Oral DDAVP Research Articles

8533 Salt on the Kidneys A case of DDAVP induced arginine vasopressin resistance

Abstract Disclosure: M.M. Jordan: None. J.R. Islam: None. R. Hassan: None. A 63-year old female with a history of head trauma complicated by polyuria and excessive fatigue diagnosed with central DI and started on treatment with oral Desmopressin. She had no other known pertinent medical history. Patient was lost to follow-up with an eventual visit to the emergency department with complaints of bilateral leg cramps, nausea and persistent headaches. She was noted to have been initiated intranasal desmopressin in addition to oral DDAVP. On initial lab work, Sodium was 114 along with acute kidney injury. She was admitted to ICU and treated with hypertonic saline. DDAVP was withheld until sodium normalized and stabilization of renal functions. GFR still remained impaired on discharge at 40 mL/min/1.73m*2. She was then discharged on DDAVP with reestablished follow up in the endocrinology clinic with complaints of persistent polyuria. Once more, she was sent to the emergency room and was admitted for acute renal injury secondary to dehydration in the setting of polyuria and altered mentation. Upon review of her medications, the patient continued both oral and inhaled DDAVP. No other medications or supplements were reported. During this subsequent hospitalization, sodium remained between 131-135 with urine output 4.5L/ day despite increasing doses of oral DDAVP and oral sodium supplementation. At which point, suspicion for mixed DI was hypothesized (central DI and arginine vasopressin resistance). Other causes of polyuria were ruled out. Labs for persistent AKI revealed gross proteinuria. Renal biopsy was performed during hospitalization which showed acute to chronic vascular thrombotic microangiopathy and focal segmental glomerulosclerosis with collapsing features. Extensive workup for chronic infections, autoimmune conditions and hematological malignancies were negative. This showed concerns for possible DDAVP induced renal injury. Presentation: 6/2/2024

A rare diagnosis of Langerhans cell histiocytosis made on thyroid histology with coexisting papillary thyroid cancer and AVP deficiency.

A 48-year-old Asian male, presented to the hospital for an elective total thyroidectomy in the context of 6.3 cm thyroid nodule. The fine needle aspiration cytology of the nodule confirmed papillary thyroid cancer (PTC) with some atypical histiocytes. He has a history of idiopathic arginine vasopressin deficiency (AVP-D) and has been taking oral DDAVP 100 µg daily, self-adjusting the dose based on thirst and polyuria. Additionally, he also has a history of recurrent spontaneous pneumothorax. His total thyroidectomy was aborted due to significant intraoperative bleeding, and his admission was further complicated by post-operative hyponatraemic seizure. Thyroid histology revealed the diagnosis of Langerhans cell histiocytosis (LCH), and further investigation with contrast CT demonstrated multi-organ involvement of the thyroid, lungs, and bones. Langerhans cell histiocytosis (LCH) is a condition that can affect one or more organ systems, including the pituitary, where it can present as AVP deficiency. Strict monitoring of fluid balance, as well as serial monitoring of serum sodium, is essential in all patients with AVP-D in the perioperative setting. Iatrogenic hyponatraemic seizure is an uncommon but serious complication of DDAVP treatment in hospitalised patients with AVP-D. DDAVP dosing must be carefully monitored. LCH with multisystem involvement is an important mimic for metastatic conditions, and histological diagnosis is essential to guide treatment and prognosis. Although LCH without bone marrow involvement is unlikely to increase the risk of bleeding, its effect on tissue integrity may make surgery more challenging. BRAF-V600E mutation is an important driver mutation and a potential therapeutic target in the treatment of LCH.

FRI351 Pituitary Stalk Epidermoid Cyst: A Rare Cause Of Diabetes Insipidus

Abstract Disclosure: J.T. Batch: None. F. Warda: None. P. Natter: None. R. Makary: None. G.Y. Gandhi: None. Introduction: Epidermoid cysts are benign squamous epithelial cysts filled with keratin. They are rarely found in the central nervous system, constituting 0.2-1.8% of intracranial masses, with the majority located in the cerebellopontine angle. Case Report: A 34-year-old female presented with blurred vision, debilitating headaches, milky breast discharge, and no menstrual periods for three years. Prolactin was mildly high on two occasions at 40.3 and 52.8 ng/mL (3.0-30.0 ng/mL). Estradiol was low at 15 pg/ml in the setting of inappropriately normal FSH (10.1 mIU/mL) and LH (5.8 mIU/mL). ACTH, cortisol, TSH, free thyroxine, and IGF-1 were in the normal range. A pregnancy test was negative. A 1:100 diluted prolactin did not detect the hook effect. MRI revealed a 1.8 x 1.4 x 1.4 cm suprasellar mass centered along the pituitary stalk with peripheral enhancement and central cystic vs. necrotic components. It caused a mass effect on the optic chiasm. Formal visual field testing revealed a left inferior temporal defect. Subsequently, the patient reported increased thirst (consuming 4-5 L of water daily) and urination (confirmed with a 24-hour urine output of 4 L). Following 12 hours of overnight water deprivation, morning labs confirmed diabetes insipidus with high serum sodium of 146 mmol/L, high serum osmolality of 306 mOsm/kg, and low urine osmolality of 204 mOsm/Kg. Initiation of oral DDAVP 0.1 mg nightly resulted in a resolution of nocturia and dramatic improvement in thirst. The patient underwent transsphenoidal resection, during which the neurosurgeon identified a suprasellar cystic lesion with classic epidermoid pearl white material. The lesion and capsule were resected, and patient started on dexamethasone 6 mg IV every 6 hours to prevent chemical meningitis. Pathology was consistent with an epidermoid cyst. Prolactin stained several cells, possibly from compression of the pituitary stalk by the epidermoid cyst. Postoperatively, the patient had severe headaches, and photophobia thought to be associated with chemical meningitis. Lumbar puncture revealed elevated CSF neutrophils and aseptic culture. The patient was continued on dexamethasone with slow taper upon discharge. DDAVP was increased to 0.1 mg twice daily as polyuria and polydipsia worsened. Discussion: There have been six reported cases of epidermoid cysts involving the pituitary stalk. Visual disturbance and headaches are common, while galactorrhea and amenorrhea are uncommon. Preoperative polyuria can be a frequent presenting symptom that can evolve into permanent postoperative diabetes insipidus. Surgical resection is the treatment of choice. It may be difficult to achieve complete excision due to the adherence of the cyst wall to the adjacent structures. The most common complications after resection include chemical meningitis (noted in our patient), hydrocephalus, infectious meningitis, and cranial nerve palsies. Presentation: Friday, June 16, 2023

Management of Central Diabetes Insipidus in Disabled Children with Diluted Oral Desmopressin Lyophilisate Formulation Administered Through Nasogastric Tube: A Retrospective Case Series.

Experience with nasogastric administration of oral DDAVP [desamino-D-arginine-8-vasopressin] lyophilisate (ODL) for central diabetes insipidus (CDI) in disabled children with swallowing coordination difficulties is limited. We aimed to assess the safety and efficacy of nasogastric use of ODL in disabled children with CDI. Time to serum sodium normalisation was compared with that of children with normal intellect and CDI treated with sublingual DDAVP. Clinical, laboratory and neuroimaging characteristics were evaluated for 12 disabled children with CDI treated with ODL through nasogastric tube at Dr Behcet Uz Children's Hospital, Turkey,between 2012 and 2022. Six boys and six girls with a mean (±SD) age of 43 (± 40) months were evaluated. These children (mean [±SD] weight standard deviation score [SDS] -1.2 ± 1.7; mean [±SD] height SDS -1.3 ± 1.4) presented with failure to thrive, irritability, prolonged fever, polyuria and hypernatraemia (mean serum sodium 162 [±3.6] mEq/L). At diagnosis, mean serum and urine osmolality were 321 (± 14) mOsm/kg and 105 (± 7.8) mOsm/kg, respectively. Arginine vasopressin (AVP) levels were undetectable (<0.5pmol/L) at diagnosis in all patients. Nasogastric tube administration of DDAVP lyophilisate (120µg/tablet) dissolved in water (10mL) was commenced at a dose of 1-5µg/kg/day in two divided doses together with controlled water intake to avoid hyponatraemia. The frequency and dose of DDAVP were titrated based on urine output and serum sodium concentration. Serum sodium declined at a rate of 0.11± 0.03mEq/L/h and reached normal range in a mean duration of 174 ± 46.5 h. Serum sodium declined faster in children with normal intellect and CDI treated with sublingual DDAVP (1.28± 0.39mEq/L/h; p=0.0003). Three disabled children needed rehospitalisation because of hypernatraemia due to unintentional DDAVP omission by caregivers. No episode of hyponatraemia was observed. Weight gain and growth were normal during the median (± interquartile range) follow-up duration of 32 ± 67 months. Nasogastric administration of oral DDAVP lyophilised formulation was safe and effective in the treatment of CDI in disabled children in this small retrospective series.

Abstract #1405536: Hyponatremia After Placement of an External Lumbar Drain Following Transsphenoidal Surgery in a Patient with Preoperative Diabetes Insipidus

Hypernatremia due to diabetes insipidus (DI) is perhaps the most anticipated electrolyte abnormality after transsphenoidal surgery (TSS), but hyponatremia is more common and occurs in over 15% of patients undergoing TSS. Postoperative placement of an external lumbar drain (ELD) is a well-known risk factor for hyponatremia following TSS. We present an unusual case of refractory hyponatremia occurring after ELD placement in a patient with preoperative DI. A 68-year-old male underwent TSS for resection of a recurrent sella meningioma. History was notable for multiple recurrences and resections of the tumor, and the patient was treated for longstanding central DI and hypopituitarism (>10 y). Surgery was complicated by bleeding, requiring placement of an ELD. Preoperative serum sodium levels were in the reference range (136-145 mM), but within 48 h of ELD placement, serum sodium level fell to 127 mM. Spot urine sodium level and osmolality were <10 mM and 162 mOsm/kg, respectively. The patient received stress dose glucocorticoids after surgery, and free T4 level was in the reference range (0.5-1.3 ng/dL). Other causes of hyponatremia and pseudohyponatremia, including hyperglycemia, renal tubular acidosis, paraproteinemia, and hyperlipidemia were excluded. While the lumbar drain was in place, serum sodium levels remained 125-129 mM despite decreasing the amount and frequency of DDAVP doses for treatment of preoperative central DI. After the ELD was removed, hyponatremia resolved within 48 h, and the patient was discharged home with a serum sodium level of 140 mM on oral DDAVP (0.1 mg BID) prescribed prior to surgery. In a series of over 300 adults undergoing TSS, placement of an ELD accounted for almost half of hyponatremia cases. Cerebral salt wasting syndrome (CSWS) and syndrome of inappropriate antidiuretic hormone (SIADH) are identified as the most common causes of ELD-induced hyponatremia, though undetectable urine sodium level in this case excludes CSWS. Spot urine osmolality was surprisingly high (>100 mOsm/kg) for the patient’s longstanding central DI, appearing to indicate SIADH as the etiology of hyponatremia. The patient likely had partial central DI, and persistent hyponatremia after placement of the ELD despite significant reductions of DDAVP doses appears to be best explained by release of endogenous ADH by surviving magnocellular neurons of the supraoptic nucleus in the hypothalamus superimposed on treatment with DDAVP. This case demonstrates that ELD-induced hyponatremia is possible in patients treated for central DI prior to TSS and likely indicates only a partial deficit of endogenous ADH secretion.

Abstract #1408214: Severe Hypernatremia Due to Central Diabetes Insipidus with Adipsia: Challenges in Management

Hypernatremia (serum sodium >145meq/L) is independently associated with increased mortality as high as 40-60%. Mortality correlates with the rapidity of the rise in sodium and the degree of severity. Central Diabetes Insipidus (DI) associated with adipsia pose a unique management challenge, leading to recurrent hospital admissions due to hypernatremia. We report, a patient with Central DI who presented with severe hypernatremia following desmopressin non-compliance and inadequate water intake. A 25-year female with a past history of obstructive hydrocephalous underwent ventriculoperitoneal shunt revision and had a complicated hospital course including new onset Central DI. The patient was discharged on desmopressin and a serum sodium of 148 meq/L. She presented to the hospital 3 days later with altered mentation, dehydration, and a heart rate of 124bmp. Other vital signs were stable. CT head showed no acute intracranial abnormalities. Labs showed: serum sodium 190meq/L, serum osmolality 393mOsm/kg, urine sodium 44mEq/L, and urine osmolality 878mEq/L. She initially received IV isotonic fluid, and IV DDAVP, and later started on hypotonic fluid and oral DDAVP. Labs were monitored every 6 hours. The patient didn’t have a sense of thirst, didn’t like the taste of water, and had a suboptimal response to oral DDAVP. Multiple measures were taken to stabilize her serum sodium: switched to DDAVP Nasal spray, placed alarms on her cell phone as a reminder to drink water, flavored powders were used to make the water palatable, and provided education on the importance of DDAVP, adequate water intake, and outpatient follow-ups. The patient was safely discharged home after demonstrating the ability to maintain normal serum sodium on oral fluid intake and self-administered nasal DDAVP. Thirst is a critical adaptive mechanism to protect against hypernatremia. Intense thirst may be present initially, but it dissipates as hypernatremia progresses and is absent in patients with adipsia. Destruction or improper functioning of osmoreceptors in the hypothalamus that controls the thirst mechanism can result in adipsia; this may result from a congenital malformation or acquired as in the case of stroke, trauma, or infection. It was most likely secondary to multiple intracranial procedures in our patient. This case also highlights cerebral adaptation to chronic hypernatremia. Brain shrinkage is countered by an adaptive response initiated promptly and consists of solute gain (initial uptake of sodium and potassium, followed by the later accumulation of osmolytes; mainly myoinositol and the amino acid glutamine) by the brain that tends to restore lost water. This response leads to the normalization of brain volume and accounts for the milder symptoms of hypernatremia that develops slowly, as seen in this patient. In conclusion, patients with Central DI associated with adipsia can pose a significant management challenge. This case highlights the importance of addressing all the barriers that affect patients’ compliance with DDAVP and ensuring adequate hydration to prevent recurrent hospital admission and associated morbidity and mortality.

ODP292 A Xanthomatous Hypophysitis: Always Think Twice Before Pituitary Resection.

Abstract Background A xanthomatous hypophysitis is a rare form of primary hypophysitis common in females. Clinical case: A 47-year-old male was referred for pituitary adenoma resection. The patient presented with low libido and facial and body hair loss for 3 years. He reported increased thirst and nocturia for 2 years. 24-hr fluid intake showed 4,800 ml intake and 6,700 ml output. Physical examination revealed tanner 5 pubic hair with testicle size 12 ml bilaterally. He had a normal visual field. Laboratory testing revealed low morning total testosterone level of 108 ng/dL (241-872), low LH 0.39 mIU/mL (1.14-8.75) and low FSH 1.28 mIU/mL (1.37-13.58). Other pituitary hormones showed normal TSH 0.634 uIU/ml (0.35-4.9) with low free T4 0.64 (0.7-1.48), IGF-1 107 ng/mL (74-196), prolactin 10.92 mcg/mL (3.46-19.4), morning cortisol 8.9 mcg/dL (3.7-19.4). A 1 mcg ACTH stimulation test showed an inappropriate increase in cortisol level of 16.1 mcg/dL with baseline ACTH 28 pg/mL (0-46). Regarding polyuria, biochemical testing showed serum Na 148 mmol/L (136-145), Uosm 307 mOsm/Kg (50-1300), and Sosm 307 mOsm/kg (275-290). After the therapeutic trial with oral DDAVP, urine output significantly decreased. Subsequent tests showed serum Na 144 mmol/L, Uosm of 295 mOsm/kg, and Sosm of 278 mOsm/kg. The final diagnosis was hypopituitarism and central diabetes insipidus. MRI showed an enlarged pituitary gland with 2 decreased enhancing nodules in the post-contrast study of the anterior lobe measuring 4.2 and 6.7 mm in diameter. No stalk thickening was detected. There was no compression on adjacent organs. Since the pituitary lesions could not explain the hypopituitarism and DI. The surgery was postponed, and he underwent an endoscopic transsphenoidal biopsy. The procedure yielded a milky fluid content, and a circumferential dissection of a soft-yellow capsule was done. Pathology examination revealed a chronic hypophysitis with clusters of foamy macrophages. Immunohistochemistry showed positive for CD3, CD20, and CD138. A CD68 was positive in multiple clusters of foamy macrophages, while an IgG4 was negative. The final diagnosis is xanthomatous hypophysitis. The patient was treated with hormonal replacement therapy of levothyroxine, prednisolone, testosterone, and DDAVP. Until now, there are 36 cases in the literature reporting xanthomatous hypophysitis. The prevalences of hormonal deficits are 36.1% adrenal insufficiency, 42.4% central hypothyroidism, 54.6% central DI, 36.4% hypogonadism, 63.6% GH deficiency, and 54.6% hyperprolactinemia. The common MRI characteristic is a cystic mass with a ring or peripheral enhancement. Pituitary stalk thickening is shown in 50% of cases. Conclusion This clinical case demonstrated the rare entity of xanthomatous hypophysitis presenting with secondary AI, hypogonadotropic hypogonadism, central hypothyroidism, and DI. The discrepancy between clinical history and the MRI findings was a clue for pituitary biopsy leading to the final diagnosis and avoidance of unnecessary surgery. Presentation: No date and time listed

PMON82 SARS-CoV-2 Associated Hypophysitis and Central Diabetes Insipidus

Abstract Background The SARS-CoV-2 infection, known for severe respiratory complications, has also been found to cause multiple endocrinopathies. SARS-CoV-2 enters pneumocytes through the angiotensin-converting enzyme 2 receptor. The adrenal, thyroid, testes, ovaries, hypothalamic, and pituitary tissues express ACE2 receptors, making them putative targets.2,4 Hypothalamic and pituitary involvement was first reported in 2005 and cases continue to be reported during the newest pandemic.1,3 We present a case of central DI following positive RT-PCR testing for SARS-CoV-2. Clinical Case A 44-year-old man presented with headache, multiple neurologic symptoms, polyuria, and polydipsia approximately three weeks following a positive SARS-CoV-2 test. A pituitary MRI showed thickening of the infundibular stalk and inhomogeneity of the pituitary gland, suggestive of hypophysitis. A water deprivation study demonstrated undetectable ADH and inability to concentrate urine spontaneously, but increased urine osmolality in response to DDAVP consistent with central DI. He was started on oral DDAVP with improvement of polyuria and polydipsia. Additional hormone testing showed normal thyroid function and Cosyntropin stimulation, mild hypogonadotropic hypogonadism, and mild elevation in IGF-1. Pituitary hormone abnormalities were transient and DDAVP was discontinued three months later. However, neurologic symptoms persisted. Repeat pituitary MRI three months later was unchanged. Due to spontaneous resolution of pituitary hormone abnormalities, no biopsy of the hypothalamic pituitary area was performed. Conclusion We present a case of central DI following known SARS-CoV-2 infection. The patient presented with sudden onset polyuria and polydipsia prompting need for pituitary evaluation. Testing confirmed central DI which resolved within three months. Involvement of the HPA was first noted in 2005 by Leow et al. who reported SARS causing reversible hypophysitis.1 We found three similar cases of patients developing DI approximately four weeks following SARS-CoV-2 infection; however only one case with evidence of infundibular hypophysitis.2,5,6 Two contributing mechanisms of HPA dysfunction are thought to be the result of direct hypothalamic damage or reversible hypophysitis.4 The worldwide presence of SARS-CoV-2 and myriad of complications following infection prompts need for further research and follow-up to better determine clinical recovery for SARS-CoV-2. Reference: 1. Leow MK, et al. Hypocortisolism in survivors of severe acute respiratory syndrome (SARS). Clin Endocrinol (Oxf). 2005;63(2): 197-202. 2. Misgar RA, et al. Central diabetes insipidus (Infundibuloneuro hypophysitis): A late complication of COVID-19 infection. J Endocrinol Invest. 2021;44(12): 2855-2856. 3. Nonglait PL, et al. Hypophysitis after COVID-19 Infection. Indian J Endocrinol Metab. 2021;25(3): 255-256. 4. Pal R. COVID-19, hypothalamo-pituitary-adrenal axis and clinical implications. Endocrine. 2020;68(2): 251-252. 5. Rajevac H, et al. DIABETES INSIPIDUS AS A SYMPTOM OF COVID-19 INFECTION: CASE REPORT. Chest. 2020;158(4): A2576. 6. Sheikh AB, et al. Diabetes Insipidus and Concomitant Myocarditis: A Late Sequelae of COVID-19 Infection. Journal of Investigative Medicine High Impact Case Reports. January 2021. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

LBMON139 A Case of Adipsic Diabetes Insipidus In Patient With Third Ventricular Tumor And Right Frontal Craniotomy.

Abstract Introduction Adipsic diabetes insipidus (ADI) is a rare hypothalamic disorder consisting of central diabetes insipidus (CDI) and loss of thirst. In hyperosmolar state, signals from osmosensors integrate in the central thirst center resulting in stimulatory signals between subfornical-oragan, organum-vasculosm of lamina terminalis and median preoptic nucleus increasing thirst and release of vasopressin. Disruption in this mechanism leads to adipsia. Case presentation 27 yr old male with history of prediabetes, 4.6cm third ventricular epidermoid cyst s/p endoscopic ventriculosmoy, hypogonadotropic hypogonadism, central hypothyroidism, and CDI underwent right frontal craniotomy for residual third ventricular cyst. Developed worsening DI, new onset hyperglycemia, and secondary adrenal insufficiency. Discharged with oral DDAVP 300mcg oral twice daily for CDI. 1 week later presented to ED with weakness. BP 132/112, HR 139, RR 38, SPO2 94%. Labs significant for corrected sodium of 172 (136-145mmol/L), glucose 699 (70-99mg/dl), calcium 11.8 (8.3-10.6 mg/dl). Discharged after 3 weeks with intranasal DDAVP 10mcg twice daily (BID). Again presented 1 week after for weakness. Vitals BP 105/64, HR 134, F 37.3 C, RR 31, SPO2 96%. Corrected sodium of 174 (136-145mmol/L) and glucose 708 (70-99mg/dl). Denied missing medication. Reported no increased water intake. Patient was diagnosed with adipsic DI based on subjective lack of thirst during period of significant hyperosmolar hypernatremia state. Overtime switched to 10mcg BID intranasal DDAVP and started on 4L fixed water intake. Had 5L urine output daily. Sodium levels ranged from 132-137. Discharged on intranasal DDAVP 10mcg AM/20mcg PM, 4L daily fixed water intake, and twice weekly sodium checks as outpatient. Goal sodium 135-140. DDAVP adjusted after sodium rose to 145. At recent clinic visit continued fixed 4L fluid intake with extra 500-1L intake for increased sweating/exercise, and sodium level 134. A1c 10% on insulin, and weight gain of 70lbs since surgery (8mon piror), BMI of 45. Started on GLP-1RA and sleep study. Learning points: Less than 100 cases of ADI reported worldwide and associated with increased morbidity/mortality1. This patient likely developed ADI due to disruption of central thirst center from epidermoid cyst and trans frontal craniotomy. We must be hypervigilant for ADI in patients with third ventricular tumors who undergo frontal craniotomy. Management is complex and requires patients are followed closely with weekly labs, either fixed water intake or fixed DDAVP dose and adjustment depending on labs. Important to screen these patients for obesity and sleep apnea given increased likelihood of hypothalamic dysfunction1. Reference: Cuesta, M., Hannon, M. J. &amp; Thompson, C. J. Adipsic diabetes insipidus in adult patients. Pituitary 20, 372-380 (2017). https://doi.org/10.1007/s11102-016-0784-4 Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Serum Sodium Alterations in Children with Primary Monosymptomatic Nocturnal Enuresis Using Desmopressin

Background: Hyponatremia/water intoxication has been considered a rare but serious complication of desmopressin (DDAVP) for the treatment of primary monosymptomatic nocturnal enuresis (PMNE). Objectives: This study aimed to identify the incidence and risk factors of serum sodium (Na) alterations in children with PMNE treated with oral or intranasal DDAVP. Methods: A total of 201 patients with PMNE were evaluated in 2 groups using intranasal (n = 127) or oral DDAVP (n = 74) for approximately 6 months. Treatment efficacy was defined as a more than 50% decrease in wet nights after 1 month of treatment. Serum Na was measured before, during, and after treatment in all patients. Predisposing factors of serum Na disturbance were evaluated concomitantly. Results: The mean age of patients was 8.8 ± 2.6 (5 - 17.5) years, and males outnumbered females (M/F = 1.68). Treatment efficacy was 100% in 93 (46.2%), and &gt; 90% in 157 (78.1%) cases. Oral DDAVP had significantly more therapeutic effects than intranasal treatment (P = 0.024). However, serum Na had no significant difference between the 2 groups (P = 0.52). Hyponatremia occurred in 7 (3.5%) patients (3 in oral treatment and 4 in intranasal treatment; P = 0.73) with no significant correlation to age, gender, body weight, frequency of enuresis, and initial serum Na. However, decreased serum Na &gt; 5 mEq/L was a significant risk factor for the prediction of hyponatremia in our patients (P &lt; 0.001). Conclusions: Oral DDAVP had more therapeutic effects than intranasal treatment for the treatment of PMNE. Serum Na had no significant alteration in both oral and intranasal treatments, and hyponatremia was a rare complication of DDAVP, which occurred significantly in children with a &gt; 5-mEq/L decrease of initial serum Na concentration. As a suggestion, monitoring serum Na is not an essential follow-up in asymptomatic patients in DDAVP treatment.

Pretreatment morning urine osmolality and oral desmopressin lyophilisate treatment outcome in patients with primary monosymptomatic enuresis.

To determine the association between urine osmolality (Uosm) in patients with primary monosymptomatic enuresis (PMNE) and response to desmopressin (dDAVP) lyophilisate. This was a prospective cohort study that included 419 children with enuresis seen in outpatient clinic between October 2017 and October 2019. Patient workup included symptom checklist, 48h frequency/volume chart, kidney and bladder ultrasound, uroflow, urinalysis and culture, spot urine Ca/creatinine, and first-morning Uosm. Patients < 5years, with secondary enuresis, or loss of follow-up were excluded. Oral dDAVP lyophilisate was recommended to all with PMNE and normal bladder capacity. After 1month of therapy, initial success was assessed according to ICCS. Significant predictor variables for complete response were identified and analyzed using correlation coefficients and binary logistic regression. There were 48 patients with PMNE who received dDAVP and were followed for treatment success. Partial and complete responses were achieved for 14 (29.2%) and 20 cases (41.7%), respectively. Older age and lower Uosm were found to be significantly in favor of complete response to dDAVP lyophilisate, P = 0.007 and 0.033, respectively. ROC analysis determined the Uosm of ≤ 814mOsm/kg as a cut-off value for complete success (sensitivity 65% and specificity 75%, AUC = 68.2%). The odds ratio for complete success for selected cut-off value was 5.57 (95% CI 1.588-19.551, P = 0.007). High pretreatment morning Uosm (> 814mOsm/kg) might be suggestive of an alternative treatment to dDAVP lyophilisate in PMNE because of the higher risk of treatment failure.

Central Diabetes Insipidus in a Child due to Histiocytosis X

Central diabetes insipidus (CDI) occur due to deficiency of vasopressin which is synthesized in supraoptic and paraventricular nuclei of hypothalamus and stored in posterior pituitary. There are many causes of CDI among them histiocytosis X or lymphohistiocytosis (LCH) is a rare cause. Here we are reporting a 2 years old boy with histiocytosis-Xor presented with CDI. The boy presented with polyuria and polydipsia, low urine specific gravity and osmolality with normal blood sugar and osmolality. Positive response to water deprivation test followed by oral DDAVP establish the diagnosis of CDI. X-Ray skull showed osteolytic punched out lesion and T1 weighted MRI of brain showed thickening of pituitary stalk with absence of bright signal of posterior pituitary. Trephine biopsy showed bone marrow was infiltrated by many eosinophil, some macrophage, lymphocyte and plasma cells. On the basis of all these diagnosis was made as CDI due to histiocytosis-X. Due to hypothalamic- pituitary axis infiltration CDI may be the earliest manifestation of LCH, even before it is diagnosed. Therefore, for diagnostic workup of CDI, LCH should be considered.&#x0D; Northern International Medical College Journal Vol. 11 No. 1 July 2019, Page 432-434

SUN-278 Isolated Hypothalamic Langerhans Cell Histiocytosis in an Adult Manifesting as Panhypopituitarism

Background: Langerhans Cell Histiocytosis (LCH) is a rare disease characterized by abnormal proliferation of bone marrow derived histiocytes. Although predominantly a childhood disease, LCH can occur at any age and has an incidence of one to two cases per million in adults. LCH can involve a single organ or present as disseminated disease. Sites most commonly affected are bone, skin, bone marrow and pituitary. Isolated hypothalamic LCH is a rare entity. A few reports of LCH presenting as a hypothalamic mass exist but mainly in children. Treatment of adult LCH is derived from pediatric studies, and no standard of care exists. We report a unique case of an adult with panhypopituitarism secondary to a hypothalamic mass found to be biopsy proven isolated LCH treated with Vemurafenib, a BRAF V600E inhibitor. Clinical Case: A 66-year-old previously healthy man presented with progressively increasing confusion, cognitive decline and generalized weakness requiring hospital admission. Laboratory evaluation revealed an 8AM cortisol of 2.5 ug/dL (reference [ref] 7.0–25.0 ug/dL), ACTH of 9.3 pg/mL (ref 8–42 pg/mL), TSH of 0.106 uIU/mL (ref 0.35–5.5 uIU/mL), free T4 of 0.67 ug/dL (ref 0.7–1.25 ng/dL), LH <0.2 IU/L (ref 0.5–11 IU/L), FSH 0.6 IU/mL (ref 1–12 IU/L), total testosterone <12 ng/dL (ref 193 - 824 ng/dL), free testosterone <3.3 pg mL (ref 41.7 - 180.2 pg/mL), IGF1 41 ng/mL (ref 33–220 ng/mL) and prolactin of 31.5 ng/mL (ref 3.5–15 ng/mL). Findings were consistent with panhypopituitarism, and he was started on glucocorticoid and levothyroxine replacement therapy. MRI pituitary revealed an 18.1 x 13.8 x 15.8 mm hypothalamic mass with signal intensity alteration in the optic pathway. Patient developed polyuria with a serum sodium of 148 mmol/L (ref 136–145 mmol/L), elevated serum osmolality and low urine osmolality consistent with central DI and was started on oral DDAVP.The patient underwent right sided neuroendoscopic intraventricular biopsy of hypothalamic mass. Pathology was consistent with LCH with immunohistochemistry staining for CD1a, Langerin and BRAFV600E, with occasional cells staining for CD68, CD163 and S100. Bone marrow biopsy was normal. A NM PET scan revealed a hypermetabolic hypothalamic mass compatible with LCH without evidence of involvement of other sites including the skeletal system. Given histopathologically confirmed BRAF-mutated LCH, treatment with Vemurafenib was initiated. Behavioral changes gradually improved, and repeat MRI brain three months after treatment revealed decrease in size of hypothalamic mass. Conclusion: Isolated hypothalamic LCH is exceedingly rare. No clear guidelines exist for treatment of LCH in adults. BRAFV600E mutations are found in more than fifty percent of LCH cases and are associated with worse outcomes. This case demonstrates the successful use of targeted BRAF inhibitor therapy in an adult patient with BRAF mutated hypothalamic LCH.

Analysis of Bleeding and Treatment Patterns in Children and Adolescents before and after Von Willebrand Disease Diagnosis Using Data from a US Medical Claims Database

Analysis of Bleeding and Treatment Patterns in Children and Adolescents before and after Von Willebrand Disease Diagnosis Using Data from a US Medical Claims Database

SUN-410 Central Diabetes Insipidus Refractory to Oral Desmopressin (DDAVP)

Background We report a case of CDI due to craniopharyngioma resection that became refractory to oral DDAVP after recurrence of tumor and subsequent surgical removal. Due to inability of patient to use the intranasal route, subcutaneous (SC) DDAVP was used successfully. Clinical Case An 11-year male developed CDI after craniopharyngioma removal and proton beam therapy. He developed also panhypopituitarism, hypothalamic obesity, and had an impaired thirst mechanism. CDI was managed with oral DDAVP and fix fluid intake. After 2 years he had a tumor recurrence and a surgical removal complicated by a stroke. Since then his DDAVP dose had to be increased progressively due to poor CDI control. He presented to our hospital with severe hypernatremia and a urine output of 4-5 liters a day. DDAVP dose was eventually titrated up to 800 mcg bid. He was placed on minimum fluid intake of 3 Liters a day. Even with this dose he was putting out 4 liters of urine daily. Intranasal DDAVP was not considered due to poor cooperation of patient and nasal mucosa scarring. SC DDAVP was started at a dose of 1 mcg (0.01 mcg/Kg) twice a day.Dose increments were made by 0.5 mcg every 2 days to avoid hyponatremia. Prior to therapy patient received 4 liters/day and was progressively decreased, as DDAVP dose was increased, to 1.7 liters/day. Patient was discharged home on 4.5 mcg in the morning and 5.5 mcg at night time (0.14 mcg/kg/day). Discussion The route of administration of DDAVP varies depending on the age and cooperation of the patient to use the different forms available. DDAVP has also haemostatic effect. It is used in the treatment or to prevent bleeding in patients with von Willebrand disease, haemophilia A and platelet function defects. We hypothesize that our patient became resistant to the action of oral DDAVP probably due to the development of antibodies that were interfering with the appropriate absorption from the gastrointestinal tract. The parenteral/SC route dose ranges from 0.1-1 mcg in one or two divided doses nevertheless our patient had a stroke and we were concerned about the maximum dose that it could be used without increasing the risk of causing a new thrombotic event. With no data available about the use of DDAVP in this specific setting, we decided to use as a limit the dose used to treat bleeding disorders (0.3 mcg/Kg).Since our patient had basically an adult weight (70kg) we have enough room to continue increasing the dose up until desire effect was reached keeping in mind that 20 mcg/day is the maximum dose used in adults with bleeding disorders. Since discharge his sodium has remained stable as also his urine output and he has been able to reassume his daily activities. Conclusion: We present a case of CDI refractory to oral DDAVP.SC DDAVP was used and after slow titration patient was able to reach stable sodium levels and urine output with no side effects. Final dose was less than 50% of the dose used to treat bleeding disorders.

SUN-407 A Clinical Lesson in Adipsic Diabetes Insipidus

Background: Adipsic diabetes insipidus (ADI) is a rare condition with approximately 100 reported cases word wide. Inpatient management can be challenging as patients are predisposed to dysnatremia during this time. Societal guidelines offer little guidance in management of this complex disease. Case: A 62-year-old woman with a history of acromegaly with transphenoidal resection more than 20 years ago, complicated by post-operative hypothyroidism, adrenal insufficiency and adipsic diabetes insipidus presented for admission for a planned cycle on of chemotherapy for her recently diagnosed diffuse large B-cell lymphoma. At admission her initial serum sodium was 130 mmol/L (reference 135-145 mmol/L) near her baseline level. During her 8 day stay she experienced significant fluctuations of serum sodium with a peak level of 151 mmol/L and a nadir of 123 mmol/L. Despite these shifts she experienced no adverse neurological symptoms. 3 weeks later she was again admitted for planned chemotherapy. During this admission she received the same medication treatment protocol as her prior stay, however, the management principles for ADI suggested by Cuesta et al. were applied. The result was a more stable serum sodium with a range of 130-145 mmol/L and no change in concentration by more than 5 mmol/L in a single 24 hour period. Patient was clinically stable and asymptomatic throughout her hospital stay Discussion: When compared to diabetes insipidus with intact thirst sensation, patients with ADI have been shown to be at increased risk for both hypernatremia and hyponatremia during inpatient admission. The risk is further increased when the admission is for an illness not related to pituitary dysfunction. This case represents an important clinical lesson in ADI where simple management principles led to a drastic change in the patient’s serum sodium. Fortunately, this patient tolerated the sodium shifts well, and did not require critical care interventions to correct her dysnatremia. Among the most important principles were transition from intranasal to oral DDAVP for a more predictable treatment response and the use of oral fluids instead of IV whenever possible. Applying these principles at the time of admission allowed for a better understanding of the treatment goals by the multidisciplinary healthcare team. Although ADI is rare, applying these simple interventions at the time of admission is likely to benefit all patients with diabetes insipidus.

MON-420 Diffuse Large B-Cell Lymphoma Presenting as Hypernatremia Secondary to Adipsic Central Diabetes Insipidus

Background: Central diabetes insipidus is usually characterized by polyuria and polydipsia secondary to deficiency in anti-diuretic hormone. In some cases, patients can have hypothalamic or thalamic involvement leading to an impaired thirst mechanism. Here we present a case of a primary central nervous system (CNS) diffuse large B-cell lymphoma which presented as hypernatremia secondary to adipsic central diabetes insipidus. Clinical Case: A 53-year-old female presented to the hospital with confusion and lethargy. Family noted increased urinary frequency. She had been hospitalized at a different facility three times prior for hypernatremia. On admission, she was found to have sodium elevated to 160 mmol/L (135-145). Urine studies were notable for initial urine osmolality 360 with repeat low-normal at 144 mOsm/kg (50-1400), random urine sodium 36 mmol/L, and urine specific gravity <1.005 (1.005-1.03). Further workup included hemoglobin A1C 6.5% (4-6), serum osmolality range 282-311 mOsm/kg (280-300), and normal TSH and free T4. ADH drawn when sodium was 150 mmol/L was undetectable. ACTH stimulation test was normal at 22.6 ug/dL (>18). Free water deficit was calculated at 8 liters. MRI brain showed a 4.1 x 3.5 x 2 cm mass in the right posterior pons extending to the right cerebral peduncle and thalamus with mass effect on the third ventricle. She was hydrated with intravenous D5W then with ½ normal saline. Her urine output was 3.5-5 liters/day. She was given 1 mcg/mL DDAVP injection with urine osmolality increasing from 145 mOsm/kg to 280 mOsm/kg with a greater than 50% increase consistent with central diabetes insipidus. She was started on oral DDAVP prior to discharge with improvement in mental status. She underwent stereotactic brain biopsy with pathology demonstrating primary diffuse large B-cell lymphoma. CT chest/abdomen/pelvis was negative for primary disease and bone marrow biopsy showed no evidence of lymphoma. She was started on chemotherapy with rituximab, methotrexate, procarbazine, and vincristine with CT brain two weeks later showing rapid decrease in the size of the thalamic and midbrain mass. Conclusions: Although pituitary involvement in lymphomas is rare, there are a few cases in the literature describing posterior pituitary involvement in the setting of a primary CNS lymphoma which should be considered in new-onset, non-traumatic central diabetes insipidus. In patients with impaired thirst mechanism, evaluation of the hypothalamus and thalamus should be pursued.

Neonatal central diabetes insipidus in a case of hydranencephaly

Neonatal diabetes insipidus (DI) poses both diagnostic and therapeutic challenge to the neonatologists. Neonatal central DI (CDI) is an uncommon disorder which is characterized by polyuria, hypernatremia, high plasma osmolality, and low urine osmolality. Our full-term neonate with an antenatal magnetic resonance imaging showing hydranencephaly presented to us on day 4, with persistent hypernatremic dehydration along with the polyuria which was not getting corrected by the routine management of hypernatremic dehydration. Further investigations revealed urine hypo-osmolality and high serum osmolality and a good response to oral desmopressin (DDAVP). This helped to diagnose CDI secondary to hydranencephaly. The baby was discharged on oral DDAVP, but unfortunately, the baby succumbed at 3 months of age.

Quality of life in the patients with central diabetes insipidus assessed by Nagasaki Diabetes Insipidus Questionnaire

Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia due to a deficiency of vasopressin. Currently, the treatment goal for CDI is improvement of quality of life (QOL) by desmopressin (DDAVP) without developing hyponatremia. However, there is no reliable measure for QOL in CDI patients. We evaluate our original questionnaire for QOL, consisting of 12 questions focusing on polyuria, polydipsia, and DDAVP treatment, in CDI patients who underwent a switch from nasal spray to oral disintegrating tablets of DDAVP. Twenty-five CDI patients under nasal DDAVP treatment, six with newly developed CDI, and 18 healthy individuals without known polyuric/polydipsic disorders as control subjects were enrolled. QOL scores were determined by our questionnaire at the enrollment and 3 months after the start of oral DDAVP treatment and were examined by the Wilcoxon signed-rank test. Eleven questions detected improvement in QOL. The sum of the QOL scores of the eleven questions increased from 29.2 ± 5.6 under nasal to 36.8 ± 4.5 under oral DDAVP (p < 0.001). There were no clinically relevant changes in serum levels of Na. After eliminating two questions about DDAVP treatment, the sum of QOL scores was 15.3 ± 6.5 in untreated CDI patients, 24.4 ± 5.2 in those with nasal treatment, 28.9 ± 4.9 in those with oral DDAVP, and 29.5 ± 3.6 in healthy controls. The difference among groups was significant (p < 0.05 in Steel-Dwass test) except between patients treated with oral DDAVP and healthy controls. Our questionnaire can be used to accurately assess QOL in CDI patients.

PO-0088 Hypothalamic Disturbances Can Mask Pituitary Pathologies: A Case Of Adipsic Central Diabetes Insipidus, Growth Hormone Deficiency And Hyperprolactinaemia

<h3>Background</h3> This six year old girl unusually has central diabetes insipidus without polydipsia; with accompanying growth hormone deficiency and hyperprolactinaemia. She presented with 2 years of worsening breathlessness on minimal exertion, weight gain, poor linear growth and marked sweating in all weathers. Initial assessment revealed short stature (Height SDS-3.0), obesity (BMI 98th centile) and mild dehydration. <h3>Methods</h3> Investigations demonstrated hypernatraemia (sodium 168 mmol/L), hyperprolactinaemia (prolactin 3341 miu/L), normal thyroid function and low Insulin-like growth factor-1. MRI pituitary demonstrated no microprolactinoma or other CNS lesion. Extremely low peak GH 0.5 ug/L (normal &gt;7 ug/L) on Insulin tolerance testing indicated growth hormone (GH) deficiency, but normal cortisols. Inpatient assessment demonstrated absence of thirst despite persisting hypernatraemia, high serum osmolality (356mOsmol/kg), inappropriately dilute urine (79mOsmol/kg) and urine output 4ml/kg/hour. Low serum vasopressin 1.4 pmol/L. Negative tumour markers. <h3>Results</h3> GH replacement was extremely effective with improvement in height and normalisation of BMI. Managing her adipsic DI was challenging. Increasing oral intake of 1800 ml/day was insufficient. DDAVP IM achieved urinary concentration (779mOsmol/kg), but Oral DDAVP was ineffective, despite high daily dose 1000 ug. Normalisation of serum sodium and urine output was finally achieved with nasal DDAVP, although slight hyperosmolality persists. The patient has continued to experience excessive sweating. Serial MRIs continue to be normal. <h3>Conclusion</h3> This unusual case of adipsic diabetes insipidus with excessive sweating is likely to represent hypothalamic dysfunction although no structural lesion is identified on MRI brain. Case series of adipsic diabetes insipidus have identified a high frequency of hypothalamic abnormalities associated with significant morbidity and mortality.