Michael H. Brisman, M.D., Susan Morgello, M.D., Adam Silvers, M.D., Irwin Klein, M.D., and Kalmon D. Post, M.D.
Departments of Neurosurgery, Pathology (Division of Neuropathology), and Radiology, The Mount Sinai Hospital, New York, New York; and Department of Medicine (Division of Endocrinology), North Shore University Hospital, Cornell University Medical College, Manhasset, New York
A case is described of an elderly woman who presented with headaches, hypopituitarism, and visual disturbances and was found to have idiopathic granulomatous hypophysitis, a rare lesion of the pituitary gland. Preoperative magnetic resonance imaging demonstrated a well-circumscribed lesion, which was isointense on both T1- and T2-weighted imaging and enhanced uniformly with administration of gadolinium contrast enhancement, not unlike a macroadenoma. The present case and 12 other cases from the literature are reviewed.
Key Words * pituitary * idiopathic * granulomatous * hypophysitis
Hypophysitis is a rare inflammatory disorder of the pituitary gland that takes the form of either a lymphocytic or granulomatous process. Granulomatous hypophysitis can be caused by any systemic disease that is capable of forming granulomata, most notably, sarcoidosis, syphilis, and tuberculosis. It can also be related to various other intrasellar lesions such as cysts,[1,6] adenomas, and mucoceles. Granulomatous hypophysitis, which is identified in the absence of any known underlying or associated pathology, is referred to as idiopathic. There are only 12 cases in the literature of idiopathic granulomatous hypophysitis identified at surgery [2,5,6,8,10,12,13]--as opposed to postmortem diagnoses of this entity--and only three such cases reported with a preoperative magnetic resonance (MR) image. We report a case of idiopathic granulomatous hypophysitis visualized on MR imaging and identified at surgery in an elderly woman. This case is discussed in referrence to the other 12 cases reported in the literature.
This 72-year-old woman presented with various symptoms occurring over the 12 months prior to admission, which included projectile vomiting, pleural effusion, adrenal insufficiency, and, what appeared to be, viral pericarditis. A pericardial window procedure had been performed, without a definitive diagnosis.
Examination. Because of persistent headaches, computerized tomography (CT) and MR imaging of the head were obtained; they demonstrated a sellar mass with suprasellar extension. Magnetic resonance T1- and T2-weighted images revealed a well-circumscribed, homogeneous sellar lesion with suprasellar extension measuring 1.8 cm in height. The lesion was isointense to brain parenchyma on all pulse sequences and enhanced fairly uniformly with administration of gadolinium contrast medium. The infundibulum was thickened (Fig. 1).
Fig. 1. Preoperative magnetic resonance T1-weighted gadolinium-enhanced imaging, coronal view (left) and sagittal view (right). The lesion is well circumscribed, homogeneous, and isointense. Note that the infundibulum is thickened.
Endocrinological findings revealed panhypopituitarism. Her thyroxine level was 1.1 µg/dL (normal 4.512 µg/dL), her thyroid-stimulating hormone level was 0.04 mU/L (normal 0.35 mU/L), her follicle-stimulating hormone level was 1.8 mIU/ml (normal 126 mIU/ml), her luteinizing hormone level was 0.1 mIU/ml (normal 1664 mIU/ml), and her prolactin level was 0.5 ng/ml (normal 025 ng/ml). The patient received daily doses of prednisone (5 mg) and L-thyroxine (0.1 mg). For several months the patient had also noted progressive visual difficulties. Formal vision testing demonstrated a bitemporal hemianoptic defect, with visual acuity of 20/30 in the right eye and 20/200 in the left eye.
Operation. A transsphenoidal resection of the mass was performed. At surgery, a large, yellow, firm mass was noted. The mass was adherent to the surrounding cavernous sinus and arachnoid. A gross-total removal was achieved except for the very lateral wall.
Pathological Findings and Postoperative Course. Microscopic examination of the lesion demonstrated nonnecrotizing granulomatous adenohypophysitis with dense chronic inflammation, Langhans' and non-Langhans' type multinucleated giant cells, and focal fibrosis (Fig. 2). Immunohistochemical characterization of the chronic inflammation showed predominantly T cells and macrophages, with admixed B cells and plasma cells.
Fig. 2. Photomicrographs, H & E. Left: Low-power photomicrograph displaying multiple granulomata in a background of dense chronic inflammation. Original magnification X 25. Right: High-power photomicrograph showing multinucleated cells of the Langhans' type within granulomatous inflammation. Original magnification X 100.
Staining for organisms, including Gram, acid-fast, modified Steiner's, and GrocottGomori methenaminesilver nitrate, was negative for bacteria, mycobacteria, spirochetes, and fungi, respectively. A skin purified protein derivative test for tuberculosis was negative, as were serum rapid plasma reagin levels for syphilis, and angiotensin-converting enzyme levels for sarcoid. Cultures for bacteria and acid-fast bacillus showed no growth. After surgery, the patient's vision dramatically improved: visual fields and acuity were normal. She was discharged in good condition on a course of glucocorticoid and L-thyroxine replacement therapy.
The pathological characteristics of granulomatous hypophysitis were first described in 1911 by Gougerot and Gy and in 1917 by Simmonds. In 1954, Rickards and Harvey reviewed 115 cases of granulomatous hypophysitis from the literature, including 23 idiopathic cases, all of which were diagnosed only at autopsy. Most cases of granulomatous hypophysitis are associated with systemic granulomatous diseases, most notably sarcoidosis, syphilis, and tuberculosis, but which can also include Langhans' cell granulomatosis and various bacterial and fungal processes. Granulomatous hypophysitis can also occur in the setting of other pituitary pathology such as cysts,[1,6] adenomas, and mucoceles, in which cases the inflammatory process may well represent a reaction to the local pituitary lesion.
There are 12 cases reported in the literature of patients with granulomatous hypophysitis diagnosed antemortem for which no etiology could be identified. Ours is a thirteenth case (Table 1).
Unlike lymphocytic hypophysitis, which usually occurs in young women, idiopathic granulomatous hypophysitis is more evenly distributed among men and women (five men, eight women) and occurs at an average age of 47.6 years (range 1972 years). Twelve of the 13 reported patients presented with endocrine symptoms, three presented with visual disturbances, and two presented with apoplexy (sudden headache and third nerve palsy). Unlike patients with granulomatous hypophysitis secondary to sarcoidosis, patients with idiopathic granulomatous hypophysitis present less commonly with diabetes insipidus (two of 13 cases). Nine of the 13 patients presented with hypopituitarism, and four had moderately elevated prolactin levels (20150 ng/ml). Panhypopituitarism in association with a rather modestly enlarged pituitary lesion (mostly confined to the sella turcica) may suggest the diagnosis of idiopathic granulomatous hypophysitis. Another suggestive feature is a thickened infundibulum, which was noted in four of the 13 cases.
Radiographically, idiopathic granulomatous hypophysitis shows some degree of enhancement on both CT and MR imaging and is most commonly mistaken for a pituitary adenoma. On T1-weighted MR imaging the lesion appears homogeneously isointense to brain parenchyma and enhances homogeneously. At surgery, the lesion appears as a firm mass, and postoperatively, patients uniformly do well. Surgical debulking tends to improve visual disturbances but not the hypopituitarism.
The patient described in the present case is older, at 72 years of age, than any of the patients previously reported. The pleural effusion and pericarditis are of interest, although no connection could be found between systemic inflammatory abnormalities and the patient's granulomatous pituitary disorder.
In summary, idiopathic granulomatous hypophysitis is a rare disorder of the pituitary gland that carries a good prognosis. Treatment consists of hormone replacement therapy when hypopituitarism is present, biopsy if the presence of a systemic disorder is suspected and cannot be otherwise diagnosed, and debulking if the lesion is large and the optic chiasm is compromised.
1. Albini CH, MacGillivray MH, Fisher JE, et al: Triad of hypopituitarism, granulomatous hypophysitis, and ruptured Rathke's cleft cyst. Neurosurgery 22:133136, 1988
2. Del Pozo JM, Roda JE, Montoya JG, et al: Intrasellar granuloma. Case report. J Neurosurg 53:717719, 1980
3. Cosman F, Post KD, Holub DA, et al: Lymphocytic hypophysitis: report of 3 new cases and review of the literature. Medicine 68:240256, 1989
4. Gougerot H, Gy A: Insuffisance pluriglandulaire interne thyro-testiculo-surrénale: nouvelle observation clinique et anatomique. Nouv Iconog Salpêtrière 24:449462, 1911
5. Hassoun P, Anayssi E, Salti I: A case of granulomatous hypophysitis with hypopituitarism and minimal pituitary enlargement. J Neurol Neurosurg Psychiatry 48:949951, 1985
6. Higuchi M, Arita N, Mori S, et al : Pituitary granuloma and chronic inflammation of hypophysis: clinical and immunohistochemical studies. Acta Neurochir 121:152158, 1993
7. Holck S, Laursen H: Prolactinoma coexistent with granulomatous hypophysitis. Acta Neuropathol 61:253257, 1983
8. Pamir MN, Zirh TA, Özek MM, et al: Magnetic resonance imaging in the diagnosis of idiopathic giant-cell granulomatous hypophysitis: a rare cause of hyperprolactinaemia. Neurochirurgia 36: 2025, 1993
9. Rickards AG, Harvey PW: 'Giant-cell granuloma' and other pituitary granulomata. Q J Med 23:425439, 1954
10. Scanarini M, d'Avella D, Rotilio A, et al: Giant-cell granulomatous hypophysitis: a distinct clinicopathological entity. J Neurosurg 71:681686, 1989
11. Simmonds M: Über das vorkommen von reisenzellen in der hypophyse. Virchows Arch Pathol Anat 223:281290, 1917
12. Siqueira E, Tsung JS, Al-Kawi MZ, et al: Case report: idiopathic giant cell granuloma of the hypophysis: an unusual cause of panhypopituitarism. Surg Neurol 32:6871, 1989
13. Taylon C, Duff TA: Giant cell granuloma involving the pituitary gland. Case report. J Neurosurg 52:584587, 1980
Manuscript received May 31, 1996
Accepted in final form June 17, 1996
Address reprint requests to: Michael H. Brisman, M.D., Department of Neurosurgery, The Mount Sinai Hospital, 1 Gustave Levy Place, New York, New York, 10029.
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