Water Deprivation Test Research Articles

Diagnostic Utility of Copeptin in Pediatric Patients with Polyuria-Polydipsia Syndrome: A Systematic Review and Meta-Analysis.

Pediatric patients with polyuria polydipsia syndrome (PPS) represent a diagnostic challenge for clinicians because of the technical difficulties in performing the gold standard water deprivation test (WDT). Copeptin, a stable biomarker representing the C-terminal portion of the polypeptide chain of the antidiuretic hormone, is a reliable diagnostic tool. To assess the diagnostic accuracy of baseline copeptin dosing, arginine/hypertonic saline copeptin stimulation tests, and WDT. This study aimed to establish the diagnostic utility of copeptin in pediatric patients by distinguishing between central diabetes insipidus, nephrogenic diabetes insipidus, and primary polydipsia. Comparative and non-comparative primary studies published between January 2018 and August 2024 focusing on children were searched and included in PubMed, Cochrane Library, Web of Science, ScienceDirect, Scopus, and Google Scholar. The QUADAS-2 tool was used to assess the risk of bias and applicability. Meta-analyses used fixed effects models because of low heterogeneity and the HSROC model. Eleven studies were included with an overall low bias and no significant applicability concerns. The mean pooled sensitivity = 0.98 (95% CI: 0.936-1.025), pooled specificity = 0.947 (95% CI: 0.920-0.973), and AUC = 0.972 (95% CI: 0.952-0.992), indicating excellent diagnostic accuracy. Stimulation methods for copeptin dosing represent an effective and less invasive diagnostic test for children with PPS, and future development of standard copeptin testing protocols is needed.

5086 Approaching the Enigma: Unveiling a Pituitary Stalk Lesion with Imaging and Hormonal Patterns

Abstract Disclosure: N. Rodriguez-Morales: None. P. Guido: None. Background: Pituitary stalk lesions (PSL) pose a diagnostic dilemma for endocrinologists. Multiple studies have attempted to associate hormonal imbalances and imaging patterns to a specific etiology (1,2). However, the diagnosis remains a mystery on many occasions. We describe a case of secondary hypogonadism and central DI attributed by a PSL. Clinical Case: A 39-year-old male presented with symptoms of hypogonadism and polyuria. Initial workup was consistent with secondary hypogonadism; decreased free and total testosterone levels (1.8 pg/dL and 9 ng/dL, n>35 pg/dL, n>250 ng/dL), LH (0.2 mIU/mL, n>1.5 mIU/mL), and FSH (<0.7 mIU/mL, n>1.6 mIU/mL). The remaining anterior pituitary hormones were within normal limits. The patient was also polyuric (6.5L urine output in 24hr). HgbA1c was normal. Urine Na, urine Osm demonstrated water diuresis (13 mmol/L and 54 mOsm/kg, respectively). A water deprivation test was performed. Initial urine Osm after water restriction was 119 mOsm/kg, which more than tripled to 575 mOsm/kg after administration of desmopressin, diagnostic of central DI. Pituitary MRI showed a well-circumscribed thickening of the pituitary stalk (6x6x5mm), with uniform enhancement. Evaluation for etiology to rule out germ cell tumor, lymphoma, sarcoidosis, opportunistic infection, tuberculosis, Langerhans cell histiocytosis showed a normal serum hCG, HIV, ACE, LDH, AFP. A lumbar puncture demonstrated normal cytology and was negative for AFB. Whole body bone scintigraphy and chest X-ray were normal. Pituitary deficits were treated with hormone replacement (testosterone and desmopressin), and a repeat MRI showed a stable lesion. Conclusion: Noninvasive testing is key to the evaluation of a pituitary stalk lesion. Careful consideration of inflammatory, infectious, and neoplastic etiologies along with attention to pituitary deficits is very important. Our patient most likely has a craniopharyngioma based on data from other case series (1,2). This case serves to bring additional data to the body of literature on this complicated clinical scenario.

8155 Isolated Hypothalamic-Pituitary Langerhans' Cell Histiocytosis in Adult Patients

Abstract Disclosure: A. Vu: None. M. Aguilera: None. J. Shakil: None. R. Al-Ward: None. Introduction: Langerhans cell histiocytosis (LCH) is an infiltrative disease due to clonal proliferation of immature dendritic cells mainly affecting children and seen in adults in less than 30% of cases. It can present as localized or with systemic manifestations, with isolated hypothalamic-pituitary lesions being exceptionally rare. Our report adds to the limited published literature by presenting two cases of isolated hypothalamic-pituitary LCH diagnosed in adults. Furthermore, one of the cases reveals a rare association with papillary thyroid cancer (PTC). Case 1: 35-year-old woman with no past medical history presented with 4 year history of amenorrhea and weight gain and more recently, polyuria and polydipsia. Further investigations showed hypogonadotropic hypogonadism, central hypothyroidism, and mildly elevated prolactin. She couldn’t complete water deprivation test due to extreme thirst. A dedicated pituitary MRI showed marked infundibular enlargement, concerning for hypophysitis. An extensive workup including assessments for autoimmune etiology, sarcoidosis, infections, and low-grade tumors, did not identify a definitive etiology. A PET scan was obtained (to rule out LCH and Erdheim Chester disease), which showed increased uptake in the pituitary stalk. Due to otherwise negative workup, transsphenoidal biopsy of the pituitary lesion was done. Post-procedure, diabetes insipidus (DI) was diagnosed due to elevated sodium while fasting for the procedure. Tissue examination revealed increased histiocytes and lymphocytes, and a positive BRAF V600E mutation confirming LCH as the underlying diagnosis. Case 2: 26-year-old male with history of LCH limited to the skull, in remission for 8 years after chemotherapy, presented with 4-week history of polyuria, polydipsia and weight loss. A 24-hour urine collection resulted in 6.5L of urine. During water deprivation test, there was notable increase in serum sodium, serum osmolarity, and urine osmolarity. Initial pituitary MRI was normal, but subsequent imaging revealed the loss of the posterior pituitary bright spot. PET scan showed focal FDG avidity in the right lower thyroid lobe, confirmed on fine needle aspiration as PTC with BRAF mutation. He underwent total thyroidectomy and is currently receiving chemotherapy for LCH recurrence. Discussion: LCH is infrequent in adults, presenting with variable manifestations based on affected organs. In the multifocal form, the hypothalamic-pituitary axis is involved in 5-50% of cases. Our report describes two unique cases with only four other reported cases of isolated hypothalamic-pituitary axis LCH in adults. Central diabetes insipidus can be seen before the diagnosis or as the disease progresses. Pituitary biopsy, although invasive, should be considered when the diagnosis is not clear. The association of PTC with a BRAF mutation is extremely rare and has been reported. Presentation: 6/2/2024

6616 Copeptin Use To Reduce Hospital Stay In A Complicated DI Case

Abstract Disclosure: S.S. Kowsika: None. H. Moran: None. Introduction: While there is literature describing the use of copeptin for the diagnosis of polyuria-polydipsia syndrome, its utilization remains very limited in many hospitals. We present a case where the patient, initially misdiagnosed with central diabetes insipidus (DI), was appropriately diagnosed with partial nephrogenic DI through the use of copeptin. Case: A 48-year old female with a history of cardiac arrest, anoxic brain injury and diabetes insidious (DI) presented to the emergency department with hypernatremia (Na 154 mmol/L). The patient had been initiated on desmopresin (DDAVP) at an outside facility prior to her current admission. Despite receiving high doses of DDAVP, her sodium levels remained elevated, prompting further investigation. DDAVP administration was discontinued. A water deprivation test was subsequently performed, followed by IV administration of 2 mcg of DDAVP, which resulted in an increase in urine osmolality from 191 to 331 mosm/kg, which was less than the expected 50% increase observed in central DI. Additionally, a baseline copeptin level was obtained and noted to be 31 pmol/L, confirming the diagnosis of partial nephrogenic DI. The patient was started on Amiloride, leading to normalization of sodium levels. Discussion: Many patients with polyuria-polydipsia syndrome are frequently misdiagnosed and receive incorrect treatment, potentially worsening their clinical condition. Copeptin (Carboxy-Terminal-Pro-vasopressin) is the C-terminal peptide of pro-vasopressin, co-secreted with arginine vasopressin (AVP). It has been proposed as a direct test for diagnosing polyuria-polydipsia syndrome. Baseline Copeptin testing without stimulation can accurately diagnose nephrogenic DI if elevated (>21.4, pmol/L). To differentiate between central DI and chronic polyuria, prior thirsting with hypertonic saline or glucagon stimulation is necessary, with stimulated copeptin <4.9 pmol/L diagnosing central DI. Despite its diagnostic potential, Copeptin is underutilized in many settings. In this case, using Copeptin to accurately diagnose our patient led to appropriate treatment and the resolution of hypernatremia. Presentation: 6/1/2024

7418 Xanthoma Disseminatum - A Rare cause of Diabetes Insipidus

Abstract Disclosure: P. Balasubramanian: None. J. Cohen: None. Z. Corbin: None. G. Panse: None. S.E. Inzucchi: None. Background: Xanthoma disseminatum is a rare non-Langerhans cell-derived benign histiocytosis of unknown etiology, characterized by mucocutaneous xanthomatosis. Systemic involvement occurs in a subset of patients, the most common manifestation being central diabetes insipidus in the setting of hypothalamic-pituitary- infundibulum infiltration, occurring in about 30-50% of the patients. We present the case of a man with biopsy proven cutaneous xanthoma disseminatum who developed central diabetes insipidus due to pituitary stalk involvement. Case Presentation: A 69-year-old male presented with a 2-year history of symmetrically distributed, erythematous to hyperpigmented macules and papules in the axillae and inguinal folds. He did not have any mucosal lesions. Skin biopsy revealed histiocytic infiltrate consistent with non-Langerhans cell histiocytosis, likely xanthoma disseminatum. He developed symptoms of polyuria and nocturia around the same time of the eruption, resulting in a large daily fluid intake of 100-120 ounces/day for several months. Laboratory evaluation revealed normal electrolytes. After an overnight water deprivation test, serum osmolality was 299mOsm/kg, serum sodium was 144mmol/L and urine osmolality was 280mOsm/kg, consistent with partial central diabetes insipidus. MRI pituitary with and without IV contrast showed thickening and hyperenhancement of the pituitary stalk. Anterior pituitary function was intact except for mild hypogonadotropic hypogonadism. He was started on DDAVP with good response and resolution of symptoms. Conclusion: Xanthoma disseminatum is characterized by extensive mucocutaneous xanthomatosis with occasional systemic involvement. The natural history of xanthoma disseminatum is usually benign, indolent, and slowly progressive with spontaneous regression described in a few cases. Hypothalamic and pituitary involvement may cause hyperprolactinemia, central diabetes insipidus, and variable degrees of hypopituitarism. Diabetes insipidus is often mild and sometimes transient. Occasionally, central diabetes insipidus can precede the skin lesions. Prognosis is generally good. Central nervous system involvement outside the hypothalamus/pituitary carries a poor prognosis. Presentation: 6/2/2024

6379 Clonidin does not stimulate copeptin release

Abstract Disclosure: G. Binder: None. K. Weber: None. A. Peter: None. R. Schweizer: None. Background: Copeptin is secreted in isomolar amounts along with arginine vasopressin peptide from the posterior pituitary. Its stability makes it a perfect candidate for a biomarker of AVP deficiency. In children, the infusion of arginine and bolus of insulin stimulate copeptin; the respective stimulation test could be an alternative to the water deprivation test. Here, we retrospectively studied the effect of clonidine on copeptin release. Design and patients: This is a monocentric retrospective analysis of donated residual serum samples from 42 children with suspected of GH deficiency who underwent clonidine stimulation between 2020 and 2023. Measurements: Copeptin was measured in baseline, 30-, 60-, 90- and 120-min samples by BRAHMS Copeptin proAVP Kryptor immunofluorescence assay. GH was measured using an in-house RIA calibrated against the WHO International Reference Preparation 98/574. Results: According to the test results (clonidine and arginine test), there were 20 patients with GHD and 16 without GHD. No patient had polyuria-polydipsia syndrome. Median age was 6.7 years (quartiles; 5.6-7.8), the median height was -2.92 SDS (-3.42- -2.34), and the median BMI was-0.29 SDS (-1,32 - +0,16). The median baseline level of copeptin was 5,6 pmol/l (3.4-9.6). Median copeptin mildly decreased to 4.5 pmol/l (3.0-10.0) after 30 min; this change was not significant (P=0.45). Thereafter, median values remained low at 4.6, 4.6 and 4.6 pmol/l (60, 90 and 120 min). There was no correlation between baseline copeptin levels and the diagnosis of GHD. Conclusion: The clonidine stimulation test does not stimulate copeptin release and is therefore not suitable for the assessment of AVP deficiency in children. Presentation: 6/2/2024

8301 A Rare Case of IgG4-Related Hypophysitis

Abstract Disclosure: P. Kesavan Chary: None. J.M. Silverstein: None. Background: IgG4-related disease (IgG4-RD) is an immune-mediated condition that presents as systemic inflammation and fibrosis of tissues, often affecting multiple organs. Isolated IgG4-related Hypophysitis is rare and characterized by lymphoplasmacytic infiltration of the pituitary gland by IgG4-positive plasma cells. A combination of clinical, serologic, radiologic, and histopathologic findings is used for diagnosis of IgG4-RD and approximately two-thirds of all patients have elevated serum IgG4 levels. We report a case of isolated IgG4-related Hypophysitis in a middle-aged woman serologically negative for IgG4-related disease. Case Report: A 52 year old female with history of steroid dependent severe persistent asthma, allergic rhinitis, and chronic sinusitis presented with one month of headache, polyuria, and polydipsia. MRI Brain demonstrated an enlarged, rounded pituitary gland 16 x 11 x 9 mm, with homogeneous enhancement, extension into the suprasellar cistern, and mild thickening of the infundibulum suspected to represent a pituitary adenoma. Lab evaluation revealed mild hyperprolactinemia (prolactin 83.2, normal 4.8-23.3 ng/mL) and secondary adrenal insufficiency based on an abnormal high-dose cosyntropin stimulation test in the setting of a low adrenocorticotrophic hormone (ACTH) level (<2.0 pg/mL). Remaining pituitary hormone levels were normal. Inpatient work-up for polyuria and polydipsia showed a low urine specific gravity of 1.003. An overnight water deprivation test was performed. Baseline urine osmolality (UOsm) was 95 mOsm/kg and serum sodium was 144 mmol/L; after 3 hours of water deprivation, serum Osm increased to 301 mOsm/kg (275-300 mOsm/kg) and UOsm only to 215 mOsm/kg, while her sodium increased to 145 mmol/L. Results were felt to be consistent with AVP deficiency (Central Diabetes Insipidus) and the patient was started on desmopressin. Because of the presence of AVP deficiency, further work-up was done to evaluate for an infiltrative process or malignancy. ANA, RPR, ESR, CRP, CBC, ACE level, T-SPOT, and IgG subclasses were unremarkable. Further imaging studies yielded a negative nuclear bone scan and PET/CT scan. For diagnostic purposes, the patient underwent biopsy via an endoscopic endonasal transsphenoidal approach. Pathology showed the presence of >10 IgG4+ plasma cells in a single high-power field, consistent with a diagnosis of IgG4-related Hypophysitis. Conclusion: Isolated IgG4-related Hypophysitis is the least common clinical presentation of IgG4-RD, which is itself a rare and relatively newly recognized condition. IgG4-related Hypophysitis should be suspected in patients presenting with AVP deficiency and pituitary stalk enlargement with an otherwise negative work up. Presentation: 6/2/2024

New diagnostic criterion for a 3% hypertonic saline infusion test for the differential diagnosis of diabetes insipidus and primary polydipsia

AIM: To determine the value of urine osmolality when conducting a test with 3% hypertonic sodium chloride solution, which allows for the differential diagnosis of diabetes insipidus (DI) and primary polydipsia (PP).METHODS: An interventional cross-sectional study was conducted at the (Endocrinology Research Center. The study included 90 patients with polyuria-polydipsia syndrome from September 2021 to September 2023. All patients underwent sequential two tests with osmotic stimulation: 3% hypertonic saline infusion test and a water deprivation test. The final diagnosis was established based on the results of a fluid deprivation test, the patient’s anamnestic data (previous operations, diseases of the hypothalamic-pituitary region, the presence of mental illnesses), MRI data (the presence of a hyperintense signal from the posterior pituitary on T1-weighted images, a detected tumor or infiltrative formation of the hypothalamic-pituitary area, presence of Rathke’s pouch cyst).RESULTS: 48 patients with a final diagnosis of DI and 42 with a final diagnosis of PP were analysed. A cut-off point for urine osmolality during infusion test with 3% hypertonic saline was found: values less than or equal to 377 mOsm/kg support the diagnosis of DI, and values higher than 377 mOsm/kg support the diagnosis of PP. The sensitivity of the criterion is 89%, 95% CI (77%; 97%), specificity — 98% (87%; 100%), PPV — 98% (88%; 100%), NPV — 89% (76%; 96%), accuracy 93% (86%; 98%).CONCLUSION: The proposed criterion for differential diagnosis has comparable diagnostic accuracy in relation to the differential diagnosis of DI and PP, while the safety of the test may be higher.

A single-centre retrospective study looking at copeptin levels in children and young people who underwent water deprivation test

A single-centre retrospective study looking at copeptin levels in children and young people who underwent water deprivation test

Acute lymphoblastic leukemia with nephrogenic diabetes insipidus as the first symptom: a case report

BackgroundAcute lymphoblastic leukemia is the most common pediatric malignancy, characterized by fever, anemia, hemorrhage, and symptoms brought on by blasts infiltrating organs.Case presentationThis is a case report of a 9-year-old Asian patient with acute lymphoblastic leukemia who presented with polyuria alone as a presenting feature without any other clinical manifestation; primary renal disease or inherited metabolic disease was highly suspected. However, the water deprivation test and water deprivation pressurization test suggested nephrogenic diabetes insipidus, and the renal biopsy displayed diffuse lymphocytic infiltration in the renal interstitium. Bone marrow aspiration was performed immediately, and a comprehensive diagnosis of B-lymphoblastic leukemia was finally made.ConclusionsRenal infiltration with leukemic blasts mostly remains asymptomatic, but our case suggests that it can present with nephrogenic diabetes insipidus. This case fully demonstrates that the presentation of extramedullary infiltration in acute lymphoblastic leukemia is varied. When the patient has renal diabetes insipidus as the first symptom, the possibility of hematological tumor infiltration should be considered when finding the cause, and timely bone marrow cytology should be performed.

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.

How to improve ChatGPT performance for nephrologists: a technique guide.

The integration of ChatGPT into nephrology presents opportunities for enhanced decision-making and patient care. However, refining its performance to meet the specific needs of nephrologists remains a challenge. This guide offers a strategic roadmap for advancing ChatGPT's effectiveness in nephrological applications. Utilizing the advanced capabilities of GPT-4, we customized user profiles to optimize the model's response quality for nephrological inquiries. We assessed the efficacy of chain-of-thought prompting versus standard prompting in delineating the diagnostic pathway for nephrogenic diabetes insipidus-associated hypernatremia and polyuria. Additionally, we explored the influence of integrating retrieval-augmented generation on the model's proficiency in detailing pharmacological interventions to decelerate the progression from chronic kidney disease (CKD) G3 to end-stage kidney disease (ESKD), comparing it to responses without retrieval-augmented generation. In contrast to the standard prompting, the chain-of-thought method offers a step-by-step diagnostic process that mirrors the intricate thought processes needed for diagnosing nephrogenic diabetes insipidus-related hypernatremia and polyuria. This begins with an initial assessment, notably including a water deprivation test. After evaluating the outcomes of this test, the approach continues by identifying potential causes. Furthermore, if a patient's history suggests lithium usage, the chain-of-thought model adjusts by proposing a more customized course of action. In response to "List medication treatment to help slow progression of CKD G3 to ESKD?", GPT-4 only provides a general summary of medication options. Nevertheless, a specialized GPT-4 model equipped with a retrieval-augmented generation system delivers more precise responses, including renin-angiotensin system inhibitors, sodium-glucose cotransporter-2 inhibitors, and mineralocorticoid receptor antagonists. This aligns well with the 2024 KDIGO guidelines. GPT-4, when integrated with chain-of-thought prompting and retrieval-augmented generation techniques, demonstrates enhanced performance in the nephrology domain. This guide underscores the transformative potential of chain-of-thought and retrieval-augmented generation techniques in optimizing ChatGPT for nephrology, and highlights the ongoing need for innovative, tailored AI solutions in specialized medical fields.

Redefining diagnostic cut-offs for the indirect water deprivation test

Redefining diagnostic cut-offs for the indirect water deprivation test

Copeptin Stimulation by Combined Intravenous Arginine and Oral LevoDopa/Carbidopa in Healthy Short Children and Children with the Polyuria-Polydipsia Syndrome

Introduction: Stimulated copeptin may provide an alternative to water deprivation testing (WDT) in the evaluation of polyuria-polydipsia syndrome (PPS). Though best studied, arginine stimulation alone produces a modest copeptin response in children. We investigated the effectiveness of the arginine + LevoDopa/Carbidopa stimulation test (ALD-ST) for copeptin. Methods: 47 healthy short children (controls), 10 children with primary polydipsia, and 10 children with AVP deficiency received arginine hydrochloride (500 mg/kg intravenously over 30 min) and Levodopa/carbidopa (10:1 ratio; 175 mg of l-Dopa/m2 BSA) orally. Serum copeptin was measured at 0, 60, 90, and 120 min. Results: In controls, ALD-ST increased copeptin from a median of 7.0 pmol/L (IQR 5.0–10.0) to a peak of 44.0 pmol/L (IQR 21.4–181.0) between 60 and 120 min (p < 0.001). Copeptin peak was higher in subjects who experienced nausea or vomiting (57%) than in those who did not (131.0 pmol/L [IQR 42.5–193.8] vs. 22.7 pmol/L [IQR 16.0–33.7], p < 0.001). While subjects with primary polydipsia had similar baseline (8.5 pmol/L [IQR 8.0–11.0]) and stimulated (125.2 pmol/L [IQR 87.6–174.0]) copeptin levels as controls, subjects with AVP deficiency had lower baseline (2.5 pmol/L [IQR 2.0–3.1]) and peak levels (4.6 pmol/L [IQR 2.4–6.0]). A peak copeptin of ≥9.3 pmol/L best predicted absence of complete or partial AVP deficiency with a sensitivity of 100% and specificity of 80%. Conclusions: ALD-ST induced a robust peak copeptin in healthy short children and children with primary polydipsia. Nausea/vomiting, a side effect of ALD-ST, amplified the copeptin response. The ALD-ST may be a suitable initial screening test in children with PPS.

Anterior and Posterior Pituitary Function in Patients with Sheehan Syndrome - Combining the use of Insulin Tolerance Test and Copeptin Assay.

Sheehan syndrome (SS) typically involves the loss of anterior pituitary cells and rarely affects the posterior pituitary. The water deprivation test (WDT) is the gold standard for diagnosing central diabetes insipidus (CDI), but it is cumbersome. Serum copeptin measurements are an alternative for CDI diagnosis. In this study, we measured hypoglycaemia-stimulated serum copeptin in SS patients to assess posterior pituitary function alongside anterior pituitary hormone levels. This study recruited 43 patients with SS on stable hormonal replacement except for growth hormone (GH), 18 patients with CDI, and 19 body mass index (BMI) and parity-matched controls. All patients with SS and four patients with CDI underwent an insulin tolerance test (ITT), and hypoglycaemia-stimulated copeptin levels were measured at 0, 30, 45, and 90 minutes after insulin injection. The mean serum copeptin level among patients with SS (26.01 ± 12.41 pmol/L) was significantly lower than that in healthy controls (31.92 ± 7.85 pmol/L) and higher than that in patients with CDI (1.81 ± 0.14 pmol/L). Using pre-defined cut-offs for CDI, basal serum copeptin <2.69 pmol/L and stimulated levels <4.92 pmol/L for complete central DI, and basal copeptin levels >2.69 pmol/L and stimulated copeptin <4.92 pmol/L for partial central DI, 9.2% (n = 4) of patients with SS had CDI, of which half had complete CDI and half had partial CDI. A significant number of patients with SS who are on hormone replacement therapy show involvement of the posterior pituitary, despite not displaying symptoms.

Arginine vasopressin deficiency: diagnosis, management and the relevance of oxytocin deficiency.

Polyuria-polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes mellitus, the name 'central diabetes insipidus' was changed in 2022 to arginine vasopressin (AVP) deficiency and 'nephrogenic diabetes insipidus' was renamed as AVP resistance. To differentiate the three entities, various osmotic and non-osmotic copeptin-based stimulation tests have been introduced in the past decade. The hypertonic saline test plus plasma copeptin measurement emerged as the test with highest diagnostic accuracy, replacing the water deprivation test as the gold standard in differential diagnosis of the polyuria-polydipsia syndrome. The mainstay of treatment for AVP deficiency is AVP replacement with desmopressin, a synthetic analogue of AVP specific forAVP receptor 2 (AVPR2), which usually leads to rapid improvements in polyuria and polydipsia. The main adverse effect of desmopressin is dilutional hyponatraemia, which can be reduced by regularly performing the so-called desmopressin escape method. Evidence from the past few years suggests an additional oxytocin deficiency in patients with AVP deficiency. This potential deficiency should be further evaluated in future studies, including feasible provocation tests for clinical practice and interventional trials with oxytocin substitution.

The 3% hypertonic saline infusion test for the differential diagnosis of diabetes insipidus and primary polydipsia: assessment of diagnostic accuracy

AIM: assessment of the diagnostic accuracy of a 3% hypertonic saline infusion test in relation to a set of clinical and laboratory data (including a water deprivation test and MRI data) for differential diagnoses of diabetes insipidus (DI) and primary polydipsia (PP).METHODS: An interventional cross-sectional study was carried out at Endocrinology Research Centre From September 2021 to September 2023 ninety patients with polyuria-polydipsia syndrome were included. In order to assess the diagnostic characteristics, all the subjects underwent two tests with osmotic stimulation: a 3% hypertonic saline infusion test and a water deprivation test. Adverse events were assessed.RESULTS: Based on the results of clinical, anamnestic, laboratory and instrumental data, and the results of a water deprivation test, a final diagnosis of DI was made in 48 (53%) patients and PP in 42 (47%) patients. The agreement between the two samples is significant — Kappa = 0.823, 95% CI (0.707, 0.939). The operational parameters of the 3% hypertonic saline infusion test are: sensitivity 98% (95% CI: 89%; 100%); specificity 98% (95% CI: 87%; 100%), positive and negative predictive values 98% (95% CI: 89%–100%) and 98% (95% CI: 87%–100%). Respectively. Chills occurred significantly more often (31% vs. 12%), and dizziness and headache were more pronounced during the 3% hypertonic saline infusion test. The median duration of the water deprivation test in patients was 11 hours, and median duration of 3% hypertonic saline infusion test was 1.5 hour (P&lt;0.001).CONCLUSION: The 3% hypertonic saline infusion test has a high overall diagnostic accuracy 98%; 95% CI 92% to 100%)) in relation to the classical set of clinical, laboratory and instrumental data of patients (including a water deprivation test), However, it is important the advantage of the latter is its short duration and, as a consequence, better tolerability and probably better compliance, while no significant differences in adverse events frequencies during the tests were identified.

Hypokalemia Induced Partial Nephrogenic Diabetes Insipidus: A Case Report

Diabetes insipidus is a condition characterised by a large volume of diluted urine production andincreased thirst. In this case report, a 49-year-old gentleman presented with 3 months of polyuria andpolydipsia. He had a repeated history of hypokalemia. On the evaluation of polyuria and polydipsia,he was diagnosed with partial nephrogenic diabetes insipidus based on his inability to concentrateurine after a water deprivation test and his less than 50% response to exogenous desmopressin.On the evaluation of recurrent hypokalemia, the investigation reports met biochemical criteria forthe diagnosis of Gitelman syndrome. He was encouraged to increase his fluid intake as required,and potassium chloride supplementation relieved his symptoms. This case report demonstrates thereversibility of nephrogenic diabetes insipidus with a correction of hyperkalemia.

Detection of Partial Central Diabetes Insipidus in Limited Resource Setting

Antidiuretic hormone (ADH) is an endogenous prohormone peptide synthesized in the posterior hypothalamus that regulates water excretion by the kidney. Diabetes insipidus is a disorder characterized by the excretion of large amounts of urine (diabetes) that are hypotonic, watery, and tasteless (insipid). The rarity of this case is one of the causes of missed diagnosis. If not diagnosed properly, patients will receive therapy that exacerbates the disease. The Water Deprivation Test (WDT) is one of the dynamic tests that can be done to narrow the diagnosis. A 44-year-old female was admitted to the hospital with chief complaints of polydipsia and polyuria during the previous 9 months. The patient had a history of irregular menstruation, cesarean delivery due to abdominal mass, and breast lump surgery. Diabetes mellitus and thyroid disease were excluded. Her blood pressure during admission was 150/100 mmHg and her body mass index was 31.1. Fluid balance data obtained before the water deprivation test showed that the urine volume (output) was 7.150 mL per 24 hours, and the total water input was 6.290 mL. Water deprivation test results showed that the kidneys were partially respond to the administration of exogenous ADH, suggestive of partial central diabetes insipidus.

The diagnostic performance of copeptin in clinical practice: A prospective study.

Plasma copeptin is a relatively new biomarker for evaluation of arginine vasopressin (AVP)secretion. The aim of this study was to test the diagnostic performance of copeptin in patients with polyuria-polydipsia syndrome. This was a prospective study where 88 patients with polyuria-polydipsia syndrome were evaluated with a water deprivation test (WDT).Weight, urine osmolality, urine specific gravity, and plasma copeptin were collected at baseline, after 8 h, and at termination of the WDT when one of the following had been reached: (i) >3% weight reduction, (ii) urine specific gravity >1.017 or urine osmolality >600 mOsm/kg, or (iii) intolerable adverse symptoms. Of 88 patients (57 women), 21 (24%) were diagnosed with central diabetes insipidus (cDI),5 (6%) with nephrogenic DI (nDI),and 62 (71%) with primary polydipsia (PP).Median (interquartile range) copeptin at baseline was 1.7 (1.4-2.5) pmol/L in cDI, 22 (18-65) pmol/L in nDI, and 2.7 (2-4) pmol/L in PP. After 8 h of WDT, the highest copeptin in patients with cDI was 4.0 pmol/L. In patients with PP: (i) 41 had urine osmolality <600 mOsm/kg, 7 (17%) of these had copeptin >4.0 pmol/L, (ii) 21 had urine osmolality ≥600 mOsm/kg, 14 (67%) of these had copeptin >4.0 pmol/L. Copeptin >4.0 pmol/L after an overnight WDT can be used to rule out cDI and copeptin ≥21 pmol/L at baseline to diagnose nDI. The diagnostic performance of copeptin in the context of the WDT is otherwise limited in the diagnostic work-up of patients with polyuria-polydipsia syndrome.