Search Results (116)

Hypomagnesemia is a frequent and often underrecognized electrolyte disturbance with important clinical consequences, especially in hospitalized and critically ill patients. This multifactorial condition arises from impaired intestinal absorption, renal magnesium wasting, and the effects of various medications. Magnesium, the second most abundant intracellular cation, is crucial in enzymatic and physiological processes; its deficiency is associated with neuromuscular, cardiovascular, and metabolic complications. This narrative review focuses on the mechanisms and clinical consequences of drug-induced hypomagnesemia, highlighting the major drug classes involved such as diuretics, antibiotics, antineoplastic agents, and immunosuppressants. Management strategies include magnesium supplementation and adjunctive therapies like amiloride and SGLT2 inhibitors to reduce renal magnesium losses. Recognizing and addressing drug-induced hypomagnesemia is essential to improve patient outcomes and prevent long-term complications. Full article

Objective: Potassium levels (KLs) influence clinical outcomes in severe traumatic brain injury (TBI). This study investigates the relationship between KLs and clinical outcomes to improve prognosis and guide management. Method: A retrospective study was conducted at a level 1 trauma center in Queens, New York, from January 2020 to December 2023. Patients with an AIS score of 3 or higher were included. KLs were measured at the time of hospital admission, ICU admission, ICU discharge, hospital discharge, and death, if applicable. Clinical outcomes such as age, race, length of hospital stay (H LOS), ICU length of stay (ICU LOS), ventilation days (VDs), Glasgow Coma Scale (GCS), and mortality were assessed. Results: KLs were categorized into five groups: extreme hypokalemia (<2.5 mEq/L), hypokalemia (2.6–3.5 mEq/L), normokalemia (3.5–5.2 mEq/L), hyperkalemia (5.2–7.0 mEq/L), and extreme hyperkalemia (>7.0 mEq/L). Significant correlations were observed between KLs at hospital admission and age (p = 0.0113), race (p = 0.003), and H LOS (p = 0.079). ICU KLs showed positive correlations with AIS head score (p = 0.038), ISS (p = 7.84 × 10⁻⁶), and GCS (p = 2.6 × 10⁻⁶). ICU KLs were also associated with LOS in the Emergency Department (ED) (p = 6.875 × 10⁻⁶) and ICU (p = 1.34 × 10⁻²¹), as well as VDs (p = 7.19 × 10⁻⁷). ICU discharge KLs correlated with ISS (p = 2.316 × 10⁻³), GCS (p = 2.201 × 10⁻³), ED LOS (p = 3.163 × 10⁻⁴), and VDs (p = 7.44 × 10⁻⁴). KLs at discharge were linked with mortality (p < 0.0001) and H LOS (p = 0.0091). Additionally, KLs at the time of death were correlated with ISS (p = 0.01965), GCS (p = 0.01219), ED LOS (p = 0.00594), ICU LOS (p = 0.049), VDs (p = 0.00005), and mortality (p < 0.0001). Conclusions: Potassium imbalances, especially hypokalemia, significantly affect outcomes in severe TBI patients. Monitoring and managing KLs may improve prognosis. Full article

Background and Objectives: This study aimed to compare the effects of HIPEC procedures using oxaliplatin and mitomycin C on serum electrolyte, glucose, and lactate levels, with a specific focus on the carrier solutions employed. Materials and Methods: A retrospective analysis was performed on 82 patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases. Patients were assigned to one of two groups based on the chemotherapeutic agent used: oxaliplatin (n = 63) or mitomycin C (MMC, n = 19). The oxaliplatin group was further subdivided based on the carrier solution used: 5% dextrose (D5W, n = 29) or peritoneal dialysate (n = 34). The assignment of regimens was based on institutional protocols and surgeon preference. Pre- and post-HIPEC serum levels of sodium, potassium, bicarbonate, glucose, and lactate were compared. Results: Significant biochemical changes were observed across groups, depending on both the chemotherapeutic agent and carrier solution. In the MMC group (peritoneal dialysate), only lactate increased significantly post-HIPEC (p = 0.001). In the oxaliplatin–peritoneal dialysate group, significant changes were observed in bicarbonate (p = 0.009), glucose (p = 0.001), and lactate (p < 0.001), whereas sodium and potassium remained stable. The oxaliplatin–D5W group showed significant changes in all parameters: sodium (p = 0.001), potassium (p = 0.001), bicarbonate (p = 0.001), glucose (p < 0.001), and lactate (2.4 → 7.6 mmol/L, p < 0.001). Between-group comparisons revealed significant differences in sodium, potassium, glucose, and lactate changes (p < 0.05), but not in bicarbonate (p = 0.099). Demographic and clinical characteristics—including age, sex, primary disease, ICU stay, and 90-day mortality were similar across groups. Conclusions: The use of dextrose-containing solutions with oxaliplatin was associated with marked metabolic disturbances, including clinically meaningful hyponatremia, hypokalemia, and hyperglycemia in the early postoperative period. These findings suggest that the choice of carrier solution is as important as the chemotherapeutic agent in terms of perioperative safety. Closer postoperative electrolyte monitoring is recommended when using dextrose-based regimens. The retrospective design and sample size imbalance between groups are acknowledged limitations. Nonetheless, this study offers clinically relevant insights and lays the groundwork for future prospective research. Full article

Background and Clinical Significance: Although dietary supplements have often been deemed safe, some have been linked to drug-induced nephropathy due to their diverse ingredients. The aim of this report is to enhance clinical awareness of a novel and emerging cause of Fanconi syndrome due to red yeast rice supplements and to contribute new histopathological and clinical data. Case Presentation: We report two cases of renal dysfunction and Fanconi syndrome associated with the use of red yeast rice supplements. Both patients presented with renal impairment accompanied by elevated markers of tubular injury, hypouricemia, hypokalemia, and glucosuria, consistent with Fanconi syndrome. Following the discontinuation of the red yeast rice supplement and initiation of steroid therapy, Fanconi syndrome resolved, however, moderate renal dysfunction persisted. Urinary NGAL levels improved after treatment in both cases. KIM-1 normalized in one case but remained elevated in the other. Uromodulin recovery was complete in one case and partial in the other. Renal biopsy revealed mild tubulointerstitial nephritis, with notable shedding of proximal tubular epithelial cells. Immunohistochemical analysis demonstrated reduced expression of URAT-1, Na-K ATPase, and Na-Pi IIa in some tubules. Conclusions: These findings suggest that renal injury induced by red yeast rice supplements is mediated by direct proximal tubular necrosis caused by a harmful substance in the supplement, resulting in persistence of tubular dysfunction. Full article

Gastric cancer remains a significant global health burden, with curative treatment relying on surgical resection, typically total or subtotal gastrectomy. However, the procedure frequently triggers acute metabolic and nutritional disturbances that may impact recovery. Objective: This prospective study aimed to investigate whether the type of gastrectomy (total vs. subtotal) influences early postoperative biochemical and hematological alterations, with particular attention to nutritional impact. Methods: A cohort of 295 patients (123 female, 172 male) who underwent gastrectomy for gastric cancer at the Institute of Oncology Iași (2023–2024) was evaluated. Laboratory parameters, including hemoglobin, hematocrit, lymphocyte and platelet counts, serum albumin, total protein, sodium, potassium, creatinine, and urea, were analyzed preoperatively and on postoperative day 14 using standard clinical methods. Results: Anemia was observed in over 90% of patients, irrespective of sex or procedure type. Electrolyte imbalances (notably hyponatremia and hypokalemia) and indicators of nutritional deficit (hypoalbuminemia, low creatinine) were highly prevalent, with a greater frequency among female patients. Total gastrectomy was associated with more severe biochemical and nutritional alterations compared to subtotal procedures. Conclusions: Total gastrectomy significantly exacerbates early postoperative metabolic and nutritional derangements. These findings reinforce the need for proactive, personalized postoperative nutritional and electrolyte management strategies to support recovery and reduce complication risks. Full article

Background: Beach volleyball (BVb) is a highly demanding Olympic sport characterized by intense physical activity and unique environmental challenges, including varying weather conditions and sandy, unstable court surfaces. Despite its popularity, there is a notable lack of scientific research addressing the metabolic and immune responses of elite female athletes in this sport. This study aims to address this gap by investigating two world-class Olympic medalists, female BVb players, who represent a country with a rich history in the sport. Methods: Two athletes underwent a simulated competition day consisting of two matches. A standardized protocol was utilized to collect blood and urine samples at seven time points, allowing for analysis throughout the competition and recovery phases. The analysis included various electrolytes, as well as hematological, metabolic, and inflammatory markers. Additionally, we assessed selected hormones, such as insulin, serotonin, ACTH, and cortisol, along with amino acids related to energy metabolism and neurotransmitter synthesis. Results: Both athletes presented a trend toward electrolyte disturbances, especially hypokalemia, with a mean decrease of 15% and individual values reaching as low as 3.3 mmol/L post-match. This indicates that BVb may pose a risk for such disturbances. Additionally, the matches led to 20% to 60% increases in muscle injury markers, with incomplete recovery even after a day of rest, signaling persistent physiological stress post-competition. This increase was matched by stimulating stress hormones (ACTH and cortisol rose up to 4-fold and 3-fold, respectively), and markers of exercise intensity, such as lactate and ammonium. Moreover, the simulated BVb competition day impacted the amino acid response, with the Fischer ratio (BCAA/AAA) and blood tryptophan decreasing to a minimum of 60% of the initial levels and blood serotonin increasing by up to 180%, which are signs of an increased risk of central fatigue onset, according to the Fischer and Newsholme theory. Conclusions: The responses examined in this exploratory study contribute to a deeper understanding of the metabolic and immune demands placed on elite female BVb players, suggesting practical applications. By addressing the similar physiological responses observed among the athletes and emphasizing their unique individual responses—despite following the same protocol under identical conditions and sharing similar life habits for an extended period—this study highlights the critical necessity for the n-of-1 monitoring of athletes. Full article

Background: Older adults are vulnerable to adverse drug reactions (ADRs), particularly in low-income settings, yet data on ADR prevalence in Africa, including Ethiopia, remain limited. Objective: This study aimed to evaluate the incidence, severity, and preventability of ADRs among hospitalized older adults, as well as all-cause inpatient mortality. Methods: A cross-sectional observational study was conducted at Jimma Medical Center, located in Jimma town, Ethiopia, from 6 September 2021 to 26 December 2022. The study participants were older adults (n = 162) admitted to the medical wards. ADRs were assessed using the Naranjo ADR probability scale, severity was classified according to the modified Hartwig and Siegel criteria, and preventability was determined using the Schumock and Thornton criteria. Results: The median age of participants was 65 years (interquartile range: 60–70). During their hospital stay, 84 patients (51.9%) experienced at least one ADR. A total of 123 ADRs (76 ADRs per 100 admissions) were captured. Most ADRs (93.5%) were classified as mild to moderate in severity, and 84.5% (n = 105) were considered preventable. Endocrine and metabolic systems (48.8%) and diuretics (43.9%) were the most frequently affected organ systems and drug class linked to ADRs, respectively. Furosemide (41.5%) and aspirin (10.6%) were the most frequently implicated medications, commonly causing hypokalemia (35.3%) and dyspepsia (53.8%), respectively. The observed all-cause in-patient mortality rate was 6.8% (5 deaths per 1000 patient-days). The use of potentially inappropriate medications (PIMs) (aOR: 4.747, p = 0.003) and presence of digestive system disorders (aOR: 8.784, p = 0.038) were associated with an increased risk of ADRs, while a history of recent traditional medicine use (aOR: 0.285, p = 0.042) was linked to a lower risk. Conclusions: More than half of the hospitalized older adults experienced ADRs, most of which were mild to moderate in severity and considered preventable. Regular medication review for screening and minimizing PIM use in older adults may play a crucial role in lowering ADR occurrence. The borderline but statistically significant association between a history of traditional medicine use and lower occurrence of ADRs requires cautious interpretation and further investigation to explore possible explanations. Nearly seven deaths per hundred hospitalized patients were recorded. Full article

Background: The clinical significance of serum potassium levels at admission in patients with blunt hepatic trauma remains insufficiently defined. This study aimed to evaluate the prevalence and prognostic value of admission hypokalemia in this patient population. Methods: We conducted a retrospective analysis of 164 patients with radiologically confirmed blunt liver trauma admitted between 2016 and 2023. Preoperative, intraoperative, and postoperative data were collected to assess the association between serum potassium levels and trauma severity (AAST grade—American Association for the Surgery of Trauma, ISS—Injury Severity Score), in-hospital morbidity, mortality, and length of stay. Univariate and multivariate analyses were performed, including checks for normality and multicollinearity. Results: Serum potassium levels showed a significant positive correlation with age (p = 0.0064), and an inverse correlation with liver injury severity (AAST grade; p = 0.01). Lower potassium levels were associated with longer hospital stays (p = 0.0459) and higher morbidity (p = 0.022). In multivariate analysis, only age (p = 0.036) and AAST grade (p = 0.014) were independent predictors of serum potassium concentration. Potassium levels were not independently associated with mortality. Conclusions: Admission hypokalemia is a common finding in blunt liver trauma and correlates with injury severity and adverse clinical outcomes. Potassium concentration may serve as a readily available, low-cost biomarker for early risk stratification in these patients. Further prospective studies are warranted to confirm its prognostic utility. Full article

Background: Fosfomycin is used as a combination partner for the treatment of severe non-urinary tract infections. Individualized dosing of fosfomycin based on therapeutic drug monitoring (TDM) has the potential to reduce drug-related adverse events (AEs). Methods: This retrospective study used routine data from patients receiving intravenous fosfomycin therapy. Plasma concentrations of fosfomycin were categorized into three different ranges: <64 mg/L, 64–128 mg/L, and >128 mg/L. Subsequently, the influence of acute kidney injury (AKI) on reaching the specific plasma concentration ranges and the occurrence of AEs was analyzed. Results: The study included 143 patients (median age 73 years, 66.4% male) with fosfomycin plasma measurements. Beta-lactam antibiotics were most frequently used in combination (62.2%), followed by tetracyclines (12.2%), cotrimoxazole (8.1%), and other agents (17.5%). Fosfomycin concentrations were >128 mg/L in 45% (36/80) of patients with normal renal function, 70.4% (38/54) of patients with AKI stages I to III, and 77.8% (7/9) of patients with renal replacement therapy. AEs occurred in 54% (77/143), mainly hypernatremia (42.6%), hypokalemia (39.9%), and gastrointestinal symptoms (19.6%), with the median fosfomycin plasma concentration being significantly higher in patients with AEs (158 mg/L vs. 131 mg/L, p = 0.01). Multivariate logistic regression analysis revealed that patients aged ≥70 years (OR 3.70, 95% CI 1.24–11.5; p = 0.02) and patients with fosfomycin plasma concentrations > 128 mg/L (OR 3.30, 95% CI 1.09–10.4; p = 0.04) had a higher risk of AEs. Conclusions: There was a significant association between high plasma exposure and the occurrence of AEs. In particular, the impact of acute renal insufficiency on fosfomycin plasma concentrations should be considered. Individualized fosfomycin dosing based on TDM and the intensive monitoring of renal function contribute to reducing drug-related side effects. Full article

Gitelman syndrome (GS) is a rare autosomal recessive renal tubulopathy characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria due to mutations in the SLC12A3 gene. This case report presents a 54-year-old African American female with near syncope and palpitations. The patient had a history of intermittent palpitations and generalized anxiety disorder and was previously diagnosed with GS. On presentation, the patient exhibited symptoms of severe hypokalemia and hypomagnesemia, attributed to medication non-adherence. Laboratory tests confirmed critically low potassium and magnesium levels, with elevated urine sodium and chloride. Treatment was initiated with oral and intravenous potassium and magnesium, leading to the normalization of electrolyte levels. This case highlights the challenges of managing GS, particularly in patients facing socioeconomic barriers that impede medication adherence and healthcare access. Personalized patient education, combined with comprehensive healthcare resources, is essential to mitigate complications and improve long-term outcomes in such cases. Full article

Background: The standard treatment for maxillofacial abscesses is surgical drainage combined with antibiotics, a frequent procedure in maxillofacial surgery departments. However, postoperative complications following this surgery are poorly described in the literature. Identifying their incidence and risk factors could help improve patient outcomes and healthcare planning. Objectives: The primary aim was to identify postoperative complications within 30 days after maxillofacial abscess surgery; the secondary aim was to explore their associated risk factors. Methods: A monocentric retrospective cohort study included patients with maxillofacial abscesses who underwent extraoral incision and drainage under general anesthesia at the Department of Cranio-Maxillofacial and Oral Surgery at a tertiary hospital in Switzerland between January 2012 and August 2023. Postoperative complications within 30 days were recorded and classified according to the validated Dindo–Clavien classification system. Univariable and multivariable logistic regression analyses were conducted to identify risk factors for postoperative complications. Results: A total of 253 participants were analyzed. The overall complication rate was 24.1%, with 15.8% major complications (Dindo–Clavien grade ≥ 3). The most common minor complications (Dindo–Clavien grade < 3) were hypokalemia and lower-extremity edema, with an incidence of 6.4%. The most common major complications were persistent and recurrent abscesses, with an incidence rate of 10.4%. These complications occurred in the early (median range 1–5 days) and delayed (median range 14–15 days) postoperative courses, respectively. Overall, the mortality rate was 0.4%. On multivariable analysis, an American Society of Anesthesiologists (ASA) score > 2 was associated with overall and major postoperative complications (odds ratio [OR], 3.38; 95% CI 1.75–6.51; p < 0.001 and OR, 3.76; 95% CI 1.83–7.72; p < 0.001, respectively). Additionally, female sex (OR, 1.97; 95% CI 1.05–3.70; p = 0.036) and C-reactive protein level > 50 mg/L (OR, 2.25; 95% CI 1.01–4.98; p = 0.046) were associated with overall postoperative complications. Conclusions: This study introduces a novel application of the Dindo–Clavien classification to maxillofacial abscess surgery, providing a standardized framework for assessing postoperative complication severity. Through this approach, we identified ASA score > 2, female sex, and CRP level > 50 mg/L as risk factors for postoperative complications. Our findings highlight the importance of close monitoring during the first five postoperative days to detect early complications, such as persistent abscesses, and recommend standardized outpatient follow-up for at least two weeks to identify delayed complications, like recurrence. Full article

Background/Objectives: Ectopic Cushing’s syndrome (ECS) is a rare, life-threatening condition caused by uncontrolled ACTH secretion from tumors, most commonly small-cell lung cancer (SCLC). ECS is traditionally reported in 1–6% of SCLC cases; however, recent data suggest it may be much higher. This study compares the clinical presentation of SCLC-related ECS (ECS-SCLC) with other ECS etiologies and analyzes the diagnosis, treatment, and outcomes of ECS-SCLC. Methods: We retrospectively analyzed the records of 39 ECS patients diagnosed between 2000 and 2024 at a tertiary endocrinology center. Seven cases (18%) were due to SCLC. Diagnosis was based on clinical signs, biochemical testing, imaging, and histopathology. Results: ECS-SCLC patients (five men, two women; median age 61), compared to other ECS etiologies, had a shorter time to diagnosis (median 1 vs. 2 months; p = 0.03), worse general condition (ECOG 4 vs. 3; p = 0.01), greater muscle weakness (Lovett scale median 2[IQR 1–2] vs. 2[IQR 2–3]; p = 0.04), more severe hypokalemia (2.12 vs. 2.7 mmol/L; p = 0.03), and required higher potassium supplementation (200 vs. 120 mEq/day; p = 0.001). All ECS-SCLC patients experienced weight loss (median 5 kg). Cortisol-lowering therapy (metyrapone or osilodrostat) was initiated in six patients (mean initiation time 3.7 days), leading to clinical improvement. Oncological treatment (chemotherapy or radiotherapy) was administered in five patients after stabilization. The median follow-up time was 3 months. Conclusions: Early recognition of ECS-SCLC and a multidisciplinary approach are critical. Severe hypokalemia and muscle weakness should prompt timely evaluation for hypercortisolism. Cortisol-lowering therapy may improve clinical status and facilitate oncological treatment. Full article

Background and Objectives: Chronic obstructive pulmonary disease (COPD) and acute respiratory failure are critical clinical conditions associated with high mortality rates in intensive care units (ICUs). Electrolyte imbalances are significant variables that may influence all-cause ICU mortality in this patient group. In this retrospective study, we aimed to investigate the relationships between the serum levels of sodium (Na⁺), chloride (Cl⁻), potassium (K⁺), calcium (Ca²⁺), and magnesium (Mg²⁺) and all-cause ICU mortality in patients admitted with respiratory failure. Additionally, we conducted a detailed mortality analysis on the basis of sodium quartiles and pathological absolute sodium thresholds to reveal their associations with ICU mortality from all causes. Materials and Methods: A total of 1109 patients were analyzed between January 2022 and January 2024. The electrolyte levels measured at ICU admission, demographic data, APACHE II and SOFA scores, arterial blood gas results, BUN and creatinine levels, need for noninvasive mechanical ventilation, length of ICU stay, and survival outcomes were assessed. Statistical analyses were performed via Kaplan—Meier survival analysis and the Cox regression method. Results: Our findings revealed that patients with low potassium and calcium levels had significantly higher mortality rates (p < 0.05). When sodium levels were divided into quartiles, mortality risk markedly increased in both the lowest (Q1) and highest (Q4) quartiles. Cox regression analysis revealed that the mortality risk in hyponatremic patients was 2.2 times greater than that in normonatremic patients (p = 0.005). In the hyponatremic group, the increased mortality risk was statistically borderline significant (p = 0.06). In the logistic regression analysis conducted to evaluate ICU mortality, which included all electrolyte levels and clinical scoring systems, higher APACHE II and SOFA scores were identified as significant risk factors for ICU mortality. Conversely, the presence of COPD was found to be relatively protective compared with other underlying causes of respiratory failure in terms of mortality. Conclusions: Electrolyte imbalances are important predictors of mortality in patients with respiratory failure. Sodium levels exhibit a “U-shaped” relationship with mortality, with hyponatremia emerging as a prominent risk factor. Careful assessment of electrolyte imbalances is crucial in the clinical management of these patients. Full article

Ectopic adrenocorticotropic hormone syndrome (EAS) occurs when a tumor develops neuroendocrine differentiation with the secretion of ACTH resulting in hypercortisolism and possibly Cushing’s syndrome (CS). Only 5–10% of CS cases are attributed to EAS; of these, breast tumors comprise less than 1%. Two known variants of breast neuroendocrine tumors include neuroendocrine-differentiated carcinoma and ductal carcinoma with neuroendocrine features. Currently, guidelines for treatment are limited and EAS is associated with significant morbidity and mortality. A 39-year-old female presented with a rapidly enlarging breast mass. Biopsy demonstrated invasive poorly differentiated breast carcinoma with high-grade neuroendocrine features and necrosis. Staging at diagnosis confirmed metastatic disease of the liver and bone. First-line chemotherapy (Cisplatin/Etoposide/Durvalumab) was initiated with evidence of disease progression after four cycles. Given a poor response to therapy, a simple mastectomy was performed for local control and complete pathologic analysis, demonstrating high-grade neuroendocrine carcinoma with large-cell features. Second-line therapy (Adriamycin/Cyclophosphamide) was initiated for three cycles after which the patient required admission for severe and refractory hypokalemia. Workup confirmed elevated ACTH consistent with paraneoplastic EAS and further evidence of disease progression. Third-line therapy (Nab-Paclitaxel) was initiated, and genetic testing was completed, confirming the PIK3 mutation, for which access to Alpelisib therapy was requested. Given symptoms of progressive severe CS with significant liver disease limiting medical therapies, the patient underwent urgent bilateral laparoscopic adrenalectomy after which she was able to be discharged home while awaiting additional systemic therapy. EAS resulting in CS secondary to breast neuroendocrine carcinoma is a rare and challenging diagnosis. Further research is needed to inform treatment guidelines to improve outcomes. While patient survival is dependent upon the underlying disease process, laparoscopic bilateral adrenalectomy is an accepted, definitive treatment option. Full article

Background: Nephrogenic diabetes insipidus (NDI) is defined as the inability of the kidney to concentrate urine owing to the insensitivity of the distal nephron to the antidiuretic hormone, arginine vasopressin. NDI is a heterogeneous rare autosomal dominant or X-linked disease. Objective: We present a family with nephrogenic diabetes affecting three males in two generations. Methods: We report two boys with NDI: a 4-month-old infant who was treated for fever, vomiting, and failure to thrive, and his 10-year-old uncle (the mother’s brother), who was admitted concurrently for consuming 11 L of fluid per day. According to family history, the mother’s sibling passed away at the age of two from severe hypernatremic dehydration. Results: The infant’s clinical and laboratory evaluation revealed a 7.8 mL/kg/h urine output, hypernatremic hyperchloremic alkalosis, extremely low urine density (1002), and elevated copeptin level. In contrast, the uncle’s clinical and laboratory evaluation revealed marked polyuria, low urine density, and elevated copeptin, all of which were suggestive of diabetes insipidus. After starting hydrochlorothiazide treatment (2 mg/kg/body), the infant’s urine production reduced (2.85 mL/kg/h); however, severe hypokalemia and alkalosis followed. Spironolactone, an aldosterone antagonist, were added, with good therapeutic response. Hydrochlorothiazide was administered to the uncle, and his daily fluid intake decreased to 3–4 L. Given the family history, Sanger sequencing for the AVPR2 variant was performed on the boys and the infant’s mother. Analysis showed hemizygous likely pathogenic variant c.335G>A p. (Cys112Tyr) in the 2 boys and heterozygous (carrier) status of the mother. Within the same family, we observed phenotypic heterogeneity: one child died at the age of two, another lived well into ten years without therapy, and a four month-old baby could have had a poor outcome without specific treatment. Conclusions: NDI is a rare and possibly fatal genetic disorder with heterogeneous manifestations. In families with a history of NDI, molecular genetic testing is crucial for family planning. Full article