Involvement Of Pituitary Gland Research Articles

7292 Central AVP Deficiency in Erdheim-Chester Disease in the Era of Molecular Diagnostics

Abstract Disclosure: J. Hewlett: None. S. Mohan: None. C.J. Davidge-Pitts: None. J. Abeykoon: None. R. Go: None. D.Z. Erickson: None. Objective: Erdheim-Chester Disease (ECD) is a multisystem histiocytic disorder which can infiltrate the pituitary gland, often leading to endocrine dysfunction. Central Arginine Vasopressin Deficiency (cAVP-D) commonly affects ECD patients, and those harboring BRAFV600E are reported to have an increased risk. Insufficient data exist about the risk associated with other mutations, and if cAVP-D or pituitary imaging improves with targeted therapies (TT). Methods: We conducted a review of a prospectively maintained database of adults with ECD treated at a tertiary center between 1992-2023. Objectives of this study were to identify mutations associated with cAVP-D and assess for improvement in cAVP-D (remission of disease or decrease in dose of desmopressin) or pituitary gland involvement (via MRI imaging) following TT for ECD. Results: Of 148 patients with ECD, the majority were male (98, 66.2%) and the mean age at diagnosis was 56.5 years [range: 19-82]. Median length of follow-up was 24 months (95% CI, 17 to 27). Of 121 (81.8%) patients with molecular testing results, 89 (73.6%) harbored a somatic mutation. 67 of 89 (75.3%) carried BRAF mutations, with BRAFV600E in 61 (91.0%) and missense mutations/fusions in 6 (9.0%). 22 of 89 (24.7%) patients harbored other somatic mutations, with MAP2K1 in 13 (14.6%) being the most common. 35 (23.6%) patients were diagnosed with cAVP-D, and the median onset of polyuria and polydipsia prior to diagnosis of ECD was 51 months (95% CI, -120 to -6). Molecular testing was performed in 28 patients with cAVP-D: 17 (60.7%) harbored BRAF mutation and 3 (10.7%) MAP2K1 mutation. There was no significant association between the presence of cAVP-D and MAP2K1 (p=0.69, 95% CI, -0.08 to 0.21). The association between cAVP-D and BRAF did not reach statistical significance (p=0.07, 95%CI, -0.03 to 0.38). Additionally, there was no association between BRAF and timing of cAVP-D symptoms before ECD diagnosis (p=0.08, 95% CI -163.4 to 10.3). Pituitary MRI was available in 32 patients with cAVP-D (91.4%) showing infundibular involvement in 17 (53.1%) and loss of the posterior bright spot in 5 (15.6%). 28 (80%) patients with cAVP-D received systemic therapy, 18 (64.3%) of whom received TT. One patient with cAVP-D was able to discontinue desmopressin. Improvement of pituitary MRI was noted in 7 (21.9%), among whom 4 received TT, 2 received systemic non-TT, and 1 was lost to follow-up. There was no significant MRI improvement associated with TT (p=0.67, 95% CI -0.30 to 0.42). Conclusion: In this large cohort of patients with ECD, of whom the majority underwent molecular testing, we identified no association between MAP2K1 mutation and cAVP-D, and no impact of TT on the clinical course or MRI findings associated with cAVP-D. BRAF mutation carriers were more likely to have cAVP-D and more likely to have onset of symptoms closer to ECD diagnosis, but the results did not reach statistical significance. Presentation: 6/2/2024

8403 A Rare Presentation: Mucosal Melanoma with Pituitary Gland Involvement

Abstract Disclosure: L.R. Sepulveda-Garcia: None. L. El Musa Penna: None. W. Medina-Torres: None. J. Segarra-Villafane: None. Z. Maisonet-Feliciano: None. I. Arroyo-Gomez: None. L.A. Gonzalez-Rodriguez: None. M. Alvarado-Santiago: None. M. Ramirez-Vick: None. Introduction: Sinonasal mucosal melanoma (SNMM) is a rare form of aggressive melanoma with poor prognosis, compromising less than 1% of all melanoma. The most frequently reported symptoms include nasal obstruction and epistaxis, but the manifestation of symptoms may occur late and be nonspecific, causing delays in diagnosis and resulting in a less favorable prognosis. Here we report a rare case of mucosal melanoma with pituitary gland involvement initially thought to be a pituitary adenoma. Clinical Case Description: A 22-year-old male with no previous medical history was found with a biopsy proven pigmented epithelioid melanocytoma (PEM) in the palate. Three weeks after the biopsy, the patient presented with a severe headache, prompting the performance of a CT scan that revealed a pituitary macroadenoma. Several days later he developed acute right eye ptosis requiring emergency evaluation. The patient reported mild epistaxis, headaches, and nausea of 2 weeks duration associated with lack of erections and diminished libido. Physical exam was remarkable for sinus bradycardia, right eye ptosis, and a palate bluish pigmentation. Hormonal work up revealed a prolactin of 23 ng/mL (3.46-19.40), TSH of 2.22 uIU/mL (0.27-4.20), fT4 of 0.37 ng/dL (0.93-1.70), total testosterone <0.007 ng/mL (1.88-6.84), free testosterone of 0.001 ng/mL (0.032-0.168), FSH of 0.41 mIU/mL (2.6-11.0), and LH of 0.27 mIU/mL (0.4-7). Serum cortisol and ACTH levels were found to be low at <1.00 µg/dL (3.7-19.40) and 5.98 pg/mL (0.00-46.00), respectively, but these were taken while patient was given dexamethasone by neurosurgery for headaches. Brain MRI was remarkable for 3.4 cm x 3.3 cm x 3.5 cm sellar mass extending inferior into the sphenoid sinus, posteriorly into the right ethmoid air cells, superiorly into the suprasellar cistern with upward displacement of the optic chiasm, as well as bilateral cavernous sinus invasion. Case outcomes: A diagnosis of hypopituitarism was made. Physiologic doses of hydrocortisone were started after being found with central adrenal insufficiency. This replacement unmasked an arginine vasopressin deficiency also requiring desmopressin therapy. Central hypothyroidism was treated with levothyroxine and treatment for the hypogonadotropic hypogonadism was deferred in the meantime. Biopsy of right sphenoid sinus revealed a mucosal melanoma. Revised pathology slides led to the conclusion that palate PEM was an independent entity to the mucosal melanoma Case discussion: Prognosis is poor in patients with SNMM since this tumor is usually diagnosed at advanced stages. In this case, the sellar mass was initially thought to be a pituitary adenoma that later was found to be an extension of a mucosal melanoma. This case serves as a reminder of the critical role that differential diagnosis plays in evaluating sellar masses. Presentation: 6/1/2024

Clinical, Immunological, and Genetic Features in Patients with NFKB1 and NFKB2 Mutations: a Systematic Review.

Inborn errors of immunity (IEIs) encompass various diseases with diverse clinical and immunological symptoms. Determining the genotype-phenotype of different variants in IEI entity precisely is challenging, as manifestations can be heterogeneous even in patients with the same mutated gene. In the present study, we conducted a systematic review of patients recorded with NFKB1 and NFKB2 mutations, two of the most frequent monogenic IEIs. The search for relevant literature was conducted in databases including Web of Science, PubMed, and Scopus. Information encompassing demographic, clinical, immunological, and genetic data was extracted from cases reported with mutations in NFKB1 and NFKB2. The comprehensive features of manifestations in patients were described, and a comparative analysis of primary characteristics was conducted between individuals with NFKB1 loss of function (LOF) and NFKB2 (p52-LOF/IκBδ-gain of function (GOF)) variants. A total of 397 patients were included in this study, 257 had NFKB1 mutations and 140 had NFKB2 mutations.There were 175 LOF cases in NFKB1 and 122 p52LOF/IκBδGOF cases in NFKB2 pivotal groups with confirmed functional implications. NFKB1LOF and p52LOF/IκBδGOF predominant cases (81.8% and 62.5% respectively) initially presented with a CVID-like phenotype. Patients with NFKB1LOF variants often experienced hematologic autoimmune disorders, whereas p52LOF/IκBδGOF patients were more susceptible to other autoimmune diseases. Viral infections were markedly higher in p52LOF/IκBδGOF cases compared to NFKB1LOF (P-value < 0.001). NFKB2 (p52LOF/IκBδGOF) patients exhibited a greater prevalence of ectodermal dysplasia and pituitary gland involvement than NFKB1LOF patients. Most NFKB1LOF and p52LOF/IκBδGOF cases showed low CD19 + B cells, with p52LOF/IκBδGOF having more cases of this type. Low memory B cells were more common in p52LOF/IκBδGOF patients. Patients with NFKB2 mutations, particularly p52LOF/IκBδGOF, are at higher risk of viral infections, pituitary gland involvement, and ectodermal dysplasia compared to patients with NFKB1LOF mutations. Genetic testing is essential to resolve the initial complexity and confusion surrounding clinical and immunological features. Emphasizing the significance of functional assays in determining the probability of correlations between mutations and immunological and clinical characteristics of patients is crucial.

Remission of nephrogenic diabetes insipidus (arginine vasopressin resistance): description of a rare clinical case

Nephrogenic diabetes insipidus is a heterogeneous disease in the etiopathogenesis of which are involved acquired and congenital factors. In this case, the kidneys do not respond to vasopressin and continue to produce large concentrated volumes of urine. Distinctive features in the pathology of central genesis are the fact of trauma, brain tumor with involvement of pituitary gland, response to intranasal vasopressin in the form of decreased diuresis.For diagnosis it is important to perform a series of differential diagnostic tests.In this article we present a unique clinical case of a patient with a long-term course of diabetes insipidus with the development a spectrum of comorbid conditions, metabolic disorders, required kidney transplantation.

Clinical and prognostic features of Langerhans cell histiocytosis in adults.

Langerhans cell histiocytosis (LCH) is a rare disease characterized by clonal expansion of CD1a+ CD207+ myeloid dendritic cells. The features of LCH are mainly described in children and remain poorly defined in adults; therefore, we conducted a nationwide survey to collect clinical data from 148 adult patients with LCH. The median age at diagnosis was 46.5 (range: 20-87) years with male predominance (60.8%). Among the 86 patients with detailed treatment information, 40 (46.5%) had single system LCH, whereas 46 (53.5%) had multisystem LCH. Moreover, 19 patients (22.1%) had an additional malignancy. BRAF V600E in plasma cell-free DNA was associated with a low overall survival (OS) rate and the risk of the pituitary gland and central nervous system involvement. At a median follow-up of 55 months from diagnosis, six patients (7.0%) had died, and the four patients with LCH-related death did not respond to initial chemotherapy. The OS probability at 5 years post-diagnosis was 90.6% (95% confidence interval: 79.8-95.8). Multivariate analysis showed that patients aged ≥60 years at diagnosis had a relatively poor prognosis. The probability of event-free survival at 5 years was 52.1% (95% confidence interval: 36.6-65.5), with 57 patients requiring chemotherapy. In this study, we first revealed the high rate of relapse after chemotherapy and mortality of poor responders in adults as well as children. Therefore, prospective therapeutic studies of adults with LCH using targeted therapies are needed to improve outcomes in adults with LCH.

ARRAY OF MAGNETIC RESONANCE IMAGING FINDINGS IN POST-COVID MUCORMYCOSIS.

Background: ROCM is a rare but extremely fatal fungal infection targeting immunocompromised individuals. There was a surge in cases in the past 2 years amongst the patients recovered from moderate to severe COVID-19 infection. Imaging is essential for early clinical recognition of this potentially fatal disease so that timely management can be done. We Methods: conducted a cross-sectional observational study with 30 COVID 19 patients suspected of having ROCM for a period of 2 months. MRI evaluation was done using conventional sequences , TOF MR Angiography and follow up imaging was done whenever possible The infection was predominantly bilat . Results: eral in 22 patients(74%) with unilateral involvement seen in 8 cases (26%) .Staging was done in preoperative patients(15 patients) with Stage 1 disease seen in 2 cases (10%), Stage 2 disease seen in 5 cases (25%) and stage 3 disease seen in 8 cases( 40%). Cavernous sinus thrombosis was seen in 8 cases (26%), ICA thrombosis in 3 cases (10%) ,CCA thrombosis in 2 cases(10%), Optic neuritis in 8 cases (26%) , ICA infarct in 5 cases (10%), involvement of pituitary gland in 1 case (3 %), intracranial focal cerebritis in 5 cases (16%) and pachymeningitis in 5 cases (16%). Black turbinate and guitar pick signs were observed. Patients underwent endoscopic or open debridement under GA. with Orbital exenteration, ethmoidectomy and medial maxillectomy. Conclusion: ROCM is thus an emerging rapidly disseminating fungal infection aficting the COVID recovered population. Aggressive debridement, systemic antifungal therapy, and control of underlying co-morbid factors is the mainstay of therapy. Radiologists play a signicant role in it's early diagnosis, evaluation of extent, thus aiding in better and faster management.

Pituitary Imaging Abnormalities and Related Endocrine Disorders in Erdheim-Chester Disease.

Simple SummaryErdheim–Chester disease (ECD) is a rare histiocytic neoplasm that is frequently associated with hypothalamic–pituitary gland involvement leading to endocrine dysfunctions. Frequently, endocrinopathy is permanent and precedes the diagnosis of ECD and may also develop during the course of treatment. However, the exact nature and frequency of hypothalamic–pituitary involvement are unknown. We studied a natural history cohort of 61 subjects with Erdheim–Chester disease and found abnormal pituitary imaging in 47.5% of cases, associated with panhypopituitarism, diabetes insipidus, and a higher median number of pituitary endocrinopathies. These data confirm and significantly extend previous reports of centrally occurring endocrine dysfunction and highlight the need for routine imaging and systematic assessment of hypothalamic–pituitary endocrine function in patients with ECD.Purpose: We examined abnormal pituitary imaging (API) and associated endocrine dysfunction in subjects with ECD. Methods: A cross-sectional descriptive examination of a natural history cohort study diagnosed with ECD was conducted at a clinical research center. Subjects underwent baseline endocrine tests of anterior and posterior pituitary function and dedicated pituitary gland MRI scans. We determined the frequency of various pituitary imaging abnormalities in ECD and assessed its relationships with age, sex, body mass index (BMI), BRAF V600E status, high sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), pituitary hormone deficits and number, diabetes insipidus (DI), and panhypopituitarism. Results: Our cohort included 61 subjects with ECD [age (SD): 54.3 (10.9) y, 46 males/15 females]. API was present in 47.5% (29/61) of ECD subjects. Loss of the posterior pituitary bright spot (36.1%) followed by thickened pituitary stalk (24.6%), abnormal enhancement (18.0%), and pituitary atrophy (14.8%) were the most common abnormalities. DI and panhypopituitarism were more frequent in subjects with API without differences in age, sex distribution, hsCRP, ESR, and BRAF V600E status compared to normal pituitary imaging. Conclusions: We noted a high burden of API and endocrinopathies in ECD. API was highly associated with the presence of panhypopituitarism and DI. Therefore, a thorough assessment of hypothalamic–pituitary integrity should be considered in subjects with ECD.

Intravascular Lymphoma in Patient With Celiac Disease With Multi Glandular Involvement

Case Presentation: The patient is a 60 year old male with a past medical history of celiac disease, paroxysmal Afib, iron deficiency, and CAD who presented with lightheadedness, dizziness, and fatigue. Notable workup revealed that the patient had Afib with RVR, a TSH of 0.189, Free t4 0.51an LDH of 2726, hemoglobin of 8.7, AST of 155, ALT of 19, WBC of 4.5, and serum iron of 20. The patient’s cardizem dose was adjusted and repeat transthoracic echocardiogram was unremarkable compared to history. The patient presented again with complaints of abdominal distension, postural dizziness, occasional night sweats, and fevers. Repeat workups revealed pancytopenia, proteinuria, hypotension, and anasarca most pronounced in the lower extremity and scrotum. Ultimately, a kidney biopsy revealed an intravascular B cell non-Hodgkin lymphoma (IVBCL). Notable repeat labs include a CRP of 44 and a failed ACTH stimulation test. A brain MRI revealed a 6mm pituitary microadenoma. The patient placed on an R-CHOP regiment and is scheduled for repeat MRI to rule out pituitary involvement. Discussion: IVBCL’s are a rare form of diffuse B cell lymphoma and remain a diagnostic challenge due to the variety of involved systems including skin, CNS, and endocrine. IVBCL is also known to not produce a mass or lymphadenopathy. Celiac disease is a known risk factor for non-Hodgkin’s lymphoma. A literature search reveals a few case reports with common themes of increased LDH and inflammatory markers, anemia, and hepatic and renal dysfunction. Postural hypotension can also be a presenting symptom due to IVBCL’s ability to infiltrate neurovascular tissue to cause autonomic neuropathy. However, in this case, the patient’s history of primary adrenal insufficiency makes this unlikely. Hypothyroidism secondary to pituitary and thyroid involvement was suspected due to TSH level suppressed enough for central hypothyroidism. Repeated MRI showed resolution of Pituitary Microadenoma post Chemo therapy.Sylvain Raoul Simeni Njonnou, Bruno Couturier, Yannick Gombeir, Sylvain Verbanck, France Devuyst, Georges El Hachem, Ivan Theate, Anne-Laure Trepant, Virginie De Wilde, Frédéric-Alain Vandergheynst, “Pituitary Gland and Neurological Involvement in a Case of Hemophagocytic Syndrome Revealing an Intravascular Large B-Cell Lymphoma”, Case Reports in Hematology, vol. 2019, 6 pages, 2019. https://doi.org/10.1155/2019/9625075Catassi C, Fabiani E, Corrao G, et al. Risk of Non-Hodgkin Lymphoma in Celiac Disease. JAMA. 2002;287(11):1413Khan MS, McCubbin M, Nand S. Intravascular Large B-Cell Lymphoma: A Difficult Diagnostic Challenge. J Investig Med High Impact Case Rep. 2014 Mar 6;2(1):2324709614526702.Pearce C, Hope S, Butchart J. Intravascular lymphoma presenting with postural hypotension. BMJ Case Rep.Published 2018 Jan 29.

A challenging case report of IgG4‐related systemic disease involving the heart and retroperitoneum with a literature review of similar heart lesions

The IgG4-related disease is a distinct, steroid-responsive fibro-inflammatory disorder of unknown etiology. This multiorgan disease is characterized by tumefactive lesions that contain rich infiltrations of IgG4-positive plasma cells, with the pancreas, and the salivary and lacrimal glands being the main involved. The more common cardiovascular involvements include inflammatory peri-aortitis, coronary arteritis, and pericarditis. Intra-cardiac tumefactive lesions are rarely reported. Herein, we describe a challenging case of IgG4-related disease with a long-time lag between initiation of symptoms to proper diagnosis with biopsy-proven cardiac and retroperitoneal and possible pituitary gland involvement. Concerning the rarity of the cardiac lesion in our case, we conducted a literature review of similar case reports.

The role of macrophages type 2 and T-regs in immune checkpoint inhibitor related adverse events

Immune checkpoint inhibitory (ICI) therapy represents a novel approach in a variety of cancers, with impressive survival benefit. With ICIs, however, a new spectrum of immune related adverse events (irAE) including life threatening hypohysitis has emerged. This autopsy study aimed to investigate inflammatory cells, PD-1 and PD-L1 expression in cases of patients who developed hypophysitis and involvement of other organs.We analysed 6 patients, who were treated with ICIs and developed hypophysitis. Two received an additional MAP-kinase inhibitor, MEK-inhibitor and cytotoxic chemotherapy. Besides the pituitary gland, all investigated adrenal glands (5/5) were affected; three cases had other organs involved (liver (2/6), thyroid (2/6), lung (1/6), myocardium (1/6), colon (1/6). The inflammatory cells of involved organs were further specified and PD1 and PDL-1 expression was analyzed using immunohistochemistry. We observed that patients treated with ICIs alone showed T-cell predominant lymphocytic infiltrates, whereas patients receiving additional therapies demonstrated an increase in B- and T-lymphocytes. Surprisingly, the dominant inflammatory population was not T-cell, but type 2 macrophages. CD25 positive T-regs were sparse or absent.Our study suggests that T cell activation is only partially responsible for irAE. ICI therapy interaction with CTLA-4, PD-1 and PDL-1 in type 2 macrophages appears to result in disturbance of their control. Furthermore, depletion of T-regs seems to contribute significantly. Our findings with simultaneous pituitary and adrenal gland involvement underlines the systemic involvement as well as the importance of monitoring cortisol levels to avoid potentially life threatening hypocortisolism.

SAT-245 A Rare Case of Clival Primary Diffuse Large B-Cell Lymphoma Presenting with Panhypopituitarism and Unmasked Diabetes Insipidus

Background: Central adrenal insufficiency (AI) is known to conceal diabetes insipidus (DI) by impairing free water clearance from the renal system and inhibiting polyuria, which is later unmasked by the initiation of glucocorticoids. The instances of masked DI in the literature are confined to case reports - the actual incidence is unclear. There have been no documented cases of masked DI secondary to a clival tumor, which remains a rare cause of hypopituitarism. Here we discuss a case of primary diffuse large B-cell lymphoma (DLBCL) of the clivus presenting with panhypopituitarism and the development of DI upon glucocorticoid initiation. Clinical Case: A 60-year-old man with DLBCL initially presented to an outside institution with headache, diplopia, and right eye ptosis. Brain MRI showed enhancement of the clivus without obvious pituitary gland involvement. He underwent biopsy with partial resection of the tumor and pathology confirmed DLBCL. His course was complicated by persistent fevers. Extensive work-up was unrevealing and he was transferred to our institution for further management. On admission, infectious work-up was positive for C. Difficile. He later developed septic shock requiring vasopressors and broad-spectrum antibiotics. Despite prolonged antibiotics, he remained hypotensive. Due to proximity of the clivus and sella, there was concern for pituitary involvement. A random cortisol was 9.1 [3.7-19.4 ug/dL], subsequent 250ug cosyntropin stimulation test yielded 13.1 and 14.9 at 30- and 60-minutes, respectively. Given inadequate stimulation and persistent hypotension in this critically ill patient, he was then started on stress dose hydrocortisone (HC) with prompt resolution of hypotension. Further work-up of the pituitary axes was consistent with anterior hypopituitarism: ACTH 5 [6-50 pg/mL], TSH 0.336 [0.350-4.940 uIU/mL], free T4 0.5 [0.7-1.5 ng/dL], FSH 0.3/LH 0.1 [1-10 mIU/mL], IGF-1 <16 [41-279 ng/mL], prolactin <1 [3-16 ng/mL]. On day two of HC stress dosing, he developed hypernatremia and polyuria. Urine studies were consistent with DI and desmopressin was started with subsequent improvement. Conclusion:This is the first documented case of DLBCL of the clivus leading to panhypopituitarism. For tumors in close proximity to the pituitary, there should be a low threshold for pituitary axes evaluation. In addition, masked DI from central AI remains rare and requires close attention by the Endocrinologist following initiation of glucocorticoids.

Accuracy of apparent diffusion coefficient values and magnetic resonance imaging in differentiating suprasellar germinomas from chiasmatic/hypothalamic gliomas.

The aim of this study was to differentiate suprasellar germinomas from chiasmatic/hypothalamic gliomas (CHGs) using apparent diffusion coefficient (ADC) values and magnetic resonance imaging (MRI) characteristics. A cross-sectional study was conducted on 11 patients with suprasellar germinomas and 11 patients with CHGs who underwent pretreatment MRI. The ADC values (minimum and average ADC values) of the tumors were measured and the MRI characteristics were evaluated. The average and minimum ADC values of suprasellar germinomas were significantly lower than those of CHGs (p = 0.016 and 0.004 respectively). The selection of 941.15 × 10-6 mm2/s as a cutoff value of the minimum ADC value was used to differentiate suprasellar germinomas and CHGs; the best results were obtained with area under the curve of 0.889, sensitivity of 87.5%, specificity of 77.8% and accuracy of 82.4%. MRI characteristics suggested the diagnosis of suprasellar germinomas were T2W hypointensity and involvement of pituitary gland and/or stalk. MRI characteristics suggested the diagnosis of CHGs was higher degree of contrast enhancement and presence of macrocysts. ADC values have a role in differentiating suprasellar germinomas and CHGs, especially when imaging findings on conventional MRI are inconclusive. Furthermore, some MRI features are in favor of differentiation between these tumor entities including tumor location, cyst pattern, T2W hypointensity, degree of contrast enhancement, stalk and pituitary gland involvement.

4 - Pituitary Apoplexy as First Presentation of IgG4-Related Disease

Pituitary gland involvement in IgG4-related disease (RD) has been described and commonly misdiagnosed as a nonfunctional pituitary adenoma. We present a patient with pituitary apoplexy as the first presentation of IgG4-RD.

SUN-430 An Unusual Presentation of Hypopituitarism in the Setting of Metastatic Breast Carcinoma: A Case Report

Introduction: Metastasis to the pituitary gland (PM) are infrequent (1). Breast and lung cancer are the most common primary cancer of PM. We report an interesting case of metastatic breast cancer with pituitary gland involvement debuting with diabetes insipidus as the initial symptom. Clinical Case: A 59-year-old woman presented with symptoms of polydipsia, polyuria, unquantifiable weight loss, and generalized body weakness. Initial assessment showed evidence of panhypopituitarism as per: FT4 0.39 (0.60-1.32 ng/dL), TSH 1.39 (0.45-5.33 uIU/mL), Cortisol 1.8 (6.7-22.6 ug/dL), ACTH 13 (6-50 pg/mL), Prolactin 223.5 (2.74-19.64 ng/mL), Estradiol 222 (<= 31 pg/mL) while on estradiol pellets, LH 0.2 (10.87-58.64 mIU/mL), FSH 1.6 (16.74-113.59 mIU/mL), Na 146 mmol/L, Cl 112 mmol/L, and urine specific gravity 1.004. MRI of the brain reported a pituitary macroadenoma measuring 1.0x1.6x1.8 cm, extending posteriorly along the infundibulum. She was initially treated with hydrocortisone, levothyroxine, cabergoline, and desmopressin. Physical examination was remarkable for a right breast lump. Breast ultrasound showed a mass measuring 1.2x1.2 cm. A biopsy was performed reporting invasive lobular carcinoma, Nottingham histologic grade 2 [ER (85%) PR (61%) and HER2 negative with a KI67 of 2%]. Posteriorly, the patient underwent pituitary biopsy and trans sphenoidal resection with pathology report of metastatic breast carcinoma [ER 20% PR 2% HER2 negative by FISH]. Pituitary stains were negative for prolactin.Subsequent breast cancer staging with CT Abdomen/pelvis and 18F-FDG PET/CT revealed widely metastatic disease including right and left breast, bilateral axillary LAD, moderate bilateral hydronephrosis, and extensive bone disease in the axial and appendicular skeleton. Patient has been treated with 15 cycles of whole-brain radiation therapy, and the current treatment approach is no longer curative, focused on palliative chemotherapy and hormonal replacement therapy. Prolactin levels have normalized. Conclusion: Our case remarks the importance of working up pituitary macroadenomas with diabetes insipidus. Even though metastatic pituitary tumors are rare, awareness of clinical presentation is essential to keep in our differential that isolated pituitary tumors can be an initial presentation of the metastatic process, allowing early diagnosis and interventions. Keywords: Hypopituitarism, Pituitary Gland, Pituitary Metastasis

Panhypopituitarism- An unusual presenation of tuberculous meningitis

Pituitary gland involvement is a very rare entity of central nervous system tuberculosis. Tubercular meningitis (TBM) is a chronic meningitis on hypothalamic-pituitary axis which causes high morbidity and mortality hence it is the most dreaded form of extra pulmonary tuberculosis. Here we report a case of 24 year old female presenting with three months history of fever and headache along with altered sensorium since four days. There was also complain of secondary amenorrhea and generalised apathy. Neuroimaging revealed subependymal tuberculomas with meningitis and obstructive hydrocephalus. Cerebrospinal fluid (CSF) examination was also suggestive of tubercular meningitis. Endocrinological investigations showed multiple hormonal deficiencies manifesting as pituitary hypothyroidism, hypocortisolism, hypogonadotropic hypogonadism, and hypoprolactinemia. Anti-tuberculosis treatment was started, and it led to significant improvement in the general condition of the patient.

Progressive Pituitary Involvement in a Patient with Localized Granulomatosis with Polyangiitis

Granulomatosis with polyangiitis (GPA) is a life-threatening disease characterized by granulomatous inflammation and antineutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis, classically involving upper and lower respiratory tracts and kidney. Milder forms of disease restricted to respiratory tract is referred to as localized GPA (loc-GPA) [1,2]. The European Vasculitis Study Group (EUVAS) defined loc-GPA as disease restricted to ear, nose, and throat (ENT) tract and lung without clinical signs of systemic vasculitis or disruption on vital organ function [3]. Progression from loc-GPA to systemic form is rare, occurring in only 10% of patients with loc-GPA [4]. Involvement of pituitary gland as a manifestation of progression into systemic disease in loc-GPA is also unusual, not previously reported. Here we report an unusual case of ANCA-negative loc-GPA initially presented with multiple cranial nerve palsies which progressed into ANCA-positive systemic disease involving pituitary gland. Case

Diffuse Large B-Cell Lymphoma Presenting with Diabetes Insipidus: A Case Report

ABSTRACT Objective: To present a rare case of pituitary gland involvement in paranasal and central nervous system (CNS) lymphoma. Methods: We describe the clinical presentation, laboratory data at presentation and follow-up, imaging studies, and management of the patient. A brief review of literature regarding pituitary involvement in lymphoma is also presented. Results: A 53-year-old woman with a history of human immunodeficiency virus (HIV) infection was evaluated for 6-month history of polydipsia, high-volume polyuria, and headache. Laboratory work-up was consistent with diabetes insipidus. Magnetic resonance imaging showed a 6-mm lesion in the posterior pituitary and ill-defined decreased T1 signal in the clivus and sphenoid sinus. She was treated medically with desmopressin for her urinary symptoms, with symptomatic improvement. In the interim, she was admitted for acute visual loss. Repeat imaging revealed a soft tissue mass involving paranasal sinuses with intracranial extension to the sella and hy...

The incidence of secondary central nervous system involvement in patients with non-Hodgkin’s lymphoma as detected by 18F-FDG PET/CT

Secondary central nervous system (CNS) involvement is a devastating and usually fatal complication of non-Hodgkin's lymphoma (NHL). We aimed to evaluate the incidence of secondary CNS involvement and the value of (18)F-FDG PET/computed tomography (CT) imaging in the detection of secondary CNS involvement in patients with NHL. A total of 123 immunocompetent patients (58 men, 65 women; mean age: 56.5±19.2) with biopsy-proven NHL who underwent (18)F-FDG PET/CT for primary staging (n=68) and restaging (n=55) of recurrent disease were reviewed retrospectively. Those with secondary CNS involvement as diagnosed on PET/CT were identified. CNS involvement was confirmed by MRI and cerebrospinal fluid cytology. The clinical Ann Arbor stages of the patient population were as follows: stage I - 10 patients; stage II - 44 patients; stage III - 32 patients, and stage IV - 37 patients. PET/CT detected CNS involvement in six patients. The ages of patients with CNS disease ranged from 23 to 68 (mean: 47.2) years. Three patients presented with CNS involvement associated with systemic disease manifestation at initial diagnosis; one patient had isolated CNS relapse and two had relapsed systemic NHL with progression to CNS involvement. Relapse interval was 8-12 months following initial diagnosis. The types of CNS involvement in patients were as follows: parenchymal (n=2), leptomeningeal (n=2), both parenchymal and leptomeningeal (n=1), and pituitary gland involvement (n=1), which is an uncommon manifestation. Median duration of survival was 2.5 months after the diagnosis of CNS involvement. The incidence of secondary CNS involvement was 4.4% at initial diagnosis and 5.4% among patients with relapse of lymphoma in our study. PET/CT is a sensitive, objective, and valuable method for the diagnosis of secondary CNS involvement in patients with NHL. In addition, pituitary gland involvement, as a very rare manifestation of secondary CNS lymphoma, has been shown.

Hypophyseal Wegener's granulomatosis presenting by visual field constriction without hypopituitarism

The authors report a 48-year-old woman with known sysemic Wegener’s granulomatosis and recent onset bitemporal uperior quadrantanopia in whom magnetic resonance imagng, transphenoidal adenohypophysectomy and histopathology onfirmed necrotising granulomatous hypophysitis causing optic hiasm compression. Pituitary gland involvement in Wegener’s ranulomatosis is rare, first manifesting most commonly with entral diabetes insipidus, sometimes with concomitant hypopiuitarism affecting other hormonal axes and extremely rarely ith visual symptoms. The previously unreported presentation f hypophyseal Wegener’s granulomatosis with bitemporal heminopia but neither diabetes insipidus nor hypopituitarism is iscussed.

Cutaneous Rosai-Dorfman Disease With Increased Number of Eosinophils: Coincidence or Histologic Variant?

Rosai-Dorfman disease (RDD) is characterized histologically by a dense histiocytic infiltrate with emperipolesis and associated lymphocytes, plasma cells, and neutrophils. Eosinophils are not commonly associated. We report a patient with initial thymus and pituitary gland involvement by RDD, who later developed papules on the groin and axilla. Skin biopsies showed admixed histiocytic infiltrates (lymphocytes, neutrophils, and plasma cells) without emperipolesis. A prominent eosinophilic infiltrate was also observed, a feature not, to our knowledge, previously reported. Immunohistochemistry revealed positivity for CD68 (most cells) and S100 protein (scattered cells) and was negative for anti-CD1a. The diagnosis of RDD was established in the clinical context after comparison with the thymic and pituitary lesions (similar histologic features, albeit with fewer eosinophils, and immunohistochemical profiles). We present the first case, to our knowledge, of multicentric RDD with cutaneous involvement and associated prominent eosinophilic infiltrate. Thus, RDD should be included in the differential diagnosis of mononuclear infiltrates containing eosinophils.