J Neurol (2003) 250 : 1385–1387DOI 10.1007/s00415-003-0209-y

Desmond KiddPauline WilsonBronia UnwinNeil Dorward

Lymphocytic hypophysitispresenting early in pregnancy

Received: 25 March 2003Received in revised form: 11 June 2003Accepted: 24 June 2003

Sirs: A 31 year old woman pre-sented following the developmentof worsening vision in both eyesfor two weeks, associated with nau-sea, vomiting and tiredness. Therehad been a mild headache for theprevious three weeks, worse in themorning, without symptoms sug-gestive of raised intracranial pres-sure. She was in her 22nd week ofpregnancy. There were no othersymptoms, and previously she hadbeen well. This was her secondpregnancy, the first having com-pleted at term some nine monthspreviously. She had breastfed for

six weeks, and the baby was well.Her past medical history was unre-markable.

On examination she was well.Blood pressure was 100/60 withouta postural drop. The cardiovascularand respiratory examinations werenormal. The abdominal examina-tion revealed a gravid uterus of ex-pected size. The higher corticalfunctions were normal. The visualacuities were 6/6 on the right withnormal colour vision, 6/36 on theleft with absent colour vision and arelative afferent pupillary defect.The visual fields are shown inFig. 1. Ocular examination was nor-mal and the discs appeared nor-mal. Trigeminal sensory functionand the remainder of the neurolog-ical examination were normal.

Investigations:� Full blood count normal.� Serum urea was 1.3 mmol/l,

serum creatinine 55 µmol/l[60–120],

� sodium 124 mmol/l, potassium3.9 mmol/l.

� Plasma and urine osmolalitywere 256 mmol/kg [275–295]and 340 mmol/kg respectively.

� Prolactin level was 5755 mU/l(upper limit of normal at 22weeks gestation 1800 mU/l).

� Random cortisol level was58 nmol/l [200–650] rising to453 at 60 minutes after a shortsynacthen test.

� LH/FSH were both < 0.3, oestra-diol 8914 pmol/l [110–1875],progesterone 156 nmol/l (< 80).

� TSH was low at 0.1 mU/l(0.5–4.7) and free T4 7.3 pmol/l[10–25].

These results were assessed by en-docrinologists and were consid-ered to reflect anterior pituitaryfailure. The low sodium was felt tobe due predominately to cortisoldeficiency rather than posterior pi-tuitary involvement.

MRI of brain showed a massarising from the pituitary fossa en-croaching on the cavernous sinusesbilaterally and extending verticallyupwards, elevating the chiasm(Fig. 2).

Owing to concerns over the rateof change of the visual function to-gether with the height of the pro-lactin level and the early stage of

LETTER TO THE EDITORSJO

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Fig. 1 Goldman field at presentation showing constriction of the left field with apparent enlargement of the blind spot, and, on the right, a superotemporal field defect.The pattern of field loss is in keeping with a bitemporal hemianopia

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pregnancy it was decided that thelesion be removed through a trans-sphenoidal approach. At surgery apale yellow fibrous mass was seenwhich was removed piecemeal inentirety. The sample showed nor-mal adenopituitary tissue whichcontained a diffuse lymphocyticinfiltrate including plasma cellsand eosinophils (Fig. 3). Immuno-staining revealed both B and Tlymphocytes and a normal distrib-ution of hormone-producing cells.

There was no evidence of a pitu-itary adenoma on immunohisto-chemistry.

Post operatively the patient didwell on cortisol replacement onlyand without signs of diabetes in-sipidus. The pregnancy continuedand a healthy child was delivered atterm. Three months post-partumthe neuro-ophthalmic examinationwas normal with a full visual fieldand normal discs. MRI withgadolinium shows no evidence of

residual tissue, and she was on nohormone replacement.

Lymphocytic hypophysitis is arare but increasingly recognised pi-tuitary disorder which affectswomen at the end of pregnancy orin the immediate post-partum pe-riod [1] most commonly, althoughit may occur independently ofpregnancy in persons of either sex[2]. The aetiology is unknown butthere is a relationship with otherautoimmune diseases, particularly

Fig. 2 T1 weighted MRI scans (a) in the sagittalplane and (b) in the coronal plane showing enlarge-ment of the pituitary fossa due to the presence of amass lesion which extends upwards to compress theoptic chiasm. TR 500ms, TE 25ms

a b

Fig. 3 Histological section of anterior pituitary tis-sue (haematoxylin & eosin) showing a diffuse, focallydense, inflammatory infiltrate of lymphocytes,plasma cells and small numbers of eosinophils. Thereare no features of adenoma, nor were granulomataseen. Immunostaining showed that the lymphocyteswere of B and T cell types

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thyroid disease and diabetes, andantibodies directed against pitu-itary tissues have been identified[3] and shown to be an isoform ofneuron-specific enolase, alpha eno-lase. This isoform reacts with pitu-itary and human placental tissue,explaining the relationship be-tween the disorder and the preg-nant state [4]. Lymphocytic hy-pophysitis usually presents withvisual symptoms and headache dueto mass effect; anterior pituitaryfailure is common. Infundibulohy-pophysitis presents with diabetesinsipidus and frequently, althoughnot exclusively, exists without ante-rior pituitary dysfunction. Sponta-neous resolution has been re-ported, as has resolution withcortisol replacement therapy only[5, 6]; Other cases have respondedrapidly and permanently to intra-venous corticosteroids [7].

The differential diagnosis of thislesion includes an expanding pitu-itary adenoma or meningioma,both of which may enlarge consid-erably during pregnancy [8], infec-tive processes such as tuberculosis,pyogenic or fungal sinus disease ormucocoele, and granulomatousdisease, particularly sarcoidosiswhich may commonly affect thehypothalamus and pituitary [9]. Noother case has been reported soearly in pregnancy and hence aclear treatment protocol duringpregnancy is required; in post-par-tum cases a trial of steroids seems

justified, with recourse to surgeryonly if the lesion fails to resolve orgrows larger, as advocated byTubridy et al. [1]; similarly in verylate pregnancy the same treatmentplan can be used, or a delay insurgery until after a planned cae-sarian section. What, thereforeshould be done in the middletrimester? A trial of high dose in-travenous steroids may be worth-while but it is likely, since alpha-enolase expression will continue,that continuing steroid therapywould be required, which may beassociated with adverse effectsthroughout the remainder of thepregnancy. Furthermore, with in-adequate treatment, progressiveand irreversible pituitary failuremay ensue through pituitary fibro-sis. We feel, therefore, that our rec-ommendation that early surgery beundertaken was the correct man-agement decision, the risks ofanaesthesia and neurosurgery incompetent hands being lower thanmedical management.

References

1. Tubridy N, Molloy J, Saunders D, et al.(2001) Post-partum pituitary hy-pophysitis. J Neuroophthalmol 21:106–108

2. Tubridy N, Saunders D, Thom M, et al.(2001) Infundibulohypophysitis in aman presenting with diabetes insipidusand cavernous sinus involvement. JNeurol Neurosurg Psychiatry 71:798–801

3. Nishiki M, Murakami Y, Ozawa Y, et al.(2001) Serum antibodies to human pi-tuitary membrane antigens in patientswith autoimmune lymphocytic hy-physitis and infundibuloneurohypo-physitis. Clin Endocrinol 54:327–333

4. O’Dwyer DT, Clifton V, Hall A, et al.(2002) Pituitary auto-antibodies inLymphocytic Hypophysitis target bothgamma- and alpha-enolase – a link withpregnancy? Arch Physiol Biochem 110:94–98

5. Noto H, Tsukamoto K, Hayashi S, et al.(2001) Spontaneous recovery form hy-popituitarism in a man with lympho-cytic hypophysitis: a case report. En-docr J 48:483–486

6. Krimholtz MJ, Thomas S, Bingham J,et al. (2001) Lymphocytic hypophysitis:spontaneous resolution on MRI withprogression of endocrine defect. Int JClin Pract 55:339–340

7. Kristof RA, Van Roost D, Klingmuller Det al. (1999) Lymphocytic hypophysitis:non-invasive diagnosis and treatmentby high dose methylprednisolone pulsetherapy? J Neurol Neurosurg Psychiatry67:398–402

8. Kupersmith MJ, Rosenberg C, KleinbergD (1994) Visual loss in pregnant womenwith pituitary adenomas. Ann InternMed 121:473–477

9. Bullmann C, Faust M, Hoffmann A et al.(2000) Five cases with central diabetesinsipidus and hypogonadism as firstpresentation of neurosarcoidosis. Eur JEndocrinol 142:365–372

D. Kidd, MD (�) · P. Wilson, MB · B. Unwin, MPhil · N. Dorward, FRCSNeuroophthalmology Dept.Royal Free HospitalPond StreetLondon, NW3 2QG, UKTel.: +44-20/7830-2387Fax: +44-20/7431-1577E-Mail: d.kidd@rfc.ucl.ac.uk