Lymphocytic adenohypophysitis: skull radiographs and MRI

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1 Neuroradiology (1998) 40: 114±120 Ó Springer-Verlag 1998 DIAGNOSTIC NEURORADIOLOGY S. Saiwai Y. Inoue T. Ishihara S. Matsumoto Y. Nemoto T. Tashiro A. Hakuba T. Miyamoto Lymphocytic adenohypophysitis: skull radiographs and MRI Received: 12 December 1996 Accepted: 19 June 1997 S.Saiwai T.Miyamoto Department of Radiology, Kobe Central Municipal Hospital, 4±6 Minatojima-Nakamachi, Chuo-ku, Kobe, Hyogo, 650 Japan Y.Inoue ( ) ) Y. Nemoto T. Tashiro Department of Radiology, Osaka City University Medical School, Asahimachi, Abeno, Osaka, 545 Japan Tel. Nr.: ; Fax A. Hakuba Department of Neurosurgery, Osaka City University Medical School, Asahimachi, Abeno, Osaka, 545 Japan Abstract We report the skull radiograph, CT and MRI findings in three patients with lymphocytic adenohypophysitis mimicking pituitary adenoma. All cases were associated with pregnancy. CT demonstrated a pituitary mass but did not differentiate lymphocytic adenohypophysitis from pituitary adenoma. The skull radiographs showed either a normal sella turcica or minimal abnormalities; they did not show ballooning or destruction. The MRI appearances were distinctive: relatively low signal on T1-weighted images; preservation of the bright posterior pituitary lobe despite the presence of a relatively large pituitary mass, less common in macroadenomas; marked contrast enhancement compared with pituitary macroadenomas; and dural enhancement adjacent to a pituitary mass. Key words Pituitary Adenohypophysitis Magnetic resonance imaging Introduction Lymphocytic hypophysitis is an inflammatory disorder characterised by diffuse infiltration of the pituitary gland by lymphocytes and plasma cells [1]. It is rare and has usually been reported in women, often coinciding with pregnancy. The disease manifests itself as panhypopituitarism and enlargement of the pituitary gland is evident on CT or MRI. Differentiation of this disorder from pituitary adenoma has thus been difficult preoperatively. We recently had an opportunity to study three such cases with distinctive MRI findings. Case reports Case 1 A 40-year-old woman noticed a right-sided visual defect and general fatigue during the third trimester of pregnancy. After she had delivered a full-term baby, lactation did not occur. Examination demonstrated a right temporal hemianopia and decreased visual acuity; no other neurological deficit was present. Skull radiographs showed thinning of the dorsum sellae but no enlargement of the sella turcica (Fig.1a). CT and MRI demonstrated a pituitary mass with suprasellar extension, displacing the optic chiasm upwards. On T1-weighted images, the mass gave slightly lower signal than the cerebral white matter (Fig. 1 b). On contrast-enhanced MRI, the mass enhanced as markedly as the cavernous sinus (Fig.1c). There was minor dural enhancement anterior to the mass, and focal enhancement of the sphenoid sinus mucosa adjacent to the pituitary fossa (Fig. 1d).

2 115 b a c e d Fig. 1 a±e Case 1. a Lateral skull radiograph. The sella turcica shows only thinning of its dorsum. b T1-weighted coronal image. A pituitary mass displaces the optic chiasm upwards. It gives slightly lower signal than the cerebral white matter. c, d Contrastenhanced coronal and sagittal images. The mass enhances homogeneously and is as bright as the cavernous sinus. There is a short line of enhancement anterior to the mass (arrow) probably representing dural enhancement. The sphenoid sinus mucosa adjacent to the mass also enhances. e Histology of surgical specimen showing abundant infiltrating lymphocytes, plasma cells, and neutrophils. (Haematoxylin and eosin, original magnification 200) Routine laboratory data were normal. Endocrine assessment revealed mild hypopituitarism: growth hormone (GH) 1.6 ng/ml, total T4 5.3 mg/dl, free T3 3.0 pg/ml, prolactin (PRL) 0.5 ng/ml, luteinising hormone (LH) 6.2 miu/ml and cortisol 0.4 mg/dl in the unstimulated state. As visual acuity deteriorated, trans-sphenoidal surgery was performed 7 weeks after delivery. The mass was cream-coloured, very hard and difficult to aspirate and appeared poorly vascular. Pathological examination of the specimen showed chronic inflammation with prominent fibrosis: lymphocytes, plasma cells with clusters of adenohypophyseal cells were present but no neoplastic cell was seen (Fig. 1e). These findings were consistent with lymphocytic adenohypophysitis. After surgery, the right temporal hemianopia disappeared and visual acuity was markedly improved on both sides. The patient is doing well on oral hydrocortisone 50 mg/day and dessicated thyroid hormone 30 mg/day 4 years after surgery. Case 2 A 23-year-old woman developed headache and blurred vision in the 36th week of pregnancy. Examination demonstrated bitemporal hemianopia. Skull radiographs showed no enlargement of the sella turcica. CT 10 days after delivery revealed an isodense intrasellar mass with suprasellar extension, which enhanced well except for the posterior central portion (Fig. 2 a). The bitemporal hemianopia did not resolve and MRI showed the mass, with superior displacement of the optic chiasm. The mass gave slightly lower signal than white matter of the temporal lobe on T1-weighted images and was heterogeneously bright on T2-weighted images (Fig.2b, c). The posterior central portion of the mass, which did not enhance on CT, gave low signal on T1-weighted images and moderately high signal on T2 weighting. The mass enhanced

3 116 a b c d e Fig. 2 a±e Case 2. a Coronal contrast enhanced CT shows a large enhancing pituitary and suprasellar mass with a low density centre. b, c Coronal T1- and T2-weighted images. Compared with the temporal lobe white matter, the mass gives relatively low signal on the T1-weighted image and slightly high signal on the T2- weighted image. d Contrastenhanced coronal image. The mass enhances as much as the cavernous sinus, except at its centre. e There is diffuse infiltration of lymphocytes, plasma cells, and eosinophils with a few adenohypophyseal cells and fibrosis. (Masson & trichrome stain, 100)

4 117 a b c d e Fig. 3 a±e Case 3. a Coronal contrast-enhanced CT shows a homogeneously-enhancing pituitary mass with suprasellar extension. b, c Sagittal T1- and T2-weighted images. Compared with the pons, the mass gives low signal on the T1-weighted image, and high signal on T2 weighting (3c). A bright posterior lobe is seen. d Contrast-enhanced sagittal T1-weighted image. The mass enhances markedly and linear dural enhancement (arrow) is seen anterior to it. e Sagittal T1-weighted image 3 months later. The mass has decreased in height and may now be slightly small. markedly except for the posterior central portion (Fig. 2 d). A little dural enhancement was seen anterior to the mass. Routine laboratory data were normal. Endocrine investigations showed hypopituitarism: total T4 4.9 mg/dl, free T pg/ ml, TSH < 0.15 miu/ml, PRL < 0.3 ng/dl, LH 0.3 miu/ml, follicle stimulating hormone (FSH) 3.3 miu/ml. There was no detectable antithyroid antibody. Although the clinical presentation and endocrine assessment were consistent with lymphocytic adenohypophysitis, the possibility of a pituitary adenoma was still considered. Trans-sphenoidal surgery was performed 3 weeks after delivery. The mass was cream-coloured, relatively hard and difficult to aspirate. It was thought likely to be granulation tissue. The posterior central nonenhancing portion was necrotic. A small portion was removed. Pathological examination showed lymphocytic adenohypophysitis, with lymphocytes, acidophilic cells, neutrophils and connective tissue (Fig. 2 e). Postoperative recovery was uneventful. The bitemporal hemianopia improved and the patient is doing well on oral hydrocortisone 75 mg/day and dessicated thyroid hormone 40 mg/day. Case 3 A 27-year-old primigravida was admitted with complaints of blurred vision and failure of lactation. She had noticed blurred vision in the 36th week of gestation, but had not consulted her doctor due to the mildness of symptoms. Examination demonstrated bitemporal hemianopia but was otherwise normal. Skull radiographs demonstrated minimal demineralisation of the posterior wall of the sella turcica, but no enlargement. CT showed a homogeneously enhancing pituitary mass which extended into the suprasellar cistern (Fig. 3 a), confirmed on MRI. The mass was approximately 20 mm in height and gave homogeneously low signal on T1-weighted images (Fig.3c) and mildly high signal relative to the pons on T2- weighted images (Fig. 3 c). The bright posterior lobe was clearly identified on the T1-weighted sagittal image (Fig. 3 b). There was marked, homogeneous contrast enhancement (Fig.3d).

5 118 Table 1 Characteristic imaging findings in lymphocytic adenohypophysitis compared with solid pituitary macroadenomas (T1WI, T2WI T1- and T2-weighted images) Adenohypophysitis Solid macroadenoma Skull radiographs Normal or minimally abnormal sella turcica Enlargement or ballooning of sella turcica MR images Signal intensity a Relatively low on T1 WI Almost isointense on both T1- and T2WI Bright posterior lobe Preserved Not seen or, if seen, displaced or deformed Contrast enhancement As bright as cavernous sinus Moderate, less than cavernous sinus Dural enhancement Common adjacent to mass Infrequent a Compared with pons or temporal lobe white matter Routine laboratory data were normal. Further assessment revealed decreased concentrations of GH (1.6 ng/ml), LH (< 0.3 miu/ml) and PRL (12 ng/ml). Thyroid function was slightly decreased: total T4 5.3 mg/dl, free T pg/ml, free T ng/dl, and normal TSH. Several days after admission, her visual impairment resolved. Follow-up MRI showed a slight decrease in height of the mass. With a working diagnosis of lymphocytic adenohypophysitis associated with pregnancy, the patient was followed as an outpatient. She showed anorexia, pallor, and decreased blood pressure (90/ 60 mm Hg) secondary to thyrotoxicosis due to postpartum painless thyroiditis. She improved on hydrocortisone therapy and thyroid hormone concentrations returned to normal. MRI at 5 months after the initial examination showed a significant decrease in height of the mass (Fig.3e). The patient is doing well on 25 mg oral hydrocortisone daily 4 years later. Discussion Lymphocytic infiltration of the pituitary gland is associated with complete or partial hypopituitarism and a pituitary mass designated as lymphocytic hypophysitis [1]. Lymphocytic adenohypophysitis is an inflammatory disorder of the anterior lobe of the pituitary gland which occurs almost exclusively in women, often during pregnancy or in the postpartum period. The symptoms and signs are those of pituitary dysfunction, hypothyroidism and frequently hypocortism, with a pituitary mass. Endocrine deficiencies include adrenocorticotropic hormone, TSH, LH and FSH, alone or in combination. Lymphocytic adenohypophysitis was first recognized as a pathological entity in 1962 [2], but the first case diagnosed antemortem was not reported until 1980 [3]. More than 50 cases have been reported, all but 7 in women [4±9]. The majority of cases were diagnosed during late pregnancy or the early postpartum period after the patients presented with evidence of pituitary enlargement or variable hypopituitarism. There have been reports women with this disorder unrelated to pregnancy [9±14]. Although the cause is unknown, autoimmune mechanisms appear to be involved [15±18]. Antipituitary antibodies are present in 18 % of postpartum women [19]. There are also reported associatious with other autoimmune endocrine disorders, including thyroiditis and/or adrenalitis [5, 17, 20±25]. Lymphocytic hypophysitis can involve only the neurohypophysis, when it may be called lymphocytic neurohypophysitis or infundibulohypophysitis [26, 27]. There have been several reports of a combined lymphocytic infiltration of both the neurohypophysis and adenohypophysis [6, 13, 26]. In addition, there is a rare inflammatory disorder, granulomatous hypophysitis, in which histological examination demonstrates granulomatous inflammation characterised by nodular collections of epithelioid histiocytes and multinucleate giant cells, but no lymphoid follicles [28]. The clinical presentation is usually pituitary insufficiency associated with a pituitary mass and may be identical to lymphocytic adenohypophysitis. In our case 3, although a histological diagnosis was not obtained, the presentation and endocrine findings were consistent with lymphocytic adenohypophysitis and illustrate the natural history of this disorder [9, 25, 30±33]. A presumptive diagnosis of lymphocytic adenohypophysitis is thus possible and medical treatment alone, without surgical intervention, would therefore be appropriate. On occasion, biopsy may be necessary to prove the diagnosis when patients show symptoms and signs identical to those of lymphocytic adenohypophysitis with a mass on CT or MRI but unrelated to pregnancy. Decreased visual acuity or hemianopia and hypopituitarism in late pregnancy or the early postpartum period are typical of lymphocytic adenohypophysitis, but can be seen with pituitary adenomas. Rapid enlargement of a prolactinoma during pregnancy is a well-known phenomenon [34, 35]. Hypopituitarism is sometimes not the main feature of lymphocytic adenohypophysitis at the time of presentation. Therefore, appropriate imaging studies are indicated in the late third trimester or postpartum period for patients with any suggestion of lymphocytic adenohypophysitis. CT usually demonstrates an enhancing pituitary mass with or without suprasellar extension but can not differentiate adenoma from hypophysitis. We have found five characteristic imaging findings for lymphocytic adenohypophysitis, one on skull radiographs and four on MRI (Table 1). Despite the relatively large pituitary mass in these and other cases [17, 30, 31, 36±38], the

6 119 sella turcica was surprisingly normal on the skull radiographs with minimal abnormalities, if any, such as thinning or decalcification of the dorsum sellae without obvious ballooning. The sella turcica may, however, be enlarged [21, 39, 40]. Ballooning or enlargement of the sella turcica can, of course, also be assessed on CT or MR. On MRI, we found four characteristic features. First, the pituitary masses gave relatively low signal on T1- weighted images, which is uncommon in solid pituitary macroadenomas. Relatively high signal on T2 weighting may be a significant finding in lymphocytic adenohypophysitis, but is nonspecific; solid macroadenomas may occasionally give relatively high signal T2. Second, the presence of a bright posterior lobe, as in case 3, seems to be characteristic, as previously reported [9, 13]. T1- weighted sagittal images without contrast medium were unfortunately not obtained in cases 1 and 2. A posterior pituitary lobe can occasionally be seen in cases of macroadenomas, but is then deformed or displaced. Third, marked contrast enhancement of the mass also seems to characteristic of this disorder [9]. Solid pituitary macroadenomas usually show only moderate enhancement. Fourth, dural enhancement adjacent to an enlarged pituitary, seen in cases 1 and 2, seems to be typical [9], although further observations are required. Possible explanation for these findings is that in lymphocytic adenohypophysitis there is an inflammatory mass in the anterior pituitary. Any inflammatory mass has increased interstitial spaces and increased water content in the acute phase of inflammation, and less mass effect on adjacent structures than a solid tumour. A mass of lymphocytic adenohypophysitis usually does not therefore produce ballooning of the sella and grows into the less resistant suprasellar cistern instead. Increased water content will explain relatively low signal on T1-weighted images. The lesser pressure effect results in preservation of the normal configuration of the posterior lobe and since the mass is hypointense, the appearance is of a ªbright posterior lobeº. Marked enhancement can be attributed to the increased interstitial space, with free diffusion of contrast medium into the extracellular space, where an increased number of water protons is available. Dural enhancement is probably attributable to the extension of inflammation to the adjacent dura mater. In our cases, MRI was performed in the relatively early, presumably active phase of the disease. In the late or chronic stages, these MRI findings may not be expected because of shrinkage of the mass and less inflammatory and more fibrotic changes, as found in autopsy cases [2, 10, 11, 20, 23]. References 1. Thorner MO, Vance ML, Horvath E, Kovacs K (1992) The anterior pituitary. 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