[Pituitary cryptococcoma: a strange case of secondary granulomatous hypophysitis]. / Cryptococcoma hipofisiario: un extraño caso de hipofisitis granulomatosa secundaria.

Hypophysitis is a pathology with low incidence and prevalence. Likewise, deep fungal infections in immunocompetent patients also represent a rare phenomenon. Even rarer is the case described below, where these two mentioned elements are combined, namely: pituitary cryptococcoma or granulomatous hypophysitis caused by said pathogen in a host without altered immune response. After research in PubMed, there are limited cases in the medical literature of granulomatous hypophysitis caused by Cryptococcus spp., which simulated a pituitary macroadenoma by clinical and imaging manifestations. We did not find reports in which there is no evidence of involvement of the meningeal tissue. The fungal etiology is scarcely described in the reference guidelines for hypophysitis and we believe that Cryptococcus spp. it should be taken into account in the differential diagnosis of secondary granulomatous hypophysitis since it is a ubiquitous pathogen and the treatment is substantially different from other entities. It becomes more relevant given the current trend towards the use of high-dose systemic glucocorticoids for the treatment of hypophysitis, which could have generated greater damage if the correct diagnosis had not been made.

La hipofisitis es una afección con baja incidencia y prevalencia. Asimismo, las infecciones profundas por hongos en pacientes inmunocompetentes también representan un fenómeno infrecuente. Más raro aún es el caso que se describe a continuación, en donde se conjugan estos dos elementos mencionados, a saber: cryptococcoma hipofisario o hipofisitis granulomatosa causado por dicho patógeno en un huésped sin alteración de la respuesta inmune. Luego de una búsqueda realizada en PubMed, existen limitados casos en la literatura médica de hipofisitis granulomatosa por Cryptococcus spp., que simuló por manifestaciones clínicas e imagenológicas un macroadenoma hipofisario. No encontramos informes en los que no haya evidencia de afectación del tejido meníngeo. La etiología micótica está escasamente descrita en las guías de referencia para hipofisitis y creemos que Cryptococcus spp. debe ser tenido en cuenta en el diagnóstico diferencial de las hipofisitis granulomatosas secundarias dado que es un patógeno ubicuo y el tratamiento es sustancialmente diferente a otras entidades. Cobra mayor relevancia ante la tendencia actual al uso de glucocorticoides sistémicos a altas dosis para el tratamiento de la hipofisitis, que podría haber generado mayor daño de no haberse hecho el diagnóstico correcto.

Clinical characteristics of rheumatic disease-associated hypophysitis: A case series and review of literature.

Rheumatic diseases have been reported to sometimes involve the pituitary gland. This study aims to characterize the clinical features and outcomes of patients with rheumatic disease-associated hypophysitis. We used the electronic medical record system in our hospital to identify nine patients with pituitary involvement in rheumatoid disease. We summarized the clinical characteristics, radiographic findings, treatments, and clinical outcomes of the 9 patients. We also performed a systematic literature review of systemic lupus erythematosus (SLE) cases with pituitary involvement published in PubMed and Wanfang databases from 1995 to 2021, and eight patients with complete information were selected. In the nine-patient cohort, the median age was 54 years, and the spectrum of rheumatic diseases included immunoglobulin G4-related disease (IgG4RD) (4/9), SLE (2/9), vasculitis (2/9), and Sjögren syndrome (SS) (1/9). All patients had pituitary abnormalities on radiological assessment, 6 developed diabetes insipidus (DI), and 8 presented with anterior pituitary hormone deficiencies in the disease duration. All the patients had multisystem involvement. As compared to hypophysitis with IgG4RD (IgG4-H), the age at onset of hypophysitis with SLE (SLE-H) patients was younger [(30.4 ± 16.4) years vs. (56.0 ± 0.8) years] and the disease duration was shorter [(14.0 ± 17.5) months vs. (71.0 ± 60.9) months] (P < .05). All patients were managed with glucocorticoids (GC) in combination with another immunosuppressant, and the majority of patients improved within 4 months. Six patients achieved disease remission while four required at least one hormone replacement therapy. Hypophysitis is a rare complication secondary to a variety of various rheumatic diseases that can occur at any stage. GC combined with additional immunosuppressants could improve patients' symptoms; however some patients also required long-term hormone replacement therapy in pituitary disorders.

Secondary autoimmune hypothalamitis with severe memory impairment 7 years after the onset of diabetes insipidus due to lymphocytic hypophysitis: a case report.

BACKGROUND: Autoimmune hypothalamitis is a very rare neuroendocrine disorder that causes central diabetes insipidus, headache, visual impairment, and sometimes cognitive impairment. Autoimmune hypothalamitis may occur in association with autoimmune hypophysitis, including lymphocytic hypophysitis, or in isolation. It is not known whether autoimmune hypothalamitis and autoimmune hypophysitis are consecutive diseases. CASE PRESENTATION: A 52-year-old woman developed autoimmune hypothalamitis 7 years after developing central diabetes insipidus due to lymphocytic hypophysitis, resulting in severe memory impairment. High-dose intravenous methylprednisolone therapy improved her cognitive function and decreased the size of the lesion. CONCLUSION: This case presented a unique clinical course, with a long period of time between the onset of autoimmune hypopituitaritis and the development of autoimmune hypothalamitis.

Outcomes of Initial Management Strategies in Patients With Autoimmune Lymphocytic Hypophysitis: A Systematic Review and Meta-analysis.

CONTEXT: Lymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation, high-dose glucocorticoids (HD-GCs) or surgery. Optimal first-line management strategy, however, remains unknown. OBJECTIVE: This work aimed to assess response to first-line treatment options (observation, HD-GCs, or surgery) of clinically relevant outcomes (symptomatic, hormonal, and radiographic improvement) among patients with LyHy. METHODS: A systematic review was conducted in 6 databases through 2020. Meta-analysis was conducted when feasible using a random-effects model. RESULTS: We included 33 studies reporting on 591 patients (423 women, 72%) with LyHy. Improvement/resolution of anterior pituitary dysfunction was highest when HD-GCs was first-line treatment. Surgery was associated with the greatest proportion of patients who had regression on imaging. Subgroup analysis comparing HD-GCs to observation showed the odds of anterior pituitary hormone recovery (OR 3.41; 95% CI, 1.68-6.94) or radiographic regression (OR 3.13; 95% CI, 1.54-6.36) were higher with HD-GCs, but so was the need for additional forms of treatment (OR 4.37; 95% CI, 1.70-11.22). No statistically significant difference was seen in recovery of diabetes insipidus (OR 0.9; 95% CI, 0.26-3.10). Certainty in these estimates was very low. CONCLUSION: Observation and use of HD-GCs both are successful first-line management strategies in LyHy. Although use of HD-GCs was associated with increased recovery of anterior pituitary hormone deficit, it also was associated with greater likelihood of additional treatment after withdrawal. Optimal dosing and duration of HD-GCs remains unknown.

Lymphocytic panhypophysitis and anti-rabphilin-3A antibody with pulmonary sarcoidosis.

PURPOSE: To explore the clinical significance of anti-rabphillin-3A antibody for the differential diagnosis of lymphocytic panhypophysitis. METHODS AND RESULTS: A 58-year-old Japanese man developed uveitis of unknown cause in 2017. In 2019, he became aware of polyuria. In August 2020, he noticed transient diplopia and was diagnosed with right abducens nerve palsy. At the same time, he complained of fatigue and loss of appetite. Head magnetic resonance imaging demonstrated enlargement of the pituitary stalk and pituitary gland, corresponding to hypophysitis. Hormone stimulation tests showed blunted responses with respect to all anterior pituitary hormones. Central diabetes insipidus was diagnosed on the basis of a hypertonic saline loading test. Taking these findings together, a diagnosis of panhypopituitarism was made. Computed tomography showed enlargement of hilar lymph nodes. Biopsies of the hilar lymph nodes revealed non-caseating epithelioid cell granulomas that were consistent with sarcoidosis. Biopsy of the anterior pituitary revealed mild lymphocyte infiltration in the absence of IgG4-positive cells, non-caseating granulomas, or neoplasia. Western blotting revealed the presence of anti-rabphilin-3A antibody, supporting a diagnosis of lymphocytic panhypophysitis. Because the patient had no visual impairment or severe uveitis, we continued physiological hormone replacement therapy and topical steroid therapy for the uveitis. CONCLUSION: To the best of our knowledge, this is the first case of anti-rabphilin 3A antibody positive lymphocytic panhypophysitis comorbid with sarcoidosis, diagnosed by both pituitary and hilar lymph node biopsy. The utility of anti-rabphilin-3A antibody for the differential diagnosis of hypophysitis like this case should be clarified with further case studies.

Early Pulse Glucocorticoid Therapy and Improved Hormonal Outcomes in Primary Hypophysitis.

INTRODUCTION: The role of glucocorticoids in primary autoimmune hypophysitis (PAH) has been fraught with variability in regimens, leading to inconsistent outcomes in terms of anterior pituitary (AP) hormonal recovery. Hence, we aimed to compare the clinical, hormonal, and radiological outcomes of a standardized high-dose glucocorticoid therapy group (GTG) in PAH with a matched clinical observation group (COG). METHODS: Thirty-nine retrospective patients with PAH evaluated and treated at a single center in western India from 1999 to 2019 with a median follow-up duration of 48 months were subdivided into the GTG (n = 18) and COG (n = 21) and compared for the outcomes. RESULTS: Baseline demographic, hormonal, and radiological features matched between the groups, except pituitary height, which was significantly higher in GTG. Cortisol, thyroid, and gonadal axes were affected in 25 (64%), 22 (56%), and 21 (54%) patients, respectively, and central diabetes insipidus was seen in 7 (18%) patients. Panhypophysitis (PH) was the most common radiological subtype (n = 33, 84.6%). Resolution of mass effects was similar in both groups. Overall and complete AP hormonal recovery was significantly higher in the GTG than in the COG (12/14 [85.7%) vs. 6/14 [42.8%], p = 0.02; 10/14 [71.4%] vs. 1/14 [7.7%], p = 0.0007, respectively). Proportion of cases with empty sella were significantly higher in the COG (9/20 [45%] vs 1/17 [5.9%], p = 0.001). Among PH patients in the GTG (n = 17), we found duration from symptoms onset to treatment as the predictor of recovery. CONCLUSION: In a PH subtype-predominant PAH cohort, a standardized high-dose glucocorticoid regimen resulted in higher overall and complete AP hormonal recovery than that in the COG. Initiation of glucocorticoids in the early disease course may have been contributory.

Recurrent autoimmune hypophysitis treated with rituximab: a case report.

BACKGROUND: Autoimmune hypophysitis is a rare condition that often results in enlargement of the pituitary gland and hypopituitarism due to inflammatory infiltration. Management of autoimmune hypophysitis can include long-term hormonal replacement and close control of the inflammatory pituitary mass. Mass-related symptoms in patients with autoimmune hypophysitis are treated with anti-inflammatory therapy, surgery, and/or radiotherapy. CASE PRESENTATION: We present a 25-year-old White man with visual field defects of the right eye, headache, and weight loss. Magnetic resonance imaging showed a sellar mass, and the patient underwent transcranial surgery. Histopathology revealed autoimmune hypophysitis with predominantly CD20 positive B-cell infiltration. Progression of visual field defects necessitated postoperatively anti-inflammatory treatment with prednisolone. Azathioprine was initiated under gradual tapering of prednisolone with stable conditions at first, but relapse followed after dose reduction. Therefore, rituximab treatment was initiated, which resulted in regression of the pituitary mass. Rituximab treatment was discontinued after 25 months. The patient has continuously been in remission for 4 years after rituximab treatment was stopped. CONCLUSION: This case illustrates that rituximab might be an effective alternative treatment in B-cell predominant autoimmune hypophysitis.

Bannwarth Syndrome: A Rare Manifestation of Pediatric Lyme Neuroborreliosis.

Lymphocytic meningoradiculitis (Bannwarth syndrome) is a rare manifestation of Lyme neuroborreliosis in children. It is the most common clinical manifestation of early Lyme neuroborreliosis in adults in European countries where the disease is endemic but is rare in children. We report an imported case of Bannwarth syndrome in a pediatric patient and review the literature for other pediatric cases reported.

IgG4-related hypophysitis in adolescence.

OBJECTIVES: IgG4-related hypophysitis is a novel clinical disease entity, which is typically seen in the sixth decade of life and is typically complicated by hypopituitarism. We describe an adolescent female with IgG4-related hypophysitis with normal pituitary function and summarize the relevant literature. CASE PRESENTATION: A 11.8-year-old girl presented with headache and left VI cranial nerve palsy. MRI brain identified an enlarged pituitary gland. Endocrine investigations revealed normal pituitary function. She underwent a transsphenoidal biopsy of the pituitary gland, and histological examination confirmed the diagnosis of IgG4-related hypophysitis. Serum IgG4 concentrations were normal and no evidence of other organ involvement was found. Although the patient tested strongly positive for TB on an interferon gamma release assay, pituitary biopsy was negative for granuloma formation and acid-fast bacilli (Ziehl-Neelson staining). IgG4-related hypophysitis was treated with oral prednisolone and mycophenolate-mofetil with a good response. CONCLUSIONS: We describe to the best of our knowledge, the youngest patient in the published literature with IgG4-related hypophysitis presenting without pituitary insufficiency. A literature review identified only five cases of IgG4-related hypophysitis in adolescence. Serum IgG4 concentrations were normal in all, except one of the adolescent patients reported so far, and appear unhelpful in diagnosis in this age group.

Histopathological findings in the landscape of IgG4-related pathology in patients with pituitary dysfunction: Review of six cases.

IgG4-related hypophysitis (IgG4-RH) is increasingly being reported as an isolated entity or, less frequently, as a manifestation of a multiorgan IgG4-related disease (IgG4-RD), in which typical histopathology is a cornerstone for the diagnosis. We aimed to describe the histopathological changes in the surgical specimens from patients with clinical signs of pituitary disease that fulfilled the current diagnostic criteria for IgG4-RH. Histopathological features were correlated with clinical and radiological findings. Of 19 patients with pituitary dysfunction and inflammatory changes in the surgical pituitary specimen operated on during 2011-2019, we identified five patients with typical IgG4-related pathology (lymphoplasmacytic infiltration with more than 10 IgG4-positive plasma cells per one high power microscopic field, representing at least 40% of all plasma cells and at least focal storiform fibrosis). One patient with diabetes insipidus and pachymeningitis with IgG4-related changes in a biopsy from the dura was also included. Additional histopathological changes that typically are not part of the IgG4-RH were observed: Rathke's cleft cyst in four and granulomatous changes in two patients. One patient had an elevated serum IgG4 level and systemic manifestations that could be associated with the systemic IgG4-RD. Our findings indicate that pure IgG4-RH is uncommon. All patients with pituitary dysfunction, beyond typical IgG4-related pathology, had other pathological findings that could trigger the secondary IgG4-response. Both primary pathology and secondary IgG4-related features should be reported in patients with pituitary dysfunction because their co-occurrence may cause atypical clinical and imaging features, and unexpected response to surgical and pharmacological treatment. The current criteria for the diagnosis of IgG4-RH can lead to overdiagnosis of IgG4-RH if additional pathological changes are not taken into consideration. The classification criteria of IgG4-RD proposed by the American College of Rheumatology/European League Against Rheumatism could help classify patients more properly as IgG4-RH if applied to the pituitary gland.

Complete Resolution of the Pituitary Mass Lesion and Improvement of Pituitary Function with Corticosteroid in Autoimmune Hypophysitis: A Case Report.

BACKGROUND: Autoimmune hypophysitis is the consequence of an immune-mediated inflammation of the pituitary gland, which is rare, and most frequently occurs in females during postpartum periods. It usually responds well to corticosteroid treatment with reported resolution of the pituitary mass lesion. CASE REPORT: A 51 years male presented with a one-month history of lethargy, headache, nausea, proximal muscle weakness with intermittent flushing. He was a diabetic with metformin 500mg twice daily. No other remarkable medical history or family history of autoimmune disease. On examination, he had no neurological deficit with a normal visual field. His initial biochemical evaluation showed features of secondary hypothyroidism as evidenced by low free FT4 and suppressed TSH with normal electrolytes. The subsequent evaluation of his hormonal profile revealed panhypopituitarism. Contrast MRI of pituitary showed an enhanced homogenous mass and minimal stalk thickening with a dural tail and preserved posterior bright spot. He was managed with glucocorticoid 20 mg once daily for two weeks along with levothyroxine and testosterone replacement. After two weeks of treatment, he improved clinically. Repeat MRI imaging of the pituitary showed complete resolution of the homogenous mass. CONCLUSION: Although autoimmune hypophysitis is rare in males, a careful clinical history with necessary hormonal investigations is required for the suspicion about the inflammatory pituitary disorders This current case highlights glucocorticoid as the primary modality of treatment and the need for long-term follow-up with periodic clinical assessment.

Autoimmune Hypophysitis With Systemic Lupus Erythematosus: A Case Report and Literature Review.

Background: Autoimmune hypophysitis (AH) is a primary autoimmune inflammatory disorder of the pituitary gland, which usually presents as a mass in the sella turcica. Systemic lupus erythematosus (SLE) is another inflammatory disorder in which the immune system attacks healthy cells and tissues throughout the body. Although both diseases are autoimmune disorders, they rarely coexist, and the relationship between them is unclear. Case Report: A 66-year-old man was evaluated at the endocrinology clinic because of worsening fatigue, anorexia, drowsiness, and leg oedema. Examination revealed alertness impairment and lower limb oedema. Laboratory tests showed anterior pituitary hypofunction. The treatment approach, with glucocorticoids and immunosuppressive agents, resulted in long-term remission of symptoms of hypopituitarism and hyponatraemia. Conclusions: Our case demonstrates a potential association between AH and SLE. AH may need to be considered in the evaluation of SLE patients with headache, hyperprolactinemia, a pituitary mass, and hypopituitarism.

Autoimmune hypophysitis and viral infection in a pregnant woman: a challengeable case.

The aim of this study is to report a challengeable and rare case of autoimmune hypophysitis possibly induced by viral infections. A young pregnant female developed optic neuropathy due to enlarged sellar mass responsible for hypopituitarism. Investigations exclude neoplasia and systemic diseases. High level of sedimentation rate and magnetic resonance imaging (MRI) findings supported the diagnosis of autoimmune hypophysitis. The patient reported a history of bronchitis treated with antibiotics and corticosteroids and positive serologies for hepatitis B antigen (Hbs antigen), herpes simplex 1 and rubella. Final examination showed complete recovery of visual function and sellar archnoidocele after antiviral treatment and mild dose of corticosteroids.

Role of 18F-fluorodeoxyglucose (FDG) and 18F-2-fluorodeoxy sorbitol (FDS) in autoimmune hypophysitis: a case report.

BACKGROUND: Autoimmune hypophysitis is a rare disease characterized by the infiltration of lymphocytic cells into the pituitary gland. 18F-fluorodeoxyglucose (FDG) and 18F-2-fluorodeoxy sorbitol (FDS) positron emission tomography (PET) are well-established and emerging techniques, respectively, which may aid in the diagnosis and classification of autoimmune hypophysitis. CASE PRESENTATION: Here, we report a 40-year-old female diagnosed with central diabetes insipidus and multiple pituitary hormone deficiencies, and MRI revealed homogeneous signals in the pituitary gland as well as thickened in the pituitary stalk. FDG PET localized the pituitary and pituitary stalk lesions and displayed an SUVmax of 5.5. FDS, a sensitive radiotracer for bacterial infections but remains unproven under aseptic inflammation, also demonstrated elevated radioactivity, with an SUVmax of 1.1 at 30 min and 0.73 at 120 min. Transnasal biopsy suggested a diagnosis of autoimmune hypophysitis, and the patient displayed radiological and clinical improvement after treatment with glucocorticoids and hormone replacement. CONCLUSIONS: Autoimmune hypophysitis can display elevated FDG uptake, which aids in the localization of the lesions. In addition to revealing bacterial infection specifically, FDS can also accumulate under autoimmune conditions, suggesting that it could serve as a potential radiotracer for both bacterial and aseptic inflammation. TRIAL REGISTRATION: The patient was enrolled in study NCT02450942 (clinicaltrials.gov, Registered May 21, 2015).

A Remarkable Response of Granulomatous Hypophysitis to Infliximab in a Patient With a Background of Crohn's Disease-A Case Report.

Background: Hypophysitis is primary or idiopathic or secondary to another disease process. The histologic subtypes of hypophysitis are lymphocytic, granulomatous, xanthomatous, xanthogranulomatous, or IgG4-related. Granulomatous hypophysitis is the second most common form and is characterized by multinucleated giant cells with granulomas and histiocytes. It can be idiopathic or secondary to another process such as infection, sarcoidosis, vasculitis, dendritic cell disorders, Crohn's disease (CD) or a reaction to rupture of a Rathke's cyst or pituitary adenoma. We present a case of granulomatous hypophysitis in a patient with CD who had resistance to corticosteroids but a dramatic response to immunosuppressive therapy with anti-tumor necrosis factor (TNF)-α therapy. Case description: A 43-year-old woman with a 9-year history of ileal and colonic CD presented to the Pituitary Center with headaches, visual disturbance, fatigue, nausea, and secondary amenorrhea. She was not on active therapy for her CD at the time of presentation and had no gastrointestinal symptoms. Hormonal evaluation revealed hyperprolactinemia, secondary hypothyroidism and adrenal insufficiency. MRI revealed a 12 × 12 × 19 mm sellar lesion abutting the optic chiasm, reported as a macroadenoma. The patient underwent endoscopic transsphenoidal biopsy of the pituitary mass. Pathology revealed granulomatous hypophysitis. Evaluation for secondary causes of hypophysitis, apart from CD, was negative. Despite a course of high dose prednisone, her symptoms and MRI findings worsened and she developed symptoms consistent with diabetes insipidus. Using a personalized medicine approach, she was started on anti-(TNF)-α therapy with infliximab combined with azathioprine, which are indicated for treatment of CD. Her headaches and polyuria resolved and her menstrual cycles resumed. MRI at 3 months and more than 1.5 years after initiation of anti-TNF-α therapy revealed durable resolution of the pituitary mass. Conclusion: To our knowledge, this is the first report of successful use of anti-TNF-α therapy for a patient with granulomatous hypophysitis, in this case associated with a previous diagnosis of CD. Although glucocorticoids are used frequently as first-line therapy for primary hypophysitis, granulomatous hypophysitis can be corticosteroid resistant and other immunosuppressive approaches may need to be considered within the context of the patient.

Recurrent myelitis and asymptomatic hypophysitis in IgG4-related disease: case-based review.

IgG4-related disease (IgG4-RD) is a disorder with various clinical manifestations. Central nervous system (CNS) involvement is well recognized, with hypertrophic pachymeningitis and hypophysitis being the most common manifestations. Spinal cord involvement is an extremely rare manifestation. We present the first case of an IgG4-RD patient with spinal cord parenchymal disease and concurrent hypophysitis. We review also the current literature about CNS parenchymal involvement in the context of IgG4-RD. A young female presented with clinical symptoms of myelitis. Cervical spinal cord magnetic resonance imaging (MRI) displayed features of longitudinally extensive transverse myelitis (LETM). Brain MRI showed a small number of high-intensity lesions in the deep white matter and enlargement of hypophysis with homogeneous gadolinium enhancement (asymptomatic hypophysitis). Diagnostic workup revealed elevated IgG4 serum levels (146 mg/dL). Our patient fulfilled the organ-specific diagnostic criteria of IgG4-hypophysitis. Treatment with intravenous glucocorticoids led to rapid clinical response, and to the substantial resolution of imaging findings. Azathioprine was used as a maintenance treatment. One relapse occurred 2 years after the initial diagnosis and patient was re-treated with glucocorticoids. Three years after relapse, patient is in remission with azathioprine. We present the first case of myelitis with radiological features of LETM associated with increased IgG4 serum levels and the simultaneous presence of asymptomatic IgG4-related hypophysitis.

Pituitary dysfunction in granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis of small vessels that affect the pituitary gland in less than 1% of cases being exceptionally rare. To describe the clinical, biochemical, radiological findings, treatment, and outcomes of 4 patients with GPA-related hypophysitis. A systematic review of published cases with the same diagnosis is presented as well. A cross-sectional case series of patients with hypophysitis due to GPA from 1981 to 2018 at a third level specialty center. Literature review was performed searching in seven different digital databases for terms "granulomatosis with polyangiitis" and "pituitary gland" or "hypophysitis," including in the analysis all published cases between 1950 and 2019 with a minimum follow-up of 6 months. We found 197 patients with GPA in our institution of whom 4 patients (2.0%) had pituitary involvement. Clinical characteristics and outcomes are described. We also reviewed 7 case series, and 36 case reports describing pituitary dysfunction related to GPA from 1953 to 2019, including the clinical picture of an additional 74 patients. Pituitary dysfunction due to GPA is rare. Treatment is targeted to control systemic manifestations; nevertheless, the outcome of the pituitary function is poor. Central diabetes insipidus, particularly in younger women with other systemic features, should raise suspicion of GPA.Key Points• Involvement of the pituitary gland is an uncommon manifestation in GPA patients. The presence of central diabetes insipidus in the setting of systemic symptoms should prompt its suspicion.• In patients with pituitary involvement due to GPA, affection of other endocrine glands is rare, neither concomitant nor in different times during the disease course. This may arise the hypothesis of a local or regional pathogenesis affection of the gland.• There is no consensus on the best therapy strategy for GPA hypophysitis. Although the use of glucocorticoids with CYC is the most common drug combination, no differences in the outcome of the pituitary function and GPA disease course are seen with other immunosuppressants.• Poor prognosis regarding pituitary function is expected due to possible permanent pituitary tissue damage that results in the need of permanent hormonal replacement.

Clinical aspects of autoimmune hypothalamitis, a variant of autoimmune hypophysitis: Experience from one center.

OBJECTIVE: Autoimmune hypothalamitis (AHT) is a rare inflammatory disorder that involves the hypothalamus. It remains unclear whether autoimmune hypophysitis (AH) and AHT represent different diseases or different aspects of the same disease. Thus, further investigation of AHT is required. METHODS: A retrospective review of medical and pathological records of AHT patients from the Chinese PLA General Hospital were examined from January 1, 2005 to May 1, 2017. Clinical data, treatments, and outcomes were investigated. RESULTS: Five female patients were identified (median age, 42.6 years). Symptoms included central diabetes insipidus, hypopituitarism, hyperprolactinemia, headache, and hypothalamic syndrome. The following hormonal deficits were noted: follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, thyroid stimulating hormone, and growth hormone. One patient underwent high-dose methylprednisolone pulse treatment (HDMPT) and azathioprine plus intensity modulated radiation therapy (IMRT), and two patients underwent HDMPT and two rounds of replacement therapy. During follow-up, one patient died because of non-compliance with therapy and the others were in remission or they recovered. CONCLUSIONS: AHT had similar MRI results, pathology, and treatment compared with AH. Thus, it may be a subtype of AH, and AHT patients may also show hypothalamic syndrome.

Isolated Langerhans cell histiocytosis in the hypothalamic-pituitary region: a case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease that mainly affects children, but this disease is significantly rarer in patients who are older than 15 years. In this disease, any organ can be involved. The skeleton, skin and lung are commonly affected, and isolated hypothalamic-pituitary (HP) involvement is relatively rare. Here we report a 17-year-old adolescent with isolated HP-LCH of enlarged pituitary stalk presented with central diabetes insipidus (CDI). CASE PRESENTATION: A 17-year-old male adolescent with polydipsia and polyuria accompanied with elevated serum sodium level and low urine osmolality for 3 weeks was referred to our hospital. After admission, hormonal evaluation showed that his growth hormone (GH) was slightly elevated, and serum osmolality and glucose were normal. The fluid deprivation-vasopressin test demonstrated CDI. Imaging examination showed an obvious thickening of the pituitary stalk. Lymphocytic hypophysitis, sarcoidosis and granulation tissue lesions were suspected. After oral 1-deamino-8-Darginine vasopressin (DDAVP) and prednisone were administered for 2 months, symptoms were relieved, and he discontinued taking the drugs by himself. On reexamination, imaging revealed changes in the size and shape of the pituitary stalk, with thickened nodules. Then, a diagnostic biopsy of the pituitary stalk lesion was performed. Immunohistochemistry confirmed the definitive diagnosis of LCH. The clinical symptoms subsided with oral hormone replacements. CONCLUSION: CDI is a rare symptom in children and adolescents. Most of the causes are idiopathic, while others are caused by central nervous system (CNS) disorders. Meanwhile, lymphocytic hypophysitis, germinoma, LCH and other CNS disorders can all present as thickening of the pituitary stalk, diffuse enlargement of the pituitary gland, and weakening of high signal intensity in the neurohypophysis on magnetic resonance imaging (MRI). The differential diagnosis among these diseases depends on immunohistochemistry evidence.