HAVE THEN DEVELOPEDSERIOUS FAILURE OF VISION Although we havehad no personal experience, it is clear from theEuropean literature that many female patientswill develop amenorrhoea or anovulatory bleed-ing after a pituitary operation and with drug

926

Visualfailure from pituitary andparasellar tumours occurring in pregnant women

therapy can be made to ovulate and encouragedto conceive and have normal children. Occasion-ally a patient with a treated pituitary tumour cando this spontaneously. It is therefore not sur-prising that the occurrence of severe visualfailure has sometimes occurred in such preg-nancies.

In 1964, for instance, Gemzell and Kjesslerfrom Uppsala reported that a 35 year old woman,after the operative removal of a pituitary tumourfollowed by 6 000 rads of radiation therapy, haddeveloped amenorrhoea with diabetes insipiduswhich was treated by cortisone and thyroidtherapy.This therapy was stopped after two years andovulation was induced by daily intramuscular injec-tions of human pituitary gonadotrophin (HPG) for10 days, followed by injections each day for the nextthree days of 3 000 IU of human chorionic gonado-trophin (HCG) plus 100-120 units of luteotrophichormone (LH). As expected, ovulation occurred andshe promptly conceived. At full term she wasdelivered of a healthy boy by caesarean sectionbecause of a transverse presentation.By 1973 Gemzell was able to report that at

Uppsala during a 10 year period they hadtreated for infertility five women, aged between26 and 35 years, who had all previously under-gone operations for the removal of a pituitarytumour with consequent amenorrhoea or ano-vulatory bleeding. All five infertile women weretreated by injections of HPG, post-menopausalgonadotrophin (HMG), and HCG. Ovulationtook place after each treatment. Four of thewomen conceived and of these, three gave birthto twins and one to a single infant. One of thewomen went into labour spontaneously, whilethree were delivered by caesarean section close toterm. Only one woman did not conceive. Thus,from this group of five, all previously operatedfor a pituitary tumour, four gave birth to seveninfants. One woman even breast fed her baby.Gemzell and his colleagues thought that all thishad been possible because a small fragment ofhealthy pituitary tissue must have been leftbehind in the sellar cavity after removal of thepituitary tumour.

Others have reported successful pregnancyafter the use of fertility drugs in women withamenorrhoea after the removal of a pituitarytumour followed sometimes by full radiotherapy

to the pituitary region, including, on theContinent, Linquette et al. (1970), Corral et al.(1972), and Jorgensen et al. (1973), while Burkeet al. (1972) have done so in Great Britain. Muchearlier, Brimble (1937) had reported that a 27year old acromegalic patient, from whom apituitary tumour had been removed four yearsearlier followed by postoperative radiationtherapy, had subsequently regained spontaneousmenstruation, and had in due course becomepregnant and given birth to a child. This was inthe days before modern fertility drugs wereknown. It is therefore not surprising that inrecent years there have been at least three reportswhere pregnancy after induced ovulation has ledto the stimulation of a pituitary tumour thatcaused failing vision during the later stages ofpregnancy, necessitating an urgent pituitaryoperation while the pregnancy continued.Kaytar and Tomkin (1971) reported a 30 year

old woman with a history of secondary amenor-rhoea for 14 months.Menstruation which started at 15 years was regularuntil the age of 19 years. After marriage at 28 yearsshe had only two irregular menstrual bleedings andshe desired a child. Radiographs of the sella turcicashowed that it had a double floor but she had novisual symptoms. She was treated with clomiphenecitrate, human FSH and LH (Pergonal), and HCG.Conception occurred and as the pregnancy pro-gressed she developed frontal headache towards theend of the first month. By the eighth month she wasfound to have a severe bitemporal hemianopia. Thesella turcica was enlarged radiologically. During the35th week of gestation a large chromophobe pituitarytumour was removed by craniotomy. The patientmade an excellent recovery oncortisone and thyroxinereplacement therapy, and her visual fields returnedto normal. At 38 weeks she went into spontaneouslabour and had a low forceps delivery of a healthyinfant (2.4 kg). Lactation was not established.Kaytar and Tomkin (1971) suggested that, whenevera diagnosis of hypothalamic dysfunction has beenmade and then treatment for infertility is requested,radiographs of the pituitary fossa should be takenbefore gonadotrophin stimulation of the ovaries isbegun.

Emperaire et al. (1972) reported a 21 year oldwoman with secondary amenorrhoea for fiveyears.Three months earlier she had had transient troublewith vision in the left eye which deteriorated from

927

M. A. Falconer and M. A. Stafford-Bell

9/10 to 6/10 with a temporal notch in the centre ofthe left visual field. By the time Emperaire saw her,vision was normal and examination showed normalsecondary sexual characteristics, while the sellaturcica was radiologically normal. Her thyroid func-tion was low. Peritoneoscopy showed small ovariesbut no other abnormality. A diagnosis of secondaryamenorrhoea was made and substitution therapy(not specified) was given to ensure regular menstrualbleeding. Two years later she still complained ofinfertility and after other tests clomiphene was givenbut without success. In January 1971 she was startedon HMG (human FSH and LH). Ovulation and thenpregnancy occurred and she was given progesteroneto protect this. At the end of the first month shedeveloped frontal headache and during the sixth weekshe suddenly developed a right third nerve palsy withbilateral diminution of the visual acuity and hemi-anopia affecting particularly the right eye. Radio-graphs of the sella turcica now showed it to beenlarged. A suprasellar extension of an intrasellartumour was demonstrated by carotid arteriographyand pneumoencephalography. During the eighthweek an intracapsular removal of a chromophobepituitary tumour was carried out. Postoperativelyshe developed diabetes insipidus which was con-trolled by chlorothiazide. She was discharged ontwelfth postoperative day on dexamethasone andthyroglobulin. Her pregnancy continued but shesubsequently required two temporary periods ofhospitalization, one for thrush, and one for anepisode of vomiting and weight loss. She startedlabour two days after term and was delivered bylow forceps of a 3.2 kg boy. Post-partem haemor-rhage due to uterine inertia was controlled byoxytocin. Lactation started on the third or fourthday but was suppressed. Menstruation never re-turned and her vision evidently was good, but detailsof the visual fields were not published. Dexametha-sone and thyroglobulin were still required.

Burke et al. (1972) described a woman who,when aged 24 years, presented with infertilityand secondary amenorrhoea ofa year's duration.She had no overt sign of pituitary disease except forsome galactorrhoea on breast expression. She hadlow urinary gonadotrophins, normal cortisol excre-tion, and normal thyroid functions. Radiographs ofthe sella turcica showed a minimal double floorappearance but it was not enlarged. Treatment withHMG (Pergonal) resulted in a single child preg-nancy. During the first eight weeks she complainedof increasing headache, and radiographs of the skullnow showed some undercutting of the tuberculumsellae. By the fourteenth week she complained ofsome blurred vision in the left eye, and during the

next two weeks a bitemporal visual field defectrapidly developed. She was treated by a high doseimplantation of two yttrium seeds, and pituitarybiopsy revealed an active eosinophilic adenoma.Subsequently the vision evidently improved and pre-cautionary steroid replacement (prednisone 5 mgdaily) was continued throughout the remainder ofthe pregnancy. The serum free thyroxine factor re-mained normal, but severe pre-eclamptic toxaemiasupervened and the pregnancy was terminated bycaesarean section at 33 weeks. Subsequently themother and baby both made good progress. Lacta-tion was established and all was going well when thecase was reported six months after birth. No re-placement therapy was given.

Yet another case of visual failure due topituitary tumour making its effects in pregnancyafter induction of ovulation has been reported bySwyer et al. (1971), a 23 year old woman withincreasing oligomenorrhoea and occasionalgalactorrhoea.After six courses of treatment with HMG and HCG,conception occurred. Towards the end of the seventhmonth she developed cloudiness of vision in the lefteye and soon afterwards a defect in the outer lowerquadrant of vision in that eye. Radiography of theskull showed erosion of the posterior clinoid pro-cesses of the sella turcica. A suprasellar tumour wassuspected. Vision continued to deteriorate until shewas nearly blind in that eye. Consequently in theninth month labour was induced, and a normal babygirl delivered (2.2 kg). On the day after delivery hereyesight began to improve and rapidly returned tonormal. The occurrence of lactation was not re-ported. As a brain scan, carotid arteriogram, and apneumoencephalogram performed within two weeksof delivery failed to show any definite abnormality,the authors could not believe that a pituitary tumourhad caused the symptoms, and even thought of thepossibility of demyelinating disease. Her opticfundi were pale, particularly on the left. However,the posterior clinoid processes remained eroded.This case, when taken in conjunction with others wehave cited, almost certainly had a pituitary tumourand following the general rule in such cases, this re-gressed rapidly after delivery.

CONCLUSIONS

We have progressed a long way since Duke-Elder in 1947 wrote that, during pregnancy,adenomatous change might be stimulated oraccelerated in the pituitary. We now know thatsometimes in the latter half of pregnancy para-

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Visual failure from pituitary and parasellar tumours occurring in pregnant women

sellar tumours as well as pituitary tumours canexpand and lead to chiasmal compression, onlyto regress promptly after parturition. Thissequence may then return in successive preg-nancies, eventually going on to complete blind-ness, unless surgery or other treatment to thepituitary region is undertaken.

In the past decade, new problems have beenraised by gynaecologists and endocrinologists. Itseems possible that a woman with primary orsecondary amenorrhoea due to a pituitarytumour with consequent sterility can be made toovulate and to conceive, and then to progress toterm and give birth to a normal infant. It is,therefore, not wise to give fertility drugs to awoman with amenorrhoea unless a radiograph ofthe skull has first been taken to ensure that thereis no abnormality of the sella turcica. If there isan abnormality, even slight, periodic radiographyof the sella turcica should be made at, say,monthly intervals to ensure that the sella is notenlarging. The same precaution should be takenif visual symptoms arise.To revert to our own patients, it is not beyond

the bounds of possibility that our second patient,in whom menstruation has returned after re-moval of an eosinophilic adenoma and a fullcourse of postoperative irradiation, could bemade to ovulate and conceive if she wantedanother child, because there is probably a frag-ment of normal pituitary remaining within hersella turcica. In our first patient, in whom thepituitary stalk was inadvertently severed, a fur-ther pregnancy, even with new drugs, seemsunlikely.We started this discussion by quoting the view

of the leading British ophthalmologist of twodecades ago saying that the evidence was strongthat during pregnancy adenomatous changescould be stimulated or accelerated in the pituit-ary. Let us finish by quoting his present dayAmerican counterparts in neuro-ophthalmology,Walsh and Hoyt (1969). Although they concedethat adenomas may arise during pregnancy andquote Finlay, an early writer on the subject, aswell as Lepoire (1961), they write'that a large percentage of pregnant women developdefects in their visual fields chiefly during the laterstages of pregnancy, and that these field defectsrapidly disappear after pregnancy. Generalised con-tractions and bitemporal constriction have been

described in many papers in such convincing fashionthat for a time many clinicians thought that thealtered fields were normal for gravid women. Otherselsewhere were unable to find the field defects de-scribed by Finlay and attributed most of the fielddefects as functional'.Are they right in their summing up, or have theyfallen into the same trap as Swyer and his col-leagues-namely, believing that, as the visualfailure rapidly regresses after delivery, andneuro-radiological studies show no suprasellarextension of the gland, a pituitary tumour isunlikely?

However, all writers seem agreed that aphysiological enlargement of the pituitary doesoccur in pregnancy, probably due to an increaseof those acidophil cells associated with thesecretion of prolactin (Goluboff and Ezrin,1969). Normally, this physiological enlargementdoes not compress the optic nerves or chiasm.However, when a small adenoma or parasellartumour is present, this expansion during preg-nancy and rapid regression after delivery may beresponsible for the episodes of visual failureobserved in the pregnancies of various patientswe have been considering. The evidence so farassembled seems to indicate that, dependentupon the degree of visual failure, the neuro-surgeon can justifiably operate upon the pituitaryat any stage of pregnancy, while the obstetricianand the endocrinologist should be able to ensurethat the pregnancy proceeds to term.

We wish to thank Dr K. S. Maclean and Dr R. K. Knightwho together guided us in replacement therapy, DrR. D. Hoare for the radiological studies, Mr T. L. T.Lewis and Dr H. Amini for the obstetrical details, MrJohn McArthur and Dr S. H. Mortazavi for the radio-therapeutic information in case 2, and Dr A. Hanied,and Dr H. Kasravi for follow-up information about ourtwo patients.

REFERENCES

Brimble, C. G. (1937). Cited by Rand (1957).Burke, C. W., Joplin, G. P., and Fraser, R. (1972). Pituitarytumour treated by pituitary implantation of yttrium90during and after pregnancy (two cases). Proceedings of theRoyal Society of Medicine, 65, 486-488.

Clifford, J. R., and Echols, D. H. (1973). Extrasellar expan-sion of a pituitary adenoma with a normal-sized sellaturcica and impaired vision from an atheromatous carotidartery: case report. Journal of Neurosurgery, 39, 398-400.

Corral, J., Calderon, and Goldzieher, J. W. (1972). Inductionof ovulation and term pregnancy in a hypophysectomizedwoman. Obstetrics and Gynecology, 39, 398-400.

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Duke-Elder, Sir W. S. (1947). Pituitary hyperplasias. In Text-Book of Ophthalmology, vol. 4, pp. 3508-3509. Kimpton:London.

Emperaire, J.-L., Riemens, V., Dubecq, J.-L., Palmade, J.,and Leuret, L. Ph. (1972). Hypophysectomie d'urgence adeux mois du grossesse apres induction de l'ovulation.Bordeaux Medical, 5, 1901-1904.

Enoksson, P., Lundberg, 'N., Sjostedt, S., and Skanse, B.(1961). Influence of pregnancy on visual fields in supra-sellar tumours. Acta Psychiatrica et Neurologica Scandi-navica, 36, 524-538.

Gemzell, C. (1973). Induction of ovulation in patients follow-ing removal of a pituitary adenoma. American Journal ofObstetrics and Gynecology, 117, 955-961.

Gemzell, C., and Kjessler, B. (1964). Treatment of infertilityafter partial hypophysectomy with human gonadotrophins.Lancet, 1, 644.

Goluboff, L. G., and Ezrin, C. (1969). Effect of pregnancy onthe somatotrophic and prolactic cells of the human adeno-hypophysis. Journal of Clinical Endocrinology and Metabol-ism, 29, 1533-1538.

Hagedoorn, A. (1937). Cited by Enoksson et al. (1961).Jorgensen, P. I., Sela, V., Buss, O., and Damkjaer, M. (1973).

Detailed hormonal studies during and after pregnancy in apreviously hypophysectomised patient. Acta Endo-crinologica, 73, 117-132.

Kaplan, N. M. (1961). Successful pregnancy following hypo-

physectomy during the twelfth week of gestation. Journalof Clinical Endocrinology and Metabolism, 21, 1139-1145.

Kaytar, T., and Tomkin, G. H. (1971). Emergency hypo-physectomy in pregnancy after induction of ovulation.British Medical Journal, 4, 88-90.

Lepoire, J., Arnould, G., Tridon, P., and Laxenaire, M.(1964). H6mianopsie, recidivante au cours des troisgrossesses chez une malade porteuse d'un ad6nomeeosinophil de l'hypophyse avec syndrome amenorrh6e-galactorrh6e. Revue d'Oto-Neuro-Ophtalmologie, 36, 203-206.

Linquette, M., Fossati, P., Dupont-Lecompte, J., Gasnault,J.-P., and Montois, P. (1970). Adenomes hypophysaires etgravido-pierp6ralite. Revue Fran!ais Endocrinologie Cli-nique, 11, 223-232.

Rand, C. W. (1957). Two cerebral complications of preg-nancy: Brain tumor and subarachnoid hemorrhage.Clinical Neurosurgery, 3, 104-141.

Sommers, S. S. (1958). The pituitary and hypothalamus. InThe Endocrinology of Reproduction, pp. 59-97. Edited byJ. T. Velardo. Oxford University Press: New York.

Swyer, G. I. M., Little, V., and Harries, B. J. (1971). Visualdisturbance in pregnancy after induction of ovulation.British Medical Journal, 4, 90-91.

Walsh, F. B., and Hoyt, W. F. (1969). Pregnancy and pituitaryaffections. In Clinical Neuro-Ophthalmology, vol. 3, pp.2124-2125. Williams and Wilkins: Baltimore.

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