Lymphocytic Hypophysitis Masking a Suprasellar Germinoma in a 12-year-old Girl<197>A Case Report

Case history, light and electron microscopic findings of a case of a lymphocytic hypophysitis in coincidence with a suprasellar germinoma in a 12-year-old girl are reported. The girl presented with a long time case history of diabetes insipidus and subsequent panhypopituitarism. Two years after the diagnosis of diabetes insipidus magnetic resonance imaging (MRI) showed a tumorous enlargement of the sellar content and pituitary stalk. A transnasal exploration was initially performed and revealed a lymphocytic hypophysitis. Light microscopy showed a dense infiltration of mature lymphocytes and plasma cells in the interstitium of the anterior pituitary gland. The stalk area could not be exposed to exclude a germinoma. One year later the lesion relapsed despite dexamethason therapy and a second operation by another neurosurgeon had to be performed. Light microscopy showed lymphocytic infiltrates, fibrosis and necrosis. The diagnosis was a lymphocytic hypophysitis again. Though transcranially exposed only pituitary tissue was removed. No infundibular mass became visible at surgery as shown by MRI. The girl developed five months later multiple cerebral lesions, which revealed to be a germinoma. Lymphocytic hypophysitis in children is very rare and a coincedence with a germinoma has not been described from histopathological aspect until now. The origin of the pituitary infiltration is discussed.     

淋巴细胞性垂体炎三例并文献复习

目的提高临床医师对淋巴细胞性垂体炎的认识。方法分析3例淋巴细胞性垂体炎的临床特点和病理结果。结果3例患者均为青年女性,例1产后起病,例2和例3在非妊娠或产后期间发病;影像学特点:病变广泛,不仅局限于鞍区和垂体柄,并向下丘脑扩展呈“舌状”改变侵犯海绵窦;增强后病变均匀或环状强化;主要临床表现:(1)垂体功能受损和尿崩症;(2)有局部受压症状,如头痛,视交叉受压;(3)病变侵犯海绵窦,引起动眼、外展神经麻痹;2例经病理证实为淋巴细胞性垂体炎,垂体组织见大量淋巴细胞、浆细胞、组织细胞浸润;2例大剂量甲泼尼龙治疗后,症状明显好转。结论淋巴细胞性垂体炎亦可发生在非妊娠或产后期间的年轻女性,大剂量甲泼尼龙冲击治疗能有效缩小病变和改善垂体功能。     

Pituitary and systemic autoimmunity in a case of intrasellar germinoma

Germinomas arising in the sella turcica are difficult to differentiate from autoimmune hypophysitis because of similar clinical and pathological features. This differentiation, nevertheless, is critical for patient care due to different treatments of the two diseases. We report the case of an 11-year-old girl who presented with diabetes insipidus and growth retardation, and was found to have an intra- and supra-sellar mass. Initial examination of the pituitary biopsy showed diffuse lymphocytic infiltration of the adenohypophysis and absent placental alkaline phosphatase expression, leading to a diagnosis of hypophysitis and glucocorticoid treatment. Because of the lack of clinical and radiological response, the pituitary specimen was re-examined, revealing this time the presence of scattered c-kit and Oct4 positive germinoma cells. The revised diagnosis prompted the initiation of radiotherapy, which induced disappearance of the pituitary mass. Immunological studies showed that the patient’s serum recognized antigens expressed by the patient’s own germinoma cells, as well as pituitary antigens like growth hormone and systemic antigens like the Sjögren syndrome antigen B and alpha-enolase. The study first reports the presence of pituitary and systemic antibodies in a patient with intrasellar germinoma, and reminds us that diffuse lymphocytic infiltration of the pituitary gland and pituitary antibodies does not always indicate a diagnosis of autoimmune hypophysitis.     

A case of cystic lymphocytic hypophysitis with cacosmia and hypopituitarism

Lymphocytic hypophysitis is a rare inflammatory disease of the pituitary gland that is being increasingly recognized as a cause of hypopituitarism. This condition may be due to an autoimmune pituitary destruction which usually occurs in young women during pregnancy or in the immediate postpartum period. We describe a case of cystic pituitary mass in a thirty-eight year-old woman presenting with nausea, vomiting, cold intolerance, blurring of vision and the presence of disagreeable odors for a one-month period. She had secondary amenorrhea and galactorrhea for three months. Combined anterior pituitary stimulation test confirmed the diagnosis of hypopituitarism. Magnetic resonance imaging scan with enhancement showed a huge cystic sellar mass with suprasellar extension and thickening of the pituitary stalk. Transsphenoidal exploration was performed with preoperative diagnosis of pituitary macroadenoma with cystic necrosis. Histological examination revealed lymphocytic hypophysitis characteristic of diffuse, dense lymphocytes and plasma cells infiltration with surrounding interstitial reactive fibrosis. Postoperatively, the patient's olfactory function returned to normal but combined anterior pituitary stimulation test showed persistence of hypopituitarism with mild hyperprolactinemia. Prednisolone, thyroxine and estrogen replacements were started and clinical symptoms were much improved. In summary, we report an extremely rare case of a woman with cystic lymphocytic hypophysitis with cacosmia and hypopituitarism, confirmed by histological examination.     

Idiopathic giant cell granulomatous hypophysitis with hypopituitarism, right abducens nerve paresis and masked diabetes insipidus

A 38-year-old man presented with headache, fever, and double vision associated with right abducens nerve paresis. He had neither nuchal rigidity nor visual field defect. Laboratory data revealed elevated erythrocyte sedimentation rate (ESR), eosinophilia, and lymphocytic pleocytosis in the cerebrospinal fluid (CSF). Provocation tests of pituitary hormones showed partial hypopituitarism. Magnetic resonance imaging (MRI) revealed swelling of the hypophysis and a mass lesion expanding into the right cavernous sinus. The supplement dose of dexamethasone for hypothalamic hypocortisolism manifested diabetes insipidus. Biopsy, carried out through the transsphenoidal approach, revealed giant cell granuloma. Systemic granulomatous diseases were ruled out, and the lesion was considered to be idiopathic giant cell granulomatous hypophysitis. Right abducens nerve paresis, diabetes insipidus and dysfunction of the anterior lobe were amended by the treatment with prednisolone for 4 months, and findings of the pituitary gland and stalk were normalized. The present case shows that glucocorticoid has an effect on amendment of idiopathic giant cell granulomatous hypophysitis.     

糖皮质激素联合硫唑嘌呤治疗复发性淋巴细胞性垂体炎三例报道

报道3例复发性淋巴细胞性垂体炎(LYH)患者均为女性,其中病例2为老年女性.病例1主要累及垂体前叶,并侵犯海绵窦和视交叉,病例2则主要累及下丘脑和漏斗部,病例3则是垂体前叶和垂体柄均受累.病例1手术后4个月第一次复发,给予大剂量甲基泼尼龙治疗(HDMPT)有效,但停药后14个月再次复发;病例2中等剂量强的松治疗停药16个月后复发,而病例3则在HDMPT治疗,糖皮质激素减量的过程中复发.3例患者复发后均以糖皮质激素联合硫唑嘌呤治疗16周,疗效良好,停药后随访3例患者,MRI显示LYH均无复发,而且病例1和3垂体功能正常.

Abstract：

All three cases of recurrent lymphocytic hypophysitis were female, one of them being 70-yearold postmenopausal woman.Adenohypophysis, cavernous sinus, and optic chiasm were involved in case 1,hypothalamus and neurohypophysis were invaded in case 2, and adenohypophysis and hypophyseal stalk were involved in case 3.Relapse occured 4 months after operation in case 1, then high dosage methylprednisolone pulse therapy (HDMPT) brought about a remission lasting for 14 months before second relapse set in.Relapse occurred in case 2 at 16 months after prednisone treatment was discontinued, and case 3 recurred during the period of dose reduction.All three patients were then treated with glucocorticoid plus azathioprine for 16 weeks, and good response was seen in 3 cases.During follow-up, the symptoms were relieved and significant reduction of lesion was revealed by MRI in all thee patients, and the pituitary function was resumed in case1and 3.     

A case of lymphocytic infundibuloneurohypophysitis associated with systemic lupus erythematosus

A 27-year-old man was admitted to our hospital with facial erythema and general malaise. He had previously suffered from orbital myositis, central diabetes insipidus (DI), peripheral neuritis, and hypogonadotropic hypogonadism. Physical and immunological examinations revealed that he was suffering from systemic lupus erythematosus (SLE). Magnetic resonance imaging of the hypothalamic-pituitary region demonstrated a significant enlargement of the pituitary stalk and posterior pituitary. Endocrinological examinations showed that he had not only DI and hypogonadotropic hypogonadism but also hypoadrenalism and hypothyroidism, which were ascribed to the pituitary stalk lesion. Lymphocytic infundibuloneurohypophysitis associated with SLE was diagnosed. Administration of 30 mg/day of prednisolone for one month resulted in a marked reduction of the pituitary stalk thickening and posterior pituitary. It is recommended that a pharmacological dose of glucocorticoid be used in the treatment of lymphocytic hypophysitis patients who show significant thickening of the pituitary stalk and/or a large pituitary mass.     

A case of apoplectic lymphocytic hypophysitis complicated by polymyalgia rheumatica

A case of apoplectic lymphocytic hypophysitis complicated by polymyalgia rheumatica (PMA) is described. A 72-year-old man was admitted to our hospital due to severe headache. Two months prior to admission, the patients had exhibited recent-onset stiffness and myalgia of shoulder and pelvic girdle that was compatible with PMR. Magnetic resonance imaging revealed a mass lesion in the pituitary fossa with focal hemorrhage. Endocrinologic studies demonstrated hypopituitarism. The headache and myalgia were improving with corticosteroid treatment; however, a trans-sphenoidal surgery was performed due to visual field loss. A white-colored mass was resected, and histologic examination showed diffuse infiltration of lymphocytes and plasma cells consistent with lymphocytic hypophysitis. Post-operatively, the headache and visual field loss resolved completely. This is the first documented case of apoplectic lymphocytic hypophysitis complicating PMR, and a possible mechanism for this rare association was discussed.     

A case of suspected lymphocytic hypophysitis and organizing pneumonia during maintenance therapy for autoimmune pancreatitis associated with autoimmune thrombocytopenia

A 75-year-old man with a medical history of autoimmune pancreatitis associated with autoimmune thrombocytopenia was emergently admitted to our hospital because of anorexia, vomiting, and transient loss of consciousness. Serum sodium was 115 mEq/l and the endocrinologic data indicated impaired secretion of ACTH, TSH, and gonadotropin, a preserved GH response, and increased PRL. Dynamic magnetic resonance imaging revealed marked swelling of the pituitary gland and stalk, with enhancement on early phase. The findings were consistent with lymphocytic hypophysitis according to the diagnostic criteria. Chest computed tomography revealed consolidation adjacent to the pleura in the right upper lobe, lower lobe, and left lower lobe. Because lymphocytic hypophysitis and associated organizing pneumonia were suggested, 50 mg of prednisolone was started and the dose was tapered. Swelling of the pituitary gland, lung lesion, and the LH and FSH response on the stimulation test were all markedly improved. Autoimmune pancreatitis, pituitary lesion, and organizing pneumonia might all be components of a systemic autoimmune fibrosclerosing disease in our case, although further studies are required to confirm this hypothesis.     

Hypothalamitis: a diagnostic and therapeutic challenge

To report an unusual case of biopsy-proven autoimmune hypophysitis with predominant hypothalamic involvement associated with empty sella, panhypopituitarism, visual disturbances and antipituitary antibodies positivity. We present the history, physical findings, hormonal assay results, imaging, surgical findings and pathology at presentation, together with a 2-year follow-up. A literature review on the hypothalamic involvement of autoimmune hypophysitis with empty sella was performed. A 48-year-old woman presented with polyuria, polydipsia, asthenia, diarrhea and vomiting. The magnetic resonance imaging (MRI) revealed a clear suprasellar (hypothalamic) mass, while the pituitary gland appeared atrophic. Hormonal testing showed panhypopituitarism and hyperprolactinemia; visual field examination was normal. Pituitary serum antibodies were positive. Two months later an MRI documented a mild increase of the lesion. The patient underwent biopsy of the lesion via a transsphenoidal approach. Histological diagnosis was lymphocytic “hypothalamitis”. Despite 6 months of corticosteroid therapy, the patient developed bitemporal hemianopia and blurred vision, without radiological evidence of chiasm compression, suggesting autoimmune optic neuritis with uveitis. Immunosuppressive treatment with azathioprine was then instituted. Two months later, an MRI documented a striking reduction of the hypothalamic lesion and visual field examination showed a significant improvement. The lesion is stable at the 2-year follow-up. For the first time we demonstrated that “hypothalamitis” might be the possible evolution of an autoimmune hypophysitis, resulting in pituitary atrophy, secondary empty sella and panhypopituitarism. Although steroid treatment is advisable as a first line therapy, immunosuppressive therapy with azathioprine might be necessary to achieve disease control.     

A case of lymphocytic infundibuloneurohypophysitis showing diabetes insipidus followed by anterior hypopituitarism associated with thrombasthenia

We report a case of a 42-year old male patient with diabetes insipidus followed by anterior hypopituitarism associated with thrombasthenia. The patient had been diagnosed with thrombasthenia since the age of 19. He was admitted and diagnosed as diabetes insipidus in 1995. Although T1-weighted image of magnetic resonance imaging (MRI) showed empty sella and partial pituitary stalk hypertrophy, the anterior pituitary functions were normal at that time. Three years later, he was re-admitted after an episode of general malaise and impotence in 1998. Endocrinological studies revealed adrenal insufficiency, hypothyroidism and hypogonadism. T1-weighted image of MRI demonstrated the thickening of pituitary stalk and neurohypophysis. Analysis of anti-pituitary antibodies by immunoblotting identified a major band at 61.5 kDa. The diabetes insipidus was controlled by desmopressin acetate and the shrinkage of pituitary stalk was seen after hormonal replacement therapy including glucocorticoid and thyroid hormone. We suggested that this case represented lymphocytic infundibuloneurohypophysitis, in which a chronic inflammatory process occurred in infundibulum and/or neurohypophysis and that hypopituitarism developed possibly due to damage to the pituitary portal vessels caused by a thickened pituitary stalk, although a pituitary biopsy was not done because of the risk of bleeding in thrombasthenia. The pituitary autoantibodies in sera from patients with hypopituitarism may be helpful to characterize the patient with lymphocytic hypophysitis.     

Intermediate lobe immunoreactivity in a patient with suspected lymphocytic hypophysitis

Lymphocytic hypophysitis is an organ-specific autoimmune disease characterised by destruction of pituitary hormone-secreting cells due to attack by self-reactive T lymphocytes. The spectrum of pituitary autoantibodies characterised by indirect immunofluorescence (IF) in these patients has not been substantially defined. The purpose of this study was to determine the spectrum of pituitary autoantibodies in 16 lymphocytic hypophysitis patients. Pituitary sections were prepared from guinea pigs and sera from 16 lymphocytic hypophysitis patients (13 biopsy proven and 3 suspected cases) and 13 healthy controls were evaluated for immunoreactivity to the pituitary tissue by immunofluorescence. A single patient was found to have high titre pituitary autoantibodies against guinea pig pituitary tissue. Immunoreactivity was directed against cells of the intermediate lobe. We present the case report of the patient who is a 24 year old woman that presented with headaches, polyuria and polydipsia. A uniformly enlarged pituitary mass was visible on MRI and a diagnosis of suspected lymphocytic hypophysitis was made. Based on our IF study, we postulate this patient has an autoimmune process directed towards the major cell type in the intermediate lobe, the melanotroph. Pre-adsorption with peptides representing adrenocorticotropic hormone, α-melanocyte stimulating hormone or β-endorphin did not affect the IF signal suggesting our patient’s pituitary autoantibodies may target some other product of Proopiomelanocortin (POMC) processing, such as corticotrophin-like intermediate peptide or γ-lipoprotein. Alternatively, the autoantibodies may target a peptide completely unrelated to POMC processing.     

A case of autoimmune hypophysitis associated with asymptomatic primary biliary cirrhosis.

We report a 61-year old male patient with panhypopituitarism complicated with asymptomatic primary biliary cirrhosis (PBC). T1-weighted magnetic resonance imaging demonstrated high intensity of the anterior pituitary gland. There was no mass lesion or enlargement of the pituitary gland or the stalk. Immunoblot analysis of the patient's sera with rat pituitary antigens revealed a band with a molecular size of 22 kD. Anti-M2 mitochondrial antibody has been consistently positive for five years. Liver biopsy revealed portal hepatitis with periportal infiltration of the inflammatory cells. This is the first case report of autoimmune hypophysitis complicated with asymptomatic PBC.     

Autoimmune hypophysitis treated with intravenous glucocorticoid therapy

A 46-year-old man presented with frontal headache, a visual field defect and general fatigue. Magnetic resonance imaging (MRI) of the brain showed symmetrical enlargement of the pituitary gland and stalk due to the presence of a mass lesion extending toward the optic chiasm. Gadolinium injection further revealed homogeneous strong enhancement with involvement of the adjacent dura (dural tail). Basal plasma levels of ACTH, free thyroxine and gonadotropins were decreased, and 24-h urinary 17-OHCS excretion was reduced. An elevated anti-thyroglobulin antibody titer indicated the presence of autoimmune thyroiditis. Under the suspicion of autoimmune hypophysitis, 60 mg/day prednisolone sodium succinate was intravenously administered for two weeks followed by a decreasing dose of oral prednisolone. Clinical symptoms and pituitary dysfunction recovered during steroid treatment and MRI showed marked shrinkage of the pituitary mass. Early initiation of an intravenous dose of glucocorticoid followed by oral steroid administration therefore seems to be an efficient treatment for autoimmune hypophysitis even in patients with visual dysfunction.     

Lymphocytic hypophysitis: unusual features of a rare disorder

OBJECTIVE Lymphocytic hypophysitis is a rare disorder which usually affects women and Is often associated with pregnancy. We reviewed our experience of this disorder In order to see whether these features were universal amongst our patients. DESIGN A retrospective review of case notes. PATIENTS Four patients with histologically proven lymphocytic hypophysitis. MEASUREMENTS Each patient had undergone full radiological and biochemical assessment of anterior and posterior pituitary function. RESULTS Only one woman presented during pregnancy, one patient was a man with coexistent active acromegaly, and one progressed over 5 years to panhypopituitarism. In one further patient, histological analysis revealed normal anterior pituitary tissue adjacent to lymphocytic follicles. CONCLUSIONS Lymphocytic hypophysitis should be considered in the differential diagnosis of any patient with a pituitary mass. We suggest that the entire removal of such a mass is warranted both for accurate diagnosis and definitive treatment.     

Lymphocytic hypophysitis in a patient with systemic lupus erythematosus

A case of lymphocytic hypophysitis in a patient with systemic lupus erythematosus is described. A 20-year-old woman was admitted to our hospital with generalized myalgia and facial rash in May 1998. The patient had a medical history, physical examination, and laboratory findings compatible with systemic lupus erythematosus (SLE). Headache and nausea had developed 3 months previously and worsened over the following months. Hormonal investigation showed hypopituitarism except for prolactin. A magnetic resonance image of the brain showed a mass lesion in the pituitary fossa. A trans-sphenoidal surgical procedure was performed which revealed a dark-yellowish hematoma. Microscopic examination showed diffuse infiltration of lymphocytes and plasma cells with fibrosis in the anterior pituitary. Post-operatively the patient's headaches and nausea resolved. This indicates that lymphocytic hypophysitis may be associated with SLE.     

Idiopathic giant-cell granulomatous hypophysitis mimicking acute meningitis.

A 32-year-old woman presented with severe headache, photophobia, fever, nausea, vomiting, and worsening vision. She had also noted several months of amenorrhea. She was febrile to 38.9 degrees C. Laboratory evaluation revealed a markedly elevated erythrocyte sedimentation rate. Lumbar puncture revealed a cerebrospinal fluid lymphocytic pleocytosis and an elevated protein level. Endocrine studies revealed evidence of panhypopituitarism without diabetes insipidus. A magnetic resonance imaging study showed a 2-cm pituitary mass with optic chiasmal compression. The patient had a trans-sphenoidal resection of the mass. Pathology revealed multinucleated giant cells in necrotic debris, but no evidence of pituitary tumor. Studies looking for evidence of systemic granulomatous disease were negative. The patient was considered to have idiopathic giant-cell granulomatous hypophysitis. After surgery, the patient's vision improved and hormone replacement therapy was initiated. This case illustrates that idiopathic giant-cell granulomatous hypophysitis should be considered in the differential diagnosis of a patient presenting with a pituitary mass, hypopituitarism, and meningitis-like symptoms.     

Spontaneous recovery from hypopituitarism in a man with lymphocytic hypophysitis: a case report

A 50-year-old man presented with hypopituitarism and a pituitary lesion on magnetic resonance imaging scan. He was diagnosed as having lymphocytic hypophysitis, and replacement therapy with hydrocortisone and thyroxine was started. He regained normal pituitary function after 10 months. Reports of spontaneous recovery from lymphocytic hypophysitis in men are rare. While the natural history of lymphocytic hypophysitis remains elusive and its management is not well established, our report shows that spontaneous resolution may occur with steroid supplementation even in men.     

Pituitary autoimmune disease: nuances in clinical presentation

Pituitary autoimmune disease is considered an autoimmune organ-specific disorder, characterized by a pituitary infiltration of lymphocytes, macrophages, and plasma cells that could lead to loss of pituitary function. Hypophysitis may be secondary to systemic diseases or infections. Primary pituitary hypophysitis is classified into lymphocytic, granulomatous, xanthomatous, mixed forms (lymphogranulomatous, xanthogranulomatous), necrotizing and IgG4 plasmacytic, according to the histological findings. Concerning lymphocytic hypophysitis (LH), it is characterized by lymphocytic infiltration and can be subclassified according to the affected area on: lymphocytic adenohypophysitis, lymphocytic infundibulo-neurohypophysitis and lymphocytic panhypophysitis. LH had always been considered a rare disease. Nevertheless, with improved imaging techniques, especially magnetic resonance imaging (MRI), LH diagnosis has been increased. This disease usually affects young women during pregnancy or postpartum period with headache, visual impairment, ACTH deficiency and a homogenous sellar mass with thickening of pituitary stalk in MRI. Definitive diagnosis depends on histopathological evaluation; nevertheless, a presumptive diagnosis could be done in a typical case. As no specific autoantigen was identified in LH, there is no antipituitary antibody (APA) method available for helping diagnosis. However, APA used in some centers for research could support an autoimmune origin for some hypopituitarism previously named as idiopathic, confirming nuances in clinical presentation of pituitary autoimmune disease. Therapeutic approach should be based on the grade of suspicious and clinical manifestations of LH.     

Lymphocytic panhypophysitis in a young man with involvement of the cavernous sinus and clivus

Lymphocytic hypophysitis is an unusual inflammatory lesion that is caused by autoimmune destruction of the pituitary gland. We report a case of 42-year-old man who presented with a 6-month history of severe headache, blurred vision in the right eye, hearing loss, polyuria, polydipsia, and impotence. Medical history showed that he and his mother had osteopetrosis. The results of the physical examination and laboratory tests showed that secondary hypothyroidism, hypogonadism, and hypocortisolism had developed. Central diabetes insipidus was diagnosed by water deprivation test. MRI of the sella showed pituitary enlargement with symmetrical suprasellar expansion, compression of the chiasma, thickened infundibulum, and involvement of both bilateral cavernous sinuses and clivus. Hormonal substitution with hydrocortisone, levothyroxine, and DDAVP resulted in rapid improvement of all symptoms and signs. Transsphenoidal biopsy was diagnostic of lymphocytic hypophysitis. In spite of extensive literature reviewing, we have not been aware of any case of lymphocytic hypophysitis with clivus involvement. The present case represents a variant of lymphocytic hypophysitis which has progressed to involve bilateral cavernous sinuses and the clivus.