Mikulicz's disease combined with IgG4-related hypophysitis: a case report.

BACKGROUND: IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines. CASE PRESENTATION: A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz's disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size. CONCLUSION: Mikulicz's disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.

[A case of suspected IgG4-related hypophysitis presented with panhypopituitarism and central diabetes insipidus].

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.

The early-stage clinical course of anti-pituitary-specific transcription factor-1 hypophysitis diagnosed post-immune checkpoint inhibitor treatment: A case with review of literature.

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.

Effect of steroid therapy in a 16-year-old girl observed for lymphocytic hypophysitis.

Not required for Clinical Vignette.

Unique case of lymphocytic hypophysitis with normal pituitary hormone serology mimicking a non-functioning pituitary adenoma.

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.

Successful treatment of medically and surgically refractory lymphocytic hypophysitis with fractionated stereotactic radiotherapy: a single-center experience and systematic literature review.

PURPOSE: To explore the potential role of focused radiotherapy in managing the lymphocytic hypophysitis (LH) refractory to medical therapy and surgery. METHOD: A systematic literature review was conducted following PRISMA guidelines to identify the studies on radiation treatment for hypophysitis, along with the experience in our institution. RESULTS: The study included eight patients, three from our institution and five from existing literature. The age at presentation ranged from 37 to 75 years old, with a median age of 58. The presenting symptoms involved headache in seven patients and diplopia in two patients. Pre-radiation visual field defects were noticed in four patients. All patients exhibited variable degrees of hypopituitarism before radiation, with oral corticosteroids being the initial medical treatment. Immunosuppressive therapy was attempted in two patients prior to radiation. Seven patients had a history of transsphenoidal surgery with a histologically confirmed LH. Three patients underwent stereotactic radiosurgery (SRS), while the remaining received FSRT, with a mean irradiation volume of 2.2 cm3. A single-session total dose of 12 -15 Gy was administered in the SRS group. In the FSRT group, doses ranged from 24 to 30 Gy with a median dose of 25 Gy, delivered in 2 Gy fractions. Four patients achieved a resolution of visual field defects, while another two patients demonstrated improvement in their associated focal neurologic deficits. No change in pre-existing endocrine status was shown after radiation, except in one patient. Clinical response was achieved in seven patients after a single course of radiation, while one patient required the second course. Six patients remained stable on low-dose glucocorticoid during at least a 12-month follow-up period, and one discontinued it entirely without experiencing relapse. Three patients demonstrated a complete radiologic response, while the remaining showed a partial radiologic response. CONCLUSIONS: Focused radiation, including FSRT, can play a role in symptomatic relief, effective mass shrinkage, and minimizing radiation exposure to critical surrounding structures in patients with refractory LH. However, further research efforts are necessary to better clarify its effects and optimal dose planning.

Is There A Connection Between Primary Hypophysitis and Celiac Disease?

AIM: To investigate the autoimmune and genetic relationship between primary hypophysitis (PH) and celiac disease (CD). METHODS: The study was retrospective and patients with PH followed in our clinic between 2007 and 2022 were evaluated. Clinical, endocrinologic, pathologic, and radiologic findings and treatment modalities were assessed. Patients diagnosed with CD in the Gastroenterology outpatient clinic in 2020-2022 were included in the study as a control group. Information such as sociodemographic data, year of diagnosis, human leukocyte antigen (HLA) DQ2/8 information, CD-specific antibody levels, pathologic results of duodenal biopsy, treatment received, follow-up status, additional diseases, hormone use, and surgical history was obtained from patient records at PH.In patients diagnosed with PH, a duodenal biopsy was obtained, and the tissue was examined for CD by experienced pathologists. Anti-pituitary antibody (APA) and anti-arginine-vasopressin (AAVP) antibody levels of individuals with PH and CD were measured. RESULTS: The study included 19 patients with lymphocytic hypophysitis, 30 celiac patients, and 30 healthy controls. When patients diagnosed with lymphocytic hypophysitis were examined by duodenal biopsy, no evidence of CD was found in the pathologic findings. The detection rate of HLA-DQ2/8 was 80% in celiac patients and 42% in PH (p=0.044). (APA and AAVP antibodies associated with PH were tested in two separate groups of patients and in the control group. APA and anti-arginine vasopressin (AAVP) levels in PH, CD and healthy controls, respectively M [IQR]: 542 [178-607];164 [125-243]; 82 [74-107] ng/dL (p=0.001), 174 [52-218]; 60 [47-82]; 59 [48-76] ng/dL (p=0.008) were detected. The presence of an HLA-DQ2/8 haplotype correlates with posterior hypophysitis and panhypophysitis (r=0.598, p=0.04 and r=0.657, p=0.02, respectively). CONCLUSION: Although patients with PH were found to have significant levels of HLA-DQ2/8, no CD was found in the tissue. Higher levels of pituitary antibodies were detected in celiac patients compared with healthy controls, but no hypophysitis clinic was observed at follow-up. Although these findings suggest that the two diseases may share a common genetic and autoimmune basis, the development of the disease may be partially explained by exposure to environmental factors.

Clinical features of anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis: a new aspect of paraneoplastic autoimmune condition.

The pathogenesis of anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis was gradually revealed as cases emerged. Our comprehensive analysis, including all reported cases, identified a new instance of anti-PIT-1 hypophysitis postimmune checkpoint inhibitor therapy. All 9 patients exhibited extremely low growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) levels; 2 had a slightly atrophic pituitary gland; 4 had thymoma, and 5 had malignant neoplasms of diffuse large B-cell lymphoma (DLBCL) and other origins. Patients with thymoma showed multiple autoimmune diseases. HLA-A*24:02 and/or A*02:06 were present in six and DR53 in 5 cases analyzed. High anti-PIT-1 antibody titers and ectopic PIT-1 expression in the cytosol and nucleus of the tumor tissues were observed in patients with thymoma or DLBCL, whereas it was exclusively observed in the nuclei of a bladder cancer patient. These findings provide new insights into the pathophysiology of paraneoplastic autoimmune hypophysitis.

[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.

[Primary hypophysitis: diagnosis and treatment multicenter study]. / Hipofisitis primaria: diagnóstico y tratamiento. Estudio multicéntrico.

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.

Introducción: La hipofisitis es una enfermedad infrecuente que plantea un desafío en el diagnóstico y tratamiento. El objetivo de este estudio multicéntrico y retrospectivo fue describir: a) características de pacientes con hipofisitis primaria (HP), b) métodos diagnósticos, y c) tratamientos realizados. Además, evaluar: a) presentación clínica, b) bioquímica, c) radiológica, d) oftalmológica al diagnóstico y evolución según el tratamiento recibido. Métodos: Estudio retrospectivo donde se estudiaron 28 pacientes (23 mujeres/5 varones) con HP, edad promedio de 38±11.1 años. Resultados. Los síntomas fueron: cefalea: 68%, poliuria- polidipsia: 50% y alteraciones visuales: 48%. El examen de laboratorio inicial informó disfunción adenohipofisaria en 71% de los pacientes, siendo el eje gonadal el más afectado. Los hallazgos radiológicos más frecuentes fueron: lesión simétrica:78.5%, aumento homogéneo post contraste: 78.5% y engrosamiento de tallo:70%. En 4/23 mujeres (17%) se relacionó con embarazos o puerperio La conducta inicial fue expectante (CE) en 14 pacientes, cirugía de resección/descompresión en 8 y tratamiento con inmunosupresores en 6. Quince pacientes tuvieron confirmación histológica, 9 resultaron hipofisitis linfocitaria, 5 hipofisitis por IgG4 y una xantomatosa. Trece fueron diagnosticados por criterios clínicos establecidos. El tamaño de la lesión disminuyó en 43% de pacientes con CE, 62.5% con cirugía y 50% con inmunosupresores. Los síntomas compresivos mejoraron en los 3 grupos, con escaso efecto sobre la función adenohipofisaria, sin resolución de la diabetes insípida. Discusión: En pacientes sin síntomas compresivos adoptamos CE. En aquellos pacientes sin certeza diagnóstica o con síntomas compresivos graves, se optó por cirugía transesfenoidal.

Concurrent IgG4-related hypophysitis and clinically nonfunctioning gonadotroph pituitary neuroendocrine tumor.

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-ß 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.

Paraneoplastic autoimmune hypophysitis: a novel form of paraneoplastic endocrine syndrome.

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.

Two children with lymphocytic hypophysitis presenting with positive anti-rabphilin-3A antibody.

Lymphocytic hypophysitis (LYH) is a rare chronic inflammatory disease characterized by lymphocytic infiltration of the anterior or posterior pituitary gland and hypothalamus. LYH is subdivided into lymphocytic adenohypophysitis (LAH), lymphocytic infundibulo-neurohypophysitis (LINH), and lymphocytic panhypophysitis (LPH) depending on the primary site. Most cases occur in adults, with few cases reported in children, and it is especially important to distinguish LYH from suprasellar malignancies, such as germ cell tumors and other neoplastic diseases. Although a biopsy is necessary for definitive diagnosis, it is desirable to be able to diagnose the disease without biopsy if possible, especially in children, because of the surgical invasiveness of the procedure. Recently, serum anti-rabphilin-3A antibodies have attracted attention as diagnostic markers for LYH, especially in LINH, but there are only a few reports on pediatric patients. In the present study, we experienced two children with LPH and LAH, respectively, who tested positive for anti-rabphilin-3A antibodies. This is the first report of children with LYH other than LINH positive for anti-rabphilin-3A antibodies, and anti-rabphilin-3A antibodies may be a useful non-invasive diagnostic marker not only for LINH but also for LYH in general. We also discuss the sensitivity and specificity of anti-rabphilin-3A antibody testing in cases where histological diagnosis has been made.

Executive summary of the consensus document on hypophysitis of the Neuroendocrinology Area of Knowledge of the Spanish Society of Endocrinology and Nutrition.

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.

Pregnancy-related hypophysitis revisited.

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.

Inhibition of IRAK1 Is an Effective Therapy for Autoimmune Hypophysitis in Mice.

Autoimmune hypophysitis (AH) is an autoimmune disease of the pituitary for which the pathogenesis is incompletely known. AH is often treated with corticosteroids; however, steroids may lead to considerable side effects. Using a mouse model of AH (experimental autoimmune hypophysitis, EAH), we show that interleukin-1 receptor-associated kinase 1 (IRAK1) is upregulated in the pituitaries of mice that developed EAH. We identified rosoxacin as a specific inhibitor for IRAK1 and found it could treat EAH. Rosoxacin treatment at an early stage (day 0-13) slightly reduced disease severity, whereas treatment at a later stage (day 14-27) significantly suppressed EAH. Further investigation indicated rosoxacin reduced production of autoantigen-specific antibodies. Rosoxacin downregulated production of cytokines and chemokines that may dampen T cell differentiation or recruitment to the pituitary. Finally, rosoxacin downregulated class II major histocompatibility complex expression on antigen-presenting cells that may lead to impaired activation of autoantigen-specific T cells. These data suggest that IRAK1 may play a pathogenic role in AH and that rosoxacin may be an effective drug for AH and other inflammatory diseases involving IRAK1 dysregulation.

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.