RARE DISEASE
Arginine vasopressin deficiency
Arginine vasopressin deficiency
Arginine vasopressin deficiency
Synonyms: CDI, Neurogenic diabetes insipidus
Synonyms: CDI, Neurogenic diabetes insipidus
Synonyms: CDI, Neurogenic diabetes insipidus
Drug discovery
0
drugs
With orphan designations
Overview
Arginine Vasopressin Deficiency (AVP-D) is a rare disorder of water homeostasis caused by deficient synthesis or secretion of antidiuretic hormone (AVP), leading to uncontrolled diuresis (3-30 L/day) and polydipsia. Etiologies include genetic mutations, hypothalamic-pituitary lesions (trauma, tumors), or idiopathic causes. Diagnosis involves urine/plasma osmolality, water deprivation tests, and hypertonic saline-stimulated copeptin measurements. Treatment focuses on desmopressin replacement (intranasal/oral/IV) with careful sodium monitoring to prevent hyponatremia [1][12][18].
Burden
Chronic dehydration risks: Hypernatremia, hypovolemic shock, and cognitive impairment if untreated [2][8].
Lifetime management required; 30% of untreated cases develop acute kidney injury [4][14].
Economic burden: Frequent hospitalizations and complex monitoring (e.g., sodium levels, urine output) [14][16].
Therapies
Desmopressin: First-line synthetic AVP analog (oral/IV/nasal); dosage adjusted to prevent breakthrough polyuria or hyponatremia [3][13][16].
Adjunctive measures: Thiazides for partial AVP-D; strict fluid balance protocols during acute illness [6][13].
Emerging diagnostics: Copeptin-based testing (e.g., hypertonic saline/arginine stimulation) improves diagnostic accuracy [12][18].
Categories: rare endocrine diseases
Research Papers
423 drug discovery papers about Arginine vasopressin deficiency, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
423 drug discovery papers about Arginine vasopressin deficiency, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-12 | Sustained remission of chronic post-traumatic arginine vasopressin deficiency despite absent posterior pituitary bright spot on MRI: a case series.
Absence of the posterior pituitary bright spot (PPBS) on T1-weighted MRI is often observed in chronic post-traumatic arginine vasopressin deficiency (AVP-D), but its association with permanent AVP-D remains unclear. We report five patients with chronic-phase post-traumatic AVP-D (156-965 days post-injury) who were transferred to our rehabilitation center. All patients had received long-term desmopressin therapy and exhibited persistent absence of the PPBS on T1-weighted MRI at admission. Despite these findings, desmopressin therapy was successfully tapered and discontinued in all five cases. Case 3 presented a diagnostic challenge, in which resolution of post-traumatic AVP-D was obscured by concomitant adrenal insufficiency and was confirmed only after stabilization of glucocorticoid replacement. In Cases 3, 4, and 5, detectable plasma arginine vasopressin levels (1.0-1.9 pg/mL) were observed following desmopressin withdrawal despite persistent radiologic absence of the PPBS. All patients maintained stable water balance without desmopressin therapy, with no recurrence of polyuria or clinically significant hypernatremia during follow-up. Endogenous vasopressin secretion may be retained in selected patients with chronic TBI, even when MRI suggests persistent neurohypophyseal abnormalities. Our cases demonstrate that absence of the PPBS is not a definitive marker of lifelong post-traumatic AVP-D. These observations support periodic reassessment and supervised trial discontinuation of desmopressin therapy in the neurorehabilitation setting, suggesting that preserved endogenous vasopressin function may remain unrecognized years after the initial insult.
2026-06-10 | Severe IL-6-dominant immune-mediated inflammatory response complicated by probable arginine vasopressin deficiency following ivonescimab-based therapy in advanced EGFR-mutant lung squamous cell carcinoma: a case report.
Ivonescimab, a novel PD-1/VEGF bispecific antibody, has shown promising efficacy in advanced lung cancer. Yet severe immune-related adverse events are not well studied outside clinical trials. We report a 72-year-old man with stage IV squamous NSCLC harboring an EGFR mutation and PD-L1 tumor proportion score of 90% who developed persistent fever shortly after first exposure to ivonescimab combined with nab-paclitaxel and carboplatin. His prior treatments included concurrent chemoradiotherapy, osimertinib, the investigational EGFR inhibitor BH-30643, afatinib, and recent gamma knife for cerebellar metastases plus palliative radiotherapy for bone metastases. After cycle 1, he developed persistent high fever with markedly elevated IL-6 and no response to antimicrobials. Corticosteroids brought rapid relief, pointing to an IL-6-mediated process. Re-exposure to ivonescimab triggered a more severe reaction. He then developed sudden polyuria with low urine osmolality and elevated serum osmolality. Brain MRI showed no typical hypophysitis features. Symptoms improved with corticosteroids, tocilizumab, and desmopressin, consistent with probable arginine vasopressin deficiency (AVP-D), possibly secondary to hypophysitis-though pituitary metastasis cannot be ruled out without biopsy. Ivonescimab can trigger severe IL-6-dominant inflammatory reactions and endocrine toxicity presenting as AVP-D in susceptible patients. Advanced age, EGFR-mutant/PD-L1-high tumor biology, recent radiotherapy, and Parkinsonism may have contributed to the inflammatory environment, though none can be proven causal in a single case and each deserves prospective study. Early recognition of persistent steroid-responsive fever, serial IL-6 monitoring, thorough endocrine workup, and timely IL-6 blockade are critical.
2026-06-08 | Synaptic alterations are preceding the axonal loss in optic atrophy of Wolfram syndrome mouse model.
Wolfram syndrome is a rare autosomal recessive disorder characterized by antibody-negative early-onset diabetes mellitus, optic atrophy, sensorineural hearing loss, arginine-vasopressin deficiency, and progressive neurodegeneration of the brainstem and cerebellum. It is caused primarily by pathogenic variants in the WFS1 gene, which encodes a transmembrane endoplasmic reticulum-resident protein involved in the unfolded protein response and cellular calcium homeostasis. Although multiple rodent models of Wolfram syndrome have been developed and shown to exhibit visual defects, some studies have reported significant vision loss prior to any detectable axonal degeneration or myelin abnormalities, and the mechanisms underlying these early visual deficits remain poorly understood. Recent in vitro studies have demonstrated altered synaptic contacts and aberrant neurite morphology in WFS1-deficient cerebral organoids and human iPSC-derived neurons, respectively. These findings prompted us to investigate, for the first time in vivo, whether synaptic and dendritic abnormalities occur in the retina of Wfs1 knockout mice. Using confocal microscopy, we examined retinal and optic nerve histology in Wfs1 knockout mice at 4 and 7 months of age. Our analysis reveals progressive synaptic alterations in the inner plexiform layer, driven by early presynaptic compartment failure. These changes represent the earliest detectable phenotype associated with vision loss in this model and precede overt axonal degeneration. These findings identify early synaptic preservation as a promising therapeutic target for vision loss in Wolfram syndrome.
2026-07-12 | Sustained remission of chronic post-traumatic arginine vasopressin deficiency despite absent posterior pituitary bright spot on MRI: a case series.
Absence of the posterior pituitary bright spot (PPBS) on T1-weighted MRI is often observed in chronic post-traumatic arginine vasopressin deficiency (AVP-D), but its association with permanent AVP-D remains unclear. We report five patients with chronic-phase post-traumatic AVP-D (156-965 days post-injury) who were transferred to our rehabilitation center. All patients had received long-term desmopressin therapy and exhibited persistent absence of the PPBS on T1-weighted MRI at admission. Despite these findings, desmopressin therapy was successfully tapered and discontinued in all five cases. Case 3 presented a diagnostic challenge, in which resolution of post-traumatic AVP-D was obscured by concomitant adrenal insufficiency and was confirmed only after stabilization of glucocorticoid replacement. In Cases 3, 4, and 5, detectable plasma arginine vasopressin levels (1.0-1.9 pg/mL) were observed following desmopressin withdrawal despite persistent radiologic absence of the PPBS. All patients maintained stable water balance without desmopressin therapy, with no recurrence of polyuria or clinically significant hypernatremia during follow-up. Endogenous vasopressin secretion may be retained in selected patients with chronic TBI, even when MRI suggests persistent neurohypophyseal abnormalities. Our cases demonstrate that absence of the PPBS is not a definitive marker of lifelong post-traumatic AVP-D. These observations support periodic reassessment and supervised trial discontinuation of desmopressin therapy in the neurorehabilitation setting, suggesting that preserved endogenous vasopressin function may remain unrecognized years after the initial insult.
2026-06-10 | Severe IL-6-dominant immune-mediated inflammatory response complicated by probable arginine vasopressin deficiency following ivonescimab-based therapy in advanced EGFR-mutant lung squamous cell carcinoma: a case report.
Ivonescimab, a novel PD-1/VEGF bispecific antibody, has shown promising efficacy in advanced lung cancer. Yet severe immune-related adverse events are not well studied outside clinical trials. We report a 72-year-old man with stage IV squamous NSCLC harboring an EGFR mutation and PD-L1 tumor proportion score of 90% who developed persistent fever shortly after first exposure to ivonescimab combined with nab-paclitaxel and carboplatin. His prior treatments included concurrent chemoradiotherapy, osimertinib, the investigational EGFR inhibitor BH-30643, afatinib, and recent gamma knife for cerebellar metastases plus palliative radiotherapy for bone metastases. After cycle 1, he developed persistent high fever with markedly elevated IL-6 and no response to antimicrobials. Corticosteroids brought rapid relief, pointing to an IL-6-mediated process. Re-exposure to ivonescimab triggered a more severe reaction. He then developed sudden polyuria with low urine osmolality and elevated serum osmolality. Brain MRI showed no typical hypophysitis features. Symptoms improved with corticosteroids, tocilizumab, and desmopressin, consistent with probable arginine vasopressin deficiency (AVP-D), possibly secondary to hypophysitis-though pituitary metastasis cannot be ruled out without biopsy. Ivonescimab can trigger severe IL-6-dominant inflammatory reactions and endocrine toxicity presenting as AVP-D in susceptible patients. Advanced age, EGFR-mutant/PD-L1-high tumor biology, recent radiotherapy, and Parkinsonism may have contributed to the inflammatory environment, though none can be proven causal in a single case and each deserves prospective study. Early recognition of persistent steroid-responsive fever, serial IL-6 monitoring, thorough endocrine workup, and timely IL-6 blockade are critical.
2026-06-08 | Synaptic alterations are preceding the axonal loss in optic atrophy of Wolfram syndrome mouse model.
Wolfram syndrome is a rare autosomal recessive disorder characterized by antibody-negative early-onset diabetes mellitus, optic atrophy, sensorineural hearing loss, arginine-vasopressin deficiency, and progressive neurodegeneration of the brainstem and cerebellum. It is caused primarily by pathogenic variants in the WFS1 gene, which encodes a transmembrane endoplasmic reticulum-resident protein involved in the unfolded protein response and cellular calcium homeostasis. Although multiple rodent models of Wolfram syndrome have been developed and shown to exhibit visual defects, some studies have reported significant vision loss prior to any detectable axonal degeneration or myelin abnormalities, and the mechanisms underlying these early visual deficits remain poorly understood. Recent in vitro studies have demonstrated altered synaptic contacts and aberrant neurite morphology in WFS1-deficient cerebral organoids and human iPSC-derived neurons, respectively. These findings prompted us to investigate, for the first time in vivo, whether synaptic and dendritic abnormalities occur in the retina of Wfs1 knockout mice. Using confocal microscopy, we examined retinal and optic nerve histology in Wfs1 knockout mice at 4 and 7 months of age. Our analysis reveals progressive synaptic alterations in the inner plexiform layer, driven by early presynaptic compartment failure. These changes represent the earliest detectable phenotype associated with vision loss in this model and precede overt axonal degeneration. These findings identify early synaptic preservation as a promising therapeutic target for vision loss in Wolfram syndrome.
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