Low Urine Osmolality Research Articles

Congenital nephrogenic diabetes insipidus with a novel variant of AVPR2 gene mutation: A case report

ABSTRACT Congenital nephrogenic diabetes insipidus (CNDI) is a rare genetic disorder characterized by impaired water reabsorption despite normal or elevated levels of antidiuretic hormone. We report a 6-month-old male with classical symptoms of CNDI, such as fever, excessive thirst, polyuria, and failure to thrive. Laboratory investigations revealed hypernatremia, low urine osmolality, and a lack of response to a vasopressin challenge, confirming the diagnosis. Genetic testing identified a hemizygous base pair deletion in the AVPR2 gene, leading to a frameshift mutation and premature protein truncation. Treatment strategies, including hydrochlorothiazide and amiloride therapy, aim to manage symptoms and improve quality of life. Long-term management involves monitoring growth, hydration status, and genetic counseling for affected families. This case highlights the importance of early recognition and management of CNDI to prevent long-term sequelae. Further research into genetic variations and novel therapeutic approaches is warranted to improve outcomes for these children.

Low daily water intake profile-is it a contributor to disease?

Few previous review articles have focused on the associations between inadequate daily water intake (LOW) or urinary biomarkers of dehydration (UD; low urine volume or high urine osmolality) and multiple diseases. Accordingly, we conducted manual online searches (47 key words) of the PubMed, Embase, and Google Scholar databases with these inclusion criteria: English language, full-text, peer reviewed, no restriction on research design, and three publications minimum. Initially, 3,903 articles were identified based on their titles and abstracts. Evaluations of full length .pdf versions identified 96 studies that were acceptable for inclusion. We concluded that the evidence is insufficient or conflicting for seven disorders or diseases (i.e. suggesting the need for additional clarifying research) and it is lacking for all-cause mortality. Differential characterizations among women and men have been reported in the results of nine studies involving five diseases. Finally, the evidence for associations of LOW or UD is strong for both kidney stones and type 2 diabetes with hyperglycemia. This suggests that great public health value (i.e. reduced disease risk) may result from increased daily water intake-a simple and cost-effective dietary modification.

A case of central diabetes insipidus after COVID-19 as a probable diagnosis of lymphocytic infundibulo-neurohypophysitis with positive anti-rabphilin-3A antibodies with review of literature.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, and various complications have been reported. Furthermore, there have been increasing reports of endocrinopathy related to COVID-19 following the pandemic. We report a 49-year-old healthy woman who developed rapid onset of polydipsia and polyuria three weeks after COVID-19. Laboratory tests indicated low urine osmolarity and increased serum osmolarity, and antidiuretic hormone (ADH) was undetectable. Urine osmolality remained low with water deprivation. Similarly, plasma ADH responses to hypertonic-saline infusion were blunted and urine osmolality increased in response to desmopressin. There was no clear evidence of anterior pituitary dysfunction. T1-weighted magnetic resonance imaging (MRI) showed pituitary stalk thickening and absence of posterior pituitary bright signal spots, suggesting the presence of hypophysitis. Based on these results, we made a probable diagnosis of lymphocytic infundibulo-neurohypophysitis (LINH) which have caused central diabetes insipidus. Positive findings for serum anti-rabphilin-3A antibodies, reported as a potential diagnostic marker for LINH, were also noted. Following oral desmopressin administration, polydipsia and polyuria were quickly improved, though treatment with desmopressin was still required over four months. This is the first report of a patient with a probable diagnosis of LINH after COVID-19 who tested positive for anti-rabphilin-3A antibodies. Positive findings for those antibodies suggest that pituitary dysfunction associated with COVID-19 is hypophysitis involving an abnormal immune mechanism. The presence of anti-rabphilin-3A antibodies may be useful as a non-invasive diagnostic marker of LINH and potentially serve as a valuable diagnostic aid in cases of LINH associated with COVID-19.

FRI333 Neurosarcoidosis Induced Panhypopituitarism​

Abstract Disclosure: K. Alfares: None. H. Jeong Han: None. S. Athimulam: None. Introduction: We hereby present a rare case of neurosarcoidosis causing panhypopituitarism. According to Martin-Grace et al who conducted a literature search for the timeframe of 2002 to 2014, there were only 8 cases of neurosarcoidosis associated pan hypopituitarism. Case Report: A 35-year-old male with a known diagnosis of sarcoidosis on skin biopsies presented to the hospital for altered mental status, hypernatremia, hypotension and hypothermia. He reported symptoms of polyuria and polydipsia for several weeks prior to admission. MRI of the brain revealed a 3cm mass in the suprasellar region involving the hypothalamus and bilateral optic tracts with mass effect on the anterior third ventricle. No discrete pituitary or stalk lesion was identified. A ventriculostomy tube was placed for developing hydrocephalus. Biopsy of the suprasellar mass revealed non-caseating granuloma, confirming neurosarcoidosis. Laboratory work up revealed elevated serum sodium at 167 mmol/L, high serum osmolality at 381 mOsm/kg and low urine osmolality at 381 mOsm/kg, consistent with diabetes insipidus. Anterior pituitary hormone profile work up revealed low 8am serum cortisol (1.9 mcg/dL) and inappropriately normal ACTH (34 pg/ml), low serum free testosterone (<2.5 ng/dL) and low Luteinizing hormone (0.7 mIU/ml) and low follicular stimulating hormone (< 2.6 mIU/ml), low free T4 at 0.4 ng/dL and inappropriately normal TSH at 2.77 uIU/mL. Serum prolactin was mildly elevated at 86.8ng/mL. Angiotensin converting enzyme level was within normal range at 33 U/L. A diagnosis of panhypopituitarism was made. Treatment was initiated with high dose IV corticosteroids for management of secondary adrenal insufficiency and neurosarcoidosis. He was also started on IV desmopressin and IV levothyroxine for management of his panhypopituitarism. He was transitioned to oral therapy on discharge. Discussion: Panhypopituitarism secondary to neurosarcoidosis is a rare presentation. Panhypopituitarism from sarcoidosis can occur due to infiltration of the pituitary gland or infiltration of the hypothalamus affecting the hypothalamic-pituitary axis. Sarcoidosis should be considered a differential when evaluating patients with symptoms consistent with panhypopituitarism. Prompt diagnosis and initiation of corticosteroids and deficient hormones can be lifesaving. Presentation: Friday, June 16, 2023

FRI355 Hypokalemia-induced Nephrogenic Diabetes Insipidus In A Patient With Medullary Thyroid Carcinoma And Paraneoplastic Cushing’s Syndrome

Abstract Disclosure: S. Jhawar: None. S. Jumani: None. Y. Sterrett: None. H. Elenius: None. P. Veeraraghavan: None. C. Ryan: None. J. Del Rivero: None. S.M. Sadowski: None. N. Nilubol: None. J.G. Verbalis: None. L.K. Nieman: None. E. Globa: None. M.S. Zemskova: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Introduction: Nephrogenic diabetes insipidus (NDI) is commonly associated with the use of medications such as lithium, antibiotics, and chemotherapeutic agents or with renal disorders. Rarely, NDI can be a manifestation of paraneoplastic conditions. We describe a case of NDI caused by severe hypokalemia in a patient with metastatic medullary thyroid cancer (MTC) and paraneoplastic Cushing’s syndrome (CS). Clinical Case: A 47-year-old male with sporadic, metastatic MTC (RET M918T pathogenic variant) was referred to our institution for further management. The patient had florid metastases to the liver, lungs, and skeleton, with a calcitonin of 158,535 pg/mL [normal (NL): <14.3], and a CEA of 3,634 pg/mL (NL: 0.8-3.4), but surprisingly, without an intrathyroidal primary tumor. Vandetanib and octreotide were previously trialed but discontinued due to financial constraints. The patient had diarrhea, but no other symptoms. Physical exam revealed cervical lymphadenopathy, facial plethora, dorsocervical fat pad, and a single purple stria on the chest. Further work up revealed markedly elevated 24-hr urine free cortisol (12,460 mcg/24hr; NL: 35-45), ACTH 116 pg/mL (normal 5.0-46.0), and an undetectable serum aldosterone and plasma renin activity, raising suspicion for paraneoplastic ectopic-CS. Immunostaining of the MTC biopsy specimen showed ACTH positivity. During the inpatient admission, polyuria of >3L/day was noted on two consecutive 24-hour urine measurements. Laboratory investigations revealed hypernatremia (serum sodium: 147 mmol/L; NL: 136-145), elevated serum osmolality (303 mOsm/Kg; NL: 278-298), and a low urine osmolality (215 mOsm/kg; NL: 300-900), thus establishing the diagnosis of DI. A simultaneous, elevated plasma copeptin (36.3 pmol/L; NL: <13.1) further suggested NDI. Also noted was severe hypokalemia (serum potassium: 1.7 mmol/L; NL: 3.5-5.1), with normal serum magnesium and calcium. A thorough review of patient’s medication list did not reveal any culprit drug for hypokalemia or NDI. Hypokalemia was managed with aggressive oral and intravenous potassium repletion. A bilateral adrenalectomy was performed to treat the ectopic-CS, which improved the hypokalemia and resolved the NDI. Three months later, the patient unfortunately died due to progression of MTC. Conclusion: Severe hypokalemia causes autophagic degradation of aquaporin-2 channels in the renal tubules and is an under-recognized cause of NDI. Profound hypercortisolism in ectopic-CS may result in cortisol-mediated overactivation of mineralocorticoid receptors that can cause renal potassium loss leading to NDI. Only 0.6% of MTCs are associated with ectopic-CS (PMID: 16029131). Our report highlights hypokalemia-induced NDI as a manifestation of paraneoplastic CS resulting from MTC. Presentation: Friday, June 16, 2023

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

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

FRI326 Hypophysitis: A Formidable Diagnostic Challenge

Abstract Disclosure: S. Pandey: None. C. Houston: None. Background: Hypophysitis, defined as inflammation of the pituitary gland, may pose a formidable diagnostic challenge due to its protean clinical manifestations and growing spectrum of potential causes. We present a case of a young man with presumed hypophysitis in whom the etiology remains unknown. Case Summary: A previously healthy 20-year-old male with bilateral gynecomastia was referred to the endocrinology clinic. He reported a 1-year history of worsening fatigue, weight gain, intermittent headaches, bilateral breast enlargement, lack of morning erections, polydipsia, and polyuria. His childhood growth and pubertal development were reportedly normal. He denied prior head or testicular trauma, major systemic illnesses, and chronic opiate or glucocorticoid use. His physical exam was remarkable only for scant facial hair and bilateral nontender gynecomastia. His visual fields were normal, and sense of smell was intact. Laboratory evaluation at 8am revealed low total and free testosterone of 32 ng/dL (240-950) and 0.98 ng/dL (5.25-20.7), respectively, with LH of 1.4 mIU/mL (1.0-12.0) and FSH of 1.9 mIU/mL (1.0-12.0). Free T4, prolactin, IGF-1, and serum sodium were all within normal ranges. Serum cortisol was modestly elevated at 22.3 ug/dL (3.7-19.4) with normal ACTH of 49 pg/mL (7.2-63.0). Pituitary MRI showed diffuse thickening and enhancement of the pituitary stalk, compatible with infundibular hypophysitis, without evidence of mass effect upon the native gland or surrounding structures. Additional testing showed normal levels of serum calcium, iron, ferritin, ESR, and antinuclear antibodies. After overnight water deprivation, his serum sodium was elevated at 156 mmol/L (134-144) with low urine osmolality of 121 mOsmol/kg (300-900). He was started on desmopressin and testosterone, and close clinical monitoring was enacted. Conclusion: The diagnosis of hypophysitis poses multiple challenges. Its clinical manifestations can vary widely, including symptoms related to mass effect and/or symptoms of pituitary dysfunction. Diagnosis is often presumptive based on history and exam, biochemical evaluation, and neuroimaging. The spectrum of potential causes is broad and growing, including infiltrative, infectious, neoplastic, immunoglobulin G4-related, immunotherapy-induced, other autoimmune, and paraneoplastic causes. It is often a humbling experience for clinicians to narrow this exhaustive differential. Pituitary biopsy is the gold standard for diagnosis but poses significant risks, so is reserved for cases when the diagnosis remains uncertain or malignancy is suspected. Close clinical monitoring and re-evaluation is an acceptable alternative in select cases. Presentation: Friday, June 16, 2023

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

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

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

Prostaglandin E2, Osmoregulation, and Disease Progression in Autosomal Dominant Polycystic Kidney Disease.

Prostaglandin E2 (PGE2) plays a physiological role in osmoregulation, a process that is affected early in autosomal dominant polycystic kidney disease (ADPKD). PGE2 has also been implicated in the pathogenesis of ADPKD in preclinical models, but human data are limited. Here, we hypothesized that urinary PGE2 excretion is associated with impaired osmoregulation, disease severity, and disease progression in human ADPKD. Urinary excretions of PGE2 and its metabolite (PGEM) were measured in a prospective cohort of patients with ADPKD. The associations between urinary PGE2 and PGEM excretions, markers of osmoregulation, eGFR and height-adjusted total kidney volume were assessed using linear regression models. Cox regression and linear mixed models were used for the longitudinal analysis of the associations between urinary PGE2 and PGEM excretions and disease progression defined as 40% eGFR loss or kidney failure, and change in eGFR over time. In two intervention studies, we quantified the effect of starting tolvaptan and adding hydrochlorothiazide to tolvaptan on urinary PGE2 and PGEM excretions. In 562 patients with ADPKD (61% female, eGFR 63±28 ml/min per 1.73 m 2 ), higher urinary PGE2 or PGEM excretions were independently associated with higher plasma copeptin, lower urine osmolality, lower eGFR, and greater total kidney volume. Participants with higher baseline urinary PGE2 and PGEM excretions had a higher risk of 40% eGFR loss or kidney failure (hazard ratio, 1.28; 95% confidence interval [CI], 1.13 to 1.46 and hazard ratio, 1.50; 95% CI, 1.26 to 1.80 per two-fold higher urinary PGE2 or PGEM excretions) and a faster change in eGFR over time (-0.39 [95% CI, -0.59 to -0.20] and -0.53 [95% CI, -0.75 to -0.31] ml/min per 1.73 m 2 per year). In the intervention studies, urinary PGEM excretion was higher after starting tolvaptan, while urinary PGE2 excretion was higher after adding hydrochlorothiazide to tolvaptan. Higher urinary PGE2 and PGEM excretions in patients with ADPKD are associated with impaired osmoregulation, disease severity, and progression.

Central diabetes insipidus following COVID-19 mRNA vaccination: a case report

The coronavirus disease 2019 (COVID-19) has been a major public health emergency worldwide. Vaccines were rapidly developed and approved to prevent the spread of viral infection. However, various side effects of the COVID-19 messenger RNA (mRNA) vaccines have been reported after their commercialization. A 24-year-old man visited our emergency department with polyuria and polydipsia that occurred after he received a COVID-19 mRNA vaccine 10 days beforehand. The initial laboratory findings showed very low urine osmolality with hyperosmolar hypernatremia. Based on these findings, diabetes insipidus was suspected, and sella magnetic resonance imaging showed an enlarged pituitary gland and the absence of posterior pituitary higher intensity. After 12 hours of using oral desmopressin acetate, urine volume decreased, and after 5 days of administration, serum electrolyte and serum osmolality improved. This case report of diabetes insipidus occurring after vaccination with the BNT162b2 mRNA COVID-19 vaccine is presented as a reminder that close monitoring is necessary for patients with polyuria and polydipsia after vaccination.

Transient diabetes insipidus in critically ill COVID19 patients

PurposeVasopressin has become an important vasopressor drug while treating a critically ill patient to maintain adequate mean arterial pressure. Diabetes insipidus (DI) is a rare syndrome characterized by the excretion of a large volume of diluted urine, inappropriate for water homeostasis. We noticed that several COVID19 patients developed excessive polyuria suggestive of DI, with a concomitant plasma sodium-level increase and/or low urine osmolality. We noticed a temporal relationship between vasopressin treatment cessation and polyuria periods. We reviewed those cases to better describe this phenomenon. MethodsWe retrospectively collected COVID19 ECMO patients' (from July 6, 2020, to November 30, 2021) data from the electronic medical records. By examining urine output, urine osmolality (if applicable), plasma sodium level, and plasma osmolality, we set DI diagnosis. We described the clinical course of DI episodes and compared baseline characteristics between patients who developed DI and those who did not. ResultsOut of 37 patients, 12 had 18 episodes of DI. These patients were 7 years younger and had lower severity scores (APACHE-II and SOFA). Mortality difference was not seen between groups. 17 episodes occurred after vasopressin discontinuation; 14 episodes were treated with vasopressin reinstitution. DI lasted for a median of 21 h, with a median increase of 14 mEq/L of sodium. ConclusionsTemporary DI prevalence after vasopressin discontinuation in COVID19 ECMO patients might be higher than previously described for vasopressin-treated patients.

AW-NI-6: MINERALOCORTICOID RECEPTOR ACTIVATION LEADS TO HIGH BLOOD PRESSURE DUE TO BODY POTASSIUM AND WATER LOSS

Objective: Mineralocorticoid receptor (MR) activation is known to reduce renal Na+ elimination and increase body fluid, resulting in arterial hypertension. We have reported earlier that high salt intake, chronic renal failure and psoriasis occur blood pressure increases initiated by body water loss. Here we tested the hypothesis that DOCA treatment induces a similar adaptive water conservation response that also causes arterial hypertension. Design and method: Male C57BL/6J mice on the low-salt diet (<0.1% NaCl) were divided into four groups: tap water (control), tap water with subcutaneous 25 mg DOCA (DOCA), 1% NaCl water with DOCA (DOCA salt), 1.44% NaHCO3 water with DOCA (DOCA NaBic). We performed continuous metabolic cage studies. Na+, K+, and water were measured in mice tissue by desiccation and consecutive dry ashing. Blood pressure was measured by telemetry. We also studied body composition, glucocorticoid-receptor (GR) protein/chromatin interaction, skin blood flow perfusion and renal vascular resistance. Metabolome and key enzyme activities of energy production in kidney, skeletal muscle and in liver were compared between four groups. Results: Compared to control mice, DOCA mice showed increased urine volume, lower urine osmolality and increased blood pressure. DOCA salt developed arterial hypertension within 3 days of the experiment (P < 0.001, Fig. 1A). In DOCA salt mice, K+ and water loss occurs in the initiation phase of arterial hypertension (Fig. 1B), indicating solute and water loss from the intracellular space. Further water loss was then prevented by secondary Na+ accumulation, indicating that the initial MR-driven dehydration reverted back to normal body fluid level by means of Na+ accumulation. Additional physiological adaptation to DOCA salt-driven body water loss included increased vascular resistance (Fig. 1C) and catabolic amino acid breakdown (Fig. 1D). DOCA NaBic mice showed similar massive primary K+ loss and secondary Na+ retention, but no arterial hypertension occurred (Fig. 1A). While DOCA salt decreased skin blood flow, DOCA NaBic increased it (Fig. 1C). DOCA salt mice showed renal glutamine catabolism as well as muscle protein catabolism (Fig. 1D). This catabolic state was coupled with glucocorticoid receptor binding in skeletal muscle. Conclusions: DOCA salt leads to pronounced initial K+ and water loss with hypertension. Na+ retention occurs only secondarily and is a compensatory response that reverts initial body water loss back to normal body water levels. Additional NaBic feeding reveals that the blood pressure level in mice with MR activation is determined by changes in blood flow independent of body Na+ or water content.

ODP332 Maternal Central Diabetes Insipidus Immediately after Delivery, Owing to Vasospasm of the Internal Carotid Artery

Abstract Background Sheehan's syndrome is a cause of hypopituitarism during the postpartum period, but it rarely manifests immediately after birth. Clinical Case We report the case of a 30-year-old woman who delivered her second child, lost 1,050 mL of blood in the process, but did not receive a blood transfusion. A few hours after delivery, the patient complained of headache, nausea, and thirst, and her urine production increased to 9 L/day. No menstrual irregularities or abnormalities during pregnancy or childbirth had been reported. None of hypotension, external eye muscle paralysis, or visual impairment were identified on physical examination. The laboratory findings were low urine osmolality and high serum osmolality and sodium concentration. The concentrations of thyroid hormones, growth hormone (GH), and anti-diuretic hormone (ADH) were found to be low. The IgG4 concentration was not high (4.7 mg/dL; normal <105 mg/dL) and the patient was negative for anti rabphilin-3A antibody. Pituitary magnetic resonance imaging (MRI) on the day of admission showed enlargement of the pituitary gland and stalk, and magnetic resonance angiography showed stenosis of the left internal carotid artery. The patient showed a poor response to GH-releasing peptide 2 and thyroid releasing hormone stimulation. Hypertonic saline administration did not cause an increase in ADH concentration. We diagnosed adult growth hormone deficiency (aGHD), central hypothyroidism, and central diabetes insipidus (DI). The enlargement of the pituitary gland was slightly less marked and the stenosis of the left internal carotid artery improved 7 days after admission. After 6 months, the pituitary gland was almost normal in size, although the aGHD, central hypothyroidism, and central DI remained. Sheehan's syndrome or lymphocytic hypophysitis could have been responsible for the postpartum hypopituitarism. This case was not typical of lymphocytic hypophysitis with respect to the hormone deficiency pattern, the MRI findings, and the lack of anti rabphilin-3A antibody. Sheehan's syndrome is caused by ischemic necrosis of the anterior pituitary gland after severe postpartum hemorrhage. The prevalence of central DI is estimated to be 2%–3%. Typically, pituitary dysfunction progresses slowly and develops several years after childbirth. In contrast, in the present patient, stenosis of the left internal carotid artery developed and improved during short periods of time. The vasospasm of the internal carotid artery caused reductions in flow through the superior and inferior hypophysial arteries, which resulted in ischemia and necrosis of the pituitary gland, similar to Sheehan's syndrome. Clinical Lesson: Although rare, maternal central DI can be caused by ischemia and vasospasm immediately after the delivery of a child. The possibility of a pituitary stroke in the presence of neoplastic disease should not be ruled out, and imaging and pituitary gland function should be followed over the long term. Presentation: No date and time listed

ODP388 Hypernatremia in a Male Adolescent Leading to Diagnosis of Septo-optic Dysplasia

Abstract Introduction Septo-optic dysplasia (SOD) is a rare, heterogeneous condition defined by any combination of optic nerve hypoplasia, midline radiologic abnormalities and pituitary hypoplasia. The majority of cases are sporadic, but a number of familial cases have been described. Mutations in genes such as HESX1, SOX2 and SOX3 have been identified. Typically, SOD is diagnosed in newborns and infants with a reported incidence of 1: 10,000 live births. The diagnosis can be made when two or more features of the classic triad are present. If familial, genetic testing can be obtained to confirm the diagnosis. Clinical Case A 17 year and 7-month-old male patient with a history of cerebral palsy, paraplegia and obesity was admitted for management of a right arm osteomyelitis. We were initially consulted for incidentally discovered pre-diabetes (HbA1c: 6.4%), likely secondary to unhealthy eating patterns (negative pancreatic antibodies). He was made NPO prior to surgery and subsequently developed hypernatremia (161 mmol/L), which was initially thought to be iatrogenic due to large volume of normal saline received. Despite discontinuation of normal saline and replacement of free water, hypernatremia persisted (159-172 mmol/L). He had an elevated serum osmolality (321 mOsm/kg) with a low urine osmolality (240 mOsm/kg) and low specific gravity (<1. 005). He was also polyuric (urine output 4.7 mL/kg/hr). With mentioned findings and a Copetin level of 2mol/L, a diagnosis of compensated central DI was established. He initially required a vasopressin drip in addition to slow replacement of free water in order to normalize his sodium level. After his sodium was stabilized, he was started on treatment with oral desmopressin. An MRI obtained was remarkable for small optic nerves and a small optic chiasm. Ophthalmology evaluation confirmed small, hypoplastic optic nerves. Constellation of findings were indicative of septo-optic dysplasia, presenting with central diabetes insipidus. Other than an IGF-1 on the low side (155 ng/L, z-score: -2.7), there was no evidence of additional pituitary hormone deficiencies. Conclusion The presence of cerebral palsy and central diabetes insipidus generated suspicion of midbrain defects, which may be associated with SOD. SOD is typically diagnosed in the newborn period, but this case points to the possibility of a more delayed presentation and diagnosis. SOD is a rare, highly heterogeneous condition. Both the age of presentation and which pituitary hormone deficiencies are present are variable. With early diagnosis, hormonal deficiencies can be monitored and replaced as required. A high index of suspicion is essential if features of the classic triad are present, regardless of age of presentation. Presentation: No date and time listed

RF25 | PMON113 Subarachnoid Hemorrhage Complicated by Nephrogenic and Central Diabetes Insipidus

Abstract Introduction Diabetes insipidus (DI) is a rare complication of subarachnoid hemorrhage (SAH) and associated with worse prognosis and increased mortality. We present a case of combined nephrogenic and central DI together with osmotic diuresis as a result of SAH and discuss the pathophysiology. Case A 63-year-old female without significant past medical history was found unresponsive. CT head followed by angiography confirmed extensive SAH arising from a saccular anterior communicating artery (Acoma) aneurysm. She underwent emergent coil embolization and right frontal external ventriculostomy drain placement. Postoperatively, she developed polyuria (300-400 mL/hour) and hypernatremia (156 mEq/L) concerning for the development of DI. Serum osmolality was elevated at 316 mOsm/kg, urine osmolality inappropriately low relative to serum osmolality at 289 mOsm/kg but also unexpectedly high for complete DI, serum potassium 2.9 mEq/L and urine potassium elevated urine at 9 mEq/L. Serum copeptin was 6 pmol/L and inappropriately low for nephrogenic DI, suggesting a mixed central and peripheral process as well as contribution from osmotic diuresis. Intravenous (IV) desmopressin (DDAVP) only slightly reduced the polyuria. Management was complicated by adypsia and persistent hypokalemia requiring ongoing replacement. IV fluid, which had initially consisted of high-osmolality Plasma-Lyte (294 mOsm/L), matched to urine output, was switched to D5W, leading to a significant decrease in polyuria. On post-operative day 17, DDAVP was discontinued with normalization of sodium (137 mEq/L), potassium (3.8 mEq/L) and urine output. Three months post-operatively, she was asymptomatic with intact pituitary function and no hypokalemia. Discussion Hypokalemia in patients with SAH is thought due to acute intracellular shift of potassium caused by excessive β2-adrenergic activity generated endogenously by the sympathetic nervous system. In our patient, there was also likely contribution from distal tubular delivery of sodium from osmotic diuresis, leading to increased urinary potassium losses and hypokalemia-induced partial nephrogenic DI which was further complicated by partial central DI as suggested by the inappropriately low copeptin level for nephrogenic DI in face of a high serum osmolality and inappropriately low urine osmolality. As the vascular supply to anterior hypothalamus is derived from the Acoma, rupture may compromise perfusion affecting neuronal populations in the lamina terminalis that regulate thirst and AVP secretion in response to hyperosmolarity. Early detection of DI is critical because hypovolemia can predispose to cerebral vasospasm and worsen outcomes. This case also depicts the importance of careful consideration of sources of osmolar loads such as the composition of administered IV fluids, and aggressive potassium replacement to maintain DDAVP sensitivity. Conclusion DI should be considered in polyuria syndrome with hypernatremia after a neurosurgical event. Nephrogenic and central DI and adypsia can manifest following SAH, with sources of iatrogenic osmolar load further complicating the clinical picture. Early recognition and treatment may reduce morbidity and mortality. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.

Contributions of renal water loss and skin water conservation to blood pressure elevation in spontaneously hypertensive rats.

We recently reported that skin vasoconstriction to suppress transepidermal water loss (TEWL) leads to hypertension in renal injury model rats with impaired urine concentration ability. In this study, we investigated the pathogenesis of hypertension in spontaneously hypertensive rats (SHRs) from the perspective of renal water loss and skin water conservation. We compared the urinary concentration ability, body sodium and water balance, blood pressure, and TEWL in SHRs and control normotensive Wistar-Kyoto rats (WKYs). SHRs showed significantly higher urine volume and lower urinary osmolality than those of WKYs, while there were no significant differences in water intake, urinary osmolyte excretion, and plasma osmolarity between the groups. SHRs exhibited significantly higher blood pressure, skin sodium content, and lower TEWL compared with those is WKYs. Skin vasodilation, induced by elevating body temperature, increased TEWL in both SHRs and WKYs, and significantly reduced blood pressure in SHRs but not WKYs. These findings suggest that physiological adaptation can reduce dermal water loss in SHRs to compensate for renal water loss. Vasoconstriction required for successful cutaneous water conservation explains SHR hypertension. Renal concentration ability and skin barrier function for water conservation may become a novel therapeutic target for essential hypertension.

Genetic deletion of the nuclear factor of activated T cells 5 in collecting duct principal cells causes nephrogenic diabetes insipidus.

Water homeostasis is tightly regulated by the kidneys via the process of urine concentration. During reduced water intake, the antidiuretic hormone arginine vasopressin (AVP) binds to the vasopressin receptor type II (V2R) in the kidney to enhance countercurrent multiplication and medullary osmolality, and increase water reabsorption via aquaporin-2 (AQP2) water channels. The importance of this AVP, V2R, and AQP2 axis is highlighted by low urine osmolality and polyuria in people with various water balance disorders, including nephrogenic diabetes insipidus (NDI). ELF5 and nuclear factor of activated T cells 5 (NFAT5) are two transcription factors proposed to regulate Aqp2 expression, but their role is poorly defined. Here we generated two novel mouse lines with principal cell (PC)-specific deletion of ELF5 or NFAT5 and phenotyped them in respect to renal water handling. ELF5-deficient mice (ELF5PC-KO ) had a very mild phenotype, with no clear differences in AQP2 abundance, and mild differences in renal water handling and maximal urinary concentrating capacity. In contrast, NFAT5 (NFAT5PC-KO ) mice had significantly higher water intake and their 24 h urine volume was almost 10-fold greater than controls. After challenging with dDAVP or 8h water restriction, NFAT5PC-KO mice were unable to concentrate their urine, demonstrating that they suffer from NDI. The abundance of AQP2, other AQPs, and the urea transporter UT-A1 were greatly decreased in NFAT5PC-KO mice. In conclusion, NFAT5 is a major regulator of not only Aqp2 gene transcription, but also other genes important for water homeostasis and its absence leads to the development of NDI.

WATER INTOXICATION: A CASE OF HYPONATREMIA AND ACUTE RENAL FAILURE

WATER INTOXICATION: A CASE OF HYPONATREMIA AND ACUTE RENAL FAILURE