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Autoimmune/lymphocytic hypophysitis is one of the rare causes of central diabetes insipidus in adults and is most common among women in the second or third trimester of pregnancy. Numerous studies have shown that lymphocytic hypophysitis is characterized by a very variable clinical signs with the development of neurological symptoms, visual disturbances and hypopituitarism with partial or complete loss of pituitary function, as well as a number of features in magnetic resonance imaging (MRI). Isolated lymphocytic indibuloneurohypophysitis occurs in fewer cases and involves the posterior lobe and stalk of the pituitary gland with a clinical presentation of diabetes insipidus. The above clinical case describes the development of hypophysitis in a pregnant woman with a predominant lesion of the posterior pituitary gland and an outcome in diabetes insipidus, which persists 6 years after pregnancy and childbirth. In the article some aspects of the differential diagnosis of diabetes insipidus in pregnant women, as well as instrumental diagnosis and treatment approaches of hypophysitis are discussed.

A 78-year-old man complained of subacute general fatigue and anorexia, following diplopia and gait disturbance. He demonstrated wide-based and small-stepped gait without objectively abnormal ocular movements. Brain ‍MRI showed enlargement of the pituitary stalk and gland with uniform contrast enhancement. PET-CT showed FDG ‍uptake in the pituitary gland, mediastinal lymph nodes, and left hilar lymph nodes. Blood investigations revealed panhypopituitarism and high serum IgG4 levels up to 265 ‍mg/dl. Histopathological examination revealed no IgG4-positive cell infiltration in the biopsied mediastinal lymph nodes. However, we suspected IgG4-associated hypophysitis based on the clinical symptoms and MRI findings, which were markedly resolved with steroid. Central masked diabetes insipidus was manifested, but was improved with oral desmopressin. We should pay close attention to the fact that IgG4-related hypophysitis may present with various symptoms regarded as indefinite complaints related to aging or underlying diseases, especially in elderly patients with multimorbidity.

Anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis, a paraneoplastic syndrome resulting from an autoimmune response against PIT-1, typically manifests with undetectable levels of growth hormone (GH) and prolactin (PRL), and significantly low levels of serum thyroid-stimulating hormone (TSH) at diagnosis. These hormonal levels are highly specific to this disease and serve as key diagnostic indicators. Herein, we present a detailed clinical course of a 69-year-old male with a history of gastric cancer and lymph node metastases who developed anti-PIT-1 hypophysitis after the initiation of immune checkpoint inhibitor (ICI) therapy, specifically nivolumab, oxaliplatin, and capecitabine. The patient was referred to our department owing to decreased TSH, free triiodothyronine (T3), and free thyroxine (T4) levels after two doses of nivolumab. Initially suspected as central hypothyroidism due to ICI-related hypophysitis, further assessment confirmed the diagnosis of anti-PIT-1 hypophysitis. Notably, GH, PRL, and TSH levels markedly declined, leading to complete deficiencies 2 months after the first nivolumab dose-a pattern consistent with that of previous cases of anti-PIT-1 hypophysitis. Therefore, this report not only presents an atypical subset of ICI-related hypophysitis but also delineates the process of hormone impairment leading to complete deficiencies in anti-PIT-1 hypophysitis. This case highlights the importance of vigilant monitoring for endocrine issues in patients undergoing ICI therapy, given the escalating incidence of immune-related adverse events associated with the extensive use of ICI therapy for various cancers., (© 2024 British Society for Neuroendocrinology.)

A 75-year-old woman presented with nausea and vomiting. Magnetic resonance imaging (MRI) revealed that she had a pituitary mass. A biopsy revealed lymphocytic hypophysitis (LYH). Symptoms were improved by hormone replacement therapy. Although she was asymptomatic, follow-up MRI revealed an increase in the size of the mass. Intravenous methylprednisolone (IVMP) reduced the size of the mass; however, right ophthalmalgia and oculomotor nerve palsy developed. MRI showed that the pituitary mass had enlarged to the right oculomotor nerve in the cavernous sinus and to the right internal carotid artery (ICA), causing stenosis of the ICA. After IVMP administration, the symptoms dramatically improved, but ICA stenosis persisted.

Background: Lymphocytic hypophysitis is a rare autoimmune condition that usually presents during pregnancy and causes inflammation of the pituitary gland. Although the pathophysiology is not well understood, it often presents with headaches, visual disturbances, and symptoms of hypopituitarism. However, not all cases may present with hypopituitarism which can make this rare disease with an incidence of ~ 1 in 9 million much more difficult to diagnose., Case Presentation: We present a 35-year-old G4P4 woman with progressive vision loss and intermittent frontal headaches during her first trimester through 2 months postpartum. She presented with no symptoms of hypopituitarism and her hormone panel only showed elevated prolactin, possibly due to her breastfeeding. She was treated with a right pterional craniotomy with decompression of both optic nerves, partial resection of the suprasellar mass, and glucocorticoid therapy for headaches and visual disturbances., Conclusion: This case is notable for a presentation of lymphocytic hypophysitis without symptoms of hypopituitarism. This is important for outpatient providers to be aware of, especially those that care for pregnant patients so that unfavorable outcomes can be avoided., (© 2024. The Author(s).)

Introduction: Lymphocytic hypophysitis (LH) is a rare inflammatory disorder of the pituitary or/and hypothalamus with variable disease course: from spontaneous remission to pituitary atrophy. The diagnosis, treatment and follow-up remain challenging. The aim of the study is to present long-term data and an individualized therapeutic approach and propose an algorithm for the follow-up of patients with probable LH., Material and Methods: A retrospective analysis of 18 consecutive adult patients (13 W/5 M, mean age 45.2 years) with LH diagnosed and treated in a tertiary referral center., Results: The first manifestations were headaches (50.0%), polyuria/polydipsia (33.3%) and symptoms of hypopituitarism (16.7%). Somatotropic, adrenal, gonadal and thyroid axis insufficiencies were found in 44.4%, 33.3%, 33.3%, and 27.8% of patients, respectively. Arginine vasopressin deficiency was diagnosed in 8 patients (44.4%). Some of the dysfunctions were transient. Magnetic resonance imaging (MRI) revealed thickened pituitary stalk in all but 2 cases. In 2 patients an anterior pituitary lesion, most likely inflammatory was described. Four patients were given steroids (severe headaches) with clinical recovery and stable/improved MRI. One woman was operated on due to the progressive mass-related symptoms - histopathological examination confirmed LH. In the remaining 13/18 patients watchful waiting approach allowed to obtain hormonal and radiological stabilization/improvement., Conclusions: LH is a disease with a complex clinical picture and challenging diagnosis. Treatment requires an individual approach: vigilant observation is the cornerstone of therapy, with steroid/surgical treatment reserved for cases with mass-related symptoms. Further multicenter research might help in better understanding of the LH and creating standards of care in this rare disease.

Paraneoplastic syndromes are defined by symptoms or signs resulting from damage to organs or tissues that are remote from the site of malignant neoplasms or its metastasis. They are due to tumor secretion of functional hormones or peptides or are related to immune cross-reactivity with the host tissue. In particular, paraneoplastic endocrine syndromes are mainly caused by ectopic hormone production by the tumor such as PTHrP in humoral hypercalcemia in malignancy and ACTH in ectopic ACTH syndrome. Recently, it has been reported that a specific form of hypophysitis is caused as an immune-mediated paraneoplastic syndrome; paraneoplastic autoimmune hypophysitis, in which an ectopic pituitary antigen expression in the tumor evoked autoimmunity against pituitary-specific antigens, resulting in hypophysitis and exhibiting the injury of specific anterior pituitary cells by cytotoxic T cells. This novel clinical entity, paraneoplastic autoimmune hypophysitis consists of several conditions such as anti-PIT-1 hypophysitis and a part of isolated ACTH deficiency and immune checkpoint inhibitor-related hypophysitis with common mechanisms. These conditions can explain at least in part, the underlying mechanisms of acquired specific pituitary hormone deficiencies. In addition, it is important to apply a comprehensive discipline of onco-immuno-endocrinology to understand the pathophysiology and this approach; the expansion and application of immune-mediated paraneoplastic syndrome to endocrine diseases may give a new clue to understand pathophysiology of the autoimmunity against endocrine organs.

Background: Some patients develop immunoglobulin G4 (IgG4)-related hypophysitis associated with systemic diseases. More than 30 cases of IgG4-related hypophysitis have been reported. However, biopsy has rarely been performed in these patients, and none have had an associated pituitary neuroendocrine tumor (PitNET). We present a case of concurrent IgG4-related hypophysitis and PitNET., Case Presentation: A 56-year-old Japanese man arrived at the hospital with visual impairment, bitemporal hemianopia, and right abducens nerve palsy. Magnetic resonance imaging revealed pituitary body and stalk swelling as well as a small poorly enhanced right anterior lobe mass. Laboratory and loading test results suggested hypopituitarism. Because IgG4 level was elevated, a systemic examination was performed; multiple nodules were found in both lung fields. The diagnosis was based on an endoscopic transnasal biopsy of the pituitary gland. A histopathological examination revealed a marked infiltration of plasma cells into the pituitary gland, which was strongly positive for IgG4. The histological features of the resected tumor were consistent with those of gonadotroph PitNET, which was immunohistochemically positive for follicle-stimulating hormone-β and steroidogenic factor-1, and no plasma cell infiltration was observed. Based on the histopathological examination results, steroid therapy was initiated, which reduced pituitary gland size and serum IgG4 levels., Discussion and Conclusions: This is the first reported case of IgG4-related hypophysitis with PitNET. Although no pathological findings indicating a relationship between the two conditions were found, we were able to preoperatively differentiate multiple lesions via detailed diagnostic imaging., (© 2023. The Author(s).)

The term hypophysitis is used to designate a heterogeneous group of pituitary conditions characterized by the presence of inflammatory infiltration of the adenohypophysis, neurohypophysis, or both. Although hypophysitis are rare disorders, the most common in clinical practice is lymphocytic hypophysitis, a primary hypophysitis characterized by lymphocytic infiltration, which predominantly affects women. Other forms of primary hypophysitis are associated with different autoimmune diseases. Hypophysitis can also be secondary to other disorders such as sellar and parasellar diseases, systemic diseases, paraneoplastic syndromes, infections, and drugs, including immune checkpoint inhibitors. The diagnostic evaluation should always include pituitary function tests and other analytical tests based on the suspected diagnosis. Pituitary magnetic resonance imaging is the investigation of choice for the morphological assessment of hypophysitis. Glucocorticoids are the mainstay of treatment for most symptomatic hypophysitis., (Copyright © 2023 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: The aim of the study is to assess the distinguishing features of pregnancy-related hypophysitis (PR-Hy) compared to non-pregnancy autoimmune hypophysitis and to evaluate the changing therapeutic approaches and outcomes in PR-Hy over time., Design: Retrospective analysis of all published cases with PR-Hy and 6 own cases., Methods: A PubMed search was performed and abstracts screened for publications with information on cases with PR-Hy from which full-text review was performed. Clinical features, diagnostic findings, and outcome in relation to treatment modalities in PR-Hy were assessed., Results: One hundred and forty-eight cases with PR-Hy were identified. PR-Hy was significantly delimited from non-PR-Hy by the frequent occurrence of the chiasmal syndrome (50% vs 13%, P < .0001), higher rate of intrasellar origin (94% vs 74%, P = .0005), lower rate of pituitary stalk involvement (39% vs 86%, P < .0001), and low rate of diabetes insipidus (12% vs 54%, P < .0001). The role of surgery in PR-Hy decreased over time while noninvasive treatment modalities increased. The recurrence rate after high-dose glucocorticoid therapy (33%) was high and exceeded that of surgery (2%) and conservative management (2%). In contrast to initial reports on PR-Hy, recent literature regarding outcome of mother's and child's health was positive. The frequency of spontaneous preterm delivery was not increased. Recurrent PR-Hy in a subsequent pregnancy was reported in only two females., Conclusion: PR-Hy has distinct features that delineate the disorder from non-PR-Hy. With increasing experience in diagnosis, availability of adequate replacement therapy, and improved treatment modalities, PR-Hy has lost its threat and the outcome is encouraging., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of (ESE) European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Primary hypophysitis (PH) is a rare disease that represents a challenge among differential diagnosis and management. Our aim was to describe clinical characteristics, diagnostic criteria and different treatment outcomes in patients with PH. Multicentric, retrospective study. Clinical presentation, endocrine function, magnetic resonance imaging findings, visual field defects at diagnosis and treatment outcomes were recorded., Methods: Twenty-eight patients (23 women), with PH were included. Median age: 37., Results: The most frequent symptoms: headache: 68%, polyuria-polydipsia: 50% and visual disturbances: 48%. At diagnosis, anterior pituitary deficiency was present in 71%, being hypogonadotrophic hypogonadism the most frequent manifestation. The radiological findings: symmetric lesion: 78.5%, homogeneous enhancement: 78.5% and pituitary stalk thickening: 70%. Association with pregnancy or puerperium was found in 4/23 women (17%). Fourteen patients did not receive any treatment ("wait and see" group), 8 underwent surgery for mass reduction or resection and 6 were treated with immunosuppression therapy. Among 15 patients with histopathological diagnosis, 9 were lymphocytic hypophysitis, 5 IgG4 related hypophysitis and 1 xanthomatous hypophysitis. Thirteen were diagnosed by established clinical criteria. Mass reduction was observed in 43% of "wait and see group" patients, 62.5% of operated patients and 50% with immunosuppression therapy. Compressive symptoms showed improvement in the 3 groups, with modest effect on anterior pituitary function, diabetes insipidus did not resolve in any patients., Discussion: In patients without severe compressive symptoms, we adopted a "wait and see" approach. In patients with uncertain diagnosis of PH or severe compressive symptoms, transsphenoidal surgery was the best option.

Pituitary inflammation due to IgG4-related disease is a rare condition and is sometimes accompanied by central diabetes insipidus. Central diabetes insipidus produces a strong thirst sensation, which may be difficult to distinguish when complicated by salivary insufficiency. A 45-year-old man was admitted to our department for a thorough examination of his thirst and polyuria. He had suddenly developed these symptoms more than one year earlier and visited an oral surgeon. Swelling of the left submandibular gland, right parotid gland, and cervical lymph nodes had been observed. Since his IgG4 level was relatively high at 792 mg/dL and a lip biopsy showed high plasmacytoid infiltration around the gland ducts, he had been diagnosed with IgG4-related disease. He had started taking 0.4 mg/kg/day of prednisolone, and his chief complaint temporarily improved. However, since the symptom recurred, he was referred to our institution. After admission, to examine the cause of his thirst and polyuria, we performed a water restriction test, vasopressin loading test, hypertonic saline loading test and pituitary magnetic resonance imaging. Based on the findings, we diagnosed him with central diabetes insipidus due to IgG4-related hypophysitis. We increased the dose of prednisolone to 0.6 mg/kg/day and started 10 μg/day of intranasal desmopressin. His symptoms were subsequently alleviated, and his serum IgG4 level finally normalized. We should remember that IgG4-related disease can be accompanied by hypophysitis and that central diabetes insipidus is brought about by IgG4-related hypophysitis. This case report should remind physicians of the fact that pituitary inflammation due to IgG4-related disease is very rare and can be masked by symptoms due to salivary gland inflammation, which can lead to pitfalls in the diagnosis in clinical practice.

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., Competing Interests: All data were collected in medical record files of Peking University People’s Hospital. The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© 2022. The Author(s).)

Objective: Hypophysitis is considered a rare inflammatory disease of the pituitary gland. For a long time, primary autoimmune hypophysitis has stood out as the most relevant type of hypophysitis. However, with the advent of immunotherapy for the treatment of malignancies and identification of hypophysitis as an immune-related adverse event, hypophysitis has garnered increasing interest and recognition. Therefore, awareness, early recognition, and appropriate management are becoming important as the indication for immunomodulatory therapies broaden., Methods: In this review, we discuss the epidemiology, diagnosis, and treatment of hypophysitis with a focus on recent data and highlight subtypes of particular interest while recognizing the gaps in knowledge that remain., Results: Regardless of cause, symptoms and signs of hypophysitis may be related to mass effect (headache and visual disturbance) and hormonal disruption that warrant prompt evaluation. In the vast majority of cases, a diagnosis of hypophysitis can be made presumptively in the appropriate clinical context with radiologic findings consistent with hypophysitis and after the exclusion of other causes., Conclusion: Although subtle differences currently exist in management and outcome expectations between primary and secondary causes of hypophysitis, universally, treatment is aimed at symptom management and hormonal replacement therapy., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Granulomatous hypophysitis is a rare inflammatory condition of the pituitary gland with an imaging appearance that can overlap with that of pituitary adenoma. Differentiating the two before surgical resection can have important treatment implications. The purpose of our study was to determine whether it was possible to differentiate between granulomatous hypophysitis and pituitary adenoma on the basis of diffuse enhancing infrasellar basisphenoid bone marrow., Materials and Methods: We present 3 cases, initially thought to be pituitary adenomas, that were pathology-proved granulomatous hypophysitis. The preoperative MR images were reviewed for diffuse, enhancing infrasellar basisphenoid bone marrow. For comparison, we reviewed 100 cases of pathology-proved pituitary adenoma for the same finding. Additionally, imaging findings including the sphenoid sinus pneumatization pattern, clinical history, laboratory values, and pathology results were reviewed., Results: All 3 cases of granulomatous hypophysitis had diffuse enhancing infrasellar basisphenoid bone marrow. Conversely, this was not seen in any of the 100 pituitary adenomas. The patients with granulomatous hypophysitis were all women. Two patients had idiopathic granulomatous hypophysitis, and 1 had secondary granulomatous hypophysitis with sarcoidosis. Of the 100 patients with pituitary adenomas, 67 were women. The basisphenoid pneumatization patterns was as follows: 15 (type 2), 40 (type 3), and 45 (type 4)., Conclusions: We present 3 cases of granulomatous hypophysitis with diffuse enhancement of the infrasellar basisphenoid bone marrow that was not seen in our 100 cases of pituitary adenomas. This imaging feature may be valuable for suggesting a diagnosis of granulomatous hypophysitis and avoiding surgical resection of what might otherwise be misdiagnosed as a pituitary adenoma., (© 2022 by American Journal of Neuroradiology.)

Purpose: IgG4-related hypophysitis (IgG4-RH) is a rare chronic inflammatory condition of the pituitary gland. This study reports the presentation, management and outcomes for patients with histologically proven IgG4-related hypophysitis., Methods: A prospectively maintained electronic database was searched over a 14-year period from 1 January 2007 to 31 December 2020 at a single academic centre to identify all patients with a histological diagnosis of IgG4-RH. A retrospective case note review from electronic health records was conducted for each case to extract data on their presentation, management and outcomes., Results: A total of 8 patients (5 male) with a median age of 51 years were identified. The most common presenting symptoms were headache (4/8; 50%), fatigue (3/8; 37.5%) and visual impairment (2/8; 25%). Three patients were initially treated with high-dose steroids aiming for reduction of the pituitary mass. However, ultimately all patients underwent transsphenoidal surgery. Post-operative changes included radiological reduction in pituitary mass in all patients that had imaging (7/7; 100%), improvement in vision (1/2; 50%), residual thick pituitary stalk (5/7; 71.4%), persistent anterior hypopituitarism (4/8; 50%) and panhypopopituitarism including diabetes insipidus (3/8; 37.5%)., Conclusions: IgG4-RH is an increasingly recognised entity presenting with a variety of symptoms and signs. Clinical presentation is similar to other forms of hypophysitis. It is therefore important to consider IgG4-RH as a differential and to have a low threshold for pituitary biopsy, the diagnostic gold standard. The diagnosis of IgG4-RH will guide decisions for additional workup for IgG4-related disease, multi-disciplinary team involvement and follow-up., (© 2022. The Author(s).)

Recent advances in tumor immunology have enabled to develop immune checkpoint inhibitors and to save many patients with advanced cancer. Various endocrine diseases are caused by autoimmune mechanisms; it is important to understand that many endocrine organs are targeted by autoimmunity. In addition, some of malignant tumors ectopically produce hormones and lead to a clinically relevant ectopic hormone syndrome as an endocrine paraneoplastic syndrome. Thus, interplay between oncology, immunology, and endocrinology is important. We have defined a new clinical entity "paraneoplastic autoimmune hypophysitis" as "hypophysitis associated with autoimmunity against pituitary antigens caused by an ectopic expression of these antigens in the tumor and resulting in a breakdown of immune tolerance". To understand the pathophysiology of paraneoplastic autoimmune hypophysitis requires a fusion of the fields of oncology, immunology, and endocrinology; therefore, I propose a new concept of Onco-Immuno-Endocrinology., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The differential diagnosis of IgG4-related hypophysitis and other inflammatory diseases or tumors involving sellar region is challenging even after sellar biopsy. Sellar germinoma is usually infiltrated by lymphocytes or plasma cells, and may be confused with hypophysitis., Case Presentation: A 36-year-old man with diabetes insipidus, elevated serum IgG4 level (336 mg/dl), and sellar mass was suspected to have IgG4-related hypophysitis, and no other lesion of IgG4-related disease was detected. After treated by prednisone and mycophenolate mofetil, the serum IgG4 decreased to 214 mg/dl. However, after withdrawal of the drugs, the IgG4 level increased to 308 mg/dl. Endocrine assessments revealed panhypopituitarism, and the sellar mass enlarged. Transsphenoidal sellar exploration and biopsy was conducted. Pathological examination showed that the lesion was germinoma with lymphocytes and plasma cells infiltration, and IgG4-staining was positive (70/HPF, IgG4/IgG ratio = 10%). The patient was then treated by cisplatin and etoposide. After four cycles of chemotherapy, the serum IgG4 was 201 mg/dl, and the sellar mass was invisible., Conclusion: Sellar germinoma can mimic the clinical characteristics of IgG4-related hypophysitis. Poor response to glucocorticoids can be used as an exclusion criterion in the clinical diagnosis of IgG4-related hypophysitis., (© 2022. The Author(s).)

Hypophysitis is defined as inflammation of the pituitary gland. It is a heterogeneous condition as it can originate from different parts of the pituitary gland, can be caused by different pathophysiological processes, and can be isolated or the manifestation of a underlying systemic disease. Hypophysitis usually presents with endocrine deficiencies, including diabetes insipidus, with varying patterns. A subset of patients presents with mass effects. The last decades major progress has been made in the understanding of this disease. New forms are now recognized, new diagnostics are being developed, and specific treatments are proposed. This review provides an overview of the current knowledge on hypophysitis using an aetiology-based approach and provides the clinician with a stepwise approach to the patient with (suspected) hypophysitis., (Copyright © 2021. Published by Elsevier Masson SAS.)

Introduction: Hypophysitis is an inflammation of the pituitary gland and a rare case of hypopituitarism. Despite the expanding spectrum of histological variants and causative agents, its pathogenesis is far to be fully understood. The present review is focused on recent evidence concerning the pathogenesis of autoimmune hypophysitis by searching through online databases like MEDLINE and Scopus up to May 2021., Areas Covered: Hypophysitis frequently develops in the context of a strong autoimmune background, including a wide spectrum of subtypes ranging from the commonest form of lymphocytic hypophysitis to the newly described and less common IgG4-, anti-PIT-1, and ICI-induced forms. A peculiar combination of genetic predisposition, pituitary damage and immunological setting represents the pathogenetic basis of autoimmune hypophysitis, which is characterized by diffuse infiltration of the gland by lymphocytes and variable degrees of fibrosis followed by pituitary cell destruction. Anti-pituitary antibodies (APA) have been described in sera from patients suffering from autoimmune hypophysitis, though their pathophysiological significance remains largely unknown and their diagnostic value limited., Expert Opinion: In recent years hypophysitis has gained interest due to the increased number of new diagnoses and the recognition of novel subtypes. Further studies could lead to improvements in biochemical/immunological diagnosis and targeted treatments.

Idiopathic hypothalamitis is a rare condition that can cause anterior pituitary dysfunction and central diabetes insipidus (CDI), occasionally accompanied by a disturbance of autonomic regulation known as hypothalamic syndrome. This condition has been described as a subtype of autoimmune (lymphocytic) hypophysitis; however, some cases of isolated hypothalamic involvement with no inflammatory lesions in either the pituitary gland or infundibulum have been reported. The detailed epidemiology and pathophysiology of isolated hypothalamitis have not been clarified. We herein report a case of a solitary hypothalamic lesion in a young woman who showed spontaneous development of CDI and panhypopituitarism accompanied by hyperphagia. The hypothalamic lesion increased from 11 × 7 to 17 × 7 mm over 16 months based on the sagittal slices of magnetic resonance imaging examinations. The negative results for anti-pituitary antibodies and anti-Rabphilin-3A antibodies suggested that upward extension of lymphocytic adenohypophysitis or infundibulo-neurohypophysitis was unlikely. Infectious disease, granulomatosis, Langerhans cell histiocytosis, vasculitis, and systemic neoplastic diseases were excluded by the findings of a laboratory investigation, cerebrospinal fluid examination, and imaging studies. To make a definitive diagnosis, we performed a ventriculoscopic biopsy of the hypothalamic lesion. Histology revealed an infiltration of nonspecific lymphoplasmacytes with no evidence of neoplasm, which was consistent with a diagnosis of idiopathic hypothalamitis. Subsequently, the patient was treated with methylprednisolone pulse therapy followed by oral prednisolone. The hypothalamic lesion improved and remained undetectable after withdrawal of the prednisolone, suggesting that the glucocorticoid treatment was effective for isolated hypothalamitis while the patient remains dependent on the replacement of multiple hormones.

Once central diabetes insipidus (CDI) has been diagnosed, every effort should be made to reveal its underlying cause. Autoimmune CDI should be considered in the differential diagnosis of idiopathic CDI and also of mass lesions of the sella region. An autoimmune etiology of CDI was first suggested in 1983 by the detection of autoantibodies to hypothalamic vasopressin-producing cells (AVPcAb) in adults and also in children with the disease, using the indirect immunofluorescence test. The major autoantigen for autoimmune CDI has now been recognized as rabphilin-3A, a protein of secretory vesicles of the neurohypophyseal system. The detection of autoantibodies to rabphilin-3A by Western blotting or of AVPcAb provides strong evidence for the diagnosis of autoimmune CDI. Autoimmune CDI is recognized mostly in patients who had also been diagnosed with endocrine autoimmune disorders. The radiological and morphological correlate with autoimmune DI is lymphocytic infundibuloneurohypophysitis (LINH) as detected by magnetic resonance imaging and biopsies that show massive infiltration of the posterior pituitary and the infundibulum with lymphocytes and some plasma cells, and fibrosis in the later stages of the disease. LINH may be associated with lymphocytic anterior hypophysitis. Both may either appear spontaneously or on treatment with immune checkpoint inhibitors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

As a rare condition characterized by inflammation of the pituitary gland, hypophysitis usually results in hypopituitarism and pituitary enlargement. The most critical outcome of hypopituitarism is caused by secondary adrenal insufficiency. Glucocorticoid deficiency is a life-threatening condition, and patients who develop this deficiency require prompt diagnosis and treatment. However, a delayed diagnosis of hypopituitarism may occur due to its non-specific clinical manifestations. A common presenting sign of glucocorticoid deficiency is hypoglycemia. The amelioration of hyperglycemia has been observed in diabetic patients with adrenal insufficiency. We report the case of a 70-year-old Japanese woman who had suffered from fatigue and anorexia for several months; she was admitted based on refractory hyponatremia (sodium 125-128 mEq/L) and hypoglycemia (glucose 58-75 mg/dL). Laboratory findings and magnetic resonance imaging findings led to the diagnosis of panhypopituitarism caused by autoimmune hypophysitis. After receiving 10 mg/day of hydrocortisone, the patient developed severe hyperglycemia (glucose >500 mg/dL). Undetectable C-peptide levels and positive results of both insulinoma-associated antigen-2 antibodies and insulin autoantibodies indicated that she had experienced a recent onset of type 1 diabetes. The pathophysiological process indicated that overt hyperglycemia could be masked by the deficient action of glucocorticoids even in a diabetic patient with endogenous insulin deficiency. This uncommon case reinforces the importance of the prompt diagnosis and treatment of hypopituitarism. Clinicians should remain aware of the possibility of hidden diabetes when treating hypoglycemia in patients with adrenal insufficiency.

Objective: To analyze clinical features, diagnosis, treatment and prognosis of pregnancy-related lymphocytic hypophysitis (LyH). Methods: The clinical data of 16 cases diagnosed as pregnancy-related LyH at Chinese PLA General Hospital between October 2010 and November 2019 were reviewed. Results: Sixteen patients were included (aged 20-40 years). All patients' symptoms occurred from the last 2 months of pregnancy to 12 months postpartum, with 6 cases in the third trimester and 10 cases during postpartum, and all the patients were diagnosed after delivery. Six patients had lymphocytic adenohypophysitis (LAH), 4 patients had lymphocytic infundibuloneurohypophysitis (LINH), 4 patients had lymphocytic panhypophysitis (LPH), and 2 had lymphocytic hypothalamitis. Eight patients presented with symptoms of intracranial space-occupying lesions, 14 patients had symptoms of anteriorpituitary hormone deficiencies, 9 patients had central diabetes insipidus (CDI), and 2 had hyperprolactinemia. Pituitary MRI showed that the pituitary presented with diffuse enlargement, pituitary stalk thickening, disappearing of high-intensity signals in posterior pituitary and space-occupying lesions in the infundibulum of hypothalamus. Nine patients were treated with immunosuppressive agent, 3 patients alleviated the space-occupying effects after surgery, and 4 patients recovered spontaneously. Fourteen patients were followed up with a period of 3-98 months. Four patients had a relapse, 2 patients had a complete remission, and 12 patients needed long-term hormone replacement therapy. Conclusions: Clinical manifestations of pregnancy-related LyH are diverse. LyH should be suspected in pregnant or postpartum women with a sellar mass to avoid missed diagnosis or misdiagnosis. Immunosuppressant therapy is effective. Overall, LyH patients have a favorable prognosis.

We report the case of a pituitary stalk germinoma initially misdiagnosed and treated as infundibuloneurohypophysitis (INH). A 27-year-old man presented with a 1-year history of polydipsia, polyuria, nycturia consistent with central diabetes insipidus and a hyperintense pituitary stalk lesion on MRI. A possible INH diagnosis was considered, after excluding other pathologies. Lesion biopsy was discarded at that time on the ground of a small target and the high risk of added morbidity. Oral desmopressin led to initial symptoms resolution but, in the following months, an anterior panhypopituitarism developed, in spite of appropriate treatment and, by that time, the brain MRI also revealed lesion growth, which prompted a biopsy recommendation. The pathology analysis revealed a germinoma. After chemotherapy and radiotherapy, there was complete disappearance of the pituitary lesion, but the panhypopituitarism persisted. In conclusion, this case highlights the importance and difficulty of precise diagnosis in the initial assessment of pituitary stalk lesions and the need for close monitoring of treatment response. Diagnostic reassessment and biopsy in atypical cases is the only path to achieve the correct diagnosis and treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Hypophysitis, which is often accompanied by pituitary dysfunction, is classified into several subtypes based on the cause, histology, and the location of inflammation in the pituitary gland. A definitive diagnosis requires pituitary biopsy, which is invasive, and the process is limited to specialized clinical settings. In this opinion paper, we review the literature associated with hypophysitis, and provide the guidelines of the Japan Endocrine Society for the diagnosis and treatment of autoimmune and IgG4-related hypophysitis.

IgG4-related hypophysitis is a rare disease, due to a lymphoplasmocytic IgG4 positive infiltration of the pituitary. Literature data are scarce, even though the description of cases has drastically increased over the last years. The aim of this review is to better characterize the natural history, the diagnosis and the management of IgG4-related hypophysitis, based on a clinical case, an exhaustive Pubmed research, and a reappraisal of the criteria for diagnosis. We will specifically focus on the differences with other etiologies of hypophysitis, in the aim of improving the diagnostic procedures for all the physicians who could have to take care of such patients., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

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Hypophysitis is a heterogeneous condition that leads to inflammation of the sella and/or suprasellar region, potentially resulting in hormonal deficiencies and/or mass effects. A preponderance of hypophysitis subtypes have an underlying autoimmune aetiology. The overall incidence and prevalence of hypophysitis has dramatically increased over the past decade, mainly due to increased awareness of the condition in the medical community, improvements in imaging techniques, and a rise in the occurrence of certain forms of hypophysitis such as IgG4 hypophysitis (IgG4Hy) and immune checkpoint inhibitor induced hypophysitis (ICIHy). The clinical presentation varies from an asymptomatic condition to a fatal disease often as a result of electrolyte abnormalities due to glucocorticoid deficiency in the context of adrenal crisis from central adrenal insufficiency. Milder forms of hypophysitis are treated with replacement of deficient hormones while more acute presentations with mass effects require glucocorticoid therapy, immunosuppressive therapy or surgery. Timely diagnosis and interventions are keys to prevention of the lethal complications of this disease. In this review, we provide an update on the recent advances in the field of pituitary autoimmunity, with an emphasis on autoimmune hypophysitis and novel forms of hypophysitis such as anti-PIT1 hypophysitis, IgG4Hy and ICIHy., Competing Interests: Declaration of Competing Interest This research was supported in part by the Intramural Research Program of the NIDDK and Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, MD., (Published by Elsevier Ltd.)

Background: Inflammation of the pituitary gland can occur in a variety of primary or secondary disorders. Idiopathic granulomatous hypophysitis is a rare inflammatory disease of the pituitary gland that can closely mimic a pituitary adenoma clinicoradiologically. Most authorities agree on minimally invasive transsphenoidal surgery as the mainstay in diagnosis and treatment of this disorder. There is still some controversy regarding pure medical management of idiopathic granulomatous hypophysitis in the literature., Case Presentation: A 47-year-old Iranian woman of Azeri ethnicity with a history of benign breast cysts with a chief complaint of galactorrhea presented to our endocrinology clinic. Her past medical history was negative for any menstrual irregularities, hirsutism, visual complaints, diplopia, polyuria and polydipsia or seizures. She was taking 100 mcg of levothyroxine daily. Her familial history and physical examination were unremarkable. Her initial laboratory work-up revealed hyperprolactinemia (82.4 ng/mL) with otherwise normal pituitary axes. Brain magnetic resonance imaging showed a pituitary macroadenoma for which she was treated with 0.5 mg of cabergoline weekly. Although her serum prolactin level dropped to 1.7 ng/mL and her galactorrhea was resolved, she continued to complain of headaches and nausea. Repeated imaging showed no decrease in size of the macroadenoma. Therefore, she underwent transsphenoidal surgery of the macroadenoma which was reported as chronic granulomatous hypophysitis by expert pathologists. Tuberculosis, sarcoidosis, Wegener's granulomatosis, Langerhans cell histiocytosis, and syphilis were ruled out by appropriate tests and she was diagnosed as having idiopathic granulomatous hypophysitis. Fortunately, her condition was not complicated by hypopituitarism and she was symptom free 9 months after transsphenoidal surgery., Conclusions: Idiopathic granulomatous hypophysitis, a rare inflammatory disease of the pituitary gland, is a diagnosis of exclusion for which both medical and surgical management are reported in the literature. We present a case of idiopathic granulomatous hypophysitis who was symptom free with no complications of hypopituitarism following its transsphenoidal resection after 9 months of follow-up.

Immune checkpoint (IC) therapy provides substantial benefits to cancer patients but can also cause distinctive toxicities termed immune-related adverse events (irAEs). Biomarkers to predict toxicities will be necessary to improve management of patients receiving IC therapy. We relied on serological analysis of recombinant cDNA expression libraries to evaluate plasma samples from patients treated with IC therapy and identified autoantibodies, both in pretreatment and on-treatment samples prior to the development of irAEs, which correlate with the development of immune-related hypophysitis (anti-GNAL and anti-ITM2B autoantibodies) and pneumonitis (anti-CD74 autoantibody). We developed an enzyme-linked immunosorbent assay and tested additional patient samples to confirm our initial findings. Collectively, our data suggest that autoantibodies may correlate with irAEs related to IC therapy, and specific autoantibodies may be detected early for the management of irAEs., Competing Interests: Competing interest statement: J.P.A. has ownership in Jounce, Neon, BioAtla, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak, ImaginAb, Hummingbird, Dragonfly, Lytix, and Tvardi Therapeutics and serves as a consultant for Jounce, Kite Pharma, Neon, Amgen, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak, ImaginAb, Tvardi Therapeutics, Lytix, Hummingbird, and Dragonfly. P.S. has ownership in Jounce, Neon, Constellation, Oncolytics, BioAtla, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak, ImaginAb, Lytix, Hummingbird, and Dragonfly and serves as a consultant for Constellation, Jounce, Kite Pharma, Neon, BioAtla, Pieris Pharmaceuticals, Oncolytics Biotech, Merck, BioMx, Forty-Seven, Polaris, Apricity, Marker Therapeutics, Codiak, ImaginAb, Hummingbird, Lytix, and Dragonfly. J.G. serves as a consultant for ARMO Biosciences, AstraZeneca, CRISPR Therapeutics, Jounce, Nektar, Polaris, Pfizer, and Symphogen. C.G.D. and J.P.A. are coauthors on a 2016 workshop report.

Purpose: New-onset pituitary gland lesions are observed in up to 18% of cancer patients undergoing treatment with immune checkpoint blockers (ICB). We aimed to develop and validate an imaging-based decision-making algorithm for use by the clinician that helps differentiate pituitary metastasis (PM) from ICB-induced autoimmune hypophysitis (HP)., Materials and Methods: A systematic search was performed in the MEDLINE and EMBASE databases up to October 2018 to identify studies concerning PM and HP in patients treated with cytotoxic T-lymphocyte-associated protein 4 and programmed cell death (ligand) 1. The reference standard for diagnosis was confirmation by histology or response on follow-up imaging. Patients from included studies were randomly assigned to the training set or the validation set. Using machine learning (random forest tree algorithm) with the most-described six imaging and three clinical features, a multivariable prediction model (the signature) was developed and validated for diagnosing PM. Signature performance was evaluated using area under a receiver operating characteristic curves (AUCs)., Results: Out of 3174 screened articles, 65 were included totalising 122 patients (HP: 60 pts, PM: 62 pts). Complete radiological data were available in 82 pts (Training: 62 pts, Validation: 20 pts). The signature reached an AUC = 0.91 (0.82, 1.00), P < 10 -8 in the training set and AUC = 0.94 (0.80, 1.00), P = 0.001 in the validation set. The signature predicted PM in lesions either ≥ 2 cm in size or < 2 cm if associated with heterogeneous contrast enhancement and cavernous extension., Conclusion: An image-based signature was developed with machine learning and validated for differentiating PM from HP. This tool could be used by clinicians for enhanced decision-making in cancer patients undergoing ICB treatment with new-onset, concerning lesions of the pituitary gland., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Hypophysitis is a rare entity characterized by inflammation of the pituitary gland and its stalk that can cause hypopituitarism and/or mass effect. Etiology can be categorized as primary or secondary to systemic disease, but may also be classified according to anatomical and hispathological criteria. Newly recognized causes of hypophysits have been described, mainly secondary to immunomodulatory medications and IgG4-related disease. Diagnosis is based on clinical, laboratory and imaging data, whereas pituitary biopsy, though rarely indicated, may provide a definitive histological diagnosis. For the clinician, obtaining a broad clinical and drug history, and performing a thorough physical examination is essential. Management of hypophysitis includes hormone replacement therapy if hypopituitarism is present and control of the consequences of the inflammatory pituitary mass (e.g. compression of the optic chiasm) using high-dose glucocorticoids, whereas pituitary surgery is reserved for those unresponsive to medical therapy and/or have progressive disease. However, there remains an unmet need for controlled studies to inform clinical practice., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The pituitary gland and the hypothalamus can be affected by autoimmune-mediated structural and functional disruption. These autoimmune-mediated diseases occur more commonly in females and are often found during pregnancy or in the post-partum period. Autoimmune diseases can either affect parts of the pituitary or hypothalamus, or can involve both sellar and suprasellar structures. Most of these cases comprise primary hypophysitis (PRH). Over the years, there has been a tremendous increase in the number of reported PRH cases and related disorders, including hypophysitis induced by immune checkpoint inhibitors. With this increasing data, more light is being shed on the spectrum of clinical presentations, biochemical and imaging abnormalities of these disorders. Regardless, these disorders are still relatively rare. The clinical presentation can vary vastly, based on the type of pituitary cell or the area of the suprasellar region affected. The severity can range from clinically silent disease to progressive and rapid deterioration and death, likely due to unrecognized central adrenal insufficiency. Although biopsy remains a gold standard for diagnosing these disorders, the current standard of practice is biochemical assessment for hormonal deficiencies and imaging studies. In several instances, these disorders spontaneously resolve, but medical or surgical intervention might be necessary to treat symptomatic disease. Due to the subtlety and a vast spectrum of clinical manifestations which could often be asymptomatic, and the rarity of the occurrence of these diseases in clinical practice, the diagnosis can be easily missed which could potentially lead to substantial morbidity or mortality. Therefore, it is crucial to have a strong clinical suspicion and pursue timely biochemical and imaging studies to initiate prompt treatment. In this article, we review the various autoimmune conditions that affect the sellar and suprasellar structures, their diagnostic approach and management of these disorders.

Purpose of Review: IgG4-related disease (IgG4-RD) is increasingly recognized as a fibroinflammatory disease with a plethora of organ-specific manifestations but a particular predilection for head and neck tissues, including the nervous system. This review discusses general features and organ-specific presentations of IgG4-RD as well as treatment considerations, particularly emphasizing features of neuro-ophthalmic interest., Recent Findings: IgG4-RD is emerging as a common cause of several fibroinflammatory disorders in the head and neck that were previously considered idiopathic, such as sclerosing orbital pseudotumor, orbital myositis, hypophysitis, and hypertrophic pachymeningitis. New and unusual presentations continue to be described, including a number of vascular manifestations. Substantial progress has been made in elucidating the cell types involved in IgG4-RD, and new pathogenic models are being proposed. Although clinicopathologic correlation remains the cornerstone of diagnosis, ancillary tests such as flow cytometry for circulating plasmablasts and PET-computed tomography have high sensitivity, and certain radiologic features are recognized to be particularly suggestive, such as infraorbital nerve enlargement in IgG4-RD orbitopathy. IgG4-RD often responds to steroids but incomplete responses and relapses are common. Rituximab is emerging as a promising new therapy., Summary: The current review summarizes manifestations of IgG4RD that are of particular relevance to neuro-ophthalmic practice.

Hypophysitis is a rare condition characterised by inflammation of the pituitary gland, usually resulting in hypopituitarism and pituitary enlargement. Pituitary inflammation can occur as a primary hypophysitis (most commonly lymphocytic, granulomatous or xanthomatous disease) or as secondary hypophysitis (as a result of systemic diseases, immunotherapy or alternative sella-based pathologies). Hypophysitis can be classified using anatomical, histopathological and aetiological criteria. Non-invasive diagnosis of hypophysitis remains elusive, and the use of currently available serum anti-pituitary antibodies are limited by low sensitivity and specificity. Newer serum markers such as anti-rabphilin 3A are yet to show consistent diagnostic value and are not yet commercially available. Traditionally considered a very rare condition, the recent recognition of IgG4-related disease and hypophysitis as a consequence of use of immune modulatory therapy has resulted in increased understanding of the pathophysiology of hypophysitis. Modern imaging techniques, histological classification and immune profiling are improving the accuracy of the diagnosis of the patient with hypophysitis. The objective of this review is to bring readers up-to-date with current understanding of conditions presenting as hypophysitis, focussing on recent advances and areas for future development. We describe the presenting features, investigation and diagnostic approach of the patient with likely hypophysitis, including existing conventional techniques and those in the research/development arena. Hypophysitis usually results in acute and persistent pituitary hormone deficiency requiring long-term replacement. Management of hypophysitis includes control of the inflammatory pituitary mass using a variety of treatment strategies including surgery and medical therapy. Glucocorticoids remain the mainstay of medical treatment but other immunosuppressive agents (e.g. azathioprine, rituximab) show benefit in some cases, but there is a need for controlled studies to inform practice., (© 2018 European Society of Endocrinology.)

Competing Interests: Competing interests: None declared.

Primary autoimmune hypophysitis (PAH) is considered an underdiagnosed disease, due to the difficulty in reaching a definitive diagnosis. PAH clinical diagnosis remains an exclusion diagnosis. We aimed to correlate PAH neuro-radiological signs to endocrine features and evaluate their prognostic role. 24 PAH cases were enrolled and classified according to neuro-radiological signs: in 12 adeno-hypophysitis (AHs), 8 infundibulo-neuro-hypophysitis (INHs) and 4 pan-hypophysitis (PHs). Secondary hypogonadism developed more frequently in INHs as compared to AHs (54.5% vs. 27.3%, p = 0.05), without no difference with PHs (p = 0.6). Diabetes insipidus occurred more frequently in INHs cases (72.7%, p < 0.001) and in PHs cases (27.3%, p = 0.007), as compared to AHs cases (0%). Similarly, all cases of GHD occurred in INHs (100%) as compared to AHs (0%, p < 0.001) and PHs (0%, p < 0.001). The pituitary stalk (PS) showed a pseudo-triangular shape (larger at the optical chiasma) in INHs and a pseudo-cylindrical shape (larger both at the optical chiasma and at the pituitary insertion) in PHs. The PS pseudo-triangular shape correlated to the occurrence of GHD and diabetes insipidus (p < 0.001/p = 0.03). At the 1-year follow-up, improvement of baseline radiological features positively correlated with the loss of the neuro-pituitary "bright spot" on T1-weighted images (OR 0.16; 95% CI 0.03-0.9 p = 0.02) and with a PS diameter at the optical chiasma level larger than 4.1 mm (AUC 0.97, sensibility 80%, specificity 100%, OR 6; 95% CI1.1-28.8, p = 0.01) Our data suggest that neuro-radiological PAH classification in PH, AH and INH can predict pituitary dysfunction and that some neuro-radiological features, such as the pituitary stalk diameter and the loss of the neuro-pituitary bright spot on T1w images can play a role as a positive prognostic marker of the radiological hypophysitis outcome.

Hypophysitis of the pituitary gland is a rare inflammatory disorder and broadly classified as primary and secondary hypophysitis. Primary hypophysitis is mainly of lymphocytic, granulomatous, and xanthomatous types. Among the various primary hypophysitis, granulomatous hypophysitis is rare type with an incidence of 1 in 10 million. The various forms of hypophysitis are misdiagnosed as pituitary adenoma in 40% cases. Idiopathic granulomatous hypophysitis is even rarer inflammatory disorder accounting for <1% of cases involving panhypopituitarism with headache and visual disturbances. We report idiopathic granulomatous hypophysitis in a 28-year-old female presenting with blurring of vision and headache., Competing Interests: There are no conflicts of interest