Genetic analysis of nephrogenic diabetes insipidus patients: A study on the Iranian population.

INTRODUCTION: Nephrogenic diabetes insipidus (NDI) is a rare genetic disease that causes water imbalance. The kidneys play a crucial role in regulating body fluids by controlling water balance through urine excretion. This highlights their essential function in managing the body's water levels, but individuals with NDI may have excess urine production (polyuria), that leads to excessive thirst (polydipsia). Untreated affected individuals may exhibit poor feeding and failure to thrive. This disease is caused by mutations in the AVPR2 and the AQP2 genes which have the X-linked and autosomal recessive/dominant inheritance, respectively. Both of these genes are expressed in the kidney. METHODS: Twelve Iranian patients from 10 consanguineous families were studied in this project. DNA was extracted from the whole blood samples of the patients and their parents. All coding exons and exon-intron boundaries of the AVPR2 and AQP2 genes were sequenced in the affected individuals, and the identified variants were investigated in the parents. All variants were analyzed according to the ACMG (American College of Medical Genetics and Genomics) guidelines. RESULTS: In this study, 6 different mutations were identified in the patients, including 5 in the AQP2 gene (c.439G>A, c.538G>A, c.140C>T, c.450T>A, and the novel c.668T>C) and 1 in the AVPR2 gene (c.337C>T) in the present study. DISCUSSION: As expected, all the detected mutations in this study were missense. According to the ACMG guideline, the identified mutations were categorized as pathogenic or likely pathogenic. Unlike previous studies which showed more than 90% of mutations were in the AVPR2 gene, and only less than 10% of the mutations were in the AQP2 gene, it was found that more than 90% of our identified mutations located in the AQP2 gene, and only one mutation was observed in the AVPR2 gene, which seems it may be a result of the high rate of consanguineous marriages in the Iranian population. We observed genotype-phenotype correlation in some of our affected individuals, and some of the mutations were observed in unrelated families from same ethnicity which could be suggestive of a founder mutation.

Endocrinopathies in a Pediatric Patient Post-anatomical Hemispherectomy for Rasmussen's Encephalitis Treatment: A Case Report.

Hemispherectomy is a neurosurgical procedure that is frequently performed in pediatric patients diagnosed with Rasmussen's encephalitis. Postoperative complications include immediate complications such as hydrocephalus and hemorrhage and behavioral complications such as language impairments and contralateral weakness. However, there are limited studies or case reports that address the potential endocrinopathies associated with this and other pediatric epileptic surgeries. This case report describes the endocrinopathies following an anatomical hemispherectomy procedure. A four-year-old African-American female had a right anatomical hemispherectomy for the treatment of Rasmussen's encephalitis in 2020. The postoperative course was immediately complicated by central diabetes insipidus which was stabilized with desmopressin. The patient's labs in 2021 were consistent with central precocious puberty with elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Additionally, the patient was found to have secondary adrenal insufficiency in which she failed a low-dose adrenocorticotropic hormone (ACTH) stimulation test. Oral hydrocortisone therapy was initiated for secondary adrenal insufficiency in addition to initiating leuprolide injections for central precocious puberty. Furthermore, at the age of seven years, the patient had her first menarche. This case report emphasizes the need for closer and long-term surveillance for endocrine issues in postepileptic surgical pediatric patients as well as a surveillance plan for the development of other potential endocrine abnormalities throughout the patient's life.

Antidiuretic hormone deficiency secondary to inactive hydrocephalus: a case report.

BACKGROUND: Diabetes insipidus is a syndrome characterized by polyuria, which is almost always associated with polydipsia. The most frequent cause is central diabetes insipidus, which is the result of an inadequate secretion of the antidiuretic hormone, and diagnosis involves differentiating it from other causes of polyuria and polydipsia. CASE PRESENTATION: Here, we present a clinical case of a previously healthy 13-year-old Nepali boy, who, in December 2022, was found to have intense polydipsia accompanied by polyuria. He had bilateral lower limb weakness at the time of presentation. Biochemical evaluation demonstrated raised serum sodium (181 mEq/L), serum creatinine (78 µmol/L), and serum uric acid (560 µmol/L) with suppressed serum potassium (2.7 mEq/L), which was the major concern to the clinicians. Further laboratory workup revealed an increased serum osmolarity (393.6 mOsm/kg) with reduced urine osmolarity (222.7 mOsm/kg). On contrast magnetic resonance imaging of the brain, a thick-walled third ventricular cyst with bilateral foramen obstruction, thin membrane-like structure at top of aqueduct of Sylvius with gross obstructive hydrocephalus (inactive), and compressed and thinned pituitary gland with no bright spot was observed. The laboratory findings, radiological findings, and case presentation provided the provisional diagnosis of diabetes insipidus due to hydrocephalus and third ventricular cyst. CONCLUSIONS: Central diabetes insipidus due to hydrocephalus, though rare, can have serious complications including the predilection to develop a deficit of other pituitary hormones. Thus, even if hydrocephalus is dormant with normal intracranial pressure, it must be addressed during investigations of central diabetes insipidus.

The influence of insulin-induced hypoglycemia on copeptin concentrations.

Plasma copeptin is a biomarker that reflects arginine vasopressin (AVP) secretion. In this study we measured copeptin during insulin tolerance test (ITT) in 65 patients referred to our department for evaluation of anterior pituitary function. Plasma for measurements of copeptin were collected at the start of the test and regurarly up to 120 minutes thereafter. Of 60 patients who developed significant hypoglycemia and were included in the analyses, 13 (22%) had corticotropic deficiency, 11 (18%) had thyreotropic deficiency, 33 (55%) had growth hormone deficiency and 4 (6%) had AVP deficieny (AVPD). Thirty-seven (62%) patients had at least one anterior pituitary deficiency. In patients without AVPD, median (range) copeptin increased from 4.5 pmol/L (1.3-33.0) to a maximum of 6.2 pmol/L (2.0-34.4; p<0.001). Baseline copeptin was similar in men and women, but maximal copeptin during ITT was higher in men. Copeptin concentrations were not affected by age, BMI, somatotropic, or corticotropic function. Copeptin concentrations were lower in patients with AVPD than patiets without AVPD, and in patients with thyrotropic deficiency, compared to patients with intact thyrotropic function, both at baseline and during ITT. In conclusion, copeptin increases significantly during insulin induced hypoglycemia but is of limited value in predicting anterior pituitary hormonal function.

Persistent hypernatremia secondary to adipsic central diabetes insipidus in a patient with herpes-induced meningoencephalitis and COVID-19 infection: a case report.

Central diabetes insipidus (CDI) typically manifests as a polyuria-polydipsia syndrome, in which normonatremia is generally maintained through the polydipsia. A 53-year-old woman presented with diabetic ketosis and hyperosmolar hyperglycemic syndrome. Her medical history included herpes meningoencephalitis, which was associated with confusion and amnesia. On physical examination, she was apyretic, confused, and had signs of extracellular dehydration. Her capillary glucose concentration was high and her urine was positive for ketones. Laboratory investigations revealed severe hyperglycemia, hypernatremia (plasma hyperosmolarity of 393.6 mOsm/L), and mild acute renal failure. In addition, she had a paucisymptomatic COVID-19 infection. Intravenous rehydration with isotonic saline solution and insulin therapy were effective at controlling the ketosis and ameliorating the hyperglycemia, but failed to normalize the hypernatremia and hyperosmolarity. She was not thirsty and had a urine output of 1 L/day, with urinary hypotonicity. Desmopressin administration reduced the hypernatremia and hyperosmolarity to within their normal ranges, and the patient's urinary osmolarity increased to 743 mOsm/L. Therefore, adipsic CDI was diagnosed. Endocrine investigations revealed isolated central hypothyroidism. The results of pituitary magnetic resonance imaging were normal. Thus, patients with impaired thirst may have an atypical presentation of CDI. In addition, the diagnosis of adipsic CDI is particularly challenging.

Congenital nephrogenic diabetes insipidus treated with acetazolamide.

Congenital nephrogenic diabetes insipidus (CNDI) is a rare disorder. The condition is characterised by an inability of distal nephron segments to respond to normal or raised concentrations of serum antidiuretic hormone. In this report, we describe the case of a 13-year-old male known with CNDI who experienced a pedestrian vehicle accident leading to coma following a head injury. Intra-operatively, severe hypernatraemia and polyuria were observed. Following an inadequate response to conventional therapy, acetazolamide was prescribed resulting in an immediate response to therapy. To the best of our knowledge, acetazolamide has not been previously documented as a therapeutic option for CNDI. Additional research is necessary before considering the recommendation of acetazolamide for cases of NDI that do not respond adequately to conventional treatments.

Evaluation of copeptin in children after stimulation with clonidine or L-Dopa.

OBJECTIVES: Arginine-stimulated serum copeptin has been proposed as a new method to diagnose arginine vasopressin (AVP) deficiency in children and adolescents. Herein we investigated the secretagogic potential of clonidine or L-Dopa on the copeptin serum levels in children. METHODS: Eight stimulation tests (4 with clonidine and 4 with L-Dopa) were performed in eight children (5 boys and 3 girls) with a median age of 6.5 years-old, evaluated for short stature due to possible growth hormone deficiency. Serum copeptin levels were measured at 30, 60, 90, and 120 min after administration of clonidine or L-Dopa. RESULTS: Copeptin levels in serum did not show any significant change in either test (clonidine or L-Dopa). The values of copeptin levels compared to the baseline value did not deviate more than 5 % in the clonidine arm (p=0.60) or 8 % in the L-Dopa arm (p=0.75) respectively. CONCLUSIONS: Data do not support the use of L-Dopa or clonidine as stimulants for evaluating AVP relating disorders in clinical pediatric practice.

Pituitary stalk interruption syndrome due to novel ROBO1 mutation presenting as combined pituitary hormone deficiency and central diabetes insipidus.

OBJECTIVES: The genetic causes of pituitary stalk interruption syndrome (PSIS) remain elusive in 95 % of cases. The roundabout receptor-1 gene (ROBO1) plays critical roles in axonal guidance and cell migration. Recently, mutations in the ROBO1 gene have been reported patients with PSIS. CASE PRESENTATION: We report a 2.9-year-old boy with PSIS who presented with combined pituitary hormone deficiency, central diabetes insipidus, and the classical triad of MRI findings. Through clinical exome sequencing using next-generation sequencing techniques, a previously unidentified novel heterozygous frame shift mutation in the ROBO1 gene was identified. This is the first report of ROBO1 mutation associated with posterior pituitary dysfunction. CONCLUSIONS: We conclude and emphasize that ROBO1 should be investigated in patients with PSIS. Our case is unique in the published literature in that we are first time reporting posterior pituitary dysfunction as manifestation of ROBO1 mutation. The full clinical spectrum of the mutations may not be fully known.

Diagnosis and management of congenital hypopituitarism in children.

Hypopituitarism (or pituitary deficiency) is a rare disease with an estimated prevalence of between 1/16,000 and 1/26,000 individuals, defined by insufficient production of one or several anterior pituitary hormones (growth hormone [GH], thyroid-stimulating hormone [TSH], adrenocorticotropic hormone [ACTH], luteinizing hormone [LH], follicle-stimulating hormone [FSH], prolactin), in association or not with diabetes insipidus (antidiuretic hormone [ADH] deficiency). While in adults hypopituitarism is mostly an acquired disease (tumors, irradiation), in children it is most often a congenital condition, due to abnormal pituitary development. Clinical symptoms vary considerably from isolated to combined deficiencies and between syndromic and non-syndromic forms. Early signs are non-specific but should not be overlooked. Diagnosis is based on a combination of clinical, laboratory (testing of all hormonal axes), imaging (brain magnetic resonance imaging [MRI] with thin slices centered on the hypothalamic-pituitary region), and genetic (next-generation sequencing of genes involved in pituitary development, array-based comparative genomic hybridization, and/or genomic analysis) findings. Early brain MRI is crucial in neonates or in cases of severe hormone deficiency for differential diagnosis and to inform syndrome workup. This article presents recommendations for hormone replacement therapy for each of the respective deficient axes. Lifelong follow-up with an endocrinologist is required, including in adulthood, with multidisciplinary management for patients with syndromic forms or comorbidities. Treatment objectives include alleviating symptoms, preventing comorbidities and acute complications, and optimal social and educational integration.

Correction of In-Patient Severe Hypernatremia in an 81-Year-Old Female With Hypopituitarism.

Hypernatremia has been significantly associated with in-hospital mortality and discharge to long-term care facilities. The appropriate correction of electrolyte disturbances, especially sodium, is important to consider to prevent the addition of central nervous system disturbances, such as cerebral edema and eventual brain injury. The importance of maintaining a proper correction of hypernatremia has been well studied and used in clinical practice. Choosing to use a hypotonic solution is a key principle. It is of utmost importance to adjust the rate of correction based on the patient's symptoms, underlying etiology, and associated comorbidities. This case demonstrates how a correction formula was used and adjusted accordingly in an 81-year-old female with severe hypernatremia and metabolic encephalopathy with multiple comorbidities, including hypopituitarism. It is noteworthy to examine the correction rate, how it was calculated and delivered, and how the main cause of the hypernatremia was determined. Considering all these factors can help to properly administer any additional corrective medications, such as desmopressin (DDAVP) in a patient with diabetes insipidus (DI) secondary to hypopituitarism, or adjust the correcting rate based on signs, symptoms, and laboratory findings.

Nephrogenic diabetes insipidus in a geriatric patient affected by SARS-CoV-2: complexity of a diagnosis, complexity of a virus.

Background: Coronavirus disease 2019 (COVID-19) has an important impact on the kidney through direct and indirect damage mechanisms. Most previous studies have highlighted lesions caused by this virus in the early segments of the nephron. However, due to the antigenic characteristics of the virus, with almost ubiquitous receptors, and the molecular release it triggers, the distal segments of the nephron could also be affected. Methods: A 71 year-old-man with respiratory failure while suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia presented with typical symptoms of diabetes insipidus after ~20 days of hospitalization. The water deprivation test led to the diagnosis of nephrogenic diabetes insipidus. The aetiological study was complex, in particular because of the patient's previous lithium therapy. Results: The sequence of pathognomonic events typical of diabetes insipidus associated with anamnestic, clinical and laboratory evidence strongly supported the diagnosis of nephrogenic diabetes insipidus due to SARS-CoV-2 rather than other aetiologies. Conclusions: The collecting duct could represent a target for SARS-CoV-2 infection, directly or indirectly, as a result of lesions of upstream portions of the nephron, which would cascade into the distal segment. Other molecules, besides angiotensin 2 converting enzyme, might be involved in facilitating the viral aggression. The complexity of the geriatric patient shows the importance of a comprehensive approach that integrates careful monitoring of clinical signs and symptoms and laboratory and instrumental tests. This is especially important in the context of SARS-CoV-2 infection and in the management of its unexpected complications.

[Panhypopituitarism, Diabetes Insipidus and Bone Pain - Is There a Systemic Disease Behind it?]

INTRODUCTION: A 27-year-old man presented due to unilateral leg pain. He had a history of diabetes insipidus and panhypopituitarism. Laboratory analysis revealed hormonal undersupply. MRI showed a large contrast medium-absorbing mass in the pituitary gland extending into the hypothalamus. FDG-PET/CT examination revealed a hypermetabolic soft tissue lesion around the left femoral shaft. After biopsy of the lesion, a diagnosis of multisystemic Langerhans cell histiocytosis was made.

Chronic Lithium Intoxication: A Challenging Diagnosis.

Lithium has been used in clinical practice since the 1970s. This medication is commonly used to treat and prevent bipolar disorder, but it has a narrow therapeutic index, making toxicity a frequent occurrence. Chronic lithium intoxication can arise due to progressive accumulation, particularly in contexts of dehydration. The effects of chronic lithium intoxication on the nervous, renal, and cardiac systems, as well as on the thyroid and parathyroid glands, are well documented in the literature. The authors present the case of a 66-year-old woman with schizoaffective psychosis and chronic kidney disease, admitted due to altered mental status and dysarthria. Notwithstanding an earlier clinical recommendation to cease lithium administration more than a year ago, the patient continued its usage, culminating in neurological, cardiac, renal, and endocrine manifestations. Although the diagnosis was delayed, her clinical progression was favorable, obviating the need for renal replacement therapy. This case highlights the importance of a detailed medical history and the diagnostic challenges in clinical practice. The use of this drug without proper monitoring can lead to multisystem dysfunction.

Diabetes insipidus: Vasopressin deficiency….

Diabetes insipidus is a disorder characterized by hypo-osmotic polyuria secondary to abnormal synthesis, regulation, or renal action of antidiuretic hormone. Recently, an expert group, with the support of patient associations, proposed that diabetes insipidus be renamed to avoid confusion with diabetes mellitus. The most common form of diabetes insipidus is secondary to a dysfunction of the neurohypophysis (central diabetes insipidus) and would be therefore named â€Ìƒvasopressin deficiency’. The rarer form, which is linked to renal vasopressin resistance (nephrogenic diabetes insipidus), would then be named â€Ìƒvasopressin resistance’. The etiology of diabetes insipidus is sometimes clear, in the case of a neurohypophyseal cause (tumoral or infiltrative damage) or a renal origin, but in some cases diabetes insipidus can be difficult to distinguish from primary polydipsia, which is characterized by consumption of excessive quantities of water without any abnormality in regulation or action of antidiuretic hormone. Apart from patients’ medical history, physical examination, and imaging of the hypothalamic-pituitary region, functional tests such as water deprivation or stimulation of copeptin by hyperosmolarity (induced by infusion of hypertonic saline) can be proposed in order to distinguish between these different etiologies. The treatment of diabetes insipidus depends on the underlying etiology, and in the case of a central etiology, is based on the administration of desmopressin which improves patient symptoms but does not always result in an optimal quality of life. The cause of this altered quality of life may be oxytocin deficiency, oxytocin being also secreted from the neurohypophysis, though this has not been fully established. The possibility of a new test using stimulation of oxytocin to identify alterations in oxytocin synthesis is of interest and would allow confirmation of a deficiency in those patients presenting with diabetes insipidus linked to neurohypophyseal dysfunction.

Targeted long-read sequencing identified a causal structural variant in X-linked nephrogenic diabetes insipidus.

BACKGROUND: X-linked nephrogenic diabetes insipidus (NDI) is a rare genetic renal disease caused by pathogenic variants in the AVPR2 gene. Single nucleotide variants and small insertions/deletions in AVPR2 are reliably detected by routine clinical sequencing. Nevertheless, structural variants involving AVPR2 are challenging to identify accurately by conventional genetic testing. Here, we report a novel deletion of AVPR2 in a Czech family identified for the first time by targeted long-read sequencing (T-LRS). METHODS: A male proband with X-linked NDI underwent clinical sequencing of the AVPR2 gene that failed and thus indicated possible whole-gene deletion. Therefore, PCR mapping and subsequent targeted long-read sequencing (T-LRS) using a Pacific Biosciences sequencer were applied to search for the suspected deletion. To validate the deletion breakpoints and prove variant segregation in the family with X-linked NDI, Sanger sequencing of the deletion junction was performed. Quantitative real-time PCR was further carried out to confirm the carrier status of heterozygous females. RESULTS: By T-LRS, a novel 7.5 kb deletion of AVPR2 causing X-linked NDI in the proband was precisely identified. Sanger sequencing of the deletion junction confirmed the variant breakpoints and detected the deletion in the probands´ mother, maternal aunt, and maternal cousin with X-linked NDI. The carrier status in heterozygous females was further validated by quantitative real-time PCR. CONCLUSIONS: Identifying the 7.5 kb deletion gave a precise molecular diagnosis for the proband, enabled genetic counselling and genetic testing for the family, and further expanded the spectrum of structural variants causing X-linked NDI. Our results also show that T-LRS has significant potential for accurately identifying putative structural variants.

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

OBJECTIVE: 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. DESIGN, PATIENTS AND MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

Coronavirus as a trigger of lymphocytic hypophysitis in an adolescent girl: An exceptional case report.

INTRODUCTION AND IMPORTANCE: Lymphocytic hypophysitis is an underestimated disease and the pathogenesis is still poorly elucidated. Post-coronavirus lymphocytic hypophysitis is a new emerging entity. CASE PRESENTATION: A 16-year-old previously healthy girl presented with pituitary tumor syndrome. She suffered from frontal headaches, polyuria-polydipsic syndrome, and impaired visual acuity. She was diagnosed with COVID-19 infection three weeks before. Contrast-enhanced magnetic resonance imaging (MRI) revealed pituitary enlargement with intense homogenous enhancement postgadolinium on T1 weighted images. The diagnosis of lymphocytic hypophysitis was made after ruling out other differential diagnosis. She was started on methylprednisolone. Improvement of clinical symptoms was seen on day 5 with a significant decrease in headache intensity. CLINICAL DISCUSSION: The article summarizes data from cases reported in the literature and our case to highlight coronavirus as a new trigger of lymphocytic hypophysitis. Despite the rarity of this complication, patients with a suspicion of hypophysitis after a recent COVID-19 infection should be carefully evaluated. CONCLUSION: COVID-19 infection can cause lymphocytic hypophysitis. However, it seems premature to conclude on the causal link between COVID-19 and endocrine diseases. Further studies on larger samples are needed to comprehend the pathogenesis of autoimmune endocrinopathies after COVID-19 infection.

Simplified drug efficacy evaluation system for vasopressin neurodegenerative disease using mouse disease-specific induced pluripotent stem cells.

Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disorder in which vasopressin-secreting neurons degenerate over time due to the production of mutant proteins. We have demonstrated therapeutic effects of chemical chaperones in an FNDI mouse model, but the complexity and length of this evaluation were problematic. In this study, we established disease-specific mouse induced pluripotent stem cells (iPSCs) from FNDI-model mice and differentiated vasopressin neurons that produced mutant proteins. Fluorescence immunostaining showed that chemical chaperones appeared to protect vasopressin neurons generated from iPSCs derived from FNDI-model mice. Although KCL stimulation released vasopressin hormone from vasopressin neurons generated from FNDI-derived iPSCs, vasopressin hormone levels did not differ significantly between baseline and chaperone-added culture. Semi-quantification of vasopressin carrier protein and mutant protein volumes in vasopressin neurons confirmed that chaperones exerted a therapeutic effect. This research provides fundamental technology for creating in vitro disease models using human iPSCs and can be applied to therapeutic evaluation of various degenerative diseases that produce abnormal proteins.

Transient Central Diabetes Insipidus (Arginine Vasopressin Deficiency) Following SARS-CoV-2 Vaccination: A Case Report and Literature Review.

INTRODUCTION: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people, causing the COVID-19 global pandemic. The use of novel technologies led to the development of different types of SARS-CoV-2 vaccines that have reduced severe disease courses and related deaths. Besides the positive impact of vaccination on the pandemic, local and systemic side effects have been reported; they are usually mild to moderate, although also serious adverse events have been described. CASE PRESENTATION: A 21-year-old female was referred to our hospital for the recent onset of severe polyuria and polydipsia, with the need for about 8 liters of daily water intake. The symptoms developed seven days after the administration of the second dose of the mRNA-based (Pfizer-BioNTech® BNT162b2) SARS-CoV-2 vaccine. In the suspicion of central diabetes insipidus (DI) development, she started treatment with desmopressin (Minirin® tablets) 60 mg/day with an improvement of symptoms and thirst. A thickening of the pituitary stalk was observed at the pituitary MRI with loss of the posterior pituitary bright spot on T1 weighted images. To confirm the diagnosis of central DI, both the water deprivation test and arginine stimulated copeptin test were performed; whilst the former gave no clear-cut indication of DI, the latter showed a reduced copeptin peak after arginine infusion consistent with the diagnosis of partial central DI. Furthermore, the development of symptoms right after the second dose of the vaccine strengthened the hypothesis that DI was related to the vaccination itself. After our evaluation, there was a progressive reduction of desmopressin dose to a complete discontinuation with the maintenance of a normal hydroelectrolytic balance. Clinical and biochemical follow-up was performed by repeating a pituitary MRI and a second arginine-stimulated copeptin test 15 months after the diagnosis. This time, copeptin levels reached a significantly higher peak after arginine stimulation that completely excluded central DI and at pituitary MRI, the thickening of the pituitary stalk previously described was no longer visible. CONCLUSION: Neurohypophysitis can have an abrupt onset independently of the etiology. Central DI is a rather exceptional event after SARS-CoV-2 vaccination but should be recalled in case of sudden polyuria and polydipsia. DI is indeed reported even after SARS-CoV-2 infection, thus, this report should not discourage the use of mRNA-based vaccines. Furthermore, our case demonstrates that full recovery of posterior pituitary function is possible after immunization with anti-Covid-19 BNT162b2 vaccine. Further studies are needed to clarify the possible mechanism relating to SARS-CoV-2 vaccination and this rare adverse event.

Paediatric perspectives in the diagnosis of polyuria-polydipsia syndrome.

The elucidation of the underlying cause of polyuria-polydipsia syndrome (PPS) is a challenging-especially in the differentiation of partial defects of arginine vasopressin (AVP) secretion or action from primary polydipsia. The water deprivation test has been utilized for many decades, and its application in the paediatric population has been applied using parameters predominantly established in adult cohorts. In more recent times, the development of automated commercial assays for copeptin, a surrogate marker for AVP, has represented a significant advancement in the diagnostic approach to PPS. Measurement of copeptin concentrations has major advantages and has essentially superseded measurement of AVP in diagnostic protocols for PPS. Additionally, stimulated-copeptin protocols utilizing hypertonic saline infusion, arginine, and glucagon have been investigated, and are promising. However, further studies are required in the population-incorporating the differences in physiological regulation of water homeostasis, and safety requirements-before there is widespread adoption into clinical practice.