MEDICINE

Large Nonfunctioning Pituitary Adenoma Presenting with Visual LossDuring Late Pregnancy—Challenges in Management

Lia Manuela Terhes1 & Elena Baciu1& Ana Curt1 & Andrei Malutan2,3

& Stefan Florian2,4& Carmen Georgescu1,2

&

Ioana Rada Ilie1,2

Accepted: 30 July 2019# Springer Nature Switzerland AG 2019

ABSTRACTNonfunctioning pituitary adenomas (NFPA) are very rare during pregnancy since fertility is usually impaired. A 31 year oldhirsute woman was referred to the Endocrine Clinic for a large pituitary tumor, discovered at 35 weeks of gestation. Shecomplained of increasing headache and abnormal vision, particularly in her left eye in the previous few weeks. An MRIscan showed a pituitary mass: 3.1 ×2.7 ×1.8 cm (LL/CC/AP) with suprasellar extension, and compression of the opticchiasm. Serum prolactin and the results of other endocrine investigations were normal, so she was diagnosed withNFPA. Both inducing labour or medication (bromocriptine) administration while proceeding to a safe term for pregnancywere considered. However, we chose to only follow her closely. There was no further deterioration and, at 38 weeks, acaesarian section was performed and a healthy boy was delivered. Two weeks after delivery, she underwent craniotomy(by right lateral subfrontal approach) with resection of the NFPA, followed by complete regression of the visualdisturbances. The postoperative MRI demonstrated empty sella and no residual tumor, while the hormonal evaluationdetected no significant pituitary insufficiency. Although cost-effective, combined histologic and immunophenotypicstudies, especially extended IHC tests, can reduce the incidence of misdiagnosed large-cell lymphoma. As exemplifiedin this present case, obtaining appropriate and sufficient tissue from the tumor could possibly increase the chance offinding an accurate diagnosis.

Keywords large nonfunctioning pituitary adenoma . pregnancy . visual disturbances . pituitary gland . visual field defect

Introduction

Pituitary tumors constitute 10 to 15% of all intracranialneoplasms tumors. When a pituitary tumor appears duringpregnancy or a patient with a pituitary tumor achieves

pregnancy, the difficulties in recognizing and establishingthe diagnosis and choosing the appropriate managementare even greater. Prolactinomas, representing about 40%of all pituitary adenomas in the general population, are themost common causes of pituitary enlargement duringpregnancy. [1] Nonfunctioning pituitary adenomas(NFPAs), accounting for approximately 25 to 35% of pi-tuitary tumors, are not common during pregnancy. [2]This can be explained by the fact that they are associatedwith decreased fertility in these patients, due to impair-m e n t i n g o n a d o t r o p i n s e c r e t i o n a n d / o rhyperprolactinemia, prevalent in 36–96% of patients withmacroadenomas. [1, 3]

The growth of NFPA during pregnancy is unexpected, asestrogenic stimulation does not seem to influence this kind ofadenoma. [3]

This article reports the case of a hirsute woman diagnosedwith NFPA that led to visual field abnormalities during hersecond spontaneous pregnancy, representing the largest NFPAdiagnosed in a pregnant woman.

This article is part of the Topical Collection on Medicine

* Ioana Rada Ilieioanamanaila@yahoo.com

1 Endocrinology Department, County Emergency Hospital,Cluj-Napoca, Romania

2 Iuliu Hatieganu” University of Medicine and Pharmacy,Cluj-Napoca, Romania

3 “Dominic Stanca” Obstetrics and Gynecology Clinic, “IuliuHatieganu” University of Medicine and Pharmacy,Cluj-Napoca, Romania

4 Neurosurgery Department, “Iuliu Hatieganu”University of Medicineand Pharmacy, Cluj-Napoca, Romania

https://doi.org/10.1007/s42399-019-00120-2SN Comprehensive Clinical Medicine (2019) 1:758–763

/Published online: 14 August 2019

Case Report

A 31-year-old, G2P1, 35-week pregnant woman was re-ferred to our clinic for a large pituitary tumor diagnosed2 days before presentation. The patient reported a historyof bifrontal headache, which had intensified in the previous2 months, with a frequency of 1–2 episodes/week and in-tensity increasing from 5/10 to 7/10 on pain rating scale.However, she did not pay too much attention to this head-ache and no diagnostic and therapeutic interventions in thisrespect were performed. Starting with week 32 of gesta-tion, abnormal vision, particularly affecting the left eye,occurred. She insisted that the complaints were not presentbefore pregnancy or in the first part of pregnancy. Duringweek 33 of gestation, she visited an ophthalmologist,where she was treated on outpatient basis. The exam re-vealed visual acuity of 0.8 in the right eye (1 with correc-tion) and 0.2 in the left eye (0.3 with correction). The full-

field 120-point screening test demonstrated right temporalhemianopia and the patient reported that she could not seethe bright spot with the left eye. She was suspected ofhaving optic (retrobulbar) neuritis and was directed to neuro-logical examination and cerebral MRI. The next day she suf-fered sudden severe headache and blurred vision. A neurolog-ical examination was performed in the emergency department.Everything was normal (no limitation of eye movements, nosign of meningeal irritation, no asymmetries in the limbs)except for reduced visual acuity in the left eye and the pres-ence of frontal headache. Paracetamol IV was administeredand this alleviated the headache. A suspicion of cerebralthrombosis was raised, and a cerebral MRI was indicatedagain. However, this was only performed 12 days later. TheMRI revealed a macroadenoma with the size of 3.1 × 2.7 ×1.8 cm (LL/CC/AP), lobulated, with some nodular lesions(suggesting either a macroadenoma with necrosis or hemor-rhage with delayed presentation) with suprasellar extension

Fig. 1 PreoperativeMRI demonstrates a large pituitary adenomawith suprasellar extension and compression of the optic chiasma. a Sagittal T1 cerebral-weighted MRI with contrast. b Coronal FLAIR T2-weighted MRI with contrast. c Axial T2 weighted MRI with contrast

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and compression of the optic chiasm, particularly on the leftside (Fig. 1).

The patient came to our clinic 2 days after performing theMRI and 2 weeks after that episode of severe headache andblurred vision (which did not repeat meanwhile). Physicalexamination revealed a conscious and well-oriented youngwoman. She was not pale, icteric, or febrile. Blood pressureon admission was 100/70 mmHg and the pulse rate was 90beats per minute, regular, and of good volume. There were nosigns or symptoms of acromegaly, of Cushing syndrome, or,on the contrary, of adrenocortical insufficiency. Confrontationvisual field testing revealed loss of vision in the temporal field,more pronounced in the left eye. Of note was also the presenceof hirsutism (a Ferrimann-Gallwey score of 22).

There were no specific past medical or surgical histories.Three years before she delivered a healthy child by cesareansection because of obstetrical indication. She admitted signif-icant menstrual irregularities before the first pregnancy butregular periods after that. Therefore, we thought that she mighthave been suffering from polycystic ovary syndrome (PCOS).

Relevant investigations were ordered. The results were asfollows: serum prolactin (PRL= 1785.8 μUI/ml (normal values,127–637/normal values 3rd trimester, 1107–7390) and repeated100.3 ng/ml (normal values, 1.3–20) (prolactin, dilution 1:10 =86.5 ng/ml and 1:100 = 147 ng/ml)), serum freeT4 = 8.58 pmol/l(normal values, 10.6–22.7/normal values 3rd trimester, 8.39–15.6), TSH= 1.62 μUI/ml, serum cortisol was low–normal =366 nmol/l (normal values, 172–497/normal values 3rd trimester,331–1380), andACTH=62.84 pg/ml (normal values, 7.2–63.3).To emphasize, PRL levels, measured twice, were appropriate forher gestational age. Therefore, she was diagnosed as having anonfunctioning pituitary tumor.

Abdominal-pelvic ultrasound revealed a live singleton fe-tus at 35 weeks with cephalic presentation and anterior pla-centa. The fetal heart rate was 130/min.

Both the obstetric team and patient herself were reluctant tocesarean section at that moment. So we decided to repeat theperimetry to check if there is a rapidly progressive visual loss.The ophthalmological exam showed visual acuity of 0.8 in theright eye (1 with correction) and 0.3 in the left eye (0.6 withcorrection) and the visual field testing revealed no furthervisual loss. Since the headache was not significant at the mo-ment of presentation, there was no further deterioration ofvisual abnormalities and the patient was very reluctant to takedrugs‚ close monitoring of the patient and her pregnancy, asoutpatient, has been chosen until reaching a gestational agecloser to the term. No glucocorticoids or dopamine agonistswere initiated, and she was scheduled for cesarean section atthe beginning of week 38 of gestation.

The patient was seen weekly for another 2 weeks for as-sessments of symptoms such as headache and visual prob-lems. At 38 weeks of gestation, a cesarean section was per-formed (with steroid coverage—during the procedure) and ahealthy 3070 g boy, with Apgar scores of 9, was delivered.Postpartum, the patient was keen to breast-feed. The patientand the newborn were discharged without complications5 days after delivery. The hormonal assessment was repeated:the results were normal again, as follows: prolactin =57.5 ng/ml, serum freeT4 = 1.01 ng/dl, serum cortisol =15.6 μg/dl (normal values 5–25 μg/dl).

Two weeks after delivery, she underwent a craniotomy-right lateral sub-frontal approach (with perioperative gluco-corticoid support) with resection of the pituitary adenoma.The neurosurgeon decided to perform craniotomy instead of

Fig. 2 The postoperative MRI demonstrates empty sella and no residual tumor. a, b Sagittal and coronal T2-weighted MRI

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transsphenoidal surgery due to the location of the tumor andits relationship to the optic chiasm, the optic nerve, and theright cavernous sinus, considering that using this approach hehas better control over the adenoma and the neurovascularstructures. Microscopical examination of the excised massrevealed adenoma cells with round, basophilic nuclei and eo-sinophilic or clear cytoplasm (a pituitary adenoma). The visualloss regressed completely after surgery. The postoperativeMRI performed 3 months later demonstrated empty sellaand no residual tumor (Fig. 2), whereas the hormonal evalua-tion detected no significant pituitary insufficiency (except fora reduction in the gonadotropin reserve).

The visual field was normal, as well (Fig. 3).The hormonal levels were as follows: cortisol 8 a.m. =

13.1 μg/dl; TSH = 0.94 μUI/ml; FT4 = 1.01 ng/dl; FSH =3.10/3.97 U/l; LH = 0.51/1.87 U/l; estradiol = 54.7/37.1 pg/ml; prolactin = 10.5 ng/ml; testosterone = 0.25 ng/ml;DHEAS = 1.03 μg/ml.

Discussions

As far as we know, this is the largest reported case of NFPAdiagnosed de novo in pregnancy. In patients with NFPAs,fertility is usually impaired by the destruction of gonadotrophcells or hyperprolactinemia caused by pituitary stalk destruc-tion. Pregnancy is, therefore, a rare event in patients with suchtumors.

On the other hand, the growth of a NFPA during pregnancyis unexpected, as estrogenic stimulation does not seem to in-fluence this kind of adenoma [4]. The enlargement of a

pituitary adenoma can be due to tumor growth, infarction, orhemorrhage of tumor. [5]

However, it has been shown that approximately 20% ofmacroadenomas may lead to abnormalities in visual fields orother neurologic signs, usually in the first half of pregnancy.On the other hand, the lactotroph hyperplasia that occurs in allpregnancies may increase pituitary gland size up to 136% or12 mm in height [4, 5], thus pushing the pre-existing pituitarytumor towards the optic chiasm. However, some authors sug-gested that this physiologic phenomenon is usually notenough to lead to compressive symptoms, unless the tumoritself grows. [6] Furthermore, these changes almost alwaysrevert to normal after delivery, so aggressive therapy forknown pituitary adenomas is not indicated except in cases ofrapidly progressive visual loss. [7]

The best approach for patients with asymptomatic NFPA isthe wait-and-see policy. However, in cases of symptomatictumor enlargement with rapidly progressive visual loss andwhen the fetus is immature, medical treatment using dopa-mine agonists can be considered to reduce physiologiclactotroph cell hyperplasia, and surgery should be consideredduring the second trimester. [8]

Our patient was diagnosed with this large NFPA only inthe 3rd trimester (week 35 of gestation), actually very closeto term. Obvious features of symptomatic tumor expansionwere present only 3 weeks before her endocrine evaluation.Most likely, the combined factors of physiologic enlarge-ment and incidentally detected pituitary adenoma duringpregnancy influenced her newly developed headache dur-ing pregnancy. In a national, prospective, observational,population-based case series study conducted in the UK,there were 16 cases of NFPA in pregnancy, of which 5

Fig. 3 Normal visual field aftersurgery. a Left eye. b Right eye

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were diagnosed de novo in pregnancy. Symptomatic tumorexpansion was observed in 3 of them (two in the 3rd tri-mester and one in the 2nd trimester). [9]

We can speculate that the episode of sudden severeheadache and blurred vision she suffered the day follow-ing her ophthalmological examination and 2 weeks beforewe saw here as outpatient was the result of a hemorrhageof the tumor (subacute pituitary apoplexy). In patientswith pituitary adenomas, pregnancy may result in tumorenlargement and apoplexy due to lactotroph hyperplasiaand enhanced pitui tary vascular i ty with edema.Fortunately, the episode did not repeat and she claimedthat her symptoms did not aggravate in the last weeks.The visual field test confirmed that. So, we chose not toadminister glucocorticoids at that moment; however, cor-tisol was low–normal, so steroid coverage at the time ofcesarean section and craniotomy was indicated. We didnot initiate dopamine agonists either, since the time upto term was short (2–3 weeks) so a successful effect ontumor shrinkage was unlikely. Since non-secreting pitui-tary tumors possess few dopaminergic receptors on theircell membranes, bromocriptine has been used with verylittle success in reducing tumor size. [10] Furthermore,bromocriptine did not improve diplopia and left ptosisresulting from the enlargement of nonfunctioning pituitaryadenoma during pregnancy that has not been diagnosedbefore pregnancy in another 39-year-old nulliparouswoman. [11] On the contrary, others reported that 8–16% of non-secretory pituitary adenomas do respond todopamine agonist therapy, and a direct effect of thesedrugs on tumor shrinkage was suggested. However, thebeneficial effect of bromocriptine is usually achieved byan effect on the physiologically enlarged pituitary (phys-iological lactotroph hyperplasia of pregnancy). [12] Sincethe prolactin was only 3 times the upper normal values innonpregnant women (and in ranges for the gestationalage), we can assume that the lactotroph hyperplasia wasnot significant in her case. Moreover, dopamine agonisttherapy has been considered a risk factor for pituitaryapoplexy and bromocriptine has been associated with hy-pertension, cardiac injury, and death when used in thepostpartum period in a 30-year-old nulliparous Nigerianwoman. [13] Interestingly, except for hirsutism, she wascompletely asymptomatic before this pregnancy.Moreover, she complained of oligomenorrhea before thefirst pregnancy which spontaneously resolved after givingbirth. Though the androgen hormone concentrations werewithin ranges, we might assume that she had a PCOS(clinical hyperandrogenemia + menstrual irregularities,other disorders excluded) which might have further im-paired fertility.

Fortunately, the rest of her pregnancy was uneventful, andthe surgery performed 2 weeks later was a success.

Conclusion

In conclusion, we present an interesting case of a young wom-an, most likely having PCOS with two spontaneous pregnan-cies 3 years apart, diagnosed with a large NFPA causing visualloss during the second pregnancy but with an excellent out-come. Pregnancy may lead to pituitary tumor growth and in-crease the risk of developing vision loss. On the other hand,pituitary tumor treatment may be a disturbing factor for preg-nancy. When a pituitary disorder appears during pregnancy ora patient with a pituitary disorder achieves pregnancy, it be-comes more difficult to recognize and establish the diagnosisand choose the appropriate management. As these rare condi-tions can be dangerous for bothmother and fetus, it is essentialto identify and treat them successfully. Pituitary disorders andparticularly large pituitary adenomas causing visual abnormal-ities in pregnancy are certainly challenging and require a mul-tidisciplinary approach from endocrinologists, gynecologists,radiologists, and neurosurgeons.

Finally, pituitary tumors should be taken into considerationwhen encountering pregnant women with visual disturbance.And, as regards to fertility chances, “never say never” inwomen.

Author Contributions II, AM, and SF managed the case. LT, AC, and IIdrafted the manuscript. LT, EB, II, and CG reviewed the manuscript.

Compliance with Ethical Standards

Conflict of Interest The authors declare that they have no conflict ofinterest.

Ethical Approval This article does not contain any studies with humanparticipants or animals performed by any of the authors.

Informed Consent Informed consent was obtained from the patient forbeing included in this case report.

Open Access This article is distributed under the terms of the CreativeCommons Attribution License which permits any use, distribution, andreproduction in any medium, provided the original author(s) and thesource are credited.

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