Posterior Pituitary Bright Spot Research Articles

Rathke’s Cleft Cyst Presented with Central Diabetes Insipidus in a Young Female

ABSTRACT Rathke’s cleft cyst (RCC) is a benign lesion originating from remnant of Rathke’s pouch. RCC presenting as diabetes insipidus is rare. Here we present a case of a 32 year young female presented to our outpatient department with history of polyuria, polydipsia, nocturia with preference to cold liquids and diffuse mild to moderate intensity headache for last 2 months. On investigation, she was found to have partial central diabetes insipidus without other pituitary hormone deficiency. Magnetic resonance imaging (MRI) of sellar region was done which revealed Rathke’s cleft cyst with deviation of the infundibulum and loss of posterior pituitary bright spot. Patient was given a trial of oral desmopressin, and within 2 days patient responded with reduction of urine volume.

FRI348 Ectopic Posterior Pituitary As A Cause Of Panhypopituitarism Presenting With Hyponatremia

Abstract Disclosure: C. Choo: None. Background: Ectopic posterior pituitary gland (EPP) can occur from defective embryogenesis affecting neuronal migration, or from neurodegeneration of the hypothalamic nuclei. While isolated growth hormone deficiency is most common, it is also associated with pan-hypopituitarism. The posterior pituitary function is often preserved. Clinical Case: We report a case of pan-hypopituitarism from congenital EPP, presenting with hyponatremia. A 63-year-old male with hyperlipidemia was admitted for gastroenteritis. Serum sodium was 106mmol/L [reference range 136-146mmol/L] on admission but he was otherwise asymptomatic and haemodynamically stable. This initially improved with intravenous fluids, however subsequently stagnated at 121mmol/L despite achieving euvolemia. Thyroid and cortisol axes were evaluated in view of persistent hyponatraemia. 8am cortisol was low at 119nmol/L with inappropriately normal ACTH 13.9 pg/mL [reference range 7.2 – 62.3 pg/mL]. Thyroid function test showed central hypothyroidism consistently on repeat testing with a low fT4 of 6.1 pmol/L and 7.7 pmol/L [reference range 8.8-14.4pmol/L] and inappropriately normal TSH of 2.98MU/L and 2.41MU/L respectively [reference range 0.65-3.70MU/L]. 1mcg short synacthen test done following suspicion of hypocortisolism peaked at 468 nmol/L. He had no symptoms or signs of hypocortisolism or hypothyroidism. He was a bachelor and had clinical features of hypogonadism including short stature (142cm), high-pitched voice, scarce sexual hair and pubescent sized testes. His mid-parental height is unknown as his parents were deceased. FSH, LH, testosterone and IGF-1 were all undetectable. Prolactin was otherwise normal 9.4ug/L [reference range 4.2-16.4ug/L]. Radiographs of the forearm showed unfused epiphyseal plates at the distal radius and ulna. Thus, the diagnosis of pan-hypopituitarism was made. Magnetic resonance imaging of the pituitary revealed a T1 hyperintense nodule at the floor of the third ventricle, suggestive of ectopic posterior pituitary. There was otherwise minimal normally enhancing tissue in the pituitary fossa, and the posterior pituitary bright spot and infundibulum were absent. He was started on hydrocortisone and subsequently levothyroxine replacement, with resolution of hyponatraemia (serum sodium 139nmol/L). He did not develop polyuria or polydipsia to suggest diabetes insipidus. Due to financial concerns however, he declined growth hormone and testosterone replacement therapy. Conclusion: Most reports of EPP are in the pediatric population often presenting with short stature. This was a seemingly ordinary case of hyponatraemia initially deemed to be from hypovolaemia. His atypical clinical features led to the eventual diagnosis of EPP with panhypopituitarism at a rather late age, highlighting the importance of a thorough clinical examination necessitating further evaluation. Presentation: Friday, June 16, 2023

SAT614 Clinical, Laboratory And Imaging Features Associated With Central Diabetes Insipidus (Arginine Vasopressin Deficiency) In Erdheim-Chester Disease (ECD)

Abstract Disclosure: S. Vaid: None. J. Estrada-Veras: None. W. Gahl: None. P. Nicholas: None. R. Dave: None. B. Gochuico: None. K. O'Brien: None. F. Hannah-Shmouni: None. S. Shekhar: None. Background: Erdheim-Chester disease (ECD) is a rare, non-Langerhans, histiocytic multisystemic disorder commonly associated with somatic pathogenic variants in the BRAF or MAPK pathways. In ECD, diabetes insipidus (DI) is among the most common endocrinopathies and is often the presenting feature. We analyzed the prevalence and the genetic, biochemical, and imaging features associated with DI in subjects with ECD. Methods: A cross-sectional descriptive study of subjects with biopsy-confirmed ECD was conducted from January 2011 to December 2018 at the National Institutes of Health Clinical Center. Subjects underwent molecular genetics, baseline biochemical and pituitary endocrine function studies, and dedicated pituitary MRI. DI was diagnosed based on clinical and biochemical features. Other endocrinopathies were diagnosed based on standardized criteria. Continuous data were analyzed using t-tests or nonparametric tests between subjects with and without DI. Categorical data were analyzed via Fisher's exact tests. Results: Sixty-one subjects with ECD [23 females (37.7%) and 38 males (62.3%)] were evaluated. Twenty-three subjects (38%) had DI, with a higher percentage of males (87%) vs females (13%). DI subjects compared to those without DI were younger [mean (SD):50.1(10.4) vs 57.5 (14.5) years; p=0.01] and had a higher prevalence of BRAF V600E pathogenic variants [76.19% vs 39.47%; p<0.01], lower IGF-1 [mean (SEM):136.5 (13.87) vs 161.67(10.22) ng/mL; p=0.02], and lower urine osmolality [466.6 (±260.18) vs 641.05 (±179.7) mOsm/kg; p<0.01]. DI subjects also had a higher prevalence of central hypogonadism [78% vs 34%; p<0.01], a higher prevalence of panhypopituitarism [39% vs 0%; p <0.01] and a higher number of anterior pituitary deficits [mean (SEM):1.23 (1.15) vs 0.56 (0.67); p =0.01] than non-DI subjects. Subjects with DI had a higher frequency of absent posterior pituitary bright spots [61% vs 21%; p<0.01] compared to those without DI. There were no differences in BMI, serum prolactin, vasopressin, serum osmolality, serum sodium, total cholesterol or hsCRP. The frequencies of central adrenal insufficiency, central hypothyroidism and abnormal pituitary imaging were similar between the two groups. Conclusion: DI is among the most common endocrinopathies in Erdheim-Chester disease. In DI subjects, a higher burden of anterior pituitary endocrinopathies, BRAF V600E pathogenic variants and absence of the posterior pituitary bright spot was noted, which may allow for early stratification and targeted clinical management. Presentation: Saturday, June 17, 2023

FRI339 Hypophysitis Secondary To Small Vessel Anca Vasculitistreated With Rituximab

Abstract Disclosure: A. Rivadeneira: None. N. Kumar: None. S. Banerjee: None. M. Gubbiotti: None. D. Yoshor: None. J. Kharlip: None. C.A. White: None. Introduction: Granulomatosis with polyangiitis (GPA) is an autoimmune small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCAs) that rarely involves the pituitary. Conventional treatment of GPA includes high dose glucocorticoids with cyclophosphamide. Rituximab has been used in refractory cases with high rates of remission. We present a case of pituitary GPA treated with and excellent response to rituximab. Case: 51-year-old woman with hypothyroidism, post I-131 treatment for Graves’ disease. Patient presented with 1 year of worsening fatigue, myalgias, frontal headaches, sinus congestion and epistaxis. CT sinus showed pituitary enlargement and chronic mucosal disease. MRI pituitary showed diffusely enlarged pituitary with non-visualized posterior pituitary bright spot and thickened stalk. CT chest showed 18x11 mm nodular opacity and peribronchial fibrosis. Laboratory evaluation showed ACTH 26.7 pg/mL, cortisol 13.4 mcg/dL, TSH 1.1, T4 9.7, prolactin 53 ng/dL, estradiol <20, LH 4, FSH 23. Sodium 140 and urine osm 488. There was positive p-ANCA staining and elevated serum anti-proteinase 3 antibody (PR3), 74 units (0-20). Myeloperoxidase antibody was not elevated. ESR 73 mm/h (0 - 30) and CRP 7.9 (<7.4). Due to atypical ANCA pattern (p ANCA typically is associated with MPO not PR3), pituitary biopsy was performed and showed adenohypophysis with dense lymphoplasmacytic infiltration with nodularity of the inflammatory infiltrates, some arranged peri vascularly, compatible with involvement of the pituitary gland by GPA. She began rituximab 375 mg/m2 weekly for four weeks with plan to continue every 6 months. After treatment, the patient experienced resolution of daily frontal headaches, congestion, cough and epistaxis. CT chest showed improvement of prior lung findings, and ESR/CRP normalized. Repeat pituitary MRI is pending. Discussion: Pituitary involvement is uncommon in GPA, occurring in only 3.9% of cases. It may lead to partial or complete pituitary dysfunction, particularly central diabetes insipidus (87.5%) and hypogonadism (75%). Typical MRI abnormalities include diffusely enlarged pituitary gland, thickened pituitary stalk and absence of posterior bright spot. Treatment of GPA includes a combination of corticosteroids, Cyclophosphamide, Azathioprine and Rituximab. Remission is achieved in up to two thirds of patients. Treatment of lymphocytic hypophysitis, another common cause of diffuse pituitary enlargement, relies on high dose glucocorticoids, leading to many side effects and taper is limited by worsening symptoms. This case highlights the critical role in serologic evaluation and targeted pituitary biopsy to identify the specific etiology of pituitary infiltration to help guide alternate treatment options, and the emerging role of Rituximab as a steroid sparing agent for treatment of pituitary inflammation. Presentation: Friday, June 16, 2023

ODP587 A Case of Rathke'S Cleft Cyst Presented With Central Diabetes Insipidus In A Young Female

Abstract Introduction Rathke's cleft cysts (RCC) are cystic sellar and suprasellar lesion derived from remnant of Rathke's pouch. RCC are mainly asymptomatic, but can present with headache, visual disturbance, panhypopituitarism, hypothalamic dysfunction when it enlarges causing compression to the surrounding structure. Diabetes insipidus as a presenting feature of RCC is rare. Even it presents with diabetes insipidus, it occurs more in elderly. Clinical Case A 32-year-old married female, mother of one child, having normal menstrual cycle presented with polyuria, polydipsia of recent onset. Clinical examinations was normal. Serum creatinine, potassium, calcium, plasma glucose were within normal range. Anterior pituitary hormonal evaluation was normal. Serum sodium was in the upper range of normal. Basal urine osmolality and serum osmolality were 87.49 mosm/kg (150 -1150 mOsm/kg) and 287 mOsm/kg (275 -295 mOsm/kg) respectively. Water deprivation test followed by vasopressin challenge test was done, which revealed partial central DI. Magnetic resonance imaging revealed a sellar cystic lesion hyperintense on both T1 and T2 weighted images, suggestive of rathke's cleft cyst and posterior pituitary bright spot was not visible. Tablet desmopressin 50 mcg twice daily was given and within two days patient responded well to the treatment. Urine volume reduced to 2.5 litres/day and water intake reduced to 3. 0 litres/day. Conclusion This is a rare case of Rathke's cleft cyst, presenting as diabetes insipidus as the sole manifestation in a young lady. Presentation: No date and time listed

LBMON134 Igg4 Related Hypophysitis And Skull Base Lesion: Retrospective Analysis Of 10 Years’ Experience Of A Tertiary Care Hospital Of Northern India.

Abstract Introduction 'IgG4-related' disease is a spectrum of autoimmune phenomenon that clinically manifests with multisystem disorder in nearly 50% of the cases. The nervous system involvement is noted only in 4% of cases. Hypophysitis is considered as rare inflammation of the pituitary gland and/or stalk that results in pituitary enlargement, that may or may not be associated with hypopituitarism. Design and setting: Retrospective study from a tertiary care hospital of North India. Methods and patients Biopsy proven IgG4-RD patients with various systemic manifestations registered in Postgraduate Institute of Medical Education and Research, Chandigarh between 2012 and 2022 were retrospectively analyzed. Results Among 3006 operated sellar and parasellar SOL since 2012, only 5 patients had IgG4 related hypophysitis and skull base lesion. After considering all organ systems, nearly 154 biopsy proven IgG4-RD had been reported from this institute. Three of those five patients were male and two were female. Mean age of presentation 32.2±9.49 years. Median duration of illness at presentation was 1 year. Two out of 5 cases reported with Headache, diminution of vision was the presenting complaints in rest of the three cases. Two of the 5 patients presented with some form of hypopituitarism. MRI showing Sellar space occupying lesion in 2 patients, although posterior pituitary bright-spot was absent in one case, none of them had diabetes insipidus at presentation. Three cases had stalk thickening on MRI. A female patient had retroperitoneal fibrosis leading to obstructive uropathy after four years of follow up of hypophysitis, one had associated craniopharyngioma, and one with testicular failure. Except one patient, all 3 patients had normal serum IgG4 level, data of one patient was missing. Methylprednisolone was the cornerstone of therapy for almost all the cases. Discussion Hypophysitis and inflammatory CNS lesions are not uncommon phenomena but relatively rare with IgG4-RD. IgG4-RD is diagnosed based on clinical and pathological criteria. The proposed diagnostic criteria include (1) characteristic diffuse or localized swelling or masses in single or multiple organs; (2) elevated serum IgG4 level; (3) histopathology demonstrating infiltration of lymphocytes and plasmacytes with the demonstration of IgG4 plasma cells (ratio of IgG4 to IgG cells > 40% and > 10 IgG4 plasma cells/high power field) and storiform fibrosis and /or obliterative phlebitis. The diagnosis is considered definite in the presence of all findings, probable if 1 and 3 are present, possible if 1 and 2 are present. Since they are inflammatory excellent steroid responsiveness has been documented in the literature. In this study we reported various presentation of hypophysial and skull base IgG4-RD which often confused as tumorous lesion, warrant high index of suspicion for diagnosis. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

LBODP011 Pembrolizumab Induced Hypophysitis And Resultant Isolated ACTH Deficiency Presenting As Secondary Adrenal Insufficiency.

Abstract Introduction Pembrolizumab is a novel human immunotherapeutic monoclonal antibody directed against PD-1 (programmed death receptor 1). It has been approved by the FDA for treatment of many malignancies including breast cancer. Although it has improved survival for many oncological conditions, it has been linked to a variety of endocrinopathies. We present a case of Pembrolizumab induced hypophysitis with isolated ACTH deficiency presenting as secondary adrenal insufficiency. Case presentation A 36 year old female with a history of breast cancer treated with chemotherapy and surgery, presented with intractable nausea and vomiting. She reported not being able to keep anything down for 4-5 days and had experienced multiple episodes of non-bilious, non-bloody emesis. She endorsed dizziness, but denied fever, chills, shortness of breath, abdominal pain, or problems with urination/bowel movements. She had been treated with Pembrolizumab with the last dose being 4 months prior to presentation. On arrival, vitals included temperature 98.4 F, BP 104/62 mm Hg, Heart rate 104 bpm, RR 16 with SpO2 100%. Labs were significant for WBC count 3.65 K/uL (3.81 - 8.94), Eosinophils 10.4% (0.1 - 6; she was noted to have eosinophilia prior to presentation), Hemoglobin 11.6 g/dL (11 - 14.9), Sodium 140 mmol/L (136-145), Potassium 3.4 mmol/L (3.4 - 5.1), Glucose 57 mg/dL (70 - 100), Lactate 0.7 mmol/L (0.2 -2), Lipase 23 U/L (13 - 60), Urine HCG negative, Urinalysis negative for nitrites and leukocyte esterase, TSH 1.22 uIU. ml (0.5 -5.7) and AM cortisol 0.4 ug/dL (6 - 18.4). Endocrinology was consulted and further work up was sought: ACTH <5 pg/ml (7.2 - 63) and Cortisol 30 - 60 minutes after cosyntropin stimulation 3.6 ug/dL. Prolactin, free T4, FSH and LH were within normal limits. MRI brain showed a prominent pituitary gland with enhancement and interval loss of posterior pituitary bright spot representing lymphocytic hypophysitis. She was started on Solu-Cortef and her symptoms resolved. She was discharged on hydrocortisone with education on sick day rules for secondary adrenal insufficiency. Discussion Adrenal insufficiency secondary to immunotherapy is a rare, emergent and dangerous condition. The key to successful management is early recognition. In patients treated with immunotherapy agents, non-specific symptoms such as nausea, vomiting, fatigue (which are common adverse effects of chemotherapy) should prompt urgent evaluation with hormonal workup. Evidence suggests that eosinophilia may be an early indicator before the onset of symptoms which was evident in our case. Radio-graphic imaging is helpful for diagnosis. Treatment entails high dose corticosteroids for acute crisis followed by physiological maintenance dosing. Patients should be educated on sick day rules for adrenal insufficiency. Presentation: No date and time listed

PMON84 A Unique Case of Diabetes Insipidus Revealing Hodgkin's lymphoma

Abstract Introduction While diabetes insipidus rarely presents as a symptom of non-Hodgkin's lymphoma, it is very rarely a revealing symptom of Hodgkin's lymphoma. We present a case of this unique association. Case presentation We report a case of a 25-year-old previously healthy male with no significant past medical history who presented with complaints of polydipsia, polyuria, and nocturia. A water deprivation test confirmed central diabetes insipidus. He started therapy with oral desmopressin and had clinical improvement. Magnetic resonance imaging (MRI) of his head showed thickened infundibulum and a lack of posterior pituitary bright spot, consistent with infundibulo-neurohypophysitis. There were no obvious masses within the anterior or posterior lobe, nor were suprasellar soft tissue masses noted. Diabetes mellitus (DM), autoimmune diseases, and infectious diseases were excluded. A chest x-ray revealed a superior mediastinal mass and a CT scan confirmed multiple mediastinal lymphadenopathies. A biopsy of pre-tracheal lymph node revealed nodular sclerosing Hodgkin's lymphoma. The patient received six cycles of chemotherapy with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) and achieved a complete remission. A follow up MRI head scan showed a decreasing in the thickness of infundibulum along with non-visualization of the posterior pituitary bright spot. Finally, his symptoms resolved with DDAVP therapy. Conclusions Diabetes insipidus involving the pituitary gland of Hodgkin's lymphoma is an extremely rare presentation of endocrine deficiency and malignancy. The literature describes only a few such cases. Clinicians should be aware diabetes insipidus might rarely present as a symptom of Hodgkin's lymphoma without obvious metastatic involvement of the neurohypophysial system. Continuing to report anecdotal experiences in managing similar complex scenarios is essential and remains the only reference for clinicians who handle patients with a similar presentation. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

A DELAYED PRESENTATION OF POSTERIOR HYPOPITUITARISM FOLLOWING TRAUMATIC BRAIN INJURY – A CASE REPORT OF A 24 YEAR OLD ASIAN FEMALE.

Background: Cases of post traumatic hypopituitarism are rarely contemplated in the Indian subcontinent. However global literatures disclose that the incidence rate of hypopituitarism following traumatic brain injury is around 15-30%. Most hospitals do not routinely screen patients for pituitary dysfunction following traumatic brain injury due to the lack of proper protocol supporting the same. Hence large number of cases with varying pituitary abnormalities is procrastinated, which could have been otherwise beneted from early interventions. This case is a classic example of delayed exhibition of posterior hypopituitarism post traumatic brain injury, which has signicantly compromised the quality of life of the patient in later stage due to the failure of timely screening. Case Presentation:This is a case of 24 year old female who sustained a traumatic brain injury 3 years ago allegedly due to domestic abuse. The patient presented to the urology department with the complaints of polyuria, polydipsia, secondary amenorrhea, sleep disturbance and weight gain for 6-7 months. The patient was not under regular follow-up for the traumatic injury. On further evaluation, all the anterior pituitary hormones were found to be normal. We further investigated the case with biochemical investigations and an MRI of brain (plain and contrast) which showed a thickened enhancing pituitary stalk with absence of posterior pituitary bright spot with a normal anterior pituitary gland – suggestive of Central Diabetes Insipidus. Upon initiation with Desmopressin, the patient showed signicant symptomatic improvement. Conclusion:One of the most common complications of traumatic brain injury is hypopituitarism. Early screening for hypopituitarism in such cases will help us intervene early and improve the quality of life of the patients.

Abstract 58: Favourable outcomes with therapeutic glucocorticoid regimen compared to replacement glucocorticoid regimen in primary hypophysitis

Background: Primary hypophysitis (PH) is most commonly treated with glucocorticoids. But there is considerable variation in the treatment regimens.Aims and Objectives: We aimed to compare the outcomes of therapeutic versus replacement glucocorticoid regimens in PH. Therapeutic regimen (TR) comprised oral prednisolone (1mg/kg/d) for 6-12 weeks followed by tapering. Replacement regimen (RR) comprised standard hydrocortisone. Response was defined as complete recovery of all pituitary axes, without any requirement of hormonal replacement.Results: Mean age of the cohort (n=30) was 37.8 ± 10.4 years with a female preponderance (79.3%). Response to glucocorticoids was present in 23.3% of the cohort, all on TR. There was no difference between responders and non-responders in terms of age, gender, duration of symptoms or follow-up (p>0.05). Headache was more frequent in responders than non-responders (100% vs 57.1%, p<0.05). Secondary hypocortisolism (100% vs 71.4%), hypothyroidism (71.4% vs 52.4%), hypogonadism (71.4% vs 42.8%), hyposomatotropism (57.1% vs 25%) and hyperprolactinemia (85.7 vs 57.1%) were more common among responders (p<0.05). Diabetes insipidus was not different (42.3% vs 38%, p=0.56). Pituitary enlargement (100% vs 76.2%) and absent posterior pituitary bright spot (PPBS) (71.4% vs 57.1%) were more frequent among responders (p<0.05). Asymmetric enlargement was more common in non-responders (23.8% vs 0, p<0.05). Stalk thickening (80.9% vs 85.7%) and T2 parasellar dark intensity (28.5% each) were not different (p>0.05). The mass regressed in 85.7% in responders and 57.1% of non-responders at a mean follow-up duration of 4.6 ± 2.7 years.Conclusion: Response in PH is optimal with TR. Multiple hormone deficiencies, hyperprolactinemia, symmetric pituitary enlargement and absent PPBS portend favourable response, whereas asymmetric pituitary enlargement is more common among non-responders.

Posterior Pituitary Bright Spot Normal Dimensions on MRI

Aim: To assess the measurements of posterior pituitary bright spot on MRI in Khyber Pakhtunkhwa Methods: The study was done in RMI, Peshawar. Duration is January, 2016 to February, 2019. 78 patients with normal pituitary MRI studies were selected for study. MRI without contrast was done along cranio caudal and antero posterior axis on sagital T1WI. Three cases of ectopic posterior pituitary were also included. Results: Dimensions were taken in antero posterior and cranio caudal axis on sagittal T1WI. Dimension of PPBS was 1.8--8.6mm in cranio caudal axis and 0.8-6mm in antero posteriorly. Mean±SD of cranio caudal measurement was 5.09±1.28mm and of antero posteriorly 2.42±0.9mm. Pearsons analysis showed direct correlation i.e. as value of cranio caudal diameter increased, the antero posteriorly also increased. Conclusion: PPBS was identified in 100% of normal pituitary glands. Mean PPBS size normally ranged from 1.8 to 8mm i.e. mean± SD was 5.09±1.28mm craniocaudally. There is a direct correlation in cranio caudal and antero posterior dimensions of PPBS. Keywords: Pituitary, Magnetic resonance imaging. Posterior pituitary bright spot

Absence of posterior pituitary bright spot in adults with CNS tuberculosis: A case-control study.

Current diagnostic methods used in Central Nervous System Tuberculosis (CNS TB) are limited by the paucibacillary nature of this form of tuberculosis. Posterior pituitary bright spot (PPBS) refers to an area of T1 hyperintensity in the posterior pituitary in MR imaging of the brain. It is found in 80-90% of healthy children and adults. In children with CNS TB, nearly half have absence of PPBS. This finding has not been described in adults. Our study looked for absence of PPBS in MR imaging and its association with CNS tuberculosis. To study prevalence of the absence of PPBS in patients with CNS tuberculosis when compared to a control group of normal patients. This was a retrospective case-control study of 100 patients with CNS tuberculosis and 200 controls (matched in 1:2 ratio) of patients with normal MRI brain. The MRI images were presented to a blinded radiologist in a randomised sequence to report for absence of PPBS. The data was subsequently analysed to look for association of absence of PPBS with CNS tuberculosis. Absence of PPBS (cases (47%), controls (8.5%)) was significantly associated with CNS tuberculosis in (Odds ratio-7.90, 95%CI 4.04-15.44, P-value<0.0001). The specificity, sensitivity, positive predictive value and positive likelihood ratio are 91.5%, 47%, 73.4% and 5.53 respectively. Adding of absence of PPBS as an additional radiological feature in diagnosis of CNS TB increased the sensitivity from 77% to 84%. Absence of PPBS is significantly associated with CNS tuberculosis and could be a relatively simple diagnostic aid in the diagnosis of CNS tuberculosis.

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.

Clinical Course and Management of Pembrolizumab-Associated Isolated Adrenocorticotrophic Hormone Deficiency: A New Case and Literature Review

Hypophysitis is rarely reportedin patients receiving pembrolizumab-only immunotherapies. Since the clinical presentation is usually as isolated adrenocorticotrophic hormone (ACTH) deficiency, patients may be misjudged as having clinical symptoms due to cancer or chemotherapy. A 49-year-old male with laryngeal cancer applied to our clinic just after the tenth cycle of his pembrolizumab treatment, with weakness andnausea/vomiting. Serum morning cortisol and ACTH were 0.47mcg/dl and 10.1pg/ml, respectively; the remaining anterior pituitary hormone levels were normal. Pituitary MRI revealed mild glandular enlargement and loss of posterior pituitary bright-spot. All symptoms and signs improved with low-dose prednisolone. This is the second reported case of pembolizumab-associated isolated ACTH deficiency having abnormal pituitary MRI findings as we have reviewed all reported cases in the literature.

Idiopathic Hypophysitis

Introduction: Hypophysitis is a heterogeneous condition that leads to inflammation of the sella / suprasellar region, potentially resulting in hormonal deficiencies or mass effects. Prevalence of hypophysitis ranges from 0.2% to 0.88%. Annual incidence of hypophysitis is 1 case per 9 million individuals. We present an interesting case of idiopathic hypophysitis. Clinical Case: A 52-year-old female was evaluated for secondary hypothyroidism. Patient complained of excess fatigue, weight gain, headaches, polyuria with nocturia and vision changes. She was seen by ophthalmology for formal visual field testing revealing right superior quadrantanopia. Labs significant for TSH 4 uIU/mL (ref range 0.27-4.2uIU/mL), FT4 0.72ng/dL (ref range 0.93-1.7 ng/dL), Anti TPO ab negative, AM cortisol 8.9UG/dL, ACTH 18pg/mL, IGF1 127ng/mL, prolactin 7ng/mL, FSH 102MIU/mL, LH 41 MIU/mL. MRI sella revealed homogenous enhancement of the pituitary with convex superior margin - 0.8*1*0.9cm concerning for hyperplasia. Due to the concern for hypophysitis, an extensive inflammatory workup was pursued which was negative. She was started on thyroid hormone replacement and DDAVP. An empiric trial of high dose steroids failed to provide any relief. During workup, patient complained of transient right sided face and arm tingling, diagnosed with TIA and started on aspirin. Due to worsening headaches, a pituitary biopsy was pursued. Pathology significant for glandular tissue ruling out inflammatory, neoplastic, and infectious etiologies. Neurology diagnosed the patient with hemicrania continua. Patient is currently maintained on thyroid hormone replacement and DDAVP with close follow-up. Discussion: The incidence of hypophysitis has recently increased due to increased awareness and also due to the use of medications like ICI. Primary hypophysitis is mostly due to autoimmune etiology. Secondary hypophysitis could result from infections, neoplastic conditions or an adverse effect of medications. Clinical presentations ranges from being asymptomatic to having features of hypopituitarism. Usually presents with mass effect, visual symptoms due to the upward expansion of the pituitary gland impinging the dura mater and optic chiasm. This is followed by symptoms of hormone deficiency, central DI and hyperprolactinemia. Central AI has been reported in 20%-75%, central hypogonadism in 15%-60%, central hypothyroidism in 25%-58%, GH deficiency in 5%-41%, and prolactin deficiency in 13%-25%. Typical MRI findings include, homogeneous pituitary contrast enhancement, pituitary stalk thickening and loss of posterior pituitary bright spot, ‘figure of 8’ appearance, ‘dural tail’. Treatment consists of surgery, anti-inflammatory medications, and radiotherapy. Glucocorticoid treatment is the cornerstone for medical management; however, the overall recurrence rate is high.

Magnetic resonance imaging characteristics of residual pituitary tissues following transsphenoidal resection of pituitary macroadenomas.

The present study is to investigate the pre- and post-operative magnetic resonance imaging of pituitary tissues following transsphenoidal resection of pituitary macroadenomas, as well as its clinical significance. The medical records of 108 consecutive pituitary macroadenoma patients admitted at Fuzhou 900th Hospital between September 2012 and September 2014 were retrospectively reviewed. Siemens 3. 0T magnetic resonance scanner was used to perform pre- and postoperative MRI scanning, including plain scan and contrast-enhanced scan of SE sequential T1WI and T2WI in sagittal, coronal and axial views. PACS medical imaging system was used to measure the diameter of pituitary adenoma, as well as the volumes of the adenoma and pituitary tissue. Hematoxylin-eosin staining and immunohistochemical staining were also performed. Higher height of pituitary adenoma results in lower rate of posterior pituitary bright spot (PPBS) on MR T1-weighted imaging. Preoperative MR signal intensity of PPBS was negatively related to diabetes insipidus (DI). Normal pituitary tissues were likely to be above the pituitary adenomas in growth hormone-secreting adenoma patients, while mostly located aside in gonadotropin-secreting adenoma patients. Morphological restitution of postoperative pituitary tissues was better in lateral displacement than that in superior or superolateral patterns on pre-operative MR images. Positive rate of PPBS on preoperative MRI is negatively related to adenoma height, and the signal intensity of PPBS is inversely related to postoperative DI. The relative locations of pituitary tissues and adenoma tissues may be associated with the adenoma type and may affect the postoperative remodeling of residual pituitary tissues.

Longitudinal Assessment of Neuroradiologic Features in Wolfram Syndrome.

Wolfram syndrome is a rare genetic disease with characteristic brain involvement. We reviewed the brain MR images of patients with Wolfram syndrome to determine the frequency and characteristics of common neuroradiologic findings. We retrospectively reviewed the imaging data of patients with genetically-confirmed Wolfram syndrome who had been recruited to the Washington University Wolfram Syndrome Research Clinic. These patients were evaluated between 2010 and 2019 with annual MRIs, along with other measures. MR images were assessed for clinical neuroradiologic signs at each individual's first and last follow-up visits to characterize the frequency, rate of progression, and clinical correlations of these signs. We included 30 patients (13 males/17 females; average age at first visit, 14 years; average age at last visit, 19 years). The median duration of follow-up was 5 years (range, 2-9 years). The most common findings were an absent or diminished posterior pituitary bright spot (first, 53%; last, 70%), T1/T2 pons signal abnormalities (first, 53%; last, 67%), optic nerve atrophy (first, 30%; last, 80%), white matter T2 hyperintensities (first, 27%; last, 35%), and cerebellar atrophy (first, 23%; last, 70%). Patients with Wolfram syndrome present characteristic neuroradiologic findings that involve the posterior pituitary gland, optic nerves, white matter, brain stem, and cerebellum. These abnormal findings appear at an early age and tend to increase in frequency with time. However, the neurologic significance and neuropathologic mechanisms of each sign require more investigation. Neuroradiologists should be aware of the pattern of these features in Wolfram syndrome.

MON-078 WFS1 Related Disorder in A 4-Month Old Girl

Background: Idiopathic early-onset central diabetes insipidus (CDI) may be due to mutations of arginine vasopressin-neurophysin II (AVP-NPII (AVP)) or wolframin (WFS1/2) genes (1). Clinical Case: A 4-month old girl presented to our pediatric endocrinology clinic due to severe polydipsia-polyphagia and polyuria. Plasma and urine glucose and HbA1c were normal and 24h monitoring of urinary output was elevated (4.2ml/kg/h). We proceeded to a modified 5-h water deprivation test followed by 0.1 mcg DDAVP IM. Results were compatible with partial central DI: at 5-hrs weight loss 5%, urine osmolality 155 from 111 at 0΄and 355 mOsm/kg 2hrs after DDAVP administration.Pituitary MRI was normal with presence of posterior pituitary bright spot and normal pituitary stalk.We initiated therapy with oral desmopressin acetate titrated at the dose of 70mcg x 3/day under close clinical and biochemical surveillance. Hyponatremia, with high natriuresis >100 mmol/L and elevated BNP occurred the 3rd day. Fludrocortisone 100 mcg x 2/day controlled natriuresis and supplemental oral NaCl 15% 15ml/day was needed to restore normal electrolytes (2).Marked catch-up growth was observed already at 1 month for height, weight and head circumference. Methods: Whole exome sequencing was performed targeted to a gene panel related to DI, containing AVP gene, WFS1/2 genes and AVPR2/AQP2 genes. Result: Two heterozygous variants were revealed: WFS1:NM_001145853:exon8:c. G997A:p.V333I,WFS1:NM_006005:exon8:c.G997A:p.V333I and WFS1:NM_00114585 3:exon8:c.G1832A:p.R611H,WFS1:NM_006005:exon8:c.G1832A:p.R611H reported as possibly damaging in 1/6 and 4/6 prediction programs respectively. These variants will be checked in both parents to confirm the presumed compound heterozygosity pattern in the child. Conclusion: We present a 4-month old girl with two heterozygous variants of WFS1 gene which may cause early-onset central diabetes insipidus and possibly a WFS1 related disorder (1).Reference:(1) Perrotta S et al. Early-onset central diabetes insipidus is associated with de novo arginine vasopressin-neurophysin II or Wolfram syndrome 1 gene mutations. Eur J Endocrinol. 2015 Apr;172(4):461-72(2) Papadimitriou DT, Spiteri A, Attilakos A, Papadimitriou A. Cerebral Salt Wasting Complicated by Central Diabetes Insipidus and Growth Hormone Deficiency. Indian J Pediatr. 2018 Jul;85(7):580-581

Posterior Pituitary Bright Spot – A Study in Coastal Karnataka

Posterior Pituitary Bright Spot – A Study in Coastal Karnataka

Clinical Characteristics of Pediatric Patients With Sellar and Suprasellar Lesions Who Initially Present With Central Diabetes Insipidus: A Retrospective Study of 55 Cases From a Large Pituitary Center in China.

Purpose: To increase knowledge for the early differential diagnosis and accurate therapeutic strategies for pediatric patients with sellar or suprasellar region (SSR) lesions who initially present with central diabetes insipidus (CDI).Methods: This is a retrospective review of 55 pediatric patients (≤14 years old) with identified lesions in the SSR who initially presented with CDI at a large pituitary center between 2012 and 2018. The following data were summarized: demographic, clinical, endocrine, and neuroimaging data, intraoperative findings, histopathological findings, treatments, and prognosis.Results: In our group, the etiologies of the SSR lesions included germ cell tumors (GCTs, 74.5%), Langerhans cell histiocytosis (LCH, 18.2%), and craniopharyngioma (CP, 7.3%). Almost all patients (50/55, 90.9%) showed anterior pituitary dysfunction [multiple axes dysfunction (38), and isolated axis dysfunction (14)], while the GH/IGF-I axis was the most affected. Most GCT patients presented with various clinical manifestations besides CDI and had elevated β-HCG, whereas LCH and CP patients mostly presented few non-specific symptoms besides CDI and most had normal level tumor markers. Sellar MRI demonstrated that posterior pituitary bright spot disappearance occurred in all patients, and pituitary stalk thickening was observed in 96.7% of patients. Treatment varied due to the different etiologies of the SSR lesions. After follow-up for 35.4 ± 20.2 months, the proportions of patients who needed AVP (arginine vasopressin) for GCT, LCH, and CP were 86.5, 100, and 75%, respectively, and the proportions of patients who needed HRT were 89.2, 50, and 75%, respectively.Conclusion: For pediatric SSR lesions that first manifest as CDI, we should comprehensively consider clinical characteristics and imaging features to aid in their early differential diagnosis. Tumor markers and surgical histopathology are also great complements for the differential diagnosis. Additionally, various treatment strategies should be adopted according to different causes to improve the child's prognosis and quality of life.