Journal of Neuro-Ophthalmology, June 2001, Volume 21, Issue 2

Postpartum Pituitary Hypophysitis

The case of a young woman who developed lymphocytic hypophysitis 2 weeks after delivery of a healthy baby is reported. The patient presented with clinical features suggestive of a pituitary mass lesion, but surgery was avoided when other clinical and radiologic features were considered. The patient recovered with steroid treatment only. We review the literature on this increasingly recognized condition and argue that medical management may be more suitable than previously thought.

Journal of Neuro- Ophthalmology 21( 2): 106- 108, 2001. 1 2001 Lippincott Williams & Wilkins, Inc., Philadelphia Case Report Postpartum Pituitary Hypophysitis Neil Tubridy, MD, MRCP, Jane MoUoy, MB, MRCP, Dawn Saunders, MD, MRCP, FRCR, Anthony Belli, FRCS, Michael Powell, FRCS, and Gordon T. Plant, MD, FRCP The case of a young woman who developed lymphocytic hy­pophysitis 2 weeks after delivery of a healthy baby is reported. The patient presented with clinical features suggestive of a pituitary mass lesion, but surgery was avoided when other clini­cal and radiologic features were considered. The patient recov­ered with steroid treatment only. We review the literature on this increasingly recognized condition and argue that medical management may be more suitable than previously thought. Key Words: Lymphocytic hypophysitis- Pregnancy- Ste­roid treatment. Inflammatory growths in the area of the pituitary gland should be considered in the preoperative differen­tial diagnosis of every pituitary tumor that is not associ­ated with important hormonal dysfunction, particularly in the peripartum period. It may also present in the early stages of pregnancy, with symptoms mimicking hyper-emesis gravidarum or meningeal irritation ( 1). Hypo­physitis has been reported in men and in association with a number of autoimmune diseases, including Sjogren syn­drome, Graves disease, diabetes, and rheumatoid arthritis. The precise etiology remains unclear, but animal stud­ies have shown that rubella virus glycoproteins can in­duce autoimmune lymphocytic hypophysitis in Syrian hamsters and that neonatal thymectomy prevents the dis­ease ( 2). A definitive diagnosis can be made by endo­scopic endonasal biopsy ( 3), but we suggest that histo­logic examination may not always be necessary to diagnose hypophysitis when characteristic clinical fea­tures are found, as illustrated by the present case. CASE REPORT A twenty- year- old right- handed woman presented with a week- long history of progressive bilateral visual deterioration in early January 2000. During the previous Manuscript received May 16, 2000; accepted January 31, 2001. From the National Hospital for Neurology and Neurosurgery, Lon­don, UK. Address correspondence and reprint requests to Gordon T. Plant, MD, FRCP, Consultant Neurologist, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. week, she had given birth to a baby girl by Caesarean section. Initially, she noticed visual blurring, particularly in the temporal fields of vision, when she moved her head quickly. She also began to complain of vague frontotemporal headaches without diurnal variation or change with posture. There was no nausea, vomiting, diplopia, or ocular pain. She had no other symptoms. At presentation, she had not begun to lactate. The pregnancy had been uneventful, and before conception, her men­strual cycle had been regular. She had a miscarriage 3 years previously. There was no other relevant past medi­cal history and no family history of relevance- in par­ticular, no past or family history of autoimmune disease. On examination, her visual acuity was 6/ 12 OD and 6/ 9 OS. There was a bitemporal hemianopia on field testing with normal fundus examination. There were no other ab­normal neurologic or endocrinologic signs. A computed tomograph ( CT) scan was reported as showing a pituitary macroadenoma extending into the suprasellar region. Routine hematology tests revealed a hemoglobin level of 10.7 g/ dL, an increased platelet count of 436, and a normal biochemical profile. Her prolactin level was nor­mal ( 149 nmol/ L), but her morning Cortisol level was low at 27 U/ L ( normal, 170- 720 U/ L); the low Cortisol level may have been influenced by the steroids being used in her treatment. Her thyroxine level was low (< 6.4), but her thyroid- stimulating hormone level and bone profile were normal. Before and after contrast, Tl- weighted magnetic reso­nance images ( MRI) showed a homogeneously enhanc­ing pituitary mass with suprasellar extension compress­ing the optic chiasm and the hypothalamus ( Fig. 1). The mass was intimately related to, but not surrounding, the cavernous and supraclinoid internal carotid arteries. No intracavernous extension or evidence of hemorrhage was noted. She was given 4 mg of dexamethasone four times daily for a presumed diagnosis of lymphocytic hypo­physitis. During the first 3 days of treatment, her head­aches improved, and her visual acuity improved to 6/ 4 bilaterally. There was mild red desaturation in the tem­poral field OU, indicating marked improvement in visual fields. Cortisol and thyroxine replacement was begun. 106 POSTPARTUM PITUITARY HYPOPHYSITIS 107 FIG. 1. A: Precontrast T1 - weighted sagittal image of the pituitary gland. The gland is enlarged and the suprasellar extension compresses the optic chiasm. B: The enlarged pituitary enhances homogenously after administration of gadolinium diethylene triamine penta- acetic acid. A second MRI scan was performed 4 days after the first imaging study ( Fig. 2). The homogenous enhance­ment around the pituitary gland had reduced consider­ably and was now clear of the optic chiasm. She was discharged on a reducing dose of dexamethasone and replacement thyroxine and hydrocortisone therapy. On the day of discharge, her visual function was normal, including normal fields, visual acuity, and color vision. DISCUSSION Our patient represents a classic example of this un­usual condition, the etiology of which remains unknown. FIG. 2. A: Coronal and B: sagittal postcontrast T1- weighted images. After 4 days of intravenous dexamethasone, the pituitary has reduced in size and no longer compresses the optic chiasm. The pituitary stalk remains thickened. J Neuro- Ophthalmol, Vol. 21, No. 2, 2001 108 N. TUBRIDY ETAL. She displayed features of a suprasellar lesion, and the clinical context and imaging findings suggested lympho­cytic hypophysitis. These clinical features include a rapid onset of visual impairment, often in the peripartum pe­riod ( 4). CT and MRI imaging show a diffuse pituitary mass and enlarged pituitary stalk with homogenous con­trast enhancement. Diabetes insipidus and persistent amenorrhoea may occur; later, panhypopituitarism may also occur. Dynamic MRI has been used to demonstrate an abnormality of the hypophysial vasculature, even if the pituitary disease is seen to regress on conventional MRI studies ( 5). Gallium- 67 scintigraphy may show ab­normal uptake in the lesion ( 6). Autoantibodies to human pituitary cytosol proteins have been detected in as many as 70% of patients with biopsy- proven lymphocytic hy­pophysitis ( 7) and may represent markers for an immu­nologic process affecting the pituitary gland. As many as 25% of patients may have autoimmune thyroiditis ( 8). Histologic examination of the pituitary shows a lym-phoplasmacytic infiltrate with occasional neutrophils, eosinophils, and macrophages. There may be focal or diffuse adenohypophysial destruction of variable sever­ity with associated fibrosis. Most reported cases have been managed surgically, but steroid therapy has been advocated ( 9). One prospec­tive study of nine patients with lymphocytic hypophysitis treated with high- dose methylprednisolone pulse therapy demonstrated improvement of adenopituitary function in four patients. There was also a cessation of diabetes in­sipidus in all four patients ( 10). The presumptive nonin­vasive diagnosis of lymphocytic hypophysitis seems pos­sible in a high proportion of patients, and high- dose steroids may result in improvement of clinical, endocri-nologic, and MRI findings. In the absence of a visual field defect, however, it has been recommended that sur­gery and steroid therapy be withheld with periodic reas­sessment ( 11). In the absence of a controlled clinical trial, it is possible only to speculate whether there is a higher incidence of hypopituitarism after surgery for this condition. The current report illustrates that the response to steroids may be so rapid that very little time is lost if the diagnosis is incorrect. The major differential diagno­sis includes other pituitary adenomas common in preg­nancy: meningiomas ( which may be distinguished from this condition by imaging characteristics) and neurosar-coidosis ( the initial management of which is the same as the management for lymphocytic hypophysitis). The natural history of lymphocytic hypophysitis be­gins with enlargement of the pituitary secondary to in­flammatory infiltration and progresses to atrophy of the gland with destruction of pituitary tissue and replace­ment with fibrosis. The prognosis of the condition re­mains unclear, and there are only a few reports of preg­nant women who have had an episode of lymphocytic hypophysitis ( 11). Recurrence after 2 years has also been reported ( 12). REFERENCES 1. Ozbey N, Kahraman H, Yilmaz L, et al. Clinical course of a pituitary macroadenoma in the first trimester of pregnancy: prob­able lymphocytic hypophysitis. Int J Clin Pract 1999; 53: 478- 81. 2. Yoon JW, Choi DS, Liang HC, et al. Induction of an organ- specific autoimmune disease, lymphocytic hypophysitis, in hamsters by recombinant rubella virus glycoprotein and prevention of disease by neonatal thymectomy. J Virol 1992; 66: 1210- 4. 3. Kamel N, Ilgin SD, Gullu S, et al. Lymphocytic hypophysitis and infundibuloneurohypophysitis; clinical and pathologic evaluation. Endocr J 1999; 46: 505- 12. 4. Patel MC, Guneratne N, Haq N, et al. Peripartum hypopituitarism and lymphocytic hypophysitis. QJM 1995; 88: 571- 80. 5. Sato N, Sze G, Endo K. Hypophysitis: endocrinologic and dynamic MR findings. Am J Neuroradiol 1998; 19: 439- 44. 6. Murakami H, Hirose Y, Sagoh M, et al. Probable lymphocytic hypophysitis diagnosed by short- term serial computed tomography and gallium- 67 scintigraphy- case report. Neurol Med Chir ( To­kyo) 1999; 39: 174- 8. 7. Stromberg S, Crock P, Lernmark A, et al. Pituitary antibodies in patients with hypopituitarism and their relatives. J Endocrinol 1998; 157: 475- 80. 8. Thoudou E, Asa SL, Kontogeorgos G, et al. Clinical case seminar: lymphocytic hypophysitis: clinicopathologic findings. J Clin En­docrinol Metab 1995; 80: 2302- 11. 9. Honegger J, Falbusch R, Bornemann A, et al. Lymphocytic and granulomatous hypophysitis: experience with nine cases. Neuro­surgery 1997; 40: 713- 23. 10. Kristof RA, Van Roost D, Klingmuller D, et al. Lymphocytic hypophysitis: non- invasive diagnosis and treatment by high dose methylprednisolone pulse therapy? J Neurol Neurosurg Psychiatry 1999; 67: 398- 402. 11. Gagneja H, Arafah B, Taylor HC. Histologically proven lympho­cytic hypophysitis: spontaneous resolution and subsequent preg­nancy. Mayo Clin Proc 1999; 74: 150- 4. 12. Nishioka H, Ito H, Fukushima C. Recurrent lymphocytic hypo­physitis: case report. Neurosurgery 1997; 4: 684- 6. / Neuro- Ophthalmol, Vol. 21, No. 2, 2001