Endocrine Journal 2011, 58 (6), 467-473

Or i g i n a l Primary granulomatous : a case report and literature review

Shao-bo Su, Da-jian Zhang, Shu-yuan Yue and Jian-ning Zhang

Department of Neurosurgery, General Hospital of Tianjin Medical University, Tianjin, 300052, China

Abstract. Primary granulomatous hypophysitis (PGH) is a rarely occurred inflammatory disease of unknown etiology. We retrospective review a case of PGH treated by microsurgical transsphenoidal approach and review the appropriately documented cases of PGH collected from the literatures. The patient was a 56-year-old female who presented with 4 months history of headache and 2 months history of polyuria and polydipsia. Clinic examination did not find remarkable neurological signs, except endocrinological abnormalities of secondary and hypocorticalism. MRI revealed a symmetric sellar mass, which was isointensity as gray matter on T1-weighted and T2-weighted images with heterogeneous enhancement. The mass was partially resected via transsphenoidal approach. Histological assessment revealed a non-necrotizing granulomatous lesion with chronic . Although the resection was limited, repeatedly MRI scanning in 3 months following surgery revealed almost normal pituitary soft tissue without evidence of the lesion. Searching in PubMed, we found 21 papers published from 1985 to 2009 and 37 patients with PGH were reported. In order to identify the clinical and radiological presentation, treatment strategy, and prognosis of PGH, we analyzed these 38 cases together. The results indicate that the clinical presentations and radiological signs are helpful for the diagnosis of PGH. The outcome of surgery for PGH is favorable for immediate mass reduction and histological diagnosis, but replacement is required in most cases and long-term follow up is very important.

Key words: Hypophysitis, Granulomatous, Pituitary, Sellar mass

Recently advances in endocrinological and neuro- three large surgical series of more than 6000 sellar radiological expertise have greatly facilitated the early tumors, only 8 cases of PGH were identified [1-3]. detection of pituitary lesions. Technical refinements of Here, we report a case of PGH which was treated by transsphenoidal microsurgery have also provided a safe microsurgical transphenoidal approach and analyze the and effective approach to the sellar tumor or mass, and cases from the relative literatures, trying to know the broadened the indications. Previously, rare cases of characteristics of this disease. pathological processes involving the intrasellar cavity and the were identified only dependent Case Reports on materials. Nowadays, with the increasing number of transsphenoidal microsurgery, these diseases A 56-year-old female presented with 4 months his- have been delineated in the clinical setting and emerge tory of headache and 2 months history of polyuria and as a distinct pathological entity to be included in the polydipsia. On physical examination, the visual fields, differential diagnosis of sellar lesions. Primary granu- fundoscopic and neurological examinations were unre- lomatous hypophysitis (PGH) is a rare chronic inflam- markable. Endocrinological evaluation showed sec- matory disease of pituitary gland. Literature review ondary hypothyroidism and hypocorticalism: TSH demonstrated its low incidence in population. Within < 0.01 μIU/mL (normal: 0.3-5); free triiodothyro- nine (T3) 3.3 pmol/L (normal: 3.5-6.5); free thyrox- Received Nov. 22, 2010; Accepted Mar. 18, 2011 as K10E-357 ine (T4) 9.8 pmol/L (normal:11.5-23.5); ACTH 6.4 pg/ Released online in J-STAGE as advance publication Apr. 2 3 , 2011 mL(normal :0-46); cortisol 3.6 μg/dL at 8am (normal: Correspondence to: Jian-ning Zhang, M.D., Ph.D., Department of 5-25). A water deprivation test revealed diabetes insip- Neurosurgery, General Hospital of Tianjin Medical University, 154 idus of central origin. MRI showed a symmetric sellar An Shan Dao, Heping District, Tianjin, 300052, China E-mail: [email protected] mass, with 15 mm in height, which abutted the optic

©The Japan Endocrine Society 468 Su et al.

A B

C D

Fig. 1 Preoperative coronal MRI showed a symmetric sellar mass, measuring 15 mm in height, which abutted the optic chiasm. The mass was isointensity with gray matter on T1-weighted (A) and T2-weighted (B) images and had heterogeneous enhancement after the administration of gadolinium (C and D). chiasm. The mass was isointensity with gray matter and definite, the patient was further undergone cuta- on T1-weighted and T2 -weighted images and shown neous, skeletal, visceral, and laboratory examinations in heterogeneous enhancement after the administration for systemic granulomatous disease such as tuberculo- of gadolinium (Fig. 1). The diagnosis of pituitary ade- sis, syphilis, sarcoidosis, brucellosis, and histiocytosis noma and secondary was made. She X. Due to no significant evidences of systemic granu- underwent surgical exploration via the transsphenoi- lomatous disease were found, the final diagnosis was dal approach after preoperative prednisolone, thyrox- definitely primary granulomatous hypophysitis. ine and desmopressin acetate replacement. Surgical The postoperative course was uneventful. Although exploration showed the whole pituitary fossa was the resection was limited, repeatedly MRI scanning in occupied by a fibrous and yellowish mass adherent to 3 months following surgery revealed almost normal the adjacent dural mater and only partial resection was pituitary soft tissue without evidence of the lesion (Fig. achieved. Histological examination revealed a non-ne- 3). Desmopressin acetate was able to be withdrawn in crotizing granulomatous lesion with chronic inflamma- 1 month later and glucocorticiod and thyroxine therapy tion (Fig. 2). Once the histological diagnosis was clear were able to be gradually withdrawn in 3 months. No Primary granulomatous hypophysitis 469

Fig. 2 Photomicrograph showing a granulomatous inflammation characterized by multinucleated giant cells in a background of chronic inflammation. (HE stain, original magnification: A: ×100, B: ×400)

2, 4-22]. Here, such 37 patients, add the case of ours, total 38 patients with PGH were analyzed together. In addition, Gutenberg et al. [23] reported 6 cases of PGH among a series of 31 patients with primary hypophysi- tis (21 lymphocytic, 6 granulomatous, and 4 xanthom- atous cases). However, the author did not describe the details of each patient respectively, so such 6 patients did not include in our analysis. Although it is generally thought no gender predilec- tion in PGH [6, 24], the real ratio of male to female among these 38 reviewed cases was closely to 1:2 (12:26). The mean age of these patients at presentation was 46.1 years old (range from 16 to 76 years old), and the female was 44.7 years, younger than the 49.2 years old mean age of male. Fig. 3 Coronal contrast-enhanced T1-weighted MR image 3 Clinical presentation of PGH is variable and com- months after surgery revealed almost normal pituitary soft prises four main categories of symptoms: sellar com- tissue with no evidence of the lesion pression, hypopituitarism, , and hyperprolactinemia. In the total 38 patients, headache was the most common symptom, present in 23 cases relapse occurred in 2 years of follow-up. (60.5 %). Followed by symptoms related to diabetes insipidus in 10 cases (26.3 %), visual field impairment Review of the Literature in 9 cases (23.7 %), vomiting in 8 cases (21.1 %), nau- sea in 7 cases (18.4 %), extraocular muscle paralysis in PGH is so rare that only case reports but no series 6 cases (15.8 %) and febrile in 5 cases (13.2 %). were published by now. Thus, in clinic, there are All of the 38 reported patients presented with endo- no plenty of population-based data to calculate the crinological abnormality. The incidence of diabe- real incidence of PGH. However, some authors esti- tes insipidus was 34.2 % (13 of 38 cases) and hyper- mated its rate might be less than 1% of all pituitary prolactinemia was 31.6 % (12 of 38 cases). Details disorders with a population incidence of 1 in 10 mil- of function were available in 34 lion per annum [3, 4]. Searching in PubMed via the patients. Based on the available biochemical results, key words of ‘ hypophysitis’, and ‘primary’ or ‘idio- the incidences of insufficiency of gonadal, adrenal, thy- pathic’, we found 21 literatures published from 1985 roid and growth hormone axes were 76.5 % (26 of 34 to 2009 and 37 patients with PGH were reported [1, cases), 61.8 % (21 of 34 cases), 50 % (17 of 34 cases) 470 Su et al. and 29.4 % (10 of 34 cases), respectively. headache and visual disturbance, are the most commom Preoperative diagnosis was available in 28 cases. and usually the initial complaint. Headache is consid- The most preoperative diagnosis was pituitary ade- ered to be induced by distension and distortion of the noma (78.6%; 22 of 28 cases). The diagnosis of dural mater and diaphragma sellae due to the expand- inflammatory hypophysitis was only considered in4 ing pituitary mass. Visual abnormalities, including cases (14.3%). The diagnosis of craniopharyngioma visual field defect and decreased acuity, are second- was considered in 1 case and pituitary mass with acute ary to compression of optic chiasm. Lateral expansion meningitis in 1 case. of the mass into the cavernous sinus could compress Operative findings were mentioned in 23 cases. III, IV or VI cranial nerves, resulting in diplopia and The appearances were variable, but firm or fibrous are subsequently ocular misalignment [26]. All of the 38 more common (69.6 %; 16 of 23 available cases) than reported patients were presented with endocrinological that are usually creamy and fragile abnormality, in partial or complete deficit of the poste- and ease to curette. rior and/or anterior pituitary . These defects Follow-up information was available in 31 patients. can lead to the classic signs and symptoms of diabetes Surgery is effective in achieving decompression of the insipidus, , hypoadrenalism, and hypo- sellar mass and thereby resolving headache and visual thyroidism. deficits. However, surgery had poor effect on improv- Imaging appearances of the three primary hypo- ing the preexisting endocrine defects. Most patients physitis types are very similar. The striking CT fea- required long-term replacement with one or more hor- tures are an intrasellar mass with cystic areas and ring mones. enhancement [12-14]. Currently, MRI plays a crucial role in the diagnosis of primary hypophysitis because it Discussion has distinct advantage over CT for imaging the pituitary and sellar regional lesions. The MRI findings of pri- Inflammmatory processes of the hypophysis, known mary hypophsitis include: (1) Diffuse, ill-defined, sym- as hypophysitis, can be classified as secondary when the metrical enlargement of pituitary tissue; (2) Pituitary inflammatory pituitary reaction is triggered by a defi- stalk thickened, but not deviated or unidentifiable; (3) nite etiologic agent or a known systemic disease, and Sellar floor usually intact; (4) Mostly isointensity with primary when the inflammation is confined to the pitu- gray matter on T1 weighted image, marked homoge- itary gland without identifiable etiologic association neous or heterogeneous enhancement by gadolinium [25-27]. Primary hypophysitis is histologically clas- and a strip of enhanced tissue along the dura mater (the sified into three subtypes: lymphocytic hypophysitis, so-called ‘dural tail’); (5) Delayed complete contrast ganulomatous hypophysitis, and xanthomatous hypo- enhancement of the whole pituitary in dynamic MRI physitis [3, 4, 27]. However, many authors considered (>90 sec) [1, 4, 8-12, 29-32]. Among these unusual that these three histopathological subtypes were vari- MRI scan findings, three imaging signs – pituitary dif- able appearances of a single disease since they share fuse enlargement and marked enhancement and pitu- clinical and radiological features except for histologi- itary stalk thickening, are perhaps the strongest predic- cal examination [2, 27]. Although no definite etiology tor of primary hypophysitis. has been described, the pathogenesis of primary hypo- physitis was thought to be attributed to Differential Diagnosis [9, 23, 26-28]. However, in our case, no autoimmune To diagnose PGH, we should exclude secondary background can be found. granulomatous hypophysitis. The etiology of second- ary granulomatous hypophysitis includes infection Diagnosis (tuberculosis, syphilis, fungal), systemic inflamma- The diagnosis of PGH is challenging, partly due to tory conditions (sarcoidosis, Wegener’s granulomato- the fact that many physicians do not know about it more sis, Takayasu’s arteritis, Crohn’s disease, histiocytosis precisely. Accurate diagnosis requires a high degree of X) and foreign body reactions (ruptured Rathke’s cyst, suspicion and correlation with clinical and radiologi- mucocoele). In these patients, pituitary symptoms are cal presentations. Clinical presentation of PGH is vari- not isolated but are always associated with a general able. Symptoms of sellar compression, represented by inflammation, and presenting in specific abnormalities Primary granulomatous hypophysitis 471 of chest X-ray, or biological inflammatory examination. Treatment Cheung et al. [4] have summarized the distinguish- The natural history of inflammatory hypophysitis, ing features among the different types of primary hypo- including PGH, is incompletely understood yet and its physitis, but the authors also pointed out the clinical treatment is still controversial. Satisfactory response and radiological presentation are similar among them to high-dose steroid therapy or anti-inflammatory and and mentioned that the definite diagnosis is only based immunosuppressive (methotrexate,cyclosporine A, on pathological findings. Histologically, lymphocytic azathioprine) treatments have been widely reported [2, hypophysitis is characterized by diffusely inflamma- 27, 32, 38-43]. Conservative management with close tory infiltration of the pituitary, predominant lympho- clinical observation has also been advocated as the pri- cytes with occasional plasma cells and macrophages, mary therapeutic option based on the disease’s often and sometimes neutrophilic and eosinophilic polynu- benign and transient course and spontaneous remis- clear cells with a variable degree of fibrosis [4, 9, 27, sion may occur [44]. Transsphenoidal surgery is, how- 33-36]. Granulomatous hypophysitis is characterized ever, both diagnostic and therapeutic and, therefore, by necrotizing granulomas that are formed by collec- should be performed in cases with progressive com- tion of histiocytes, multinucleated giant cell, and vari- pression, especially for those whose clinical and radio- able numbers of lymphocytes and plasma cells [4, 9, logical presentation is not typical and diagnosis is 18, 26, 27]. Xanthomatous hypophysitis, the least com- not confirmed. In fact, majority of reported PGH and mon form of primary hypophysitis, is characterized by approximately half of the primary hypophysitis were the presence of lipid-rich foamy histiocytes with vari- misdiagnosed as pituitary adenomas preoperatively able numbers of lymphocytes [4, 10, 26, 37]. [2, 9, 18, 26]. Histopathological findings of pituitary Although some PGH with typical clinical and biopsy remain the gold standard for diagnosing pri- radiological presentation, such as diabetes insipidus mary hypophysitis. Surgery provides live tissue for and pituitary diffuse enlargement and pituitary stalk histological diagnosis and can rapidly decompress the thickening, can be easily differentiated from a pitu- mass lesion, thereby resolving headache and visual itary adenoma, PGH mimicking pituitary adenomas deficits immediately [1, 11, 22]. Furthermore, surgery has been widely reported. Mild is and definitive histological diagnosis may obviate the common in granulomatous hypophysitis patients due unnecessary use of high-dose steroid therapy and facil- to the compression of the pituitary stalk or the inflam- itate the appropriate treatment of other conditions such matory process itself preventing the inhibitory regula- as infection or neoplasm. A pituitary experienced neu- tion of release by hypothalamic . rosurgeon would remove abnormal tissue and preserve However, PRL concentrations are usually much lower normal-looking tissue to minimize the risk of hypopi- than those of prolactinoma patients. Both hypophysitis turism. If primary hypophysitis is suspected, an intra- and non-functioning pituitary adenoma can cause pitu- operative histology on frozen sections is recommended itary expansion and a variable degree of hypopituitar- to confirm the diagnosis and avoid extensive unneces- ism, but the degree of pituitary failure of hypophysi- sary surgery because hypopituitarism may occur or be tis patients is out of proportion to the degree of lesion worsened following extensive surgery. volume. In patients with PGH, hypopituitarism may be Surgery had poor effect on improving the preex- present with small mass or even unenlarged pituitary, isting endocrine defects. Most patients required long- while in patients with tumor it is unusual to see such a term replacement with one or more hormones. Pituitary degree of panhypopituitarism except when the mass is deficiencies in inflammatory hypophysitis result from very large. Headache, nausea and vomiting and poste- cell destruction, so it is not surprising that hormone rior pituitary involvement are more common presenta- dysfunction respond less favorably to surgical therapy. tions of PGH than pituitary adenomas and the course of Thus, to treat primary hypophysitis, hormone replace- PGH is more rapid than in the usual cases of pituitary ment is required in most cases and long-term follow up tumor. Diabetes insipidus rarely accompanies a pitu- is very important. itary adenoma, due to compression of the stalk, but in granulomatous hypophysitis it is one of the most fre- Conclusion quent complications, due to infiltration of the stalk. PGH is a rarely occurred inflammatory disease of 472 Su et al. unknown etiology. The clinical presentations and radio- cal diagnosis and immediate mass reduction, but hor- logical signs are helpful for the diagnosis of PGH. The mone replacement is required in most cases and long- outcome of surgery for PGH is favorable for histologi- term follow up is very important.

References

1. Honegger J, Fahlbusch R, Bornemann A, Hensen J, Granulomatous hypophysitis with meningitis and Buchfelder M, Muller M, Nomikos P (1997) Lymphocytic hypopituitarism. Intern Med 31: 1147-1150. and granulomatous hypophysitis: Experience with nine 14. Scanarini M, d'Avella D, Rotilio A, Kitromilis N, cases. Neurosurgery 40: 713-722; discussion 722-723. Mingrino S (1989) Giant-cell granulomatous hypophysi- 2. Leung GK, Lopes MB, Thorner MO, Vance ML, Laws tis: A distinct clinicopathological entity. J Neurosurg 71: ER, Jr (2004) Primary hypophysitis: A single-center 681-686. experience in 16 cases. J Neurosurg 101: 262-271. 15. Kristof RA, van Roost D, Schramm J, Wichers M (1998) 3. Sautner D, Saeger W, Ludecke DK, Jansen V, Puchner Primary granulomatous hypophysitis not responsive to MJ (1995) Hypophysitis in surgical and autoptical spec- pulsed high dose prednisolone therapy: Case report. J imens. Acta Neuropathol 90: 637-644. Neurol Neurosurg Psychiatry 64: 693-694. 4. Cheung CC, Ezzat S, Smyth HS, Asa SL (2001) The 16. Fujiwara T, Ota K, Kakudo N, Rikimaru S, Sugawara T, spectrum and significance of primary hypophysitis. J Yamada K, Satoh T, Yano M, Tamate E, Miura M, Ikeda Clin Endocrinol Metab 86: 1048-1053. H, Kimura T (2001) Idiopathic giant cell granulomatous 5. Cooper R, Belilos E, Drexler S, Efron A, Ferrara E, hypophysitis with hypopituitarism, right abducens nerve Tollin SR (1999) Idiopathic giant-cell granulomatous paresis and masked diabetes insipidus. Intern Med 40: hypophysitis mimicking acute meningitis. Am J Med 915-919. Sci 318:339-342. 17. Miyamoto M, Sugawa H, Mori T, Hashimoto N, Imura 6. Brisman MH, Morgello S, Silvers A, Klein I, Post H (1988) A case of hypopituitarism due to granuloma- KD (1996) Idiopathic granulomatous hypophysitis. tous and lymphocytic adenohypophysitis with minimal Neurosurg Focus 1: e7. pituitary enlargement: A possible variant of lympho- 7. Arsava EM, Uluc K, Kansu T, Dogulu CF, Soylemezoglu cytic adenohypophysitis. Endocrinol Jpn 35: 607-616. F, Selekler K (2001) Granulomatous hypophysitis and 18. Stott V, Manning P, Hung N (2005) Idiopathic granu- bilateral optic neuropathy. J Neuroophthalmol 21: lomatous hypophysitis. N Z Med J 118: U1355. 34-36. 19. Shimizu C, Kubo M, Kijima H, Ishizu A, Katoh T, 8. Bhansali A, Velayutham P, Radotra BD, Pathak A Koike T (1998) Giant cell granulamatous hypophysi- (2004) Idiopathic granulomatous hypophysitis present- tis with remarkable uptake on gallium-67 scintigraphy. ing as non-functioning pituitary adenoma: Description Clin Endocrinol (Oxf) 49: 131-134. of six cases and review of literature. Br J Neurosurg 18: 20. Inoue T, Kaneko Y, Mannoji H, Fukui M (1997) Giant 489-494. cell granulomatous hypophysitis manifesting as an 9. Flanagan DE, Ibrahim AE, Ellison DW, Armitage M, intrasellar mass with unilateral ophthalmoplegia--case Gawne-Cain M, Lees PD (2002) Inflammatory hypo- report. Neurol Med Chir (Tokyo) 37: 766-770. physitis - the spectrum of disease. Acta Neurochir 21. Hassoun P, Anayssi E, Salti I (1985) A case of gran- (Wien) 144: 47-56. ulomatous hypophysitis with hypopituitarism and 10. Gazioglu N, Tuzgen S, Oz B, Kocer N, Kafadar A, Akar minimal pituitary enlargement. J Neurol Neurosurg Z, Kuday C (2000) Idiopathic granulomatous hypo- Psychiatry 48: 949-951. physitis: Are there reliable, constant radiological and 22. Higuchi M, Arita N, Mori S, Satoh B, Mori H, Hayakawa clinical diagnostic criterias? Neuroradiology 42: 890- T (1993) Pituitary granuloma and chronic inflammation 894. of hypophysis: Clinical and immunohistochemical stud- 11. Lee C, Chung Y, Kim S, HK. L (2003) Idiopathic gran- ies. Acta Neurochir (Wien) 121: 152-158. ulomatous hypophysitis. J Korean Neurosurg Soc 34: 23. Gutenberg A, Hans V, Puchner MJ, Kreutzer J, Bruck W, 386-388. Caturegli P, Buchfelder M (2006) Primary hypophysi- 12. Vasile M, Marsot-Dupuch K, Kujas M, Brunereau L, tis: Clinical-pathological correlations. Eur J Endocrinol Bouchard P, Comoy J, Tubiana JM (1997) Idiopathic 155: 101-107. granulomatous hypophysitis: Clinical and imaging fea- 24. McIntyre EA, Perros P (2007) Fatal inflammatory hypo- tures. Neuroradiology 39: 7-11. physitis. Pituitary 10: 107-111. 13. Yoshioka M, Yamakawa N, Saito H, Yoneda M, 25. Rivera JA (2006) Lymphocytic hypophysitis: Disease Nakayama T, Kuroki M, Tsuchida T, Sekiya M (1992) spectrum and approach to diagnosis and therapy. Primary granulomatous hypophysitis 473

Pituitary 9: 35-45. 36. Jensen M, Handwerger B, Scheithauer B, Carpenter P, 26. Caturegli P, Newschaffer C, Olivi A, Pomper MG, Mirakian R, Banks P (1986) Lymphocytic hypophysitis Burger PC, Rose NR (2005) . with isolated corticotropin deficiency. Ann Intern Med Endocr Rev 26: 599-614. 105: 200-203. 27. Bellastella A, Bizzarro A, Coronella C, Bellastella G, 37. Burt MG, Morey AL, Turner JJ, Pell M, Sheehy JP, Ho Sinisi AA, De Bellis A (2003) Lymphocytic hypophysi- KK (2003) Xanthomatous pituitary lesions: A report of tis: A rare or underestimated disease? Eur J Endocrinol two cases and review of the literature. Pituitary 6: 161- 149: 363-376. 168. 28. Moskowitz SI, Hamrahian A, Prayson RA, Pineyro M, 38. Hashimoto K, Asaba K, Tamura K, Takao T, Nakamura Lorenz RR, Weil RJ (2006) Concurrent lymphocytic T (2002) A case of lymphocytic infundibuloneurohypo- hypophysitis and pituitary adenoma. Case report and physitis associated with systemic erythematosus. review of the literature. J Neurosurg 105: 309-314. Endocr J 49: 605-610. 29. Levine SN, Benzel EC, Fowler MR, Shroyer JV, 3rd, 39. Lecube A, Francisco G, Rodriguez D, Ortega A, Codina Mirfakhraee M (1988) Lymphocytic adenohypophysi- A, Hernandez C, Simo R (2003) Lymphocytic hypo- tis: Clinical, radiological, and magnetic resonance physitis successfully treated with azathioprine: First imaging characterization. Neurosurgery 22: 937-941. case report. J Neurol Neurosurg Psychiatry 74: 1581- 30. Pamir MN, Zirh TA, Ozek MM, Sav A, Erzen C, Erbengi 1583. T (1993) Magnetic resonance imaging in the diagnosis 40. Miyake I, Takeuchi Y, Kuramoto T, Kaku H, Nakayama of idiopathic giant-cell granulomatous hypophysitis: H, Takata K, Kurita Y, Shigemori M, Hiromatsu Y, A rare cause of hyperprolactinaemia. Neurochirurgia Yamada K (2006) Autoimmune hypophysitis treated (Stuttg) 36: 20-25. with intravenous glucocorticoid therapy. Intern Med 45: 31. Sato N, Sze G, Endo K (1998) Hypophysitis: 1249-1252. Endocrinologic and dynamic mr findings. AJNR Am J 41. Thodou E, Asa SL, Kontogeorgos G, Kovacs K, Horvath Neuroradiol 19: 439-444. E, Ezzat S (1995) Clinical case seminar: Lymphocytic 32. Abe T (2008) Lymphocytic infundibulo-neurohypo- hypophysitis: Clinicopathological findings. J Clin physitis and infundibulo-panhypophysitis regarded as Endocrinol Metab 80: 2302-2311. lymphocytic hypophysitis variant. Brain Tumor Pathol 42. Tubridy N, Saunders D, Thom M, Asa SL, Powell M, 25: 59-66. Plant GT, Howard R (2001) Infundibulohypophysitis in 33. Abe T, Matsumoto K, Sanno N, Osamura Y (1995) a man presenting with diabetes insipidus and cavernous Lymphocytic hypophysitis: Case report. Neurosurgery sinus involvement. J Neurol Neurosurg Psychiatry 71: 36: 1016-1019. 798-801. 34. Beressi N, Beressi JP, Cohen R, Modigliani E (1999) 43. Yamagami K, Yoshioka K, Sakai H, Fukumoto M, Lymphocytic hypophysitis. A review of 145 cases. Ann Yamakita T, Hosoi M, Ishii T, Sato T, Tanaka S, Fujii S Med Interne (Paris) 150: 327-341. (2003) Treatment of lymphocytic hypophysitis by high- 35. Imura H, Nakao K, Shimatsu A, Ogawa Y, Sando T, dose methylprednisolone pulse therapy. Intern Med 42: Fujisawa I, Yamabe H (1993) Lymphocytic infundibu- 168-173. loneurohypophysitis as a cause of central diabetes insip- 44. Ezzat S, Josse RG (1997) Autoimmune hypophysitis. idus. N Engl J Med 329: 683-689. Trends Endocrinol Metab 8: 74-80.