CASE REPORT Clinical and Experimental Rheumatology 2000; 18: 78-80.

Lymphocytic hypo- ABSTRACT mass and the pathologic findings during A case of lymphocytic in a a transsphenoidal operation were com- physitis in a patient patient with systemic erythema- patible with lymphocytic hypophysitis. tosus is described. A 20-year-old We describe an SLE patient with head- with systemic lupus woman was admitted to our hospital ache and nausea, in whom the presence with generalized myalgia and facial of an intrasellar mass and pathologic erythematosus rash in May 1998. The patient had a findings indicated lymphocytic hypo- medical history, physical examination, physitis. J.D. Ji1, S.Y. Lee2, and laboratory findings compatible 2 2 with systemic lupus erythematosus Case report S.J. Choi , Y.H. Lee , (SLE). Headache and nausea had A 20-year-old woman was admitted to G.G. Song2 developed 3 months previously and the Korea University Anam Hospital in worsened over the following months. May 1998 with a three-month history of 1Hospital for Rheumatic Disease, Hanyang Hormonal investigation showed hypo- facial rash, fever, generalized myalgia, University Medical Center; 2Division of pituitarism except for . A hair loss and arthralgia. During the three Rheumatology, Department of Internal magnetic resonance image of the brain months before admission, she had noted Medicine, Korea University Hospital, showed a mass lesion in the pituitary intermittent headache and nausea. No Seoul, Korea. fossa. A trans-sphenoidal surgical visual disturbances were present. There Jong Dae Ji, MD; So Young Lee, MD; procedure was performed which was no family history of autoimmune or Seong Jae Choi, MD; Young Ho Lee, MD, revealed a dark-yellowish hematoma. endocrine problems. PhD; Gwan Gyu Song, MD, PhD. Microscopic examination showed On examination, the patient was severely Please address correspondence and reprint diffuse infiltration of lymphocytes and distressed. Her heart rate was 70 beats requests to: Gwan Gyu Song, MD, Division plasma cells with fibrosis in the per minute, her blood pressure 110/70 of Rheumatology, Department of Internal Medicine, Anam Hospital, College of . Post-operatively the mm Hg, and she had a temperature of Medicine, Korea University, 126-1, patient’s headaches and nausea 36.2°C. Hair loss, malar rash, and a ery- 5-Ka, Anam-Dong, Seongbuk-Gu, Seoul, resolved. This indicates that lympho- thematous rash on the palms and soles 136-705, Korea. cytic hypophysitis may be associated could be seen. Ophthalmological exami- E-mail: [email protected] with SLE. nation showed normal visual fields. The Received on April 29, 1999; remainder of the examination was nor- accepted in revised form on July 20, 1999. Introduction mal. © Copyright CLINICAL AND Lymphocytic hypophysitis is a rare in- Complete blood counts revealed: hemo- EXPERIMENTAL RHEUMATOLOGY 2000. flammatory disorder of the pituitary globin 10.6 g/dl, white blood cell count gland which is characterized by lym- 2,960/mm3, and platelet count 106,000/ Key words: phocytic infiltration and fibrosis of the mm3. Electrolytes and urinalysis were Systemic lupus erythematosus, anterior pituitary (1). Most cases have normal. Alanine aminotransferase was lymphocytic hypophysitis. been diagnosed in women during late 107 IU/l and aspartate aminotransferase pregnancy or the postpartum period. Pa- was 98 IU/l. The results of other labora- tients usually present with symptoms of tory evaluations were: antinuclear anti- an expanding intrasellar mass or vary- body (ANA) titer 1:40 (speckled pat- ing degrees of . Although tern), anti-dsDNA antibody 20.44 U/ml its causes are not known, it has been re- (normal < 5.3 U/ml), negative anti-RNP ported that lymphocytic hypophysitis is antibody, negative anti-Sm antibody, re- associated with autoimmune thyroiditis active VDRL, negative anti-SS-A and (2, 3), pernicious anemia (4), Grave’s di- anti-SS-B antibodies, erythrocyte sedi- sease (5), systemic lupus erythematosus mentation rate (ESR) 54 mm/hr (normal (SLE) (6), and autoantibodies including < 20 mm/hr), C3 55.5 mg/dl (normal 88 the antipituitary (7), antimitochondrial to 201 mg/dl), C4 15.0 mg/dl (normal (8), antiparietal (4) and antinuclear anti- 16 - 47 mg/dl). SLE was diagnosed based bodies (9). Therefore, lymphocytic hy- on the presence of malar rash, hair loss, pophysitis has been postulated to be an leukopenia, positive ANA, and positive primarily of preg- anti-dsDNA antibodies. nancy and the puerperium. Lymphocytic Headache and nausea worsened one day hypophysitis commonly manifests as a after admission. Skull x-rays revealed an pituitary mass and pre-operatively has enlarged sella and magnetic resonance been misdiagnosed as a pituitary adeno- imaging (MRI) demonstrated a round ma (7). mass lesion in the sella. T1- and T2- Our patient presented with an intrasellar weighted images revealed high signal

78 Lymphocytic hypophysitis in a patient with SLE / J.D. Ji et al. CASE REPORT

(a) (b) Fig. 1. (a) T1-weighted image and (b) gadolinium-enhanced T1-weighted image demonstrating high signal intensity of the pituitary mass. intensity of the pituitary mass (Fig. 1). A trans-sphenoidal surgical procedure toms or signs of hypopituitarism, only A gadolinium-enhanced T1-weighted was performed and revealed a dark liq- headache and nausea. Dynamic pituitary image showed high signal intensity with- uified hematoma. After the hematoma function testing showed absent cortisol in the mass (Fig. 2). Compared with the was aspirated, the could and growth responses to insu- pre-enhanced film, evidence of definite be seen. A biopsy of the pituitary gland lin, impaired TSH response to TRH, and enhancement was not seen. Further in- showed the infiltration of lympocytes hyporesponses of FSH and LH to LHRH. vestigations of pituitary function were and plasma cells with fibrosis in the an- She had an elevated prolactin level. carried out. The basal hormone level re- terior pituitary (Fig. 3). Post-operatively, Many have reported a mild elevation of vealed the following: growth hormone the patient’s headaches and nausea re- prolactin attributed to either the disrup- (GH) 4.12 ng/ml (normal 0-5), cortisol solved. Two months later her hormone tion of hypophyseal transport of prolac- 4.52 mg/ml (normal 5-20), prolactin 90.3 levels were as follows: cortisol 21.04 mg/ tin inhibitory factor by compression of ng/ml (normal 0-20), stimulat- ml, prolactin 125.74 ng/ml, TSH 1.77 IU/ the pituitary stalk, or to a direct effect of ing hormone (TSH) 1.13 IU/ml (normal ml, LH 1.86 mIU/ml and FSH 2.28 mIU/ the inflammatory process on the prolac- 0-10), lutenizing hormone (LH) 2.86 ml. The patient is currently well and re- tin cells, or to a lactotroph-stimulating mIU/ml (normal 5-25) and follicle stimu- ceiving prednisolone 15 mg and hydrox- antibody arising as a consequence of the lating hormone (FSH) 4.32 mIU/ml (nor- ychloroquine 400 mg daily. inflammatory process (2, 4, 8-10). The mal 5-20). Dynamic tests of pituitary cause of the elevated prolactin level in function were performed. TSH and pro- Discussion our patient is unclear; it could have been lactin responses to thyrotropin releasing Lymphocytic hypophysitis is a rare auto- due to either lymphocytic hypophysitis hormone (TRH) (400 mg), LH and FSH immune disease, diagnosed either by sur- or the SLE itself. Elevated serum prol- responses to lutenizing hormone releas- gical biopsy of the pituitary or at . actin levels have been reported in SLE ing hormone (LHRH) (100 mg), cortisol Many of the patients reported previously patients (11, 12), and the persistently el- and GH responses to insulin (0.1 unit/ had a large pituitary mass lesion, and evated prolatin levels in our patient af- kg body weight) were evaluated (Table most had various degrees of hypopitui- ter surgery may have been due to dis- I). tarism (7-9). Our patient had no symp- ease activity. While the causes of lymphocytic hypo- Table I. Serum levels of GH, cortisol, prolactin, TSH, LH and FSH after administration of physitis are unclear, several findings sug- TRH, GnRH and insulin. gest that is involved in the pathogenesis. Experimentally, lympho- Minute cytic hypophysitis has been induced by 0 15 30 60 90 120 injecting pituitary tissues and adjuvants GH (ng/ml) 4.12 0.6 0.28 0.32 into footpads of the rat (13). The histo- Cortisol (mg/ml) 4.52 4.35 4.35 3.89 logic features of this lesion were nearly Prolactin (ng/ml) 90.3 100.39 105.5 98.9 identical to that seen in patients with TSH (IU/ml) 1.13 3.31 2.91 3.01 lymphocytic hypophysitis. These results LH (mIU/ml) 2.86 5.78 7.07 7.49 suggest that an autoimmune reaction may be implicated in the genesis of hu- FSH (mIU/ml) 4.32 6.16 5.77 5.95 man lymphocytic hypophysitis. Similar

79 CASE REPORT Lymphocytic hypophysitis in a patient with SLE / J.D. Ji et al.

WORTH JMB, EHRLICH EN: Lymphocytic hypophysitis with selective adrenocortico- tropic hormone deficiency. Arch Intern Med 1980; 140: 1243-5. 4. MAZZONE T, KELLY W, ENSINCK J: Lymph- ocytic hypophysitis associated with antiparietal cell antibodies and vitamin B12 deficiency. Arch Intern Med 1983; 143: 1794-5. 5. BAYRAM F, KELESTIMUR F, OZTURK F, SELCUKLU A, PATIROGLU TE, BEYHAN Z: Lymphocytic hypophysitis in a patient with Fig. 3. A biopsy of Grave’s disease. J Endocrinol Invest 1998; 21: the pituitary gland 193-7. showing infiltration 6. HASEGAWA Y, MATSUMOTO M, KAMIMURA of lymphocytes and A, YAMAMOTO M: A case of systemic lupus plasma cells with erythematosus with . fibrosis (Hematoxylin Nippon Naika Gakkai Zasshi 1993; 82: 582-3 eosin stain, x100). (in Japanese). 7. MAYFIELD RK, LEVINE JH, GORDON L, POW- ERS J, GARBRAITH RM, RAWE SF: Lymphoid results have been reported in rabbits (14). standing of this disease. If a patient de- adenohypophysitis presenting as a pituitary tumor. Am J Med 1980; 69: 619-23. Also supporting an autimmune patho- velops a pituitary mass causing mild 8. ASA SL, BILBAO JM, KOVACS K, JOSSE RG, genesis is the reported association of thy- headache or visual symptoms, he should KREINES K: Lymphocytic hypophysitis of roiditis (2, 3), adrenalitis (14), pernici- be monitored closely (including visual pregnancy resulting in hypopituitarism: A clin- ous anemia (4), and Grave’s disease (5) field examinations and CT scans) with- icopathologic entity. Ann Intern Med 1981; 95: 166-71. in patients with lymphocytic hypophy- out surgical intervention. If the patient 9. GUAY AT, AGNELLO V, TRONIC BC, GRE- sitis. In 1993, Hasegawa et al. described has severe headache or marked visual SHAM DG, FREIDBERG SR: Lymphocytic hy- the case of a young woman with SLE abnornalities, however, trans-sphenoidal pophysitis in a man. J Clin Endoclinol Metab and lymphocytic hypophysitis (6). Our surgery with biopsy should be perform- 1987; 64: 631-4. case represents the second report of an ed. Hormone replacement therapy and 10. PORTOCARRERO CJ, ROBINSON AG, TAYLOR AL, KLEIN I: Lymphoid hypophysitis. An unu- association between SLE and lympho- corticosteroid therapy should be pro- sual cause of hyperprolactinemia and enlarged cytic hypophysitis. Like Hasegawa’s pa- vided as needed. sella turcica. JAMA 1981; 246: 1811-2. tient, ours was unmarried and the onset In summary, our case demonstrates an 11. JARA-QUEZADA L, GRAEF A, LAVALLE C: of the disease was not related to pregnan- association between systemic lupus ery- Prolactin and gonadal during preg- nancy in systemic lupus erythematosus. J cy. The majority of cases to be reported thematosus and lymphocytic hypophy- Rheumatol 1991; 18: 349-53. have been seen during pregnancy or in sitis. The evaluation of lymphocytic hy- 12. NEIDHART M: Elevated serum prolactin or el- the postpartum period. pophysitis may be required in SLE pa- evated prolactin/cortisol ratio are associated The unique feature of our case was the tients with headache, hyperprolactinemia, with autoimmune processes in systemic lupus erythematosus and other connective tissue dis- presence of hematoma in the sella. In our a pituitary mass, and hypopituitarism. eases. J Rheumatol 1996; 23: 476-81. patient, the hematom may have been due 13. LEVINE S: Allergic adenohypophysitis: New to bleeding from the pituitary gland. experimental disease of the pituitary gland. Many cases previously reported mani- References Science 1967; 158: 1190-1. 1. TOPLISS DJ, VOLPE R: Lymphocytic hypo- 14. KLEIN I, KRAUS KE, MARTINES AJ, WEBER fested as a pituitary mass and had been physitis. Ann Intern Med 1981; 95: 227-9. S: Evidence for cellular mediated immunity in misdiagnosed before surgery as a pitui- 2. JENSEN MD, HANDWERGER BS, SCHEIT- an animal model of autoimmune pituitary dis- tary adenoma. HAUER BW, CARPENTER PC, MIRAKIAN R, ease. Endocr Res Commun 1982; 9: 145-53. Cosman et al. (15) has suggested a man- BANKS PM: Lymphocytic hypophysitis with 15. COSMAN F, POST KD, HOLUB DA, WARDLAW isolated corticotropin deficiency. Ann Intern SL: Lymphocytic hypophysitis. Report of 3 agement paradigm for lymphocytic hy- Med 1986; 105: 200-3. new cases and review of the literature. Medi- pophysitis based on the current under- 3. RICHTSMEIER AJ, HENRY RA, BLOOD- cine (Baltimore) 1989; 68: 240-56.

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