Desmopressin

Reversible Nephrogenic Diabetes Insipidus Induced by Lithium: A Case Report.

Sevil Uygun İlikhan, Gülin Dilken, Gökhan Hazıroğlu +2 more

Lithium is an effective mood stabilizer but may cause nephrogenic diabetes insipidus (NDI) by impairing the renal collecting duct response to arginine vasopressin (AVP). We report a 52-year-old woman on long-term lithium therapy who presented with diarrhea, fatigue, polyuria, and confusion. Initial evaluation showed hypernatremia (serum sodium 156-159 mmol/L), low urine osmolality (101 mOsm/kg) despite serum osmolality of 286 mOsm/kg, daily urine output of 6.5-7.5 L, and a lithium level of 1.65 mmol/L. Renal function was preserved. Intravenous 5% dextrose was administered for free-water replacement. Bicarbonate and potassium supplementation were initiated based on blood gas and biochemical findings consistent with metabolic acidosis (pH: 7.33 and serum bicarbonate: 22.1 mmol/L) and hypokalemia, requiring potassium supplementation. Lithium was discontinued, and a thiazide-containing regimen was initiated. Without desmopressin, serum sodium normalized to 140 mmol/L within 72 h, urine output decreased to approximately 2 L/day, and mental status fully recovered. This case demonstrates that timely recognition and management of lithium-induced NDI may allow recovery of urinary concentrating ability.

The effect of centralized care on the management of postoperative fluctuations in plasma sodium concentration after pediatric suprasellar brain tumor surgery.

S C Hulsmann, D C Zaal, J P J van Gestel +9 more

Children undergoing neurosurgery for (supra)sellar tumors are at risk of developing arginine vasopressin-deficiency (AVP-D), which can cause severe sodium fluctuations and associated neurological complications, prolonged hospitalization and mortality. A previous Dutch study reported sodium shifts ≥ 10 mmol/L/24 h in 75.3% of patients with early postoperative AVP-D, with a maximum delta of 46 mmol/L/24 h. Since 2018, pediatric oncology care has been centralized in the Netherlands. We evaluated the impact of this centralization on postoperative sodium fluctuations in children with (supra)sellar tumors.

Arginine Vasopressin Deficiency and Oxytocin Deficiency in the Endocrine Clinic.

Cihan Atila, Julie Refardt, Mirjam Christ-Crain

The hypothalamo-neurohypophysial system consists of specialized neurons in the supraoptic and paraventricular nuclei that project to the central nervous system and the posterior pituitary, where they secrete arginine vasopressin (AVP) and oxytocin (OXT) into the systemic circulation. AVP is the key endocrine regulator of water balance via V2 receptor-mediated aquaporin-2 insertion in renal collecting ducts and modulates vascular tone via V1 receptors. OXT plays a central role in labor and lactation, but also influences metabolism, social behavior, emotional processing, and stress regulation. AVP deficiency (formerly central diabetes insipidus) results from hypothalamic-posterior pituitary disruptions or injury due to surgery, trauma, tumors, infiltrative or autoimmune disease, vascular events, or genetic causes. It is characterized by hypotonic polyuria, polydipsia, and dehydration risk, and is diagnosed by distinguishing it from AVP resistance and primary polydipsia, with copeptin-based tests providing high diagnostic accuracy. Treatment relies on desmopressin and careful education to prevent both dehydration and hyponatremia. In contrast, OXT deficiency has only recently been recognized as a potential clinical entity, particularly in patients with hypothalamic-pituitary disruptions or injury and concurrent AVP deficiency. Emerging evidence links it to social dysfunction, anxiety, and reduced quality of life. Diagnosis remains challenging due to unreliable basal OXT levels and limited stimulation tests; novel approaches, including 3,4-methylenedioxymethamphetamine (MDMA) challenge and neurophysin I as a surrogate marker, are under investigation. Preliminary studies suggest intranasal OXT may improve socioemotional outcomes, but robust evidence from randomized controlled trials is needed.

Dual receptor therapy with pituitrin for spinal cord injury-induced diabetes insipidus: A propensity-matched retrospective cohort study.

Lianhua Li, Jie Gao, Hao Wang +3 more

Spinal cord injury (SCI)-induced diabetes insipidus (DI) presents a unique therapeutic challenge due to concurrent autonomic hypotension unresponsive to conventional desmopressin. This study evaluates the clinical efficacy of Pituitrin, a synthetic vasopressin analog with dual V1a/V2 receptor agonism, designed to simultaneously address antidiuretic hormone deficiency and hemodynamic instability in acute SCI-related DI.

Clinical Outcomes Following Supply-Driven Transition From Intranasal to Oral Desmopressin in AVP-Deficiency-A Single Centre Experience Including The Pituitary Foundation Desmopressin Shortage Impact Report.

Trevor Tam, Amy Mach, Alam Wahid +6 more

Arginine vasopressin deficiency (AVP-D) requires lifelong desmopressin replacement. In March 2025, the national suspension of intranasal desmopressin necessitated urgent transition to oral alternatives. However, optimal conversion ratios and clinical response remain undefined. We evaluated clinical outcomes following this supply-driven transition.

Central Diabetes Insipidus as a Rare Cause of Polyuria.

Stuti Bhandari, Samyama Sagare Venkatesh, L U Chirag +1 more

Central diabetes insipidus (CDI) is a rare condition characterized by arginine vasopressin deficiency, leading to persistent polyuria and polydipsia. Although it can present at any age, idiopathic CDI in young adults is uncommon and diagnostically challenging. Inflammatory conditions such as infundibuloneurohypophysitis must be considered, particularly when magnetic resonance imaging (MRI) reveals a thickened pituitary stalk and absence of the posterior pituitary bright spot. Early recognition and differentiation from diabetes mellitus, nephrogenic diabetes insipidus, and primary polydipsia are crucial for effective management. We report the case of a 20-year-old male who presented with excessive urination and thirst for 6 weeks. Physical examination was unremarkable, and the patient had no history of trauma or systemic illness. Urine osmolality was markedly low, and MRI of the brain showed absence of the posterior pituitary bright spot and thickening of the infundibulum, suggestive of infundibuloneurohypophysitis. The patient responded well to desmopressin therapy with symptomatic improvement, thus supporting the diagnosis of CDI. This case highlights the importance of considering idiopathic CDI in young adults presenting with unexplained polyuria and polydipsia. Infundibuloneurohypophysitis should be suspected in patients with characteristic MRI findings even in the absence of overt systemic autoimmune disease. A methodical diagnostic approach, including hormone assays, imaging, and therapeutic trials, can enable early diagnosis and effective long-term management.

Use, efficacy, and safety of desmopressin for congenital nephrogenic diabetes insipidus in children: a nationwide survey.

Kento Ikegawa, Masanobu Fujimoto, Kohei Aoyama +12 more

Congenital nephrogenic diabetes insipidus (CNDI) is characterized by resistance of the distal nephrons and collecting ducts to arginine vasopressin (AVP). High doses of 1-deamino-8-D-arginine vasopressin (DDAVP), a V2-receptor-selective agonist, are effective in some cases. The present study aimed to demonstrate the use, efficacy, and safety of DDAVP and the characteristics of patients who responded to this treatment. The present, retrospective, multicentric, observational survey of patients with CNDI receiving DDAVP was based on a previous, nationwide survey conducted by the Japanese Society for Pediatric Endocrinology (JSPE) and collected data on the use (formulation, dosage, and treatment duration), efficacy (change in urine output and height SDS), and safety of DDAVP. In the initial survey, 43 of 123 JSPE council members (35.0%) observed the patients. The secondary survey of 13 patients found DDAVP to be effective in five patients (38.5%), as evidenced by a 12.6-31.6% decrease in urine output. The maximum urine osmolality on a water deprivation test and urine osmolality after vasopressin injection were lower in patients who were unresponsive to DDAVP than in those who were responsive to the drug (106 vs. 206 mOsm/H2O/kg, 140 vs. 525 mOsm/H2O/kg). The AVPR2 variants identified in the DDAVP-responsive group were p.Ala37Pro, p.Leu44Phe, p.Arg104Cys, and p.Tyr128Ser. DDAVP was effective against CNDI with residual V2R function. The water deprivation test with vasopressin injection and genetic testing may be useful for predicting responsiveness to DDAVP.

Unusual Development of Central Diabetes Insipidus after Endovascular Treatment for a Medial Tentorial Dural Arteriovenous Fistula.

Yuta Oka, Yoshinobu Horio, Munenari Matsuishi +7 more

Medial tentorial dural arteriovenous fistulas (DAVFs) are rare lesions that may cause intracranial hemorrhage or non-hemorrhagic symptoms due to venous congestion from retrograde deep venous drainage. We report a case of a medial tentorial DAVF presenting with cognitive decline and impaired consciousness, successfully treated with transvenous embolization (TVE) and straight sinus angioplasty, and complicated postoperatively by central diabetes insipidus (CDI).

Haemostasis and beyond: The expanding role of desmopressin in intensive care.

Saketh Vinjamuri, Ekta Tiwari, Sahil Kataria +1 more

Desmopressin (1-deamino-8-D-arginine vasopressin, DDAVP) is a synthetic analogue of arginine vasopressin, the body's natural antidiuretic hormone. It acts selectively on V2 receptors, promoting renal water reabsorption and stimulating the release of von Willebrand factor (vWF) and factor VIII, while exerting minimal vasoconstrictive effects through V1 receptors. Developed in the late 1960s and introduced clinically in the early 1970s for the management of central diabetes insipidus, desmopressin was engineered to provide a longer duration of action and reduced cardiovascular side effects compared to native vasopressin. Its haemostatic potential was later recognized when it was observed to enhance endogenous levels of vWF and factor VIII, leading to its incorporation into the treatment of mild haemophilia A and von Willebrand disease (vWD). This unique combination of antidiuretic and prohemostatic properties has broadened its therapeutic role across various clinical settings. In critical care, desmopressin has emerged as a potentially valuable agent in managing complex scenarios such as uremic platelet dysfunction, trauma-associated coagulopathy, intracranial hemorrhage, vWD, and central diabetes insipidus. However, despite its mechanistic appeal and broad pharmacologic utility, the full scope of desmopressin's applications in the intensive care unit (ICU) remains underrecognized. This review aims to provide a comprehensive examination of desmopressin's pharmacological characteristics, evidence-based indications in critically ill patients, therapeutic efficacy, safety profile, and practical considerations for dosing in the ICU setting.

Webb-Dattani syndrome in a 17-year-old girl.

Jamilah Saleh Alyami, Wael Mohammad Almistehi, Khalid Ibrahim Alkanhal

Webb-Dattani syndrome (WEDAS) is an extremely rare autosomal recessive disorder caused by pathogenic variants in the ARNT2 gene. It is characterized by a triad of congenital hypopituitarism, structural brain abnormalities, and multisystem developmental defects. We report the case of a 17-year-old girl with WEDAS who presented with global developmental delay, panhypopituitarism, and arginine vasopressin (AVP) deficiency, formerly known as central diabetes insipidus with adipsia, visual impairment, renal anomalies, and spastic quadriplegia. Her endocrine profile revealed deficiencies in ACTH, TSH, and ADH, and gonadotropins, with a possible growth hormone deficiency. Management included hormone replacement with hydrocortisone, levothyroxine, and desmopressin, as well as fluid regulation and supportive care. Despite multiple hospitalizations due to complications including hypernatremia and infections, the patient survived into adolescence - the longest reported survival in this condition to date - before passing away at age 17. This case expands the known clinical phenotype of WEDAS, emphasizing the importance of early recognition, genetic testing, and a multidisciplinary approach to care for affected individuals, particularly in consanguineous populations where the syndrome may be underdiagnosed.

Giant Sellar Meningocele: Intact Pituitary Function and New-onset Arginine Vasopressin Deficiency After Surgery.

Oscar Josué Gómez-Romero, Baldomero González-Virla, Guadalupe Vargas-Ortega +3 more

Sellar and sphenoidal meningoceles are rare entities that can lead to neurological, ophthalmological, and endocrine complications. We report the case of a 28-year-old man with a giant sellar meningocele who presented with chronic headache and bitemporal hemianopsia but with preserved pituitary function at diagnosis. Magnetic resonance imaging revealed a large defect of the sellar floor with herniation of meninges and displacement of the optic chiasm and pituitary gland. The patient underwent endoscopic transsphenoidal repair. Within 24 hours, he developed arginine vasopressin (AVP) deficiency requiring long-term desmopressin therapy, which persisted beyond 6 months, fulfilling the criteria for permanent AVP deficiency. No other pituitary hormone deficits were observed. Visual field impairment did not improve after surgery, although further deterioration was prevented. This case underscores that adult sellar meningoceles can present with intact anterior pituitary function but still carry a risk of isolated permanent AVP deficiency after surgical repair. To our knowledge, this is among the largest adult sellar meningoceles reported with preserved anterior pituitary function at presentation and subsequent permanent isolated AVP deficiency, emphasizing the need for careful perioperative counseling and long-term endocrine follow-up.

Treatment and outcome of a boy with lgG4-related hypophysitis caused by SARS-CoV-2 re-infection.

Hanming Li, Iatlun Leong, Jianyu He

SARS-CoV-2 infection can directly and indirectly affect the nervous system, including the hypothalamus and pituitary, and potentially cause IgG4-related hypophysitis.

Family experience with individuals of different ages and clinical presentations diagnosed with DI: do familial DI cases tolerate polyuria better?

Hakan Birinci, Emrullah Arslan, Tansu Değirmenci +1 more

Familial neurohypophyseal diabetes insipidus (DI) is a rare genetic disorder caused by vasopressin deficiency due to AVP gene mutations. This case report describes the genetic findings and clinical profiles of three generations within a family affected by hereditary central DI and managed with desmopressin.

Hyperosmolar hyperglycemic state with severe hypernatremia coexisting with central diabetes insipidus: A case report and literature review.

Congcong Yao, Lishuang Zhu, Songtao Shou +2 more

Diabetes insipidus is characterized by polyuria and polydipsia, often resulting from central or nephrogenic causes. In diabetic emergencies, hyperosmolar hyperglycemic state (HHS), severe hypernatremia, and ventricular fibrillation are life-threatening conditions that require prompt intervention. This report describes a 47-year-old male with poorly controlled diabetes mellitus, who developed coma, excessive thirst, polyuria, hyperglycemia (47.29 mmol/L), hypernatremia (195.6 mmol/L), and plasma hyperosmolality (385 mOsm/kg). Despite fluid resuscitation and insulin therapy, refractory hypernatremia persisted, leading to a diagnosis of central diabetes insipidus (CDI). The patient also developed ventricular fibrillation, which was managed with defibrillation. Concurrently, desmopressin and blood purification were administered to address CDI and severe hypernatremia. This case emphasizes the importance of considering CDI when polyuria persists despite glucose control. The occurrence of ventricular fibrillation underscores the necessity of continuous cardiac monitoring in the context of hypovolemia and severe electrolyte imbalance. We propose that diabetes mellitus-related vascular injury impairs blood flow in the hypothalamus-pituitary tract, disrupting arginine vasopressin synthesis and secretion, contributing to CDI in poorly controlled diabetes mellitus.

Functional characterization and cAMP-mediated rescue of a novel truncating AVPR2 mutation causing nephrogenic diabetes insipidus.

Diogo Manoel, Idris Mohammed, Khalid Hussain +1 more

Vasopressin plays a central endocrine role in water homeostasis by activating the arginine vasopressin receptor 2 (AVPR2) receptor in renal collecting duct cells. Mutations in AVPR2 are a leading cause of X-linked nephrogenic diabetes insipidus (NDI), a disorder marked by renal insensitivity to vasopressin, leading to polyuria, polydipsia, and hypernatremia. We identified a novel truncating AVPR2 mutation (c.570dup; D191*) in a pediatric patient with NDI and investigated its molecular and functional consequences using a renal epithelial cell model. The D191* mutant exhibited marked reduction in total and surface receptor expression due to intracellular retention and rapid proteasomal degradation. Functional assays revealed that 1-deamino-8-d-arginine vasopressin (dDAVP) stimulation failed to elicit cAMP production or activate downstream signaling targets, including CREB and ERK1/2, in cells expressing the mutant receptor. Aquaporin-2 (AQP2) membrane translocation, essential for water reabsorption, was also impaired. Notably, treatment with forskolin or 8-bromo-cAMP restored cAMP levels, reactivated downstream signaling, and rescued AQP2 localization to the apical membrane, independent of AVPR2 activation. These findings uncover the pathophysiological mechanism by which D191* impairs vasopressin signaling and suggest that bypassing the receptor via direct cAMP pathway activation offers a promising therapeutic strategy for NDI. This study highlights the endocrine relevance of precision molecular diagnostics and supports functional rescue approaches for receptor-based disorders.NEW & NOTEWORTHY This study identifies and functionally characterizes a previously unreported truncating AVPR2 mutation (c.570dup; p.D191*) causing congenital nephrogenic diabetes insipidus. Using renal epithelial cell models, the authors show that D191* leads to receptor misfolding, proteasomal degradation, absent cAMP signaling, and failure of aquaporin-2 trafficking. Remarkably, forskolin and 8-bromo-cAMP bypass the defective receptor to restore downstream signaling and water channel localization, highlighting a potential therapeutic strategy of receptor-independent cAMP activation for AVPR2-null nephrogenic diabetes insipidus.

Trametinib-induced Hyponatremia in a Patient With Craniopharyngioma and Diabetes Insipidus.

Buddhi Gunasekara, Harriet Gunn, Arif H B Jalal +2 more

Adamantinomatous craniopharyngiomas (ACPs) are rare, sellar-suprasellar benign tumors that cause considerable morbidity and mortality due to local invasion and treatment-related damage to surrounding structures, including central diabetes insipidus (CDI). Trametinib is a highly selective inhibitor of MEK1 and MEK2, which has been evaluated in both adult and pediatric cancers/ tumors with activation of the oncogenic mitogen-activated protein kinase (MAPK) pathway. Despite being thought to have fewer side effects than conventional cytotoxic chemotherapy, off-target toxicities such as hyponatremia have been described. The use of MEK inhibitors in ACPs are limited to case reports and a phase II trial is currently underway. We report a pediatric patient with multiply progressive ACP and known brittle CDI who developed severe hyponatremia associated with a significant decrease in desmopressin dosing after starting trametinib and a rapid rebound of desmopressin requirement with its cessation. We recommend close monitoring of serum sodium levels and a review of desmopressin doses in patients with CDI when started on treatment with MEK inhibitors.

Idiopathic Arginine Vasopressin Deficiency With an Incidental Non-functional Pituitary Microadenoma in an Elderly Diabetic Woman.

Mokkarala Satya Vamsi Krishna, Daruvuri Vishnu Sai Prasanna Babu, Mohini Singh +1 more

We present a case of idiopathic arginine vasopressin deficiency (AVP-D) in an elderly woman with type 2 diabetes, who presented with polyuria, polydipsia, and nocturia. Laboratory findings confirmed a euglycemic state, hyperosmolar serum, and hypoosmotic urine. Magnetic resonance imaging of the pituitary revealed the absence of the posterior bright spot and an incidental small, non-functional pituitary microadenoma, without any compressive effects on the pituitary stalk. The diagnosis of AVP-D was confirmed through a water deprivation test and a positive response to desmopressin. Common secondary causes, including inflammatory, granulomatous, and structural pathologies, were excluded. The patient responded well to oral desmopressin therapy, resulting in normalization of serum sodium and urine osmolality. This case underscores the challenges in diagnosing the cause of polyuria in a diabetic patient and the challenges in determining the etiology of AVP-D.

A Novel Pathogenic Variant of the AVPR2 Gene Leading to Arginine Vasopressin Resistance Since the Neonatal Period.

Agnieszka Szmigielska, Piotr Skrzypczyk, Dorota Czapczak +4 more

Background: Diabetes insipidus (DI) in newborns is an extremely rare condition, with the age of presentation strongly suggesting a genetic background of the disease. The differential diagnosis should include arginine vasopressin deficiency (AVD) and arginine vasopressin resistance (AVR). Some novel diagnostic tools such as copeptin evaluation and genetic tests are vital for early diagnosis. Case report: We present the case of a 1-month-old boy with polyuria observed since birth. Laboratory tests showed persistent hypernatremia, elevated plasma and low urine osmolality. An attempt at oral administration of desmopressin had no effect; additionally the copeptin level was increased. A genetic study (NGS of the AVP, AVPR2 and AQP2 genes) was considered and a new pathogenic variant in the AVPR2 gene (hemizygous c.157del) was detected. After the genetic test result was obtained, treatment with hydrochlorothiazide was started. The patient is now 3 months old, developing normally, and the weight and height are normal. Conclusions: Newborns with DI should be subjected to extensive multidisciplinary diagnostics, including endocrine and renal causes. Copeptin evaluation and prompt genetic diagnosis allows for the early diagnosis and implementation of appropriate treatment.

Diabetes insipidus as a presentation of lung adenocarcinoma: a case report.

Maryam Alsadat Tabatabaei, Reza Manouchehri Ardakani

Paraneoplastic syndromes are rare complications associated with malignancies, and central diabetes insipidus represents one of their uncommon manifestations. Central diabetes insipidus is most frequently observed in association with specific malignancies, such as lung cancer, and often results from metastatic involvement of the pituitary gland and the sellar region.

Case Report of Nephrogenic Diabetes Insipidus with a Novel Mutation in the AQP2 Gene.

Alejandro Padilla-Guzmán, Vanessa Amparo Ochoa-Jiménez, Jessica María Forero-Delgadillo +3 more

Nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by renal resistance to arginine vasopressin (AVP), resulting in the kidneys' inability to concentrate urine. Approximately 90% of NDI cases follow an X-linked inheritance pattern and are associated with pathogenic variants in the AVPR2 gene, which encodes the vasopressin receptor type 2. The remaining 10% are attributed to mutations in the AQP2 gene, which encodes aquaporin-2, and may follow either autosomal dominant or recessive inheritance patterns. We present the case of a male infant, younger than nine months of age, who was clinically diagnosed with NDI at six months. The patient presented recurrent episodes of polydipsia, polyuria, dehydration, hypernatremia, and persistently low urine osmolality. Despite adjustments in pharmacologic treatment and strict monitoring of urinary output, the clinical response remained suboptimal. Given the lack of improvement and the radiological finding of an absent posterior pituitary (neurohypophysis), the possibility of coexistent central diabetes insipidus (CDI) was raised, prompting a therapeutic trial with desmopressin. Nevertheless, in the absence of clinical improvement, desmopressin was discontinued. The patient's management was continued with hydrochlorothiazide, ibuprofen, and a high-calorie diet restricted in sodium and protein, resulting in progressive clinical stabilization. Whole-exome sequencing identified a novel homozygous missense variant in the AQP2 gene (c.398T > A; p.Val133Glu), classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria: PM2 (absent from population databases), PP2 (missense variant in a gene with a low rate of benign missense variation), and PP3 (multiple lines of computational evidence supporting a deleterious effect)]. NDI is typically diagnosed during early infancy due to the early onset of symptoms and the potential for severe complications if left untreated. In this case, although initial clinical suspicion included concomitant CDI, the timely initiation of supportive management and the subsequent incorporation of molecular diagnostics facilitated a definitive diagnosis. The identification of a previously unreported homozygous variant in AQP2 contributed to diagnostic confirmation and therapeutic decision-making. The diagnosis and comprehensive management of NDI within the context of polyuria-polydipsia syndrome necessitates a multidisciplinary approach, integrating clinical evaluation with advanced molecular diagnostics. The novel AQP2 c.398T > A (p.Val133Glu) variant described herein was associated with early and severe clinical manifestations, underscoring the importance of genetic testing in atypical or treatment-refractory presentations of diabetes insipidus.

Management of Arginine Vasopressin Deficiency (Central Diabetes Insipidus) in Neonates and Infants.

Hannah Pearlstein, Allie Dayno, Jessica Zook +4 more

Arginine vasopressin deficiency (AVP-D), previously called central diabetes insipidus (central DI), is the inability to concentrate urine despite elevated serum osmolality (i.e., volume depletion) related to inadequate production of the posterior pituitary hormone vasopressin. Without treatment, which typically consists of fluids and pharmacologic vasopressin analogs, AVP-D can quickly lead to hypernatremia and dehydration. Management of AVP-D in neonates and infants is particularly challenging for many reasons: their inability to communicate thirst, their limited renal concentrating capacity, the obligate fluids required for nutrition that may cause hyponatremia with anti-diuretic therapy, the lack of FDA-approved formulation of vasopressin analog in this age, the potential need for growth-related adjustments in nutrition, fluids, and vasopressin analogs, and a limited evidence base. Despite these challenges, multiple groups have reported experiences with the available pharmacologic options, including alternative formulations of desmopressin (buccal, standard oral tablet, orally disintegrating tablet [melt], subcutaneous) and thiazide diuretics.

Cushing's syndrome with diabetes insipidus in pregnancy: a case report.

Shinnosuke Hata, Nobuyoshi Shinokawa, Yuki Harada +6 more

Cushing's syndrome (CS) during pregnancy is a rare condition associated with significant maternal and fetal complications, including hypertension, diabetes, preeclampsia, and preterm birth. Diabetes insipidus (DI) in pregnancy is a rare but often diagnosed condition, and its effective management is crucial for maintaining maternal health during pregnancy and childbirth. This case report describes the rare coexistence of DI and CS during pregnancy, highlighting the unique complexities in diagnosis and management.

Sublingual Administration of Desmopressin Oral Disintegrating Tablet in a Neonate With Central Diabetes Insipidus.

Daisuke Watanabe, Hideaki Yagasaki, Mari Tsukahara +2 more

Precise titration of desmopressin (1-deamino-8-D-arginine vasopressin; DDAVP) is essential for managing neonatal central diabetes insipidus (CDI). Although oral administration is increasingly considered an alternative to the traditional intranasal route, the differences between DDAVP formulations and administration methods are often unclear in clinical practice. This complicates efforts to establish effective sublingual treatment protocols using oral disintegrating tablets (ODTs) in neonates. Here, we present the case of a Japanese neonate with CDI, semilobar holoprosencephaly, and a cleft lip and palate. The patient exhibited hypotonic polyuria, hypernatremia, elevated serum osmolality, and low plasma arginine vasopressin (AVP) levels within the first week of life. At 30 days of age, we dissolved a 60-µg DDAVP ODT in 5 mL of water and administered it sublingually. The initial dose of 3 µg/kg/day was titrated to 2 µg/kg/day based on the patient's clinical response. Close monitoring enabled fine adjustment of dosing. The patient achieved a stable fluid balance and did not exhibit signs of hyponatremia, seizures, or other adverse events. This case supports the potential utility of sublingual DDAVP ODTs in neonates and underscores the necessity of establishing standardized preparation and dosing protocols, which will require further clinical experience.

'Un-thirsty' hypernatremia.

Markus Koster, Katrin Ledergerber, Michael Brändle

A 38-year-old man was admitted because of transient somnolence. Five weeks previously, he had suffered a subarachnoid hemorrhage from a ruptured aneurysm of the anterior communicating artery (ACOM), which was treated by craniotomy and clipping. He had recovered well, although loss of short-term memory and a forehead paresis on the side of craniotomy persisted. Clinical examination on admission showed no new neurological deficits. Cerebral computed tomography with angiography revealed no bleeding or infarction and correctly positioned clips. Laboratory examination showed severe hypernatremia (179 mmol/L). The patient was admitted to the intensive care unit (ICU) and treated with oral fluids and 5% glucose intravenously. Remarkably, he denied being thirsty and had to be encouraged to drink. Urine osmolality quickly fell to 294 mOsm/kg, polyuria of up to 400 mL/h was measured, and serum sodium remained elevated. Therefore, diabetes insipidus (DI) was obvious. After application of desmopressin acetate, urine output dropped to around 50 mL/h, confirming central DI or vasopressin deficiency (VD). Desmopressin acetate dose and volume management were continuously adjusted to blood sodium to restore euvolemia. Drinking volume needed to be supervised because of persistent lack of thirst and amnesia of being told to drink. Adipsic VD (aAVP-D) is a rare syndrome characterized by the combination of VD and loss of thirst in response to hypernatremia. It usually occurs within days after cell damage of osmoreceptors, for example after disruption of blood supply as in clipping of an ACOM aneurysm. Management includes titrated desmopressin acetate replacement, fixed water intake, weight monitoring, patient education and sodium monitoring.

Comparative Diagnostic Performance of Copeptin After Hypertonic Saline Infusion Versus Water Deprivation Test in Pediatric Patients with Polyuria-Polydipsia Syndrome.

Diana-Andreea Ciortea, Carmen Loredana Petrea Cliveți, Iolanda Cristina Vivisenco +4 more

Differentiating central diabetes insipidus (CDI), nephrogenic diabetes insipidus (NDI), and primary polydipsia (PP) in pediatric patients with polyuria-polydipsia syndrome (PPS) remains a clinical challenge. The water deprivation test (WDT) is the traditional gold standard; however, it is time-consuming, burdensome, and prone to equivocal results. Stimulated copeptin, a surrogate marker of vasopressin, has emerged as a promising diagnostic alternative. We conducted a prospective, observational, cross-sectional study involving 27 pediatric patients (ages 2-17) presenting with PPS. Each patient underwent a WDT with desmopressin and hypertonic saline infusion (3% NaCl) for stimulated copeptin testing. Diagnostic accuracy was assessed using clinical diagnoses as a reference. The WDT showed high accuracy with an area under the curve (AUC) of 0.97, and there was an increased optimal threshold of ≥14% urine osmolality after desmopressin acetate (1-deamino-8-D-arginine vasopressin, DDAVP) administration (sensitivity 88.9%, specificity 100%). Stimulated copeptin at a threshold of <6.5 pmol/L demonstrated 100% sensitivity and specificity (AUC = 1.00) for CDI versus PP. Basal copeptin ≥21.4 pmol/L accurately identified all NDI cases. The agreement between the WDT and copeptin was low (κ = 0.06, McNemar p = 0.021), suggesting that copeptin has greater specificity, particularly for borderline or partial CDI. These results support the use of stimulated copeptin as a first-line diagnostic tool in pediatric PPS, offering improved objectivity, tolerability, and diagnostic clarity compared with the WDT. Basal copeptin also demonstrated excellent performance in rapid noninvasive NDI identification.

Ifosfamide-Induced Partial Arginine Vasopressin Resistance Responsive to Vasopressin/Desmopressin and Amiloride.

Nicholas Ma, Haley Wilt, Patrick Donabedian +1 more

This is a case of partial arginine vasopressin resistance following the sixth cycle of doxorubicin-ifosfamide-mesna therapy for recurrent spindle cell sarcoma of the thigh. Polyuria and symptomatic hypernatremia started by the second day of the two-day chemotherapy cycle. The diagnosis was confirmed with serum and urine chemistry testing showing urine hypo-osmolality (161 mOsm/kg) with polyuria (4.8 L urine output) in 24 hours, serum hyperosmolality (355 mOsm/kg), and an elevated baseline plasma copeptin of 82 pmol/L. Treatment with intravenous vasopressin followed by amiloride and supraphysiologic doses of oral desmopressin improved symptomatic hypernatremia.

The role of vasopressin deficiency in the fluid intake suppression hyper-responsivity to central glucagon-like peptide-1 in the Brattleboro rat.

Sydney A David, Destiny J Brakey, Matthew J Paul +1 more

Food and fluid intakes are physiologically and behaviorally intertwined; one often affects the other. Likewise, pharmacological manipulations that influence eating often affect drinking. For example, glucagon-like peptide-1 (GLP-1) suppresses both eating and fluid intake, but the respective elements of the GLP-1 system remain unparsed. The Brattleboro rat has emerged as a model to test for separable elements in the control of fluid or food intake. Brattleboro rats have hereditary hypothalamic vasopressin deficiency. To compensate for the resultant polyuria, they drink copious amounts of water. Eating, however, is similar to that observed in wildtype littermates and other Long Evans rats. Interestingly, treatment with a GLP-1 receptor agonist exendin-4 (Ex4) causes an exaggerated suppression of drinking in Brattleboro rats, but suppression of eating is comparable to wildtype controls. To test if this hyper-responsivity depends on the polydipsia in these rats, we normalized their drinking using desmopressin (ddAVP), a V2R agonist, before treatment with Ex4. ddAVP attenuated, but did not completely prevent, the hyper-responsivity to Ex4. Conversely, we treated wildtype rats with acute or chronic tolvaptan, a V2R antagonist, which generated a Brattleboro-like polydipsia, but this did not recapitulate the hyper-responsivity to Ex4 observed in Brattleboro rats. Based on these results, we conclude that polydipsia alone is insufficient to generate a hyper-responsive fluid intake suppression by Ex4, and that Brattleboro rats have at least some persistent hyper-responsivity to Ex4, even after alleviation of their polydipsia. These results provide important context for future studies using Brattleboro rats to study the GLP-1 system.

Exploring factors behind Arginine-Vasopressine deficiency in endoscopic endonasal surgery for PitNET: a single-center analysis of 349 patients.

Raffaele De Marco, Alice Antico, Nunzia Prencipe +8 more

Arginine-Vasopressine deficiency (AVP-D), formerly known as Central Diabetes Insipidus, is a well-known complication in surgery for sellar/parasellar masses. Although less frequent in endoscopic series than transcranial and microscopic transsphenoidal ones, AVP-D has been variably related to different factors. Focusing the work on pituitary Neuroendocrine Tumors (PitNET), all patients who were treated endoscopically at a single centre were retrospectively reviewed to analyze the occurrence of this complication. Patient's characteristics, radiological information, and operative data were collected for patients who underwent surgery for PitNET at the same Institution by a single surgeon in the period 2016-2022. AVP-D was diagnosed in the presence of new-onset hypotonic polyuria with or without hypernatremia and was defined persistent if required a treatment with desmopressine/DDAVP for more than 6 months. Out of 349 patients (mean age at surgery 57.5 years old) 44 (12.6%) developed AVP-D (25 transient and 19 permanent). Younger age, the presence of an intraoperative CSF leak, the maximum diameter of the lesion, its suprasellar extension (considering the presence of a visual deficit), consistency of the lesion (distinguishing 4 classes, soft, soft-fibrous, fibrous and fibrous-firm), the extent of resection and the functioning status showed some relationship at univariate analysis (p < 0.05) with this complication. Larger diameter and longer operative time were seen more frequently in permanent AVP-D. A more solid intraoperative consistency with the presence of adherences (class 4 vs. class 1, OR 11.14, 95%CI 1.20-103.4) and the appearance of an intraoperative CSF-leak (OR 8.27, 95%CI 3.92-17.47) maintained a statistical significance in the multivariate logistic regression, with an older age being a protective factor in developing this deficiency (OR 0.96, 95%CI 0.95-0.99). The recognition of factors that can predict the onset of AVP-D with a certain degree of accuracy enables the entire staff to pay greater attention to the patient at risk in the postoperative period, thus preventing AVP-D complications.

Intraoperative Diagnosis and Management of Arginine Vasopressin Disorder During Pituitary Tumor Resection via Transsphenoidal Endoscopic Navigation.

Delayne M Coleman, Emily Kim, Krupa Patel +2 more

Arginine vasopressin (AVP) disorders (previously called diabetes insipidus) lead to excessive urination due to reduced antidiuretic hormone (ADH) secretion or kidney resistance to ADH. This results in decreased water reabsorption, causing dehydration and electrolyte imbalances. Diagnosing these disorders during general anesthesia is challenging, but close monitoring of electrolytes and urine output, especially during high-risk surgeries such as intracranial procedures, is crucial. A 64-year-old woman with a history of asthma presented with severe bifrontal headaches and left-eye medial gaze palsy. Imaging showed a large sellar mass extending into the sphenoid sinus, requiring a transsphenoidal resection. An hour and 30 minutes into surgery, the patient developed acute polyuria (1 L urine), hyperosmolality (Na: 149 mmol/L), and colorless urine with low specific gravity (1.003), indicating an arginine vasopressin disorder. Desmopressin (DDAVP) was administered, improving urine specific gravity to 1.013, and a D5W infusion corrected a 2.5 L fluid deficit. Severe hypokalemia (K: 2.6 mmol/L) and hyperglycemia (glucose: 230 mg/dL) were also treated, with electrolyte and glucose levels stabilizing postoperatively. On postoperative day (POD) 2, the patient experienced polyuria up to 23 L and excessive thirst, requiring additional desmopressin on POD 3. She was discharged on POD 9. Arginine vasopressin disorders, especially vasopressin deficiency (central diabetes insipidus), commonly result from neurohypophyseal damage during cranial surgery. Prompt diagnosis and treatment with desmopressin and fluids can effectively manage fluid and electrolyte imbalances, preventing severe complications such as hypernatremia and neurological deficits. This case highlights the importance of intraoperative urine and laboratory monitoring to ensure timely recognition and management.

Managing Ifosfamide-Induced Arginine Vasopressin Resistance: Diagnostic and Treatment Strategies.

Avia A Williams, Arslan I Pir Muhammad, Rupam Ruchi +1 more

The early recognition of ifosfamide-related renal dysfunction, including arginine vasopressin resistance (previously referred to as diabetes insipidus), which is characterized by polyuria due to the inability of the collecting duct to concentrate urine, as well as direct proximal tubular injury, which is characterized by numerous metabolic disturbances including hypophosphatemia, metabolic acidosis, hypokalemia, and glucosuria, is paramount to timely initiation of treatment and titration of desmopressin. In this report, we present a case of a 42-year-old female with a history of spindle cell carcinoma of the left thigh, who was referred to the inpatient nephrology consult service for acute kidney injury, polyuria, and metabolic derangements following her sixth cycle of doxorubicin-ifosfamide chemotherapy. The patient was treated with supratherapeutic doses of desmopressin, with successful improvement of her polyuria. We review the pathophysiology of different forms of ifosfamide-associated nephrotoxicity, including arginine vasopressin resistance, the challenges of diagnosing arginine vasopressin disorders, and the utility of desmopressin in the management of arginine vasopressin resistance. This case also highlights the clinical implications of using copeptin in the diagnosis of arginine vasopressin resistance, leading to effective treatment and improving patient outcomes.