Arginine Vasopressin Deficiency Research Articles

The biology of water homeostasis.

Water homeostasis is controlled by a brain-kidney axis that consists of central osmoreceptors, synthesis and secretion of arginine vasopressin (AVP) and AVP-responsive aquaporin-2 (AQP2) water channels in kidney collecting duct principal cells that facilitate water reabsorption. In addition to AVP, thirst represents a second line of defense to maintain water balance. Water balance disorders arise because of deficiency, resistance or inappropriate secretion of AVP or disturbances in thirst sensation (hypodipsia, polydipsia). People with water balance disorders are prone to develop hyponatremia or hypernatremia, which expose cells to osmotic stress and activate cell volume regulation mechanisms. This review covers several recent insights that have expanded our understanding of central osmoregulation, AQP2 regulation and cell volume regulation. This includes the role of with-no-lysine kinase 1 (WNK1) as a putative central osmolality sensor and, more generally, as an intracellular crowding sensor that coordinates the cell volume rescue response by activating sodium and potassium cotransporters. Furthermore, several new regulators of AQP2 have been identified, including for AVP-dependent AQP2 regulation (yes-associated protein, nuclear factor of activated T-cells, microRNAs) and AVP-independent AQP2 regulation (epidermal growth factor receptor, fluconazole, prostaglandin E2). It is also becoming increasingly clear that long-term cell volume adaptation to chronic hypotonicity through release of organic osmolytes comes at the expense of compromised organ function. This potentially explains the complications of chronic hyponatremia, including cognitive impairment, bone loss and vascular calcification. This review will illustrate why these new insights derived from basic science are also relevant for developing new approaches to treat water balance disorders.

Apelin levels in patients with polyuria-polydipsia syndrome upon copeptin stimulation tests.

Differentiating between arginine vasopressin deficiency (AVP-D) and primary polydipsia (PP) requires a copeptin-stimulation test. We aimed to characterize changes in apelin, an endogenous hormone antagonising AVP, upon copeptin-stimulation tests. Post-hoc secondary analysis of a multicentric cross-over diagnostic study (NCT03572166). Apelin levels were measured in patients included at the University Hospital Basel. The primary outcome was the absolute difference in apelin between baseline and peak of copeptin-stimulation tests with hypertonic saline and arginine infusion. Secondary objectives included the diagnostic ability of apelin. Thirty-eight patients were analysed, 23 (60%) had PP and 15 (40%) had AVP-D. No difference was seen between baseline median [IQR] apelin levels in PP and AVP-D (1079 [912, 1225] and 910 [756, 1039] pmol/l, respectively). Upon hypertonic saline, apelin decreased by -241 [-326, -124] pmol/l in PP and -47.2 [-198, 5.86] pmol/l in AVP-D (p=0.022). The area under the curve (AUC) to differentiate PP from AVP-D was 97.1% (95%CI: 90.5, 100) for copeptin and 49.3% (95%CI: 30.4, 68.1) for apelin (p<.001). Upon arginine, apelin decreased by -39.2 [-96.4, 39.8] pmol/l in PP and increased by 25.8 [2.8, 113.0] pmol/l in AVP-D (p=0.1). The AUC was 97.1% [95%CI: 79.6, 98.0] for copeptin and 60.5% [95%CI: 39.8, 80.0] for apelin (p=0.007). Our findings suggest that apelin decreases to a greater extent in PP compared to AVP-D upon copeptin-stimulation tests. However, copeptin remains the best marker to differentiate AVP-D from PP.

Clinical characteristics and management of adipsic arginine vasopressin deficiency in children and adolescents with sellar germ cell tumors.

Adipsic arginine vasopressin deficiency(aAVP-D) is a rare, high-risk syndrome, particularly difficult to recognize and manage in children and adolescents. This investigation examined the clinical features and management of aAVP-D in children and adolescents with sellar germ cell tumors (GCTs). A retrospective survey was performed on 260 patients with sellar GCTs, categorized into aAVP-D and non-aAVP-D groups based on thirst presence. General characteristics, hypothalamic syndrome, pituitary function, metabolic indicators, and complications were compared. Biochemical indicator changes in the aAVP-D group were analyzed after systematic management, and receiver operating characteristic (ROC) curve analysis established the optimum serum sodium cut-off for predicting the aAVP-D. 25 patients (9.6%) developed aAVP-D. The aAVP-D group had larger tumors with hypothalamic involvement and more surgical resections. They also demonstrated more hypothalamic syndrome, central adrenal insufficiency, central hypogonadism, and insulin-like growth factor-1 levels below norms. Furthermore, aAVP-D patients exhibited significantly higher rates of hypernatremia (100% vs 20.9%, p < 0.001), hyperuricemia (60.0% vs 23.4%, p < 0.001), renal impairment (32.0% vs 1.7%, p < 0.001), and venous thrombosis (4.0% vs 0%, p = 0.002). Following systematic management, aAVP-D patients experienced significant reductions in serum sodium, uric acid, and creatinine levels, although these remained higher than in the non-aAVP-D group. ROC analysis indicated that a serum sodium level above 149.5mmol/L predicted aAVP-D. Conclusion Patients with aAVP-D had more tumor involvement in the hypothalamic region, surgical resections, hypothalamic syndrome, hypopituitarism, and complications. Serum sodium levels above 149.5mmol/L necessitated heightened vigilance for aAVP-D. Early identification and systematic management reduced complications, though clinical management remained challenging. What is Known •Adipsic arginine vasopressin deficiency (aAVP-D) is a rare and high-risk syndrome that is difficult to recognize and manage. •There are few reports on aAVP-D, most of which focus on adult patients. •The characteristics and management of aAVP-D in children and adolescents remain unclear. What is New •Children and adolescents with aAVP-D experienced higher rates of hypothalamic region tumor involvement, surgical resections, hypothalamic syndrome, hypopituitarism, and associated complications. •Serum sodium levels above 149.5mmol/L necessitated heightened vigilance for aAVP-D. •Early recognition and structured management of ADI lowered the risk of complications.

6672 Pituicytomas and Spindle Cell Oncocytomas: Rare Posterior Pituitary Tumors

Abstract Disclosure: Y. Park: None. A. Shen: None. M. Christie: None. J. Wentworth: None. C.J. Yates: None. J. King: None. Background: Pituicytomas and spindle cell oncocytomas (SCO) are rare non-functioning benign posterior pituitary tumors that can present as suprasellar or sellar-suprasellar masses.[1] Pituicytomas originate from the pituicytes in the neurohypophysis and infundibulum of the pituitary gland.2 SCO were previously thought to derive from the adenohypophysis,3 however, are now classified as a tumor of the neurohypophysis characterized by immunohistochemical reactivity to thyroid transcription factor 1 (TTF1).4 According to the World Health Organization 2021 classifications, pituicytomas, granular cell tumors and SCO may represent morphologic variations of the same tumor expressing TTF1.5 Due to their rarity, their clinical characteristics are not yet well-defined and can be mistaken as non-functioning pituitary adenomas. Methods: We retrospectively reviewed the clinical data of two patients with pituicytomas and two patients with SCO confirmed on histopathology at our institution, evaluating their clinical characteristics and management outcomes. Results: Two male patients, aged 59 and 79, were diagnosed with pituicytoma, and two male patients, aged 33 and 55 were diagnosed with SCO. Three presented with visual impairment from mass effects and three patients had hypogonadotropic hypogonadism. None had pre-operative arginine vasopressin (AVP) deficiency. All lesions were isointense on T1-weighted, and most were hyperintense on T2-weighted magnetic resonance imaging. Three cases had non-gross total resection due to hypervascularity. Postoperatively, two patients developed AVP deficiency and three developed persistent anterior pituitary insufficiency (Table 1). Pituicytomas had a Ki67 of 1-3%, and SCO had a Topoisomerase labelling index of &amp;lt;1%. In one case of pituicytoma, due to tumor recurrence 2 years after initial surgery, adjuvant radiotherapy was considered. However, the patient developed a severe peri-tumoral subarachnoid hemorrhage and died prior to receiving radiotherapy. In contrast, the progression of the residual SCO occurred at a slower rate. Discussions: Posterior pituitary tumor differentials are broad, including pituicytoma, SCO, granular cell tumor, craniopharyngioma, meningioma and germinoma;6 hence, histopathological diagnosis is crucial. Although benign, pituicytomas and SCO can result in increased morbidity and postoperative complications, such as AVP deficiency and hypopituitarism. Recurrence and progression are common.7, 8 Gross total resection is optimal, but this is difficult due to hypervascularity.9 Our case of peri-tumoral subarachnoid hemorrhage resulting in death emphasizes the hypervascular nature of pituicytomas. Patients with pituicytomas and SCO should be monitored for tumor progression or recurrence and hemorrhagic complications. Adjuvant radiotherapy may be considered for the management of tumor recurrence. Presentation: 6/3/2024

7227 Acute Hyponatremia Following Initiation of Antidepressant in Patient on Desmopressin Treatment for AVP Deficiency

Abstract Disclosure: M.E. Horowitz: None. Y. Gao: None. S.B. Abraham: None. P. Kishore: None. Introduction: Intranasal desmopressin (DDAVP) is indicated as antidiuretic replacement therapy in arginine vasopressin (AVP) deficiency. It increases water permeability in the distal nephron, reducing urine output, increasing urine osmolality, and decreasing serum osmolality. Treatment is titrated to normalize serum sodium and urine output (UOP). Initiation of medications affecting sodium balance or fluid status may lead to abnormalities in these markers. One of these is escitalopram, an antidepressant which can cause hyponatremia attributed to inappropriate AVP secretion. We report a case of acute hyponatremia in a patient with previously stable sodium on chronic DDAVP who was started on escitalopram. Clinical Case: A 44-year-old female with history of a craniopharyngioma resection in 2007 complicated by AVP deficiency on chronic DDAVP, bipolar disorder, and depression presented with nausea, vomiting, and dizziness for two days. Patient was found to be hyponatremic to 118 mEq/L (135-145 mEq/L). Sodium checked one month prior was 135 mEq/L, and historically was never less than 130 mEq/L since 2008. DDAVP was prescribed since resection with few dose changes, at this time four 10mcg sprays in each nostril three times daily since 2020. Escitalopram 5mg daily was initiated two months prior. Desmopressin was held in the setting of hyponatremia, which resolved appropriately to 135 mEq/L over the first five days. During this time, the patient complained of large volume diuresis at ∼three liters daily. On day six, sodium acutely increased to 146 mEq/L; subcutaneous (SC) DDAVP was given and sodium normalized. UOP decreased significantly over the next 24 hours, but large volume diuresis resumed thereafter. On day 10, DDAVP SC was given, again decreasing UOP for 24 hours. Psychiatry recommended continuing escitalopram given improvement in psychiatric symptoms since initiation. Upon discharge, the patient was prescribed DDAVP two 10mcg sprays in each nostril nightly, a significant reduction compared to her prior dose. Sodium rechecked one week later remained within normal limits. Clinical Lessons: This effect of combination DDAVP and escitalopram has not been reported previously. Prescribers should be aware of the potential for hyponatremia and the need to adjust DDAVP dose in combined use. To avoid these risks in patients on chronic DDAVP, the side effects of antidepressants and antipsychotics should be reviewed prior to initiation. Presentation: 6/2/2024

9183 Pituitary Metastasis Of Lung Adenocarcinoma Presenting As Anterior Pituitary Dysfunction

Abstract Disclosure: O. faour: None. M. Kinaan: None. S.K. Suryanarayanan: None. Introduction: The pituitary should not be overlooked as a site for metastasis and can be the first presentation of neoplastic disease in some patients. Most common presenting symptoms: headache, ophthalmoplegia, visual field defect and Arginine Vasopressin Deficiency (AVP-D). We present a case of pituitary metastasis of lung adenocarcinoma presenting as anterior Pituitary dysfunction that also showed partial AVP-D unmasked after starting steroids. Case Description: A 63-year-old male with history of tobacco use, COPD, and hypertension presented with syncope. He reported a 30lbs weight loss within prior 2 months, low energy, increased thirst, and polyuria. Physical exam was significant for cachexia, normal visual field on confrontation, and vital signs of BP 100/61, HR 83, and Weighing 180 lbs. Since he had syncope, Cortisol checked was undetectable and Free T4 was low, He was started on hydrocortisone and levothyroxine. CTA chest revealed a right hilar mass measuring 2.7 x 3 cm. Endobronchial biopsy was consistent with lung adenocarcinoma. MRI of pituitary gland revealed solid hypointense lesion with glandular thickening and diffuse heterogeneity involving most of the pituitary gland measuring up to 16 mm. No cavernous sinus invasion. Pituitary infundibulum showed diffuse thickening and enhancement of the pituitary stalk throughout with Intact posterior pituitary bright spot. Labs showed low LH, cortisol, ACTH, GH, TSH, and ADH. Initially, the patient was able to maintain a euvolemic status through increased water intake; however, he was later found to have partial central AVP-D when steroids were introduced. He responded to the use of Desmopressin, developed hyponatremia after 3 doses. He was started on a combination of carboplatin/pemetrexed/pembrolizumab but had no response and was transferred to palliative care/hospice and passed away within 7months after diagnosis.Discussion:Pituitary metastasis is rare and most commonly occurs in lung and breast cancers. Unfortunately, they are associated with poor prognosis. MRI findings of loss of posterior pituitary bright spot, thickening of the stalk, and dumbbell shape can be helpful in distinguishing between primary pituitary tumors and metastases. PET-FDG scan has limited value. Pituitary metastasis commonly presents with posterior pituitary dysfunction due to direct blood supply. Unmasking or worsening of AVP-D can happen with steroid replacement in patients requiring initiation or intensification of Desmopressin therapy. Treatment involves combination of surgery, radiation therapy, and systemic treatment for the primary cancer which can improve symptoms only but does not improve mortality. Presentation: 6/1/2024

8067 AVP Gene Mutation: A Rare Cause of Diabetes Insipidus

Abstract Disclosure: N. Navrange: None. M. Williams: None. P. Madhavan: None. Introduction: Arginine vasopressin deficiency (AVP-D), also known as neurohypophyseal or central diabetes insipidus (DI), is marked by a reduced secretion of arginine vasopressin (AVP), resulting in polyuria and polydipsia. AVP-D is a rare disorder, with a prevalence of 1 in 25,000. Typically, the disorder is acquired. However, in less than 5% of cases, it has a genetic etiology. The majority of mutations in the AVP gene are autosomal dominant. Normally, AVP encodes vasopressin, also known as antidiuretic hormone (ADH). It plays a key role in the reabsorption of water in the kidney, the regulation of blood pressure, and controlling the body’s osmotic balance. However, a mutation in this gene leads to a deficient release of ADH, leading to reduced reabsorption of water in the collecting duct and decreased ability to concentrate urine. This results in increased urine output and excessive thirst. The onset and severity of symptoms varies between individuals. Case Report: In this report, we discuss the case of a 40-year-old Caucasian female with familial neurohypophyseal diabetes insipidus. The patient presented to the clinic for follow-up care of DI and hyponatremia. She received her DI diagnosis before the age of 5 and has multiple family members with the condition including her maternal grandfather, mother, and 2 siblings. Additionally, she suspected one of her children was exhibiting excessive urination. Past medical history is also significant for seizure disorder, postpartum cardiomyopathy, Chiari malformation type I and remote history of substance abuse. Vitals were stable with blood pressure of 122/86 mmHg, heart rate of 93 bpm, body mass index of 31.8. Physical exam was unremarkable except for obesity. She is currently managed with DDAVP 0.05 mg twice daily. Previously, imaging was performed to rule out pituitary abnormalities. The patient was referred for genetic testing due to her family history and was found to have a previously described rare autosomal dominant mutation of the AVP protein. The single nucleotide polymorphism in exon 1 results in a missense mutation substituting an alanine nucleotide for threonine (c.55G&amp;gt;A). The patient was counseled to share these results with her children’s pediatrician, as they could benefit from testing for the mutation. Discussion: Our patient has a pathogenic variant in AVP, specifically a missense mutation from Alanine to Threonine at codon 19 of the AVP protein. This mutation is associated with autosomal dominant neurohypophyseal diabetes insipidus. This case provides an example of a rare cause of neurohypophyseal diabetes insipidus and emphasizes the necessity of obtaining detailed family history in patients who have DI and considering genetic testing for patients with suspicion for familial involvement. Presentation: 6/2/2024

7292 Central AVP Deficiency in Erdheim-Chester Disease in the Era of Molecular Diagnostics

Abstract Disclosure: J. Hewlett: None. S. Mohan: None. C.J. Davidge-Pitts: None. J. Abeykoon: None. R. Go: None. D.Z. Erickson: None. Objective: Erdheim-Chester Disease (ECD) is a multisystem histiocytic disorder which can infiltrate the pituitary gland, often leading to endocrine dysfunction. Central Arginine Vasopressin Deficiency (cAVP-D) commonly affects ECD patients, and those harboring BRAFV600E are reported to have an increased risk. Insufficient data exist about the risk associated with other mutations, and if cAVP-D or pituitary imaging improves with targeted therapies (TT). Methods: We conducted a review of a prospectively maintained database of adults with ECD treated at a tertiary center between 1992-2023. Objectives of this study were to identify mutations associated with cAVP-D and assess for improvement in cAVP-D (remission of disease or decrease in dose of desmopressin) or pituitary gland involvement (via MRI imaging) following TT for ECD. Results: Of 148 patients with ECD, the majority were male (98, 66.2%) and the mean age at diagnosis was 56.5 years [range: 19-82]. Median length of follow-up was 24 months (95% CI, 17 to 27). Of 121 (81.8%) patients with molecular testing results, 89 (73.6%) harbored a somatic mutation. 67 of 89 (75.3%) carried BRAF mutations, with BRAFV600E in 61 (91.0%) and missense mutations/fusions in 6 (9.0%). 22 of 89 (24.7%) patients harbored other somatic mutations, with MAP2K1 in 13 (14.6%) being the most common. 35 (23.6%) patients were diagnosed with cAVP-D, and the median onset of polyuria and polydipsia prior to diagnosis of ECD was 51 months (95% CI, -120 to -6). Molecular testing was performed in 28 patients with cAVP-D: 17 (60.7%) harbored BRAF mutation and 3 (10.7%) MAP2K1 mutation. There was no significant association between the presence of cAVP-D and MAP2K1 (p=0.69, 95% CI, -0.08 to 0.21). The association between cAVP-D and BRAF did not reach statistical significance (p=0.07, 95%CI, -0.03 to 0.38). Additionally, there was no association between BRAF and timing of cAVP-D symptoms before ECD diagnosis (p=0.08, 95% CI -163.4 to 10.3). Pituitary MRI was available in 32 patients with cAVP-D (91.4%) showing infundibular involvement in 17 (53.1%) and loss of the posterior bright spot in 5 (15.6%). 28 (80%) patients with cAVP-D received systemic therapy, 18 (64.3%) of whom received TT. One patient with cAVP-D was able to discontinue desmopressin. Improvement of pituitary MRI was noted in 7 (21.9%), among whom 4 received TT, 2 received systemic non-TT, and 1 was lost to follow-up. There was no significant MRI improvement associated with TT (p=0.67, 95% CI -0.30 to 0.42). Conclusion: In this large cohort of patients with ECD, of whom the majority underwent molecular testing, we identified no association between MAP2K1 mutation and cAVP-D, and no impact of TT on the clinical course or MRI findings associated with cAVP-D. BRAF mutation carriers were more likely to have cAVP-D and more likely to have onset of symptoms closer to ECD diagnosis, but the results did not reach statistical significance. Presentation: 6/2/2024

8403 A Rare Presentation: Mucosal Melanoma with Pituitary Gland Involvement

Abstract Disclosure: L.R. Sepulveda-Garcia: None. L. El Musa Penna: None. W. Medina-Torres: None. J. Segarra-Villafane: None. Z. Maisonet-Feliciano: None. I. Arroyo-Gomez: None. L.A. Gonzalez-Rodriguez: None. M. Alvarado-Santiago: None. M. Ramirez-Vick: None. Introduction: Sinonasal mucosal melanoma (SNMM) is a rare form of aggressive melanoma with poor prognosis, compromising less than 1% of all melanoma. The most frequently reported symptoms include nasal obstruction and epistaxis, but the manifestation of symptoms may occur late and be nonspecific, causing delays in diagnosis and resulting in a less favorable prognosis. Here we report a rare case of mucosal melanoma with pituitary gland involvement initially thought to be a pituitary adenoma. Clinical Case Description: A 22-year-old male with no previous medical history was found with a biopsy proven pigmented epithelioid melanocytoma (PEM) in the palate. Three weeks after the biopsy, the patient presented with a severe headache, prompting the performance of a CT scan that revealed a pituitary macroadenoma. Several days later he developed acute right eye ptosis requiring emergency evaluation. The patient reported mild epistaxis, headaches, and nausea of 2 weeks duration associated with lack of erections and diminished libido. Physical exam was remarkable for sinus bradycardia, right eye ptosis, and a palate bluish pigmentation. Hormonal work up revealed a prolactin of 23 ng/mL (3.46-19.40), TSH of 2.22 uIU/mL (0.27-4.20), fT4 of 0.37 ng/dL (0.93-1.70), total testosterone &amp;lt;0.007 ng/mL (1.88-6.84), free testosterone of 0.001 ng/mL (0.032-0.168), FSH of 0.41 mIU/mL (2.6-11.0), and LH of 0.27 mIU/mL (0.4-7). Serum cortisol and ACTH levels were found to be low at &amp;lt;1.00 µg/dL (3.7-19.40) and 5.98 pg/mL (0.00-46.00), respectively, but these were taken while patient was given dexamethasone by neurosurgery for headaches. Brain MRI was remarkable for 3.4 cm x 3.3 cm x 3.5 cm sellar mass extending inferior into the sphenoid sinus, posteriorly into the right ethmoid air cells, superiorly into the suprasellar cistern with upward displacement of the optic chiasm, as well as bilateral cavernous sinus invasion. Case outcomes: A diagnosis of hypopituitarism was made. Physiologic doses of hydrocortisone were started after being found with central adrenal insufficiency. This replacement unmasked an arginine vasopressin deficiency also requiring desmopressin therapy. Central hypothyroidism was treated with levothyroxine and treatment for the hypogonadotropic hypogonadism was deferred in the meantime. Biopsy of right sphenoid sinus revealed a mucosal melanoma. Revised pathology slides led to the conclusion that palate PEM was an independent entity to the mucosal melanoma Case discussion: Prognosis is poor in patients with SNMM since this tumor is usually diagnosed at advanced stages. In this case, the sellar mass was initially thought to be a pituitary adenoma that later was found to be an extension of a mucosal melanoma. This case serves as a reminder of the critical role that differential diagnosis plays in evaluating sellar masses. Presentation: 6/1/2024

Propofol-induced transient arginine vasopressin deficiency.

We describe and characterise the case of a 26-year-old female undergoing surgery for a right-sided sinonasal alveolar rhabdomyosarcoma who developed profound, transient arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus (DI)) associated with anaesthesia. In this case report, we characterise the development of AVP-D with serial copeptin and paired urine and serum osmolality measurements. Based on the anaesthetic agent's profile and the literature, we attribute this presentation to propofol exposure. We present a description of the literature on anaesthesia-associated DI as well as poignant learning points. Exposure to anaesthetic agents is a rare cause of self-limited but sudden and profound arginine vasopressin deficiency (AVP-D) or arginine vasopressin resistance (AVP-R). Sevoflurane has been associated with AVP-R and propofol with AVP-D, although the responsible agent may be difficult to identify. Differentiation of AVP-R and AVP-D can be made based on copeptin concentration, where available, or clinical response to desmopressin. Whilst the patient is anaesthetised, intravenous fluid replacement should be targeted to match urine output until the patient is able to drink to thirst. This should be clearly communicated to staff and the patient. Rapid resolution of AVP-R/AVP-D when the causative agent is discontinued has been reported with both propofol and sevoflurane. As such, switching the agent used to maintain anaesthesia may terminate increased urine output in a clinically meaningful timeframe.

Delayed onset arginine vasopressin deficiency after traumatic brain injury.

Delayed arginine vasopressin deficiency (AVP-D) can present in patients following traumatic brain injury (TBI) and may occur years after the trauma, presenting with nonspecific symptoms. The objective of this case is to highlight the importance of considering the delayed onset AVP-D in patients with a history of TBI. We report a case of a patient who had sustained severe traumatic brain injury 8 years before and who presented with polydipsia, behavioural disorder and frequent falls during the last 3 months. The diagnosis of AVP-D was confirmed by water restriction with a positive response to desmopressin, and pituitary MRI showed an absent spontaneous posterior hyperintensity on T1WI. Follow-up confirmed permanent diabetes insipidus as well as a suspected anterior pituitary deficiency. Pituitary dysfunction occurs following TBI and is correlated with severity. As in our case, symptoms are generally non-specific and are difficult to explore given the patient's neurologic sequelae. MRI 8 years post trauma showed changes in pituitary morphology. Some authors have proposed the need for active screening of post-TBI patients. This case highlights the need for clinicians to be aware that AVP-D can occur years after traumatic brain injury. Delayed onset post-traumatic arginine vasopressin deficiency may occur in patients with TBI and is correlated with the severity. The clinical picture is usually non-specific and diagnosis of AVP-D is challenging in non-verbal patients. An active screening for pituitary dysfunction is warranted in TBI patients and should be extended should one hormone deficit be identified.

Factors Associated With 30-Day Readmissions After Transsphenoidal Pituitary Surgery

PurposeDetermine the association between clinical and demographic factors and 30-day readmission risk after pituitary surgery. MethodsPatients undergoing pituitary surgery between January 2018 and December 2022 were retrospectively reviewed. Cases were extracted from a converged electronic health record that included surgeries performed at the Midwest, Southeast, and Southwest campuses of the same healthcare Enterprise. Variables were compared between patients with 30-day readmission following discharge after pituitary surgery (N = 83) and a randomly sampled patient cohort with pituitary surgery but no readmission within 30 days (N = 174). ResultsIn a multivariable regression model looking at the relationship between patient characteristics and readmission risk, every increase in the Medicare Severity Diagnosis Related Group score resulted in a nearly 2.3-fold increase in the risk of readmission (OR = 2.335, 95% CI 1.050, 5.562, P = .045). The presence of arginine vasopressin deficiency increased the odds of readmission by more than 2-fold (OR = 2.784, 95% CI 1.118, 7.124, P = .029). The Midwest site was observed to have a nearly 67% decrease in readmission risk compared to the Southwest site (OR = 0.334, 95% CI 0.134, 0.813, P = .016), with the Southeast site being comparable to the Southwest. ConclusionOur study identifies postoperative arginine vasopressin deficiency, greater co-morbidities, and geographic location as risk factors for 30-day readmission after pituitary surgery. Further investigation is required to determine how site-specific care processes can be adopted to lower readmission risk at other locations in the same healthcare enterprise.

Polyuria without Thirst: Adipsic Arginine Vasopressin Deficiency as a Sequela of Pituitary Surgery

Polyuria without Thirst: Adipsic Arginine Vasopressin Deficiency as a Sequela of Pituitary Surgery

Predictive modeling of arginine vasopressin deficiency after transsphenoidal pituitary adenoma resection by using multiple machine learning algorithms

This study aimed to predict arginine vasopressin deficiency (AVP-D) following transsphenoidal pituitary adenoma surgery using machine learning algorithms. We reviewed 452 cases from December 2013 to December 2023, analyzing clinical and imaging data. Key predictors of AVP-D included sex, tumor height, preoperative and postoperative changes in sellar diaphragm height and pituitary stalk length, preoperative ACTH levels, changes in ACTH levels, and preoperative cortisol levels. Six machine learning algorithms were tested: logistic regression (LR), support vector classification (SVC), random forest (RF), decision tree (DT), k-nearest neighbors (KNN), and extreme gradient boosting (XGBoost). After cross-validation and parameter optimization, the random forest model demonstrated the highest performance, with an accuracy (ACC) of 0.882 and an AUC of 0.96. The decision tree model followed, achieving an accuracy of 0.843 and an AUC of 0.95. Other models showed lower performance: LR had an ACC of 0.522 and an AUC of 0.54; SVC had an ACC of 0.647 and an AUC of 0.67; KNN achieved an ACC of 0.64 and an AUC of 0.70; and XGBoost had an ACC of 0.794 and an AUC of 0.91. The study found that a shorter preoperative pituitary stalk length, significant intraoperative stretching, and lower preoperative ACTH and cortisol levels were associated with a higher likelihood of developing AVP-D post-surgery.

Insulin-Induced Copeptin Response in Children and Adolescents to Diagnose Arginine Vasopressin Deficiency

Introduction: The diagnosis of arginine vasopressin deficiency (AVD, formerly central diabetes insipidus) remains a challenge. In recent years, stimulated copeptin has emerged as a promising tool to diagnose AVD. Methods: In this single centre retrospective study, we identified paediatric patients with suspected pituitary insufficiency who underwent standard insulin tolerance testing (ITT) previously. Patients with AVD and non-matched controls without polyuria-polydipsia syndrome were identified. Diagnosis of AVD was confirmed retrospectively using comprehensive clinical and diagnostic characteristics. Serum copeptin concentrations were measured using a commercially available automated immunofluorescence assay (B.R.A.H.M.S Copeptin-proAVP KRYPTOR®) in −20°C stored samples collected before and 30, 45, and 60 min after insulin injection. Cut-off analyses were performed using ROC curves. Results: Twenty-five patients with AVD and 43 non-matched controls were available for analysis. Median basal copeptin concentrations of 1.51 pmol/L (IQR: 0.91–1.95; serum osmolarity: 288.5 mmol/L, IQR: 282.3–293.5) increased at a median of 30 min to a maximum of 1.95 pmol/L (IQR: 1.31–2.39) in AVD patients (p = 0.113) and from 4.41 pmol/L (IQR: 3.36–6.68; serum osmolarity: 281.0 mmol/L, IQR: 274.0–286.0, p < 0.001) to a maximum of 8.39 pmol/L (IQR: 4.95–19.72, p < 0.001) in controls. ROC analysis resulted in a cut-off of 3.0 pmol/L for maximum copeptin (91.7% sensitivity, 94.1% specificity) for the diagnosis of AVD. Conclusion: Our results suggest that insulin-stimulated serum copeptin concentrations are a sensitive and specific diagnostic tool for AVD in paediatric patients, which allows us to test multiple pituitary hormone axes simultaneously in a single test.

Effectiveness of a bespoke educational video for healthcare professionals (HCPs) on arginine vasopressin deficiency (AVP-D) and desmopressin in sheffield teaching hospitals NHS foundation trust (STH NHS FT)

Effectiveness of a bespoke educational video for healthcare professionals (HCPs) on arginine vasopressin deficiency (AVP-D) and desmopressin in sheffield teaching hospitals NHS foundation trust (STH NHS FT)

Altered vocal communication in adult vasopressin-deficient Brattleboro rats

The neuropeptide, arginine vasopressin (AVP), has been implicated in social communication across a diverse array of species. Many rodents communicate basic behavioral states with negative versus positive valence through high-pitched vocalizations above the human hearing range (ultrasonic vocalizations; USVs). Previous studies have found that Brattleboro (Bratt) rats, which have a mutation in the Avp gene, exhibit deficits in their USVs from the early postnatal period through adolescence, but the magnitude of this effect appears to decrease from the juvenile to adolescent phase. The present study tested whether Bratt rats continue to exhibit USV deficits in adulthood. USVs of adult male and female Bratt and wild type (WT) rats were recorded in two contexts: a novel environment (empty arena) and a social context (arena filled with bedding soiled by same-sex conspecifics). The number, frequency, and duration of 50 kHz USVs were quantified by DeepSqueak after validation with manual scoring. Twenty-two kHz measures were quantified by manual scoring because DeepSqueak failed to accurately detect USVs in this frequency range. Adult Bratt rats did not exhibit deficits in the number of 50 kHz USVs: male Bratt rats emitted similar 50 kHz USVs as male WT rats, whereas female Bratt rats emitted more USVs than female WT rats. USV frequency and duration were altered in adult Bratt rats, but in a context-dependent manner. Twenty-two kHz USVs were less affected by the Bratt mutation. The present study demonstrates how chronic AVP deficiency impacts social communication across the lifespan. The present findings reveal a complex role for AVP in vocal communication, whereby disruption to the Avp gene leads to sex-, context-, and developmental phase-specific effects on the quantity and spectrotemporal characteristics of rat USVs.

Clinical complexities of adipsic arginine vasopressin deficiency

Clinical complexities of adipsic arginine vasopressin deficiency

GLP-1 receptor agonists may enhance the effects of desmopressin in individuals with AVP deficiency: a case series and proposed mechanism

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) have diverse effects on sodium and water homeostasis. They decrease thirst perception, potentially inhibit arginine vasopressin (AVP) production, and induce natriuresis. We present three cases of AVP deficiency (AVP-D) where GLP-1 RA initiation led to desmopressin dose reduction.CasesThree patients with AVP-D on stable desmopressin therapy started GLP-1 RAs for type 2 diabetes mellitus or obesity. Following weight loss and decreased thirst, all patients reduced their desmopressin dose while maintaining normal thirst and urine output.DiscussionGLP-1 RAs influence sodium and water homeostasis through various mechanisms. In individuals with intact AVP systems, GLP-1 RAs may directly suppress AVP production and induce natriuresis in the kidney leading to increased water excretion. In AVP-D, with exogenous desmopressin replacing endogenous AVP, the osmotic permeability of collecting ducts is primarily influenced by desmopressin dose. Thus, increased distal fluid delivery may allow for lower desmopressin doses to maintain water balance.ConclusionOur findings indicate a potential interaction between GLP-1 RAs and desmopressin in AVP-D. Clinicians should reassess desmopressin dosage upon initiating GLP-1 RA therapy.

Approach to the patient with suspected hypotonic polyuria.

Investigation and management of hypotonic polyura is a common challenge in clinical endocrinology. The three main causes, recently renamed to arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus), AVP-resistance (AVP-R, formerly nephrogenic diabetes insipidus), and primary polydipsia (PP) require accurate diagnosis as management differs for each. This new nomenclature more accurately reflects pathophysiology, and has now been adopted by the Systemised Nomenclature of Medicine (SNOMED). Advances in diagnosis over the last few years have centered around the use of copeptin measurement. Here, we use three patient case histories to highlight the use of this approach, and to demonstrate how it can succeed where other approaches, such as the water deprivation test, sometimes fail. We discuss the overall approach to each type of patient and the strengths and limitations of diagnostic strategies, illustrating the use of the new nomenclature.