Central Diabetes Insipidus Research Articles

A Case Report of Intracranial Germ Cell Tumor-Induced Central Diabetes Insipidus in a Child Treated with Korean Herbal Medicine

Objective: The purpose of this study is to report the case of intracranial germ cell tumor-induced central diabetes insipidus (CDI) in a child treated with Korean herbal medicine.Methods: A nine-year-old female patient diagnosed with intracranial germ cell tumor-induced CDI suffering from polyuria, polydipsia, and headache was hospitalized. Nocturia frequency and 24-hour urine volume were assessed.Results: The patient was treated with Korean medicine, including <i>Nokyong-hwan</i>. As a result of the 6-day inpatient treatment, nocturia frequency was decreased 3-4 times to 0-1 time, and 24-hour urine volume was decreased.Conclusion: Korean medicine, including <i>Nokyong-hwan</i>, may be considered an optional treatment for releasing the symptoms of intracranial germ cell tumor-induced CDI. Further studies are needed to confirm this finding.

FRI350 Prolonged Transient Central Diabetes Insipidus Induced By Traumatic Brain Injury

Abstract Disclosure: R. Marques: None. S. Sharma: None. B.S. Flores Chang: None. A. Sajan: None. Introduction: Central diabetes insipidus (CDI) is a rare complication of traumatic brain injury (TBI). Most cases of CDI due to TBI are transient and resolve within 2-5 days. We report a patient with prolonged transient CDI which lasted for 35 days after sustaining a gunshot wound to the head. Case Description: A 17-year-old male with no past medical history presented after gunshot wound in the head. He had comminuted fractures of the right temporal bone, right zygomatic arch, greater and lesser rings of sphenoid bone, right maxillary sinus, right medial orbital wall, right orbital floor and bilateral frontal sinuses. A computerized tomography of head showed subarachnoid haemorrhage of the frontal lobes as well as subdural haemorrhage of right parietal lobe, right falx cerebri and left cerebral hemisphere. On hospital day 2, he had an intracranial pressure monitor placed which was unremarkable. He underwent right hemicraniectomy with debridement and washout on hospital day 3. Shortly afterwards, his urine output increased to >500 cc/hr with serum sodium of 172 mEq/L [135-145], serum osmolality 307 mOsmol/kg [270-295], and urine osmolality of 117 mOsm/kg [300-900]; consistent with CDI. He was acutely treated with intravenous desmopressin with resolution of hypernatremia. During the next five weeks of his 3-month hospitalization, he continued to have polyuria with specific gravity as low as 1.003 [1.005-1.030], and occasional hypernatremia, with a peak serum sodium of 150 mEq/L. Intranasal desmopressin as well as free water supplementation were given daily to alleviate his polyuria and hypernatremia. Evaluation of anterior pituitary function was normal except for decreased gonadotrophins. His polyuria resolved after five weeks, and labs showed urine osmolality of 530 mOsm/kg with serum sodium 138 mEq/L and urine specific gravity 1.010, consistent with resolution of CDI. Intranasal desmopressin was discontinued. His serum sodium remained stable without desmopressin for the next 7 weeks with serum sodium at discharge of 141 mEq/L. Discussion: The damage of the hypothalamic vasopressin-producing neurons, their axons or the posterior pituitary results in permanent post-TBI CDI. In cases of transient CDI, the pathogenesis is likely related to small vessel damage or inflammatory edema rather than direct neuronal damage. In our case, the patient initially developed hypernatremia and polyuria from acute CDI due to hemicraniectomy with debridement and washout. He continued to have prolonged transient CDI due to the extensive intracranial hemorrhage and edema. The CDI resolved with desmopressin (both intravenous and intranasal) and fluid replacement. Transient CDI is a rare complication intracranial haemorrhage. Our case highlights that the severity of TBI may correlate with the duration of transient CDI. Presentation: Friday, June 16, 2023

SAT590 Complex Migraine Manifesting As CDI - A Rare Occurrence

Abstract Disclosure: M. Shahid: None. E. Sari: None. W. Timirau: None. A. Hamza: None. N. Guzman: None. S. Sultan: None. Introduction: There are many references in the literature to unexplained neurological symptoms occurring with complex migraines, however, complex migraine manifesting as central diabetes insipidus (CDI) is rare. Clinical Case: A 48-year-old female with past medical history of psoriatic arthritis, generalized anxiety disorder, and migraine presented with the worst headache of her life for 2 days, typical for her migraine but with increased severity, and minimally responsive to NSAIDs. Her headache was accompanied by nausea, photophobia, floaters, polydipsia and polyuria. She denied any neck pain/rigidity, focal deficits, or head trauma. She reported a similar episode with lesser severity 10 days ago which resolved in 3 days. She related her headache episodes with polyuria. Her medications included topiramate, escitalopram, apremilast, loratadine, and NSAIDs. She denied any new medications. Physical examination was unremarkable. Initial labs showed high-normal sodium 145 mMol/L, normal serum osmolality 292 mOsm/kg, low urine specific gravity 1.003, and low urine osmolality 117 mOsm/kg and urine sodium 32.4 mMol/L. HbA1c, B-hCG and urinalysis were normal. CT brain, CTA head and neck, MRI brain with/without IV contrast, and CSF analysis were unremarkable. The patient was started on abortive treatment for migraine. She had a negative fluid balance of 1500ml during first 24 hours. Polyuria did not resolve with water restriction but resolved with improvement of migraine; which favored the diagnosis of complex migraine manifesting with polyuria secondary to CDI. Patient was discharged on migraine prophylaxis and neurology follow-up. Conclusion: Link between migraine and endocrinological disorders has been well identified. Even though most cases are idiopathic, any disorder that acts at the hypothalamic-pituitary axis involved in ADH secretion can cause CDI, however migraines as an etiology remains rare. Early recognition of symptoms, treatment of migraine and introduction of migraine prophylaxis was crucial in our case to prevent further episodes of CDI. Presentation: Saturday, June 17, 2023

Central Diabetes Insipidus in Children as a Diagnostic Challenge.

Central diabetes insipidus (CDI) is a disorder in the pediatric population resulting from antidiuretic hormone deficiency. The excessive production of dilute urine characterizes it and manifests with polyuria, nocturia, and polydipsia. The diagnostics of CDI is often challenging, especially concerning the underlying condition of the disease. This article highlights the diverse clinical presentation of children with CDI and diagnostic difficulties among patients with polyuria and polydipsia. The article also reviews the etiology, symptoms, diagnostic workup, and management of CDI. We present 4 pediatric patients (aged 3-13.5 years) diagnosed with CDI of different etiology: 1 due to septo-optic dysplasia/optic nerve hypoplasia and 3 due to acquired processes such as Langerhans cell histiocytosis and germ cell tumor in 2 patients. Central diabetes insipidus was the first manifestation of a tumor or granuloma in all presented patients with acquired pathology. The patients sometimes need long-term follow-up to establish the proper final diagnosis.

THU106 Malignant Epithelioid Neoplasm As The Cause Of A Rapidly Growing Pituitary Mass

Abstract Disclosure: S. Riahi: None. S.S. Chaidarun: None. Background: Malignant epithelioid neoplasm is a rare cause of a pituitary mass, and should be kept on the differential whenever evaluating patients with evidence of rapid pituitary enlargement. Clinical Case: A 43 year-old man presents with 3-month history of worsening severe headaches, decreased libido, erectile dysfunction, polydipsia, polyuria (6L/day) with nocturia every hour, and fatigue. He also noted some blurry vision without loss of his peripheral vision. MRI of the brain showed a 1.5cm mass in the sellar and suprasellar region abutting the optic chiasm. Of note, he had a brain MRI performed 18 months prior for vertigo which did not demonstrate any mass in the pituitary. He presented to the endocrinology office for evaluation. His laboratory tests demonstrated mildly elevated prolactin 31.2 ng/mL (n 4.0-15.2), and findings consistent with panhypopituitarism and central diabetes insipidus, including low FT4 of 0.46 ng/dL (n 0.93-1.70), FSH 0.7 mIU/mL (n 1.5-12.4), an undetectable LH (n 1.7-8.6mIU/mL), random cortisol of 1mcg/dL (n 4.8-19.5) ACTH 6.2 pg/mL (n 7.2-63), IGF-1 of 139 ng/mL (n 44-275), total testosterone undetectable (n 240-950 ng/dL), sodium 144mmol/L (n 135-145) with low urine specific gravity 1.008 and urine osmolality of 143mOsm/Kg (n 60-1200). HCG was undetectable (n 0-2mIU/mL) but LDH was elevated at 313 unit/L (n 110-220). He was started on corticosteroids, levothyroxine, DDAVP, and referred to neurosurgery. Specimens from his transphenoidal biopsy demonstrated findings consistent with a malignant epithelioid neoplasm. Further analysis and genetic testing is still pending. He has been referred to oncology service for further management and care. Conclusion: A rapidly growing symptomatic pituitary mass with central diabetes insipidus should raise suspicion for malignant etiology beyond the more prevalent pituitary adenoma. Malignant epithelioid neoplasm are uncommon tumors of the brain, however they are known to be aggressive tumors with high mortality. Treatment commonly includes some combination of surgery, radiotherapy, and chemotherapy1. Reference: (1) Jog AP, Ronderos DM, Ali A, Niazi M, Diaz-Fuentes G. Malignant Epithelioid Neoplasm of the Brain. Cureus. 2020 Aug 27;12(8):e10079. doi: 10.7759/cureus.10079. PMID: 33005505; PMCID: PMC7523542. Presentation: Thursday, June 15, 2023

THU107 A Case Of Primary Histiocytic Sarcoma Of Pituitary Gland Presenting With Central Diabetes Insipidus

Abstract Disclosure: S. Ahn: None. Y. Kim: None. Y. Cho: None. D. Seo: None. S. Kim: None. J. Cho: None. S. Choi: None. K. Kim: None. E. Kim: None. S. Hong: None. Introduction: Histiocytic sarcoma is a rare and aggressive hematopoietic neoplasm derived from non-Langerhans histiocytic cells of the monocyte/macrophage system. Here, we reported the first case of primary histiocytic sarcoma involving pituitary gland. Methods: Medical records were reviewed. Results: A 53 years old Korean men presented with general weakness, polydipsia, polyuria, and abnormal thyroid function test suspicious for secondary hypothyroidism. Laboratory examinations showed growth hormone deficiency, hypogonadotropic hypogonadism, and central diabetes insipidus. The magnetic resonance imaging showed a well-enhanced mass involving entire posterior pituitary gland with stalk thickening. The biopsy of pituitary mass was identified as a malignant tumor consistent with histiocytic sarcoma. This malignant tumor inoperably increased within a short duration and hormone deficiency such as secondary hypothyroidism and adrenal insufficiency additionally developed. Therefore, the patient started radiation therapy with desmopressin, levothyroxine, and hydrocortisone replacement. Conclusion: The biopsy is not regarded as the mandatory procedure for diagnosing patients with central diabetes insipidus with posterior pituitary lesion since in many cases, this is the result of hypophysitis. However, since there is still the possibility of primary malignancy and metastasis involving pituitary gland, an appropriate decision for performing biopsy should be made according to the patient’s clinical situations. Presentation: Thursday, June 15, 2023

FRI354 Therapeutic Potential Of Oxcarbazepine In Central Diabetes Insipidus

Abstract Disclosure: S. Pittampalli: None. V. Pattan: None. D. Das: None. U. Munasinghe: None. Introduction: Postoperative central Diabetes insipidus is usually transient but can be persistent. Persistent central Diabetes insipidus is prone to dose fluctuations in clinically unstable patients, especially when concomitant medications influence sodium and water homeostasis. Clinical Case: A 24-year-old female with headache and confusion had sellar and suprasellar mass of 6 cm x 4 cm with moderate to severe hydrocephalus and underwent Right craniotomy with debulking of the mass and pathology showed pilocytic astrocytoma. Postoperative course was complicated by short-term memory loss, right-sided weakness, adrenal insufficiency, and visual impairment. Repeat imaging showed increased size of suprasellar mass consequently requiring a transnasal transphenoidal resection. Post-operative neurological worsening was noted along with diffuse subarachnoid/ intraventricular hemorrhage with intraparenchymal hematoma in the right frontal lobe on CTA head. Hospital course included tracheostomy with mechanical ventilation. She had panhypopituitarism including CDI. CDI was initially managed by DDAVP 10mcg intranasal nightly and free water flushes. She had central adrenal insufficiency and central hypothyroidism treated by hydrocortisone and levothyroxine respectively. Hospital stay lasted for several months with multiple adjustments to the DDAVP dosage and free water flushes due to fluctuating serum sodium levels. She was started on levetiracetam 750 mg twice daily and oxcarbazepine 300 mg twice daily for seizure like activity. After two months, the oxcarbazepine dose was increased to 450 mg twice daily and later to 600 mg twice daily for breakthrough seizures. DDAVP was then discontinued as she developed hyponatremia. The dose of oxcarbazepine was reduced to 450 mg twice daily and she was subsequently discharged to a facility off DDAVP. Discussion: Postoperative CDI managed by DDAVP was complicated with oxcarbazepine-induced hyponatremia. CDI and sodium levels were controlled with oxcarbazepine after DDAVP discontinuation. Thus, oxcarbazepine has therapeutic potential as an antidiuretic agent as it can stimulate collecting tubule V2 receptor - G protein complex independent of ADH. Presentation: Friday, June 16, 2023

FRI346 Can We Miss Panhypopituitarism After Transsphenoidal Surgery?

Abstract Disclosure: A. Makawi: None. J. Huynh: None. G. Elshimy: None. Introduction: Disorders of water and osmolality due to aberrant ADH secretion and posterior pituitary function are common causes of morbidity among patients who undergo transsphenoidal hypophysectomy surgery (TSS). Postoperatively, central diabetes insipidus (DI) may present as a complication in up to 30% of cases. Moreover, hypopituitarism is an important complication of TSS, and can manifest as adrenal crises if missed by clinicians. We present a patient who underwent TSS for pituitary adenoma with postoperative course complicated by hypogonadism that was misdiagnosed for 10 years. Additionally he developed DI, secondary adrenal insufficiency (AI), and central hypothyroidism after resolution of his central hypogonadism. Case Description: 64-year-old male with medical history significant for chronic hypogonadism on hormonal replacement therapy and diabetes, presented for sleep disturbance and deviated septum with incidental finding of a large sphenoidal mass on CT imaging. MRI of brain confirmed a 4 cm macroadenoma invading from the inferior sella into the bilateral cavernous sinuses, clivus, and sphenoid sinus. Patient was then referred to neurosurgery for transsphenoidal resection. Patient underwent surgery and perioperative course complicated by a small CSF leak. He stayed in the neuro-ICU after the surgery and was monitored by the surgical team without endocrine consultation. He was discharged without proper postoperative evaluation of the HPA axis or education on symptoms of pan-hypopituitarism. Shortly after, he experienced significant symptoms consistent with adrenal insufficiency which prompted a visit to the emergency room. Thereafter, he finally presented to the neuroendocrine clinic for follow-up. Labs were notable for cortisol 1.2 mcg/dl, TSH 0.018 mcIU/ml, FT4 0.2ng/dl, and Na 130 mEq/ml, normal testosterone 551 ng/dl, mildly persistently elevated Na 147 mEq/ml with positive water deprivation test confirming central DI. He was treated with hydrocortisone and Synthroid for adrenal insufficiency and hypothyroidism respectively and was started on desmopressin for central DI. Discussion: Pan-hypopituitarism frequently occur after neurosurgical interventions and failure to involve endocrinology in the management of these cases may lead to missed diagnoses, unnecessary morbidity and mortality. This report serves as an excellent illustration of the importance of both surgical and medical management to prevent life-threatening complication such as adrenal crises as a result from pan-hypopituitarism. Presentation: Friday, June 16, 2023

THU113 Psychopathological Characteristics In Patients With Arginine Vasopressin Deficiency (Central Diabetes Insipidus) And Primary Polydipsia

Abstract Disclosure: J. Beck: None. C. Atila: None. J. Refardt: None. Z. Erlic: None. J.B. Drummond: None. B.S. Soares: None. F. Beuschlein: None. B.F. Winzeler: None. M. Christ-Crain: None. Introduction The differential diagnosis between arginine vasopressin deficiency (AVP-D), formally known as central diabetes insipidus, and primary polydipsia (PP) is challenging. In clinical routine, psychopathologic findings are often used as a hallmark for diagnosing PP; thus, it is often referred to as psychogenic polydipsia. Yet, psychopathologic characteristics are barely assessed in patients with AVP-D, and to date, no data exist comparing AVP-D and PP with regard to these features. Therefore, in this study, we aimed to compare levels of anxiety, depression, alexithymia, and overall mental health in patients with AVP-D and PP. Methods This study combined data from two diagnostic studies conducted at three tertiary medical centers. In total, 82 participants (n=39 with AVP-D, n=28 with PP, and n=15 healthy controls [HC]) underwent a psychological evaluation with standardized questionnaires at study inclusion. Anxiety levels were assessed using the State-Trait Anxiety Inventory, mood using the Beck’s Depression Inventory, alexithymia using the Toronto Alexithymia Scale, and overall physical and mental health using the Short Form 36 Health Survey (SF-36). Higher STAI, BDI, and TAS scores indicate higher anxiety, depression, and alexithymia levels. Higher SF-36 scores indicate better health and less disability. Results Compared with HC, patients with AVP-D and PP showed increased levels of anxiety (HC 28 points [24, 31] vs. AVP-D 36 points [31, 45], p<0.01; vs. PP 38 points [33, 46], p<0.01), depression (HC one point [0, 2] vs. AVP-D 7 points [4, 14], p<0.01; vs. PP 7 points [3, 13], p<0.01), and alexithymia (HC 30 points [29, 37] vs. AVP-D 43 points [35, 54], p<0.01; vs. PP 46 points [37, 55], p<0.01). Levels of anxiety, depression, and alexithymia showed no difference between patients with AVP-D and PP (p=0.58, p=0.90, p=0.50). Compared with HC, patients with AVP-D and PP reported comparable reduced self-reported mental health scores (HC 84 [68, 88] vs. AVP-D 60 [52, 80], p=0.05; vs PP 60 [47, 74], p<0.01). Conclusion This is the first study demonstrating comparable increased levels of anxiety, depression, alexithymia, and overall reduced mental health in patients with AVP-D and PP. Based on these data, psychopathological findings should not be used as a hallmark to differentiate between both conditions. Presentation: Thursday, June 15, 2023

OR17-01 Novel Provocation Test With MDMA (‘Ecstasy’) Reveals Oxytocin Deficiency As A New Pituitary Entity In Patients With Central Diabetes Insipidus - A Randomized Placebo-Controlled Trial

Abstract Disclosure: C. Atila: None. F. Holze: None. R. Murugesu: None. N. Rommers: None. N. Hutter: None. N. Varghese: None. C.O. Sailer: None. A. Eckert: None. M. Heinrichs: None. M. Liechti: None. M. Christ-crain: None. Introduction: Despite adequate treatment, patients with arginine vasopressin deficiency (AVP-D), known as central diabetes insipidus (cDI), often report psychological symptoms such as heightened anxiety levels, difficulties describing emotions, and depressed mood. Given the anatomical proximity, disruptions of the hypothalamic-pituitary axis causing an AVP-D could also disturb the oxytocin (OXT) system. OXT regulates socio-emotional functioning, including fear reduction, attachment, emotion recognition, and empathy. Therefore, these psychological symptoms may be caused by an additional OXT deficiency. However, OXT deficiency has not been established as a pituitary entity, as no provocation test for OXT is currently available. Here, we aimed to investigate the OXT system stimulator 3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) as a novel biochemical and psychoactive provocation test to reveal an OXT deficiency in patients with cDI. Methods: Randomized, placebo-controlled, double-blind, cross-over study in 15 patients with cDI and 15 matched healthy controls. Participants underwent a psychological baseline evaluation, including the assessment of anxiety levels using the State-Trait Anxiety Inventory (STAI), mood using the Beck’s Depression Inventory (BDI), and alexithymia using the Toronto Alexithymia Scale (TAS). Participants were randomized to receive either a single oral dose of MDMA (100 mg) or placebo first. OXT samples were collected at 0, 90, 120, 150, 180, and 300 minutes after drug intake. Subjective effects in response to MDMA were assessed throughout the experiment. The primary outcome was the area under the plasma OXT concentration curve (AUC) after MDMA intake. Results: Already at baseline, patients compared with healthy controls, showed significantly higher scores in anxiety (STAI: 41 points [IQR 34-48] vs. 28 points [24-31]; p=0.02), alexithymia (TAS: 47 points [38-59] vs. 30 points [29-37; p=0.04), and depression symptoms (BDI: 6 points [3-17] vs. 1 point [0-2]; p=0.04). In response to MDMA stimulation, in patients, there was only a minimal OXT change with 66 pg/ml [16-94], while in healthy controls, OXT increased by 658 pg/ml [355-914]. The AUC was 15.8 times (1485%), i.e., 85,678 pg/ml (95%-CI [-10,800 to -63,356], p<0.001), lower in patients compared with healthy controls. This lack of OXT in patients was associated with lower subjective effects such as ‘good drug effect,’ ‘feeling high,’ ‘satisfaction,’ ‘happy,’ ‘trust,’ ‘talkative,’ ‘openness,’ and ‘fear reduction’ compared with healthy controls. Conclusion: These results lay the groundwork for OXT deficiency as a hypothalamic-pituitary entity. In patients with cDI, this lack in OXT was associated with reduced pro-social, empathic, and anxiolytic effects. 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

FRI352 Diabetes Insipidus With Hypokalemia In A 30 Week Pregnant Female

Abstract Disclosure: C.B. Stanfield: None. In this case, we will discuss a 29 year old G4P0121 African American female at 30 weeks gestation presented to women’s urgent care for nausea, vomiting and diarrhea after starting magnesium supplementation for incidentally diagnosed hypokalemia around 4 weeks prior. Vitals were significant for a BP of 133/60 and HR 110. Laboratory studies were significant for potassium of 3 mmol/L, sodium 155 mmol/L, magnesium 2.2mmol/L, AST 104, ALT 62 and UA with 2+ proteinuria. Patient admitted to the OBGYN service for preeclampsia with severe features. Patient was noted to have over 16L UOP over the first 24 hours of admission; 4.5L intake. Further labs obtained showed hemoglobin A1C of 4.9, serum osmolality of 308 mOsm/kg, urine osmolality 77 mOsm/kg and urine specific gravity 1.002. DDAVP was given with urine osmolality increasing from 77 to 137 mmol/L. Working differential diagnoses included gestational diabetes insipidus (DI), central DI or nephrogenic DI due to hypokalemia. Co-peptin assay was drawn; is a send out at our institution. Of note, the patient had no known history of brain injury, surgery, radiation or Sheehan Syndrome. However her previous pregnancies had been complicated by hypokalemia, hypertension and pre-eclampsia with emergent cesarean-section. She subsequently underwent emergency cesarean-section on hospital day 2 for non-reassuring fetal activity with delivery of viable 1230g male. After delivery, the patients hypokalemia resolved. Post-op, DDAVP for 3 days was continued per hospital DI protocol with appropriate response. Co-peptin resulted at 22.3, excluding central DI as a diagnosis. On time of discharge, patient had gone without DDAVP for >48 hours with intact thirst mechanism. Given improvement/resolution of DI and persistently low urine osmolality even after DDAVP administration prior to delivery, the DI was believed to be gestational with a component of nephrogenic DI as well due to hypokalemia. Gestational DI occurs due to increased placental vasopressinase which degrades the antidiuretic hormone (ADH). It is associated with pre-eclampsia, acute fatty liver of pregnancy and HELLP syndrome. DDAVP is a modified synthetic analog of endogenous ADH and is resistant to breakdown by placental vasopressinase and can be used to treat gestational DI. Definitive management is achieved with delivery of the fetus and can last up to six weeks after delivery. Presentation: Friday, June 16, 2023

FRI327 Lymphocytic Hypophysitis Presenting As Hypoprolactinemia In A Post-partum Female

Abstract Disclosure: J. John: None. S. Graybill: None. Lymphocytic hypophysitis is the most common presentation of primary pituitary gland inflammation. It typically presents with headache, vision changes, and sequelae of hypopituitarism, including central diabetes insipidus, anterior pituitary dysfunction, and hyperprolactinemia. Lymphocytic hypophysitis has a propensity to affect women in association with pregnancy due to an unknown underlying mechanism. A 38-year-old female presented with intractable headache and peripheral vision changes 3 weeks after giving birth to twin boys. Her post-partum course was complicated by preeclampsia with severe features. She also began experiencing blurry vision during this period. Seventeen days after delivery, she developed an acute onset headache and peripheral vision loss. She also noted sudden cessation of lactation with the onset of her headache. Initial CT head demonstrated a 1.6 centimeter enhancing pituitary mass suspicious for macroadenoma, and subsequent MRI sella revealed a 2.0 x 1.7 x 1.5 cm heterogeneously enhancing mass arising from the pituitary adenohypophysis extending to the undersurface of the optic chiasm. Initial laboratory evaluation demonstrated central hypothyroidism and inappropriately normal prolactin for a recently post-partum female. Given the patient’s impending vision loss, she was taken to the operating room for resection of suspected pituitary macroadenoma. Upon gross dissection, the abnormal appearance of the suspected mass prompted biopsy and immediate frozen section evaluation demonstrated significant lymphocytic infiltration. The resection was subsequently aborted. The patient was placed on levothyroxine and prednisone 80 milligrams daily for suspected lymphocytic hypophysitis, which was confirmed on tissue pathology. The patient’s headache and vision changes improved and after six days, she was discharged on a prednisone taper. Following three months of prednisone therapy, a repeat MRI sella demonstrated a reduction in the overall size of the pituitary gland to 1.7 x 1.2 x 1.1 cm. The patient was maintained on physiologic hydrocortisone and levothyroxine while monitoring for potential pituitary function recovery. Twelve months following her initial diagnosis, the patient did not demonstrate normalization of anterior pituitary function and required ongoing treatment for hypopituitarism. While hypoprolactinemia is atypical of hypophysitis, it is imperative to consider alternative pituitary pathology such as lymphocytic hypophysitis in the post-partum female when the clinical history is suspicious. Presentation: Friday, June 16, 2023

OR20-06 Diagnosing Central Diabetes Insipidus Using Copeptin Upon Hypertonic Saline Versus Arginine Stimulation

Abstract Disclosure: J. Refardt: None. C. Atila: None. I.O. Chifu: None. E. Ferrante: None. Z. Erlic: None. J.B. Drummond: None. B. Mantovani: None. R. Drexhage: None. C.O. Sailer: None. A. Widmer: None. S. Felder: None. A.S. Powlson: None. N. Hutter: None. D. Vogt: None. M. Gurnell: None. B. Rocha: None. J. Hofland: None. F. Beuschlein: None. M. Fassnacht: None. B.F. Winzeler: None. M. Christ-Crain: None. Background: The main challenge in the diagnosis of central diabetes insipidus (cDI) is its distinction against primary polydipsia (PP). Hypertonic saline stimulated copeptin has a high diagnostic accuracy of 97%, but comprises discomfort for patients and requires close sodium monitoring. Arginine stimulated copeptin showed similar diagnostic accuracy of 93% with better tolerability, but a head-to-head comparison is lacking. We hypothesized that arginine stimulated copeptin is non-inferior (non-inferiority margin 10%) to hypertonic saline stimulated copeptin for the diagnosis of cDI. Methods: In this prospective randomized multicentre study conducted between 2018-2022 in seven tertiary medical centres, consecutive patients with cDI and PP underwent diagnostic evaluation with hypertonic saline and arginine stimulation. Serum copeptin levels were measured at sodium-level of >149 mmol/L after hypertonic saline and 60 minutes after arginine infusion, respectively. The final diagnosis was made after treatment response assessment at three-month follow-up blinded to copeptin levels. The main outcome measure was the overall diagnostic accuracy using the pre-defined copeptin cut-off of 4.9 pmol/L for hypertonic saline and 3.8 pmol/L for arginine stimulation. Results: 158 patients underwent both tests, of which 69 (44%) were diagnosed with cDI and 89 (56%) with PP. Forty-one (59%) patients had a complete and 28 (41%) patients had partial cDI. The diagnostic accuracy [95% CI] to differentiate patients with cDI from patients with PP was 95.6% [91.1,97.8] for hypertonic saline stimulated copeptin compared to 74.4% [67.0, 80.6] for arginine stimulated copeptin. Accordingly, arginine stimulation was inferior to hypertonic saline stimulation (estimated difference [95% CI] -21.2% [-28.7, -14.3]). Side effects were less frequent and less severe under arginine stimulation, resulting in a clear 72% of patients preferring the arginine stimulation over hypertonic saline stimulation. In addition, arginine stimulated copeptin of 3.0 pmol/L diagnosed cDI with a specificity of 90.9% (sensitivity of 59.5%), while a cut-off of 5.2 pmol/L diagnosed PP with a specificity of 91.4% (sensitivity of 56.4%). Conclusion: In the diagnostic evaluation of cDI, copeptin upon hypertonic saline stimulation was superior to arginine stimulation. Arginine stimulation can be used as a first well-tolerated test diagnosing >50% of patients with high accuracy, but hypertonic saline stimulation remains the test with the highest diagnostic accuracy. Presentation: Saturday, June 17, 2023

Clinical and therapeutic outcomes of pediatric pituitary adenomas: a single pituitary center experience.

Pediatric pituitary adenomas (PPA) are rare. Although PPAs are mostly benign, they can be challenging to manage. Most studies evaluating PPA are based on surgical series. We aimed to present the clinical features, hormonal status and treatment outcomes of children with PPA managed in a joint neuroendocrine setting. In this single-center study, demographic, clinical and endocrinological data of patients under 19 years old who were followed up with the diagnosis of PPA between 2002-2022 were retrospectively reviewed. A total of 21 studies published in the past 20 years were also systematically reviewed. There were 79 patients (52 girls, 27 boys) with a median age of 15.8 years. Median follow-up time was 30 months. The most common adenoma subtype was non-functioning adenoma (NFA) (35.5%), followed by prolactinoma (29.1%), corticotropinoma (21.5%), and somatotropinoma (13.9%), respectively. The frequency of micro and macroadenomas was almost equal while 38% of all adenomas were invasive. Headache, visual impairment and menstrual irregularity were the most common complaints, while the most common hormonal deficiency at diagnosis was central hypothyroidism (31.6%), followed by hypogonadotropic hypogonadism (22.7%), growth hormone deficiency (15.2%) and central adrenal insufficiency (11.4%), respectively. Fifty patients (63.2%) underwent endoscopic endonasal transsphenoidal surgery (EETS). Following the surgery, impaired endocrine functions recovered at a rate of 62% while permanent central diabetes insipidus was observed in 6%, and new onset hypopituitarism developed in 4%. NFA was more common in this cohort than in previous reports, which is one of the largest PPA series in the literature. Hormonal disorders, which were common at the time of diagnosis, were largely resolved with appropriate endocrinological and surgical approaches, while the rate of pituitary hormonal deficiencies after EETS was relatively low. Therefore, we recommend that children with PPA be managed in the setting of a high-volume pituitary center to provide long-term low morbidity.

Psychopathological characteristics in patients with arginine vasopressin deficiency (central diabetes insipidus) and primary polydipsia

Psychopathological characteristics in patients with arginine vasopressin deficiency (central diabetes insipidus) and primary polydipsia

Lymphocytic Infundibuloneurohypophysitis Diagnosis Owing to Positive Anti-rabphilin-3A Antibody Test Result in an 8-year-old Boy with Early-onset Central Diabetes İnsipidus.

Childhood-onset lymphocytic infundibuloneurohypophysitis (LINH) has rarely been reported. Pathological evaluation via pituitary biopsy is necessary for a definitive diagnosis of LINH. However, pituitary biopsy is a highly invasive procedure. Recently, anti-rabphilin-3A antibody (RPH3A-Ab) has been reported as a promising diagnostic marker for LINH in adults; however, there are few such reports in the pediatric population. We report the case of an 8-year-old boy with central diabetes insipidus (CDI) who was clinically diagnosed with LINH based on RPH3A-Ab positivity. He was diagnosed with CDI using a water deprivation test combined with desmopressin administration. Serum and cerebrospinal fluid tumor markers were negative, and T1-weighted magnetic resonance imaging (MRI) revealed the absence of high signal intensity in the posterior pituitary gland and an enlarged pituitary stalk. Anterior pituitary function tests revealed no abnormalities. No pituitary biopsy was performed because of its invasive nature, and desmopressin treatment was initiated. Three months after CDI onset, the patient tested positive for RPH3A-Ab. MRI performed 9 months after CDI onset revealed amelioration of the pituitary stalk enlargement, and the clinical course corroborated our diagnosis of LINH. RPH3A-Ab may be useful as an early diagnostic tool for LINH in the pediatric population.

Diagnosis of psychogenic polydipsia in the type of clinical case

Polydipsia is a pathologically increased thirst, satisfied by the intake of water in large quantities, which can manifest itself in various somatic or mental diseases and at first glance is similar to a true vasopressin deficiency. Central diabetes insipidus (CDI) is a disease of the hypothalamic-pituitary region characterized by the inability of the kidneys to reabsorb water and concentrate urine, which is based on a defect in the synthesis or secretion of vasopressin and is manifested by severe thirst and excretion of large amounts of hypotonic urine. The prevalence of the disease in the population is 1:25,000, which characterizes it as a fairly rare pathology of the hypothalamic-pituitary region. The peak incidence is between 30 and 40 years of age. According to various literary sources, the disease is not characterized by gender differences in prevalence, however, on the example of the Moscow population, women prevailed in the incidence structure of CND in a ratio of 2.2:1. Insidiousness, with apparent absences in the difficulty of diagnosing primary polydipsia, lies in the manifestations of water intoxication, thus this condition requires knowledge of clear diagnostic criteria by healthcare professionals and an interdisciplinary approach in the treatment of this condition. On the example of this clinical case, we will try to highlight the differential diagnostic criteria for psychogenic polydipsia in comparison with the true deficiency of arginine vasopressin (AVP) or central diabetes insipidus (CDI), which can be applied in real clinical practice.

P04.03.B VENOUS THROMBOEMBOLISM AND OTHER VASCULAR COMPLICATIONS IN PAEDIATRIC PATIENTS FOLLOWING CRANIOPHARYNGIOMA SURGERY: A SINGLE-CENTER, RETROSPECTIVE STUDY

Abstract BACKGROUND Craniopharyngioma (CP), although slow growing and histologically benign, carries considerable morbidity, particularly in the postoperative period: hypothalamus-pituitary dysfunction and electrolyte disorders represent common complications. Moreover, in these patients, the increased risk of deep venous thrombosis (DVT) and the possible development of fusiform intracranial aneurysms are well known. However, data are still poor, especially in the pediatric population. The aim of our study was to describe the occurrence and timing of DVT and other vascular alterations in neurosurgical operated CP patients and to evaluate the role of predisposing factors in the development of post-surgical and late vascular events. MATERIAL AND METHODS This was a single-center, retrospective study. We investigated 19 patients (11 males, 8 females, mean age 10.47±4.29) diagnosed with CP, who had been subjected to neurosurgery between December 2016 and August 2022 in Meyer Children’s Hospital IRCCS in Florence. Demographic and clinical characteristics and surgical data were recorded for each participant. RESULTS Five patients (26.3%, 3 females, 2 males, median age 15 years) presented vascular events, all during sodium imbalance. Calcium at lower limits was detected in four of them. Three DVT (two with associated pulmonary embolism, including one female patient’s death) developed after surgery, more frequently at 7-10 days (two patients were central catheter carriers, one obese patient showed hypercholesterolemia and hypertriglyceridemia). In a patient in hyponatraemic state a vascular parietal alteration compatible with pseudoaneurysm was described soon after neurosurgery, requiring vascular stenting and prolonged intensive care. Superficial vein thrombophlebitis was a late complication in an overweight female patient on estrogenic replacement therapy. CONCLUSION Patients with CP undergoing neurosurgical brain tumor resection are at a higher risk of developing DVT and vascular alterations, thus careful follow-up should be done in these patients. In our study, we found that the phase of transition from central diabetes insipidus (CDI) to syndrome of inappropriate antidiuretic hormone secretion (SIADH) is probably a significative time for developing this complication; so, we recommend careful monitoring of symptoms suggestive of vascular events in CP operated patients. However, we suggest the execution of a deep vein ultrasound examination in the post-neurosurgical two-four weeks for an early diagnosis of this problem for reducing the risk of severe complications.

The therapeutic effect of oral desmopressin lyophilisate formulation in children with central diabetes insipidus.

We aimed to assess the efficacy of oral use of oral desamino-D-arginine-8-vasopressin lyophilisate (OLD) in children with central diabetes insipidus (CDI). Clinical, laboratory, and imaging characteristics of twenty-five children with CDI treated with OLD were evaluated. Fourteen boys and eleven girls with a mean age of 52.37 months were evaluated. These children (mean weight and height at admission, 26.81±14.8 kg vs. 92.52±30 cm) presented with failure to thrive, irritability, prolonged fever, polyuria and hypernatremia (mean sodium level, 143.12±8.6 mEq/L). At the time of hypernatremia, mean serum and urine osmolality were 298.2±18 mOsm/kg and 160.20±8.7 mOsm/kg, respectively. ADH levels were undetectable (<0.5 pmol/L) at admission in all cases. Oral administration of desmopressin lyophilisate (120 µg/tablet) was initiated at a dose of 5 μg/kg/day in two divided doses together with controlled water intake to avoid hyponatremia. Serum sodium levels normalised in a mean durationof 15.2±16.4 h with a mean decline rate of 0.12±0.04 mEq/L/h. Nine children needed rehospitalization because of hypernatremia due to non-compliance. Four episode of hyponatremia was observed. Weight gain and growth were normal during the mean follow-up duration of 37.79±48.2 months. Administration of OLD was practical and safe in the treatment of CDI in children with CNS malformations in this small retrospective series.