Hypophysitis Research Articles

SUN-298 Spectrum of Imaging in Immune Checkpoint Inhibitor Induced Hypophysitis

Background: Hypophysitis (HP) is a known immune related adverse event of immune checkpoint inhibitors (CPIs), commonly associated with CTLA-4 inhibitors and rarely with PD-1/PD-L1 inhibitors. Prior studies of MRIs at HP diagnosis noted pituitary enlargement with resolution within a few weeks. In this study, we examine MRI changes in patients with CPI-induced HP. Methods: Subjects with biochemical evidence of central hypothyroidism or central adrenal insufficiency and MRIs were reviewed by endocrinology and neuroradiology. MRIs were classified relative to HP diagnosis: baseline (at least 21 days prior), diagnosis (within 21 days), and follow up (over 21 days). Patient characteristics included age at CPI initiation, sex, race/ethnicity, personal and family history of autoimmunity, type of cancer and CPI. Results: Twenty-six subjects met the inclusion criteria. The mean age was 59 years; 62% were male and 86% were non-Hispanic white. Nineteen percent had a personal history and 31% a family history of autoimmunity. Fifty percent had melanoma. At HP diagnosis, 46% were on PD-1/PD-L1 inhibitors, 42% were on combination PD-1/CTLA-4 inhibitors and 12% were on CTLA-4 inhibitors.Median time from CPI initiation to HP diagnosis was 95 days. Time to HP was shorter on a CTLA-4 inhibitor combination or monotherapy (median 82 days) compared to a PD-1/PD-L1 inhibitor monotherapy (median 220 days; Wilcoxon rank sum, p <0.01). Central adrenal insufficiency was present in all patients not yet on steroids. Central hypothyroidism was common (10/19) in those without primary thyroid disease and was not associated with type of CPI (Fisher’s exact, p=0.18).Thirteen subjects had baseline MRIs, 18 had MRIs at HP diagnosis and 13 had MRIs in the follow up period. Baseline MRIs were normal in 12/13; one subject had an enlarged pituitary. At diagnosis, 10 had an enlarged pituitary, 7 a normal pituitary and 1 a partially empty sella. CTLA-4 inhibitor exposure was associated with pituitary enlargement at diagnosis: 9/11 compared to 1/7 on PD-1/PD-L1 inhibitor (Fisher’s exact, p <0.04). Of the subjects who had follow-up MRIs, 3 had an enlarged pituitary, 7 a normal pituitary and 3 a partially empty sella. Follow up imaging did not differ between treatment types (Fisher’s exact, p >0.05). Timing of MRI was significantly associated with pituitary appearance (Fisher’s exact, p <0.01). Conclusion: The MRI appearance of HP presents as a spectrum, from a partially empty sella, normal pituitary to an enlarged pituitary. HP diagnosed in the setting of CTLA-4 inhibitor treatment occurs earlier and is more likely to induce an enlarged pituitary gland compared to PD-1/PD-L1 monotherapy, which occurs later and is associated with a normal appearing MRI at diagnosis. This suggests that the pathogenesis of HP following CPI exposure may vary depending on the type of CPI.

Sellar Pathologies Mimicking Pituitary Tumors.

The most common sellar pathology that merits neurosurgical attention is the pituitary adenoma. However, some developmental, inflammatory, and neoplastic lesions may primarily or secondarily involve the sella, mimicking pituitary tumors. Advances in imaging and endocrinological assessment have helped in the recognition of these less common sellar, supra sellar pathologies, which may occasionally create confusion in management. The most common developmental anomaly is the Rathke's cleft cyst and an increasingly recognized inflammatory pathology is the spectrum of hypophysitis. Neoplasms, viz. Craniopharyngioma, Germinoma, Langerhans's cell histiocytosis or metastasis, have more distinctive features in various age groups and are more likely to be correctly diagnosed on current imaging and managed accordingly. This review looks at mainly intraparenchymal pathologies, namely Rathke's Cleft Cyst and various hypophysitides, and will discuss their management strategies.

Imaging findings in hypophysitis: a review.

Hypophysitis (HP) is a rare acute or chronic inflammatory condition of the pituitary gland. The greatest challenge in the management of HP is establishing a diagnosis through clinical criteria and non-invasive methods and predicting the patients' clinical outcome. The aim of this review is to describe the neuroradiological findings of this rare disease, providing some information regarding the possible differential diagnosis in order to avoid unnecessary surgery. Gadolinium-enhanced pituitary magnetic resonance imaging (MRI) is considered the neuroradiological investigation of choice. The features suggestive for HP include an enlarged triangular- or dumbbell-shaped gland with a thickened and not obviously deviated stalk, further supported by the absence of posterior pituitary bright spot on T1weighted images, particularly in patients presenting with diabetes insipidus. Contrast enhancement pattern is quite variable; dural enhancement has been reported in some cases after intravenous contrast administration. The characterization of the unusual sellar mass is not straightforward and generally results in a wide differential. HP should be primarily differentiated from pituitary adenomas (including pituitary apoplexy), from pituitary metastases, and from other sellar and parasellar tumors, e.g., craniopharyngiomas, germinomas, gliomas, lymphomas, meningiomas, pituicytomas, chordomas, teratomas, dermoids and epidermoids, Rathke's cleft cysts, and abscesses. In patients suspected for secondary forms related to systemic pathology, additional imaging is helpful in identifying other involved sites. Neuroradiologists need to know MRI appearance of this rare disease, as well as its typical symptoms and serological markers. A strict collaboration with endocrinologists and neurosurgeons is mandatory in order to reach a definitive diagnosis, allowing to promptly initiating an appropriate treatment.

Machine learning defined diagnostic criteria for differentiating pituitary metastasis from autoimmune hypophysitis in patients undergoing immune checkpoint blockade therapy

PurposeNew-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 methodsA 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). ResultsOut 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. ConclusionAn 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.

Diagnosis and treatment of one case of hypophysitis caused by PD-1 inhibitor

We reported a case of hypophysitis caused by a programmed death-1(PD-1)inhibitor. The patient was a 59-year-old female with metastatic malignant melanoma who participated in the phase Ⅱ clinical trial of a PD-1 inhibitor toripalimab. More than five months after the administration of toripalimab, she experienced fatigue, depression, nausea, and anorexia. Laboratory examinations showed mild hyponatremia, secondary adrenal insufficiency, and secondary hypothyroidism. MRI revealed the enlargement of her pituitary with obvious enhancement. The patient was diagnosed as hypophysitis caused by the PD-1 inhibitor and was given replacement therapy with physiological doses of corticosteroid and levothyroxine sodium. Her symptoms were then improved. MRI revealed that her pituitary size returned to normal after 8 weeks of treatment and remained stable during every 3-month follow-up. This case reminds us of the possibility of hypophysitis when patients suffere from fatigue and anorexia during the process of PD-1 inhibitor treatment. Correct diagnosis, proper therapy, and regular follow-up are important to ensure the patients′ safety, and to improve their prognosis. Key words: Programmed death-1 inhibitor; Hypophysitis

Imaging findings of lymphocytic hypophysitis easily misdiagnosed as pituitary adenoma

Objective To study the imaging features of lymphocytic hypophysitis in order to improve the accuracy of imaging diagnosis of the disease. Methods Imaging findings of 9 patients with lymphocytic hypophysitis admitted to Neurosurgery Department of Beijing Tiantan Hospital, Capital Medical University from January 2010 to December 2016 were retrospectively reviewed. All patients underwent laboratory examinations related to pituitary function. Except for 2 cases of slight increase in prolactin, the levels of other hormones were normal. All patients were examined with pre-contrast and post-contrast T1 weighted MR imaging and non-contrast T2 weighted MR imaging. Six patients received CT scan. Imaging diagnoses were all mistaken as pituitary adenomas. Results All cases showed diffuse enlargement of the pituitary, disappearance of neurohypophysis T1WI high signal and enlarged sella. Lesions showed iso-signal on both T1 and T2 weighted image with strong homogeneous or ring-like enhancement. Pituitary stalk was thickened in 5 cases. None of the cavernous sinus was involved in those cases. Lymphocytic hypophysitis was confirmed by pathologic examinations in all 9 patients. Conclusions Lymphocytic hypophysitis seems to have characteristic imaging findings. Compared with pituitary adenoma, lymphocytic hypophysitis does not destroy the sellar floor bone with no involvement of the cavernous sinus and it has diffuse pituitary enlargement and basically symmetrical shape. Those imaging findings of lymphocytic hypophysitis may help us improve the accuracy of imaging diagnosis. Key words: Autoimmune diseases; Lymphocytic hypophysitis; Magnetic resonance imaging; X-ray computed tomography

Ipilumumab induced hypophysitis

Ipilumumab induced hypophysitis

Updating the Rainbow of Flavors of Hypophysitis

Updating the Rainbow of Flavors of Hypophysitis

Ipilimumab induced hypophysitis

Ipilimumab induced hypophysitis

Nivolumab and pembrolizumab induced hypophysitis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Thyroiditis and hypophysitis caused by nivolumab

Thyroiditis and hypophysitis caused by nivolumab

Hypophysitis: Presenting Characteristics and Outcomes of 146 Patients

Hypophysitis: Presenting Characteristics and Outcomes of 146 Patients

Autoimmune hypophysitis

Autoimmune hypophysitis is an inflammation of the pituitary gland resulting from autoimmune response, which can be classified as primary hypophysitis and secondary hypophysitis according to the etiology. The clinical presentation includes hypopituitarism and a pituitary mass. The diagnosis is based on clinical findings and radiology, while the pathology serves as the golden standard. The treatment is aimed at reducing the size of the pituitary mass, replacing the defective hormones and decreasing hyperprolactinemia. This review is about the epidemiology, pathogenesis, diagnosis, and treatment of lymphocytic hypophysitis, hypophysitis secondary to cytotoxic T-4 blockade, and IgG4-related hypophysitis. (Chin J Endocrinol Metab, 2015, 31: 1008-1012) Key words: Autoimmune hypophysitis; Lymphocytic hypophysitis; Hypophysitis secondary to cytotoxic T-4 blockade; IgG4-related hypophysitis

Lymphocytic hypophysitis misdiagnosed as pituitary adenoma: One case report

Lymphocytic hypophysitis misdiagnosed as pituitary adenoma: One case report

Abstract #1251: A Case of Ipilimumab Induced Hypophysitis

Abstract #1251: A Case of Ipilimumab Induced Hypophysitis

MRI manifestation of xanthomatous hypophysitis: a case report and review of the literature.

The inflammatory lesion of the pituitary gland is unusual. A 33-year-old woman with headache, visual impairment, and menelipsis was admitted to the Second Xiangya Hospital, Central South University. The results of magnetic resonance imaging (MRI) for pituitary gland showed a sellar mass with iso-intensity on T1 weighted imaging and high signal on T2 weighted imaging. The homogeneous lesion was enhanced on contrast MRI. The pituitary stalk was thickened accompanied by the cavernous sinus invasion, which showed a "triangle" saddle occupation on the MRI coronal plane. An endocrinological examination revealed mild hypocortisolism. Th e patient was diagnosed as pituitary adenoma based on the MRI findings and endocrinological examination. Trans-sphenoidal surgery was performed. The intra-operative histological examination also suggested a pituitary adenoma. Th e histopathological examination showed accumulation of foamy cells and xanthomatous epithelioid cells, supporting the diagnosis of xanthomatous hypophysitis. Xanthomatous hypophysitis possesses certain MRI features. Th e most typical imaging features are the thickening of the pituitary stalk and the sign of "triangle" occupation on MRI coronal plane, which are very helpful to the correct diagnosis and optimal management.

Unusual IgG4-related hypophysitis: one case report and analysis of clinicopathological characteristics

Background Immunoglobulin G4 (IgG4)-related disease is a recently characterized autoimmune disease entity marked by elevated serum IgG4 levels and tissue infiltration by IgG4-positive plasma cells in multiple involved organs. Hypophysitis is a rare inflammatory disorder and IgG4-related sclerosing disease involving the ituitary alone is especially rare. Imaging studies may reveal a mass lesion in the sellar area or a thickening of pituitary stalk, mimicking a pituitary tumor. Due to its rarity and non-specific appearance in radiological examination, it is a diagnostic challenge for clinicians and histopathologists to differentiate solitary IgG4-related hypophysitis from other pituitary lesions. The aim of this study is to summarize the clinicopathological features of unusual IgG4-related hypophysitis and discuss the differential diagnosis of histologically similar inflammatory lesions in pituitary. Methods The clinical manifestation of a patient with solitary IgG4-related hypophysitis was presented retrospectively. Resected mass was routinely paraffin-embedded and stained with Hematoxylin and Eosin. Dako EnVision immunohistochemical staining system was used to detect the tumor antigen expressions, including vimentin (Vim), S-100 protein (S-100), pan cytokeratin (PCK), epithelial membrane antigen (EMA), CD3, CD20, CD68, CD1a, κ-light chain, λ-light chain and progestrone receptor (PR). Results A 47-year-old male patient presented with 1-year history of mild limb weakness and hyposexuality. Laboratory examination revealed hypopituitarism with low levels of serum testosterone, cortisol, luteinizing hormone (LH) and follicle stimulating hormone (FSH), although his serum IgG4 level was high. MRI of the pituitary gland revealed a mass lesion in the sellar area with T 1 WI mild hyperintense and homogeneous enhancement after gadolinium administration. The patient underwent a transsphenoidal mass resection of the pituitary gland. Histological examination showed bland appearing spindle cell proliferation in the sclerotic background with marked infiltration of lymphocytes, plasma cells, as well as multiple foci of meningothelial-like nodules at the periphery of tissues. Immunohistochemical staining showed that the lymphocytes were positive for CD3 and CD20. Plasma cells were distinct and the number of κ and λ-light chains was the same. There were more than 30 IgG4-positive plasma cells per high power field (HPF), which accounted for greater than 40% of the IgG-positive plasma cells. The meningothelial-like nodules were positive for Vim, EMA and PR, but negative for CD68, S-100 and CD1a. A final histological diagnosis of IgG4-related hypophysitis with meningothelial reaction was made. The patient took prednisolone orally at 35 mg/d for 2 weeks, and the symptoms of limb weakness and hyposexuality showed improvement. The mass lesion of pituitary gland demonstrated a reduction in size. The prednisolone therapy was continued at a dose of 30 mg/d to prevent recurrence of IgG4-related disease. Conclusions IgG4-related hypophysitis is a rare disease of central nervous system with good response to corticosteroid treatment. Due to the relative paucity of reported cases and similarities in histological findings, it may be difficult to differentiate IgG4-related disease from other pituitary lesions with prominent inflammatory cell infiltration and stromal fibrosis. Thorough inspection under the microscopy and more importantly elevated serum IgG4 level are necessary for correct diagnosis. doi: 10.3969/j.issn.1672-6731.2014.10.012

Diagnosis and management of granulomatous hypophysitis

Objective To investigate the diagnosis and management of granulomatous hypophysitis.Methods Seven patients with granulomatoushypophysitis were retrospectively analyzed with their signs and symptoms,radiological characteristics,diagnosis,and treatments.Results In the seven cases,six cases were misdiagnosed before operations.The clinical signs were headaches,diabetes inspidus,hyperprolactinemia,and hypopituitarism.Pituitary stalk thickening is a prominent image feature and is associated with the tongue-like extension of the sellar lesion into the suprasellar region.Surgery via the transsphenoidal route was performed on six cases and the transfrontal approach was chosen for one patient due to the additional diagnosis of onabscess preoperatively.Most of the patients had remission of clinical symptoms and signs after surgery with steroids and hormones replacement and lesions were reduced or even disappeared on MRI images.Conclusions Surgical intervention should be performed because it is difficult to make correct pathological diagnosis of granulomatous hypophysitis preoperatively and may improve symptoms and signs.Steroids and hormones replacement should be administrated after surgery and patients should be followed-up because of the natural course of the disorder. Key words: Granulomatous hypophysitis ; Diabetes inspidus ; Hyperprolactinemia; Hypopituitarism; Treatment

Recurrent lymphocytic hypophysitis successfully treated with glucocorticoids plus azathioprine: three cases report

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

MRI of lymphocytic hypophysitis

目的 描述淋巴细胞性垂体炎的MRI表现,探讨MRI的诊断价值和限度及其与垂体腺瘤的鉴别诊断.方法对5例临床以多饮、多尿及头痛为主要症状前来就诊,手术病理诊断为淋巴细胞性垂体炎患者的术前MR影像及其临床资料进行回顾性分析.结果 5例淋巴细胞性垂体炎患者MRI均表现为垂体增大,垂体蒂增粗,正常神经垂体T1WI高信号消失,病变均呈明显强化,其中2例为均匀强化,3例强化不均匀.2例可见海绵窦及相邻硬脑膜受侵犯.结论对于垂体增大合并中枢性尿崩症,伴或不伴有腺垂体功能低下的患者要考虑淋巴细胞性垂体炎的诊断。