Pituitary Bright Spot Research Articles

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.

Interesting and Rare Case of Central Diabetes Insipidus in a Patient With Acute Myeloid Leukemia

Introduction: Central Diabetes Insipidus (CDI) is the lack of antidiuretic hormone (ADH) leading to impaired urinary concentration and manifests with extreme thirst and excessive urination. Patients unable to drink fluids are at risk of severe dehydration and hypernatremia. CDI can be a rare complication of acute myeloid leukemia (AML). The occurrence of AML with CDI is extremely rare with only few case reports published. This combination of AML with CDI has been reported to be associated with monosomy 7 and inversion (3) (q21q26) and portends an overall a very poor treatment response resulting in poor outcomes.Case Presentation: 66-year-old female with hypertension, polycythemia vera diagnosed in 2006 with transformation to AML in 2020. FISH studies revealed monosomy 7. Cytogenetic studies showed inv (3)(q21q26.2). Remission induction chemotherapy was initiated. Subsequently, neutropenic fever and sepsis secondary to Clostridium difficile colitis lead to hospitalization. Her sodium (Na) level gradually trended up and reached a peak of 157 mmol/l (range 136-145) and elevated serum osmolality at 311 mOsm/K with low urine osmolality 135 mOsm/K, low urine sodium at 13 and low urine specific gravity 1.006 concerning for CDI. She developed polyuria and received desmopressin (DDAVP) leading to improvements in urine osmolality to 267 mOsm/K, 30 minutes indicating CDI diagnosis. Her Na gradually normalized to 144 mmol/l, urine osmolality improved to 580 mOsm/K and urine specific gravity to 1.025. She is now on DDAVP 0.05 mg oral twice daily and her Na is in normal range. MRI pituitary did not show any evidence of metastatic lesion with intact pituitary bright spot. Her other pituitary hormonal workup was normal except for hypogonadotropic hypogonadism.Discussion: The pathophysiology of AML and CDI is unclear. Leukemic cells infiltration of the neurohypophysis; thrombosis of small vessels in hypothalamic nuclei and the posterior pituitary; alterations of the neutrophil migration placed on the chromosome 7 leading to glycoprotein gp 130 production, a cell surface marker on granulocytes are some of hypothesis suggested. CDI has a variable onset in the course of myeloid malignancies. MRI pituitary can be normal in most of the cases.

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.

SAT-243 Lymphocytic Hypophysitis Mimicking Pituitary Apoplexy in a 27-Year-Old Woman

Introduction:Lymphocytic hypophysitis is an uncommon inflammatory disorder of the pituitary gland. Peripartum women are most often affected, but it can be seen in a wide range of patients. Patients can present with pituitary dysfunction or mass effect symptoms, making it difficult to differentiate from a pituitary adenoma. Pituitary apoplexy is an acute syndrome due to hemorrhage into the pituitary gland causing headache, visual deficits, and hypoadrenalism. We present a case of a woman with a pituitary mass presenting with symptoms mimicking pituitary apoplexy, in whom surgical pathology later revealed lymphocytic hypophysitis without evidence of hemorrhage.Clinical Case:A 27-year-old non-pregnant female presented with severe headaches, nausea, vomiting, and diplopia for four days. A presumed pituitary macroadenoma was diagnosed two years previously during a workup for irregular menses. An emergency evaluation with a CT angiogram of the head showed enhancement at the superior aspect of and surrounding the pituitary gland. MRI of the pituitary revealed an enhancing 17 x 17 mm sellar and suprasellar mass compressing the optic chiasm, without evidence of the normal pituitary posterior bright spot. Visual field testing was normal. She was referred for transsphenoidal resection of the pituitary mass due to persistent headaches, optic chiasm impingement, and suspicion of pituitary apoplexy. Intraoperatively, there was no evidence of hemorrhage. Central diabetes insipidus and hypothyroidism developed in the post-operative period. She was discharged on hydrocortisone replacement therapy (20 mg in the morning, 10 mg in the afternoon). An outpatient random cortisol level of 1.2 mcg/dL (reference: 6.7 - 22.6 mcg/dL) while off hydrocortisone for twenty-four hours confirmed hypocortisolism. Surgical pathology showed moderate lymphocytic infiltrate and focal germinal centers in the adenohypophysis consistent with lymphocytic hypophysitis.Conclusion:Although lymphocytic hypophysitis is well-described in the literature, its association with symptoms suggesting pituitary apoplexy has been reported only rarely. This atypical case shows that lymphocytic hypophysitis can present with acute symptoms mimicking pituitary apoplexy. The case highlights the difficulties in recognizing lymphocytic hypophysitis prior to surgery and emphasizes the need to consider the diagnosis in patients presenting with pituitary masses and/or symptoms of pituitary apoplexy.

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.

Isolated ACTH deficiency during single-agent pembrolizumab for squamous cell lung carcinoma: a case report

BackgroundThe programmed cell death 1 (PD-1) inhibitor pembrolizumab is a promising agent for treatment of several different malignancies, but as with all immunotherapy there is a potential risk of immune-related adverse events. Adrenocorticotropic hormone (ACTH) deficiency and hypophysitis have been reported in patients treated with a different PD-1 inhibitor, nivolumab. However, clinical characteristics of these side effects associated with pembrolizumab have yet to be described in detail.Case presentationAn 85-year-old Japanese woman was diagnosed with advanced squamous cell lung cancer. The patient was treated with 200 mg pembrolizumab every three weeks as first-line therapy. Routine examination including thyroid function, complete blood count, serum cortisol and sodium levels before each pembrolizumab infusion had shown no significant changes up to the eighth cycle. However, 8 days after the eighth cycle of single-agent pembrolizumab, she presented with rapidly worsening general fatigue and appetite loss over two days. Laboratory data revealed a low serum cortisol level (0.92 μg/dL) with inappropriately low ACTH (8.3 pg/mL), hyponatremia (122 mmol/L) and hypoglycemia (68 mg/dL). Standard-dose short ACTH testing showed an unsatisfactory cortisol response, indicating adrenal insufficiency. Pituitary magnetic resonance imaging showed diffuse substantial gadolinium enhancement, T2 hyperintensity, loss of pituitary bright spot, but no pituitary enlargement. Serum cortisol and ACTH levels were low throughout the day, and urinary free cortisol excretion fell below the lower normal limit. There was no ACTH and cortisol response in the corticotropin-releasing hormone test, despite significant responses of other anterior pituitary hormones to their corresponding challenge tests. Thus, isolated ACTH deficiency was diagnosed, and hypophysitis was suspected as the etiology. After administration of 15 mg/day hydrocortisone, the patient’s debilitation, hyponatremia, and hypoglycemia swiftly disappeared.ConclusionThis is a case of isolated ACTH deficiency possibly due to hypophysitis in a patient with advanced lung cancer, in whom recent routine examinations had shown unremarkable results. We therefore conclude that isolated ACTH deficiency can suddenly arise during pembrolizumab monotherapy, albeit probably only rarely. Caution should be exercised to make sure that adrenal insufficiency is recognized immediately in order to achieve swift recovery by steroid replacement.

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.

MRI and pathological features of Rathke cleft cysts in the sellar region.

The aim of the present study was to investigate the MRI and pathological features of Rathke cleft cysts (RCC) in the sellar region. A total of 45 RCC cases were retrospectively analyzed. RCC size, location, intracyst nodules and general signals, as well as the posterior pituitary bright spot (PPBS) were analyzed using MRI-T1 weighted images (T1WI) and T2WI. The relationship between the presence of PPBS and histopathological features was additionally evaluated. On T1WI, there were 18 cases of isointense signal, 16 cases of hyperintense signal, 9 cases of hypointense signal, 1 case of heterogeneous signal and 1 case with a stratification effect, with isointense signal in the upper part and hyperintense signal in the lower part. On T2WI, there were 5 cases of isointense signal, 27 cases of hyperintense signal, 11 cases of hypointense signal and 1 case of the stratification effect. There were 10 cases of PPBS+ and 35 cases of PPBS-. There were no significant differences in the age, sex, cyst location and size between PPBS+ and PPBS- cases. However, PPBS+ cases had significantly lower inflammation than PPBS- cases. A total of 20 cases of intracystic nodules were identified on MRI scans, most of which exhibited T2 -hypointense signals. The shape of RCC nodules varied and there were 17 cases where the nodules were non-adherent to the cyst wall. The MRI signals of RCCs varied and most nodules were floating within cysts. Intracystic nodules are characteristic features of RCCs when observed by MRI and thus are of high diagnostic value. Most patients with RCC were also PPBS-, which may be associated with an increased inflammatory response.

Diabetes insipidus and panhypopituitarism as a first presentation of silent adenocarcinoma of lung: a case report and literature review

BackgroundPituitary metastasis is a rare condition with a poor prognosis. Very few patients with pituitary metastasis are symptomatic. It is often associated with presence of co-existing metastases to other organs. Isolated pituitary metastasis as the first presentation of primary malignancy is uncommon.Case presentationA 72-year-old woman presented with a 2-month history of polyuria, increasing thirst and unexplained weight loss. Esophagogastroduodenoscopy (EGD) was scheduled as part of the investigation. She was kept nil per os for 10 h prior to EGD, after which she developed alteration of consciousness. Further investigation revealed hypernatremia with sodium level of 161 mmol/L and low urine osmolality of 62 mOsm/kg. Her urine output was 300 mL per hour. Diabetes insipidus (DI) was diagnosed based on evidence of polyuria, hypernatremia, and low urine osmolality. Her urine output decreased and urine osmolality increased to 570 mOsm/kg in response to subcutaneous desmopressin acetate, confirming central DI. Pituitary magnetic resonance imaging showed a heterogeneous gadolinium enhancing lesion at the sellar and suprasellar regions, measuring 2.4 × 2.6 × 3.9 cm compressing both the hypothalamus bilaterally and the inferior aspect of optic chiasm as well as displacing the residual pituitary gland anteriorly. The posterior pituitary bright spot was absent. These MRI findings suggested pituitary macroadenoma. There were also multiple small gadolinium-enhancing lesions up to 0.7 cm in size with adjacent vasogenic brain edema at the subcortical and subpial regions of the left frontal and parietal areas, raising the concern of brain metastases. Pituitary hormonal evaluation was consistent with panhypopituitarism. Histopathological and immunohistochemical studies of the pituitary tissue revealed an adenocarcinoma, originating from the lung. Computed tomography of the chest and abdomen was subsequently performed, showing a 2.2-cm soft tissue mass at the proximal part of right bronchus. There was no evidence of distant metastases elsewhere. The final diagnosis was adenocarcinoma of the lung with pituitary metastasis manifesting as panhypopituitarism and central DI. Palliative care along with hormonal replacement therapy was offered to the patient. She died 4 months after diagnosis.ConclusionDiagnosis of pituitary metastasis is challenging, especially in patients with previously undiagnosed primary cancer. It should be considered in the elderly patients presenting with new-onset central DI with or without anterior pituitary dysfunction.

SUN-403 Drinking Water from a Dirty Prison Sink: A Rare Case of Acute Myeloid Leukemia with Diabetes Insipidus and Panhypopituitarism

Panhypopituitarism is an extremely rare disorder in acute myeloid leukemia (AML) with only 6 cases previously reported to date. The mechanism of AML causing panhypopituitarism is unclear, but some of the leading hypotheses support leukemic infiltration or leukostasis. A 30-year-old incarcerated woman with a history of intravenous drug use and hepatitis C presented with 5 days of fevers, vomiting, and progressive abdominal pain. She reported an unintentional 30 lb weight loss and a month of polyuria and polydipsia severe enough to cause her to drink water from the dirty sink in her prison cell. Patient denied headache, visual disturbance, or galactorrhea. Initial laboratory studies showed a white blood cell count of 350K with 90% myeloblasts, consistent with AML. She received emergent leukocytapheresis and was started on cytarabine and daunorubicin chemotherapy. Upon admission, she was also noted to have hypernatremia (Na 152 mmol/L), persistent hypotension (BP 80s/40s) unresponsive to fluid resuscitation, and high urine output of 5-14 L/day. Desmopressin (DDAVP) 4 mcg IV was administered and resulted in increased urine osmolality from 116 to 451 mOsm/L with significant decrease in urine output, consistent with central diabetes insipidus (cDI). Brain MRI showed heterogeneous thickening of the infundibulum and an absence of the posterior pituitary T1 bright spot, which can be seen in cDI. Hormonal evaluation revealed low free T4 0.77 ng/dL (ref. 0.93-1.70) and normal TSH 4.03 mIU/mL (ref. 0.27-4.20), consistent with central hypothyroidism. Prolactin was mildly elevated at 39 ng/mL (ref. 4.8-23.3). She was also noted to have low AM cortisol 3 µg/dL (ref. 5-20) prompting a cosyntropin stimulation test which showed baseline cortisol of 5.9 rising to 13.2 µg/dL, which is an inadequate response. She was treated for panhypopituitarism with hydrocortisone 50 mg IV Q8H tapered gradually to a replacement dose, DDAVP 50 mcg PO QHS, and levothyroxine 50 mcg PO daily. Her remaining hospital course was complicated by neutropenic fever. She was ultimately transferred to Massachusetts General Hospital on hospital day 19 (Day 16 of chemotherapy) to be closer to her family. This is a rare case report of a young patient with new diagnosis of AML presenting with both cDI and panhypopituitarism. The mechanism remains unclear. One possible rationale is pituitary stalk involvement by leukemic infiltration which is evidenced by a thickening appearance on MRI. Another explanation is an ischemic or thrombotic effect related to hyperleukocytosis. The resulting hyperviscosity and subsequent disruption of hypophyseal portal capillary flow can impede release of hypothalamic hormones destined for the pituitary. Our patient had MRI findings of an abnormally thickened stalk and lack of “bright spot” which supports the hypothesis of leukemic infiltration and significant disruption of the hypothalamic-pituitary axes.

MON-421 A Case of Central Diabetes Insipidus in a Patient with Myxopapillary Ependymoma and GFAP Paraneoplastic Autoimmune Meningoencephalomyelitis

Background: Glial fibrillary acidic protein (GFAP) specific IgG autoantibody has been identified as a potential biomarker of immunotherapy responsive, sometimes paraneoplastic autoimmune meningoencephalomyelitis. We present one of the first cases of central diabetes insipidus (DI) in a patient with myxopapillary ependymoma and related GFAP paraneoplastic autoimmune meningoencephalomyelitis. Clinical case: A 23 year old female presented with progressive left facial and right sided weakness, extremity parasthesias, diplopia and word finding difficulty over four months. MRI brain showed 3cm left frontal periventricular white matter lesion. Stereotatic brain biopsy revealed a demyelinating process. She was found to be GFAP IgG positive concerning for GFAP astrocytopathy and glucocorticoid treatment was initiated. Four months later, she developed new polydipsia (22L water/day) and polyuria with elevated sodium 151mmol/L, serum osmolality 329 mOsm/kg (normal range 285-310), low urine osmolality 122 mOsm/kg (normal range 300-900), dilute urine specific gravity 1.003 and documented urine output greater than 4L/24hrs. Clinical presentation was consistent with central DI as the patient had an appropriate response to DDAVP administration. MRI pituitary revealed absence of the posterior pituitary bright spot with increased fullness of the posterior aspect of the pituitary gland and prior evidence of pituitary stalk thickening, suggestive of lymphocytic infundibuloneurohypophysitis. Baseline anterior pituitary function remained intact. MRI spine obtained one month later for acute worsening lower extremity weakness, urinary retention and incontinence noted diffuse leptomeningeal enhancement, nodularity and an irregular L2/L3 mass-like lesion. Biopsy confirmed a WHO grade I myxopapillary ependymoma and chemotherapy was initiated. Conclusion: While the underlying etiologies can be identified in approximately 50-70% of central DI cases, the remaining are deemed idiopathic with speculation that autoimmunity involving autoantibodies may be involved. Lymphocytic infundibuloneurohypophysitis has been linked to central DI in several case reports, albeit few. Interestingly, although various autoimmune endocrinopathies have been noted in cases of GFAP autoimmune meningoencephalomyelitis, to our knowledge, this is the first case report of associated central DI.

MON-511 Erdheim-Chester Disease: A Challenging Diagnosis in a Patient with Ataxia, Osteosclerotic Bone Lesions, and a Long-Standing History of Central Diabetes Insipidus

Background: Erdheim- Chester Disease (ECD) is a rare hematopoietic neoplasm characterized by multi-organ infiltration with CD-68 -positive, CD1a-/S100-negative foamy histiocytes causing xantho-granulomatous inflammation. ECD most commonly involves the skeleton. CNS, pulmonary and CV involvement are also reported. Clinical Case: A 47-year-old male with a prior history of central Diabetes Insipidus (DI) presented with bone pain and ataxia. He was initially referred in 1993 for evaluation of DI. It was concluded that he had lymphocytic infundibulitis (LI), based on the finding of a thickened pituitary stalk on MRI while CSF revealed no evidence of infection or neoplasm. His DI was controlled with DDAVP. He had no other anterior pituitary hormone deficiencies. Although subsequent MRI showed resolution of the pituitary stalk thickening, his DI persisted. In 2012, he developed progressive gait instability, slurred speech and impaired motor coordination. On exam, he exhibited horizontal nystagmus, dysarthria, and truncal ataxia greater than limb ataxia. A brain MRI revealed absence of the posterior pituitary bright spot, enhancement along the proximal 7th and 8th nerve complex, disproportionate cerebellar atrophy and enhancement along the bilateral cerebellar folia. He complained of progressive, chronic leg pain since 2005. In 2018, he underwent tibial bone biopsy for an osteosclerotic lesion with diagnosis of Paget’s disease (PD). His Ca, Phos, 25OH- D, PTH, and Alk Phos were normal. Subsequent X-rays noted lesions of the pedicle of the left shoulder and pelvis, medullary sclerosis in the humeral diaphysis, and symmetrical lesions in the distal femur and tibia, bilaterally. Bone scan and FDG-Pet scan showed increased activity in the lesions. A repeat tibial biopsy revealed the marrow was infiltrated with histiocytes, fibrosis and sclerosis of trabecular bone. The histiocytes were highlighted by CD163, CD68, CD14, factor XIIIa and fascin A few scattered histiocytes were BRAF V600E immuno-stain positive, consistent with a diagnosis of ECD. His symptoms improved on Vemurafenib. Conclusion: We report a male with ECD who initially presented with isolated DI and a clinical course that mimicked LI. DI is a feature that occurs early in the disease process in 25% of patients. More than 10 years later, he developed ataxia and multifocal osteosclerotic bone lesions. His bone lesions were misdiagnosed as PD, but a repeat bone biopsy led to the correct diagnosis. In contrast to PD, the bone lesions in ECD are bilateral and symmetric and affect the diaphysis of long bones, specifically. As in our case, some patients with ECD can be asymptomatic for decades. For symptomatic patients who are BRAFV600E +, the B-Raf enzyme inhibitor, Vemurafenib, is recommended. His diagnosis was challenging, because ECD is rare (500 cases) and has features that overlap with other more common medical conditions.

SUN-404 Diabetes Insipidus and Hypopituitarism in a Patient with Transient Isolated Pituitary Stalk Enlargement

Background. The differential diagnosis of pituitary stalk lesions is broad and includes neoplastic, inflammatory, infectious, and congenital disorders. Lymphocytic infundibuloneurohypophysitis (LIN) has been identified as an etiology of transient pituitary stalk enlargement leading to permanent central diabetes insipidus (DI). We present a case of transient isolated pituitary stalk enlargement complicated by both central DI and hypopituitarism. Case. A 65-year-old male presented to hospital with polyuria, polydipsia, nausea and vomiting, and a 20 lb. unintentional weight loss over three weeks. Hypernatremia (149 mM, 133-142) and inappropriately dilute urine (180 mOsm/kg) were noted on admission. Treatment with desmopressin resulted in prompt resolution of polyuria and hypertonicity. MRI was notable for nodular thickening of the pituitary stalk and loss of the posterior pituitary bright spot on T-1 weighted images, and lumbar puncture yielded clear fluid with mild lymphocytic pleocytosis, no malignant cells, and unremarkable angiotensin converting enzyme level. Evaluation of anterior pituitary function revealed secondary adrenal insufficiency, secondary hypothyroidism, secondary hypogonadism, impaired somatotroph function, and mild hyperprolactinemia (16.2 ng/mL, 3.6-13.2). The patient recovered to baseline weight and well-being on treatment with hydrocortisone, thyroxine, and intramuscular testosterone. He declined biopsy in favor of serial imaging of the pituitary stalk. Over the course of 18 months, radiographic changes in the pituitary stalk resolved, though DI and anterior pituitary deficits persist. Conclusion. Radiographic lesions confined to the pituitary stalk present a significant diagnostic challenge because biopsies are difficult and potentially injurious to patients. Diagnosis is based mostly on clinical evaluation and imaging. Epidemiological data are sparse; out of 150,045 head MRI studies at Mayo Clinic from 1987-2006, 2,700 were reviewed due to mention of “pituitary stalk” or “infundibulum” and 152 were found to have a pituitary stalk abnormality. LIN has been demonstrated on biopsy in patients with central DI and reversible pituitary stalk enlargement. In a series of 17 adult patients with LIN, central DI was persistent despite improvement in pituitary stalk abnormalities, but anterior pituitary function was preserved. A more recent series of nine children with central DI and apparent LIN followed for a mean of five years found six patients with resolution of pituitary stalk abnormalities; central DI persisted in all patients, and only one experienced loss of anterior pituitary function. Though unusual, this case illustrates that LIN may be complicated by permanent hypopituitarism in addition to central DI, possibly by injury from undetectable extension of pituitary stalk inflammation to the pituitary gland or hypothalamus.

SUN-406 Complete Recovery of Central Diabetes Insipidus Associated with Isolated Stalk Thickening in a Neurosarcoidosis Patient

Background: Neurosarcoidosis (NS) affects ~15% of patients with sarcoidosis. Hypothalamic-pituitary (HP) involvement is even rare and occurs in <1% of sarcoidosis. Clinically, NS presents as neuroendocrine dysfunction in 2.5% and radiologically, it typically manifests as HP lesion with parenchymal disease. The literature review demonstrates increased pituitary volume as the most frequent MRI abnormality observed in more than a half patients with HP involvement. Pituitary stalk thickening (PST) has been reported in combination with parenchymal abnormality but not in isolation. Central diabetes insipidus (CDI) is a known manifestation of stalk involvement. The exact mechanism of anti-diuretic hormone (ADH) dysfunction is not well understood, however CDI is mostly attributed to defective ADH release with direct infiltration of the stalk. Hormonal deficiencies are considered to be irreversible even in the setting of normalization of MRI findings after treatment. We herein report a case of NS associated with isolated PST presenting as CDI, where complete recovery was observed. Case: A 54-year-old male with pulmonary and gastrointestional (GI) sarcoidosis confirmed by gastric biopsy, developed abrupt onset of polyuria-polydipsia [Intake: 11-12 L/d, Output: 8-10 L/d] while treated with prednisone 5 mg/d. Urine osmolality (osm) was 64 mosm/kg, urine sodium (Na) 10 meq/l, serum osm 292 mosm/kg and serum Na 143 mmol/l. MRI of the Sella revealed 3.5 mm PST, absent posterior pituitary bright spot and partial empty sella. Anterior pituitary evaluation showed: Testosterone 122ng/dl, FSH 9.8mIU/ml, LH 3.3mIU/ml, Prolactin 17.8ng/ml, TSH 1.07 mcIU/ml, FT4; 0.7ng/dl, Cortisol 11.3mcg/dl, ACTH 12pg/ml and IGF-1; 129ng/ml. DDAVP 0.2mg bid controlled DI well. GI symptoms were treated with increased prednisone 40 mg/d and hydroxychloroquine. MRI showed decreased PST at 2.6 mm in 1 year and normal stalk thickness 1.8 mm in 2 years. He was successfully weaned off DDAVP, along with a slow taper of steroid. Four years since presentation, symptoms are well controlled on prednisone 3mg/d. Testosterone improved (213 ng/dl) and other anterior pituitary hormones remained in normal range. He has no polyuria, stalk measures 1.9 mm and posterior pituitary bright spot is absent. Conclusion: This case demonstrates a rare manifestation of NS presenting with isolated PST associated with CDI, without parenchymal disease. Furthermore, this is the first case report of complete resolution of CDI that correlated with normalization of MRI finding. In general hormonal deficits with HP sarcoidosis is considered irreversible and no correlation has been reported between the hormonal dysfunction and radiologic outcomes. Hence, in similar patients with isolated PST as the only manifestation of NS a trial off DDAVP may be offered, if improvement in MRI finding is noted over the course of the treatment.

The Relationship Between Posterior Pituitary Bright Spot on Magnetic Resonance Imaging (MRI) and Postoperative Diabetes Insipidus for Pituitary Adenoma Patients.

BackgroundThis study is to investigate the predictive value of posterior pituitary bright spot (PPBS) on magnetic resonance imaging (MRI) for postoperative diabetes insipidus (DI) in patients with pituitary adenoma.Material/MethodsThis was a retrospective study. In total, 65 patients with pituitary adenoma who underwent transsphenoidal surgery were enrolled. Before surgery, all patients had MRI examinations. The length of pituitary stalk and position of PPBS in T1WI sagittal and coronal sections were analyzed. The volume and height of the tumor was calculated in enhanced T1WI. Urine volume was monitored to analyze the clinical factors contributing to DI.ResultsAmong the 65 cases of pituitary adenoma, there were 54 cases of positive PPBS and 11 cases of negative PPBS. There were 32 cases of transient DI, and among these, 22 cases were positive PPBS and 10 cases were negative PPBS. However, there were 33 cases without DI, and among these, 32 cases were positive PPBS and one case was negative PPBS. The negative PPBS was significantly higher in cases with DI, compared with positive PPBS (P<0.05). Logistic regression showed that preoperative negative PPBS was an important predictor for postoperative DI (P<0.05).ConclusionsPostoperative DI should be considered when there is negative preoperative PPBS on MRI. Also, severe pituitary stalk compression indicates higher risk of postoperative DI.

Presence of the posterior pituitary bright spot sign on MRI in the general population: a comparison between 1.5 and 3TMRI and between 2D-T1 spin-echo- and 3D-T1 gradient-echo sequences.

To describe the prevalence of the posterior pituitary bright spot (PPBS) in the general population on 1.5 and 3T MRI examinations and on 2D-T1 spin-echo (SE) and 3D-T1 gradient-echo (GE) sequences. 1017 subjects who received an MRI of the brain for aspecific neurological complaints were included. MRI was performed on 1.5T in 64.5% and on 3T in 35.5% of subjects. Presence of the PPBS was evaluated on sagittal 2D T1-SE echo images with slice thickness 3mm in 67.5% and on sagittal 3D T1-GE with slice thickness 0.9mm in 32.5% of subjects. The PPBS was detectable in 95.9% of subjects. After correction for sex and age, no statistically significant difference could be seen concerning PPBS detection between 1.5 and 3T MRI examinations (p = 0.533), nor between 2D T1-SE and 3D T1-GE sequences (p = 0.217). There was a statistically significant association between increasing age and the absence of the PPBS (p < 0.001). The PPBS could not be identified in 6.2% of male subjects, compared to 2.2% of female subjects (p = 0.01). Absence of the PPBS can be seen in 4.1% of patients undergoing MRI of the brain for non-endocrinological reasons. Neither field-strength nor the use of a thick-sliced 2D T1-SE versus a thin-sliced 3D T1-GE sequence influenced the detectability of the PPBS. There is a statistically significant association between increasing age and male sex and the absence of the PPBS.