Introduction: Hyponatremia is the most common electrolyte imbalance in hospitalized patients, associated with increased morbidity and mortality. Tolvaptan effectively raises serum sodium in SIADH. However, concerns regarding rapid overcorrection and safety persist. This study evaluates the efficacy, safety, and real-world usage patterns of tolvaptan in a tertiary care setting. Methodology: A retrospective single-centre observational study was conducted at Hospital Putrajaya using the electronic records of patients treated with tolvaptan from January 2020 to December 2025. Overcorrection was defined as >10 mmol/L increase within 24 hours, and non-response as <4 mmol/L increment at 24 hours. Results: Twenty-one patients were included, with a mean age of 66.7 years; 57% were male. Most (90.5%) received 7.5 mg initially. Mean baseline sodium was 118.1 ± 4.1 mmol/L. Tolvaptan produced rapid correction, with mean sodium increasing to 127.0 mmol/L at 24 hours (mean increment 8.9 mmol/L). Only one patient (4.8%) was a non-responder at 24 hours. Median time to sodium >130 mmol/L was 1 day, with 60% achieving this within 24 hours. At discharge, mean sodium was 130.4 mmol/L. Median length of stay following initiation was 5.5 days. Overcorrection occurred in 23.8% (n = 5), all in the 7.5 mg group, particularly among those with baseline sodium 115–120 mmol/L. No cases of osmotic demyelination syndrome (ODS) were observed. The mean internal for initiation is approximately 6 days from diagnosis. Tolvaptan usage increased and peaked in the first 3 years, but subsequently dropped and plateaued over the last 2 years. Conclusion Tolvaptan is safe and effective for sodium correction; although overcorrection remains a risk, no long-term sequelae of ODS were observed, underscoring the need for vigilant monitoring. Its use in Hospital Putrajaya remains limited, with delayed initiation possibly due to tolvaptan being considered a secondary treatment after failure of other options
Hyponatremia ; Tolvaptan

Introduction: Primary adrenal insufficiency is rare and potentially lifethreatening, with an estimated prevalence of five cases per million in Southeast Asia. Local data remain limited, and diagnosis is frequently delayed due to non-specific clinical manifestations. Widespread use of traditional medication in Malaysia may further undermine recognition, particularly when steroid exposure is concealed. We report a female on prolonged use of traditional remedies presented with classic features of Addison’s disease rather than cushingoid features, confirmed by biochemical results. Case: A 65-year-old female with underlying dyslipidemia and osteoarthritis presented with 4 days of giddiness, poor intake, nausea, and diarrhea. Further history revealed prolonged use of multiple traditional Chinese medicines, discontinued months prior, raising suspicion of prior steroid exposure. She claimed her skin has become darker over the past 2 months. She denied any infectious symptoms, contact with PTB patients, or exposure to birds. There was no family history of autoimmune disease. Clinically, she was dehydrated and hypotensive. Her blood pressure improved after fluid resuscitation. There was hyperpigmentation involving the face, extremities, tongue, and buccal mucosa. Investigation results showed severe hyponatremia (119 mmol/L), hyperkalemia (4.93 mmol/L), with normal creatinine and negative infective markers. Hyponatremia persisted despite adequate hydration. Thyroid function test was normal (Free T4 12.28 pmol/L and thyroid-stimulating hormone 4.16 µIU/mL). Morning cortisol was suppressed (37 nmol/L) with markedly elevated adrenocorticotropic hormone levels (1,134 pg/mL), confirming the diagnosis of primary adrenal insufficiency. Hence, hydrocortisone was commenced, and serum sodium was normalized 2 days later. The underlying etiology remains under evaluation, although autoimmune adrenalitis is the most likely cause. Conclusion Primary adrenal insufficiency should be considered in patients presenting with unexplained hyponatremia and hypotension. In a setting where traditional medication use is prevalent, unrecognized steroid exposure may further complicate diagnosis. A thorough clinical and appropriate biochemical assessment is crucial to differentiating primary from secondary adrenal insufficiency.
Hyponatremia

Introduction: Electrolyte imbalance is common in central nervous system infections. Arginine vasopressin deficiency (AVP-D), Cerebral Salt Wasting (CSW), and Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) are important etiologies that can cause opposing extremes of serum sodium, posing diagnostic and therapeutic challenges. We report a rare case of transient central AVP-D followed by CSW secondary to tuberculous meningitis (TBM). Case: An 18-year-old female presented with a 1-month history of fever, reduced responsiveness, and visual hallucinations. Her Glasgow Coma Scale was E4V1M4 with neck stiffness and upper motor neuron signs. Initial investigations revealed severe hyponatremia (119 mmol/L) and communicating hydrocephalus with third ventricle ballooning on brain imaging. Coupled with a positive tuberculosis contact, anti-tuberculous therapy was initiated for probable TBM alongside 3% saline correction prior to insertion of external ventricular drain (EVD). Her condition deteriorated on day 5, requiring intubation for aspiration pneumonia. Repeated imaging showed worsening hydrocephalus, necessitating EVD revision. She subsequently developed polyuria (urine output [UO] 150–300 mLs/hour), with biochemical findings consistent with AVP-D (serum sodium 154 mmol/L; urine osmolality 96 mOsm/kg; urine sodium <20 mmol/L). Intravenous desmopressin 1 mcg was administered, and UO reduced to 30 mLs/hour. However, polyuria recurred on Day 9, accompanied by tachycardia, hypotension, and a rapid decline in serum sodium to 120 mmol/L. Diagnosis of CSW was established (urine sodium 204 mmol/L; urine osmolality 470 mOsm/kg). Oral fludrocortisone was initiated and titrated to 0.4 mg daily to maintain serum sodium >130 mmol/L. Due to persistent hydrocephalus, right ventriculoperitoneal shunt was inserted on Day 22, after which her UO gradually decreased, allowing tapering of fludrocortisone. She remains on fludrocortisone 0.1 mg daily with ongoing rehabilitation. Conclusion TBM can be complicated by SIADH, AVP-D, or CSW. Concurrent AVP-D and CSW have not been reported. This case highlights the dynamic electrolyte disturbances in TBM which may lead to diagnostic confusion and therapeutic error. Early recognition and tailored therapy, alongside definitive management to reduce intracranial pressure, are essential for optimal outcomes.
Hypernatremia ; Hyponatremia ; Tuberculosis, Meningeal

McKrittick-Wheelock syndrome refers to a condition characterized by a large rectal mass accompanied by excessive mucoid discharge and associated electrolyte imbalances, including hyponatremia and hypochloremia. This is a benign condition that can unexpectedly lead to serious illness in patients, making it essential for all clinicians to be aware of. We present the case of an 80-year-old female presented with a 4-year history of secretory diarrhea, hematochezia, enlarging fleshy rectal mass with copious mucoid discharge associated with hyponatremia and hypochloremia. Physical examination revealed a polypoid rectal mass secreting copious mucoid discharge with a 2cm base of stalk prolapsing 4cm FAV. The patient underwent rectal excision via trans-anal approach leading to resolution of symptoms. Postoperatively, the patient made a good recovery and was discharged. During follow-up, there was no recurrence of secretory diarrhea. Additionally, the dizziness and other symptoms had resolved. This case emphasizes the importance of recognizing McKittrick-Wheelock syndrome (MWS) when faced with a rectal mass presenting alongside chronic secretory diarrhea and associated electrolyte disturbances. Despite its rare occurrence, clinicians should consider this diagnosis in patients with a rectal mass to avoid delayed treatment and prevent serious complications.

Dyskinesia-hyperpyrexia syndrome（DHS）is an acute hyperpyrexia syndrome that is different from Parkinsonism-hyperpyrexia syndrome and serotonin syndrome in patients with advanced Parkinson's disease（PD），with the main symptoms of high fever，disturbance of consciousness，elevated creatine kinase，and dyskinesia. Syndrome of inappropriate secretion of antidiuretic hormone（SIADH）is a clinical syndrome caused by excessive secretion of antidiuretic hormone，which leads to the symptoms of dilutional hyponatremia，water retention，and increases in urine sodium and urine osmotic pressure. DHS has not received widespread attention in clinical practice，and there are rare reports of DHS comorbid with SIADH. This article reports the diagnosis and treatment processes of a case of DHS comorbid with SIADH and reviews the relevant literature，in order to guide the diagnosis and treatment of PD-related critical diseases.
Hyponatremia

An 18-day-old male infant was admitted to the hospital due to recurrent hyperkalemia for more than 10 days. The neonate had milk refusal and dyspnea. The blood gas analysis revealed recurrent hyperkalemia, hyponatremia and metabolic acidosis. Adrenocortical hormone replacement therapy was ineffective. Additional tests showed a significant increase in aldosterone levels. Family whole exome sequencing revealed that the infant had compound heterozygous in the SCNNIA gene, inherited from both parents. The infant was diagnosed with neonatal systemic pseudohypoaldosteronism type I. The infant's electrolyte levels were stabilized through treatment with sodium polystyrene sulfonate and sodium supplement. The infant was discharged upon clinical recovery. This study provides a focused description of differential diagnosis of salt-losing syndrome in infants and introduces the multidisciplinary management of neonatal systemic pseudohypoaldosteronism type I.
Infant ; Infant, Newborn ; Humans ; Male ; Pseudohypoaldosteronism/genetics* ; Hyperkalemia/etiology* ; Hyponatremia/diagnosis* ; Diagnosis, Differential

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.
Adenocarcinoma of Lung/drug therapy* ; Adrenocorticotropic Hormone/therapeutic use* ; Aged ; B7-H1 Antigen/therapeutic use* ; Humans ; Hydrocortisone/therapeutic use* ; Hyponatremia/drug therapy* ; Hypopituitarism/drug therapy* ; Immune Checkpoint Inhibitors ; Lung Neoplasms/pathology* ; Male ; Methylprednisolone/therapeutic use* ; Middle Aged ; Nausea/drug therapy* ; Pituitary Gland/pathology* ; Pneumonia ; Prednisone/therapeutic use* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Prolactin/therapeutic use*

INTRODUCTION: A physiological profiling study was conducted to evaluate thermal strain as well as fluid and electrolyte balances on heat-acclimatised men performing a 72-km route march in a field setting. METHODS: 38 male soldiers (age range 18-23 years) participated in the study, as part of a cohort that marched for 72 km, with loads for about 26 hours. Core temperature and heart rate sensors were used for the duration of the march. Fluid and food intake and output were monitored for the duration of the march. Blood samples were taken one day before the march (pre-march), immediately after the march (Post 1) and on the 15^th day after the march to ascertain recovery (Post 2) to assess fluid and electrolyte profiles. RESULTS: Mean core temperature was within safe limits, ranging from 37.1 to 38.1°C throughout the march. There was an overall decrease in serum sodium levels, a decline in serum sodium concentration in 28 participants and three instances of hyponatraemia (serum sodium concentration <135 mmol/L). CONCLUSION Our study found low thermal strain heat-acclimatised individuals during a 72-km route march. However, there was an overall decrease in serum sodium levels, even when the participants were allowed to drink ad libitum. Challenges of exercise-associated hyponatraemia during prolonged activities remain to be addressed.
Humans ; Male ; Adolescent ; Young Adult ; Adult ; Military Personnel ; Hyponatremia ; Water-Electrolyte Balance/physiology* ; Exercise/physiology* ; Sodium

Objectives: To determine if online team-based learning (TBL) is effective in improving knowledge outcomes and confidence about hyponatremia in its clinical recognition, classification, diagnostic work up, and management among fourth year medical students Study design: A quantitative evaluative design. Population and Setting: Fourth year medical students (medical clerks) rotating in the Department of Medicine, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines from July to December 2020. Methodology: A modified TBL workshop is adopted in teaching fourth year medical clerks about hyponatremia. The TBL session was held with a group of medical clerks weekly from July to December 2020. As a pre-workshop preparation, the medical clerks were assigned to read ahead of time the clinical practice guidelines on the diagnosis and treatment of hyponatremia developed by the European Renal Best Practice. After reading it, they were asked to answer an Individual Readiness Assessment Test (IRAT) composed of 20 case-based multiple-choice questions (MCQ). The group was thereafter divided into 4 subgroups and asked to discuss the same MCQ-based exam and present it as a Team Readiness Assessment Test (TRAT). As each subgroup presented their IRAT, the facilitator discussed the underlying concepts for each question and its application in actual cases of hyponatremia. The facilitator then summarized the learning outcomes at the end of the TBL workshop. For team application (TAPP), the students created a concept map and formulated admitting orders. The medical clerks were then surveyed on their confidence in hyponatremia diagnosis and management during pre-TBL workshop, after IRAT, after TRAT, and after discussion with the facilitator. Statistical Design: Descriptive statistics were used to summarize the study variables and included the mean, standard deviation, frequency, and percentage. Within-group comparisons of different outcomes across the different timeframes were conducted using one-way multivariate analysis of variance (one-way MANOVA). Cognizant that the study has multiple outcomes or dependent variables which were compared at four different timeframes, multivariate analysis was utilized to minimize the inflation of family-wise errors (FWE). Results: Comparative analysis indicated that the mean readiness scores of the respondents after TRAT was significantly higher (t=–91.61, p=0.001) compared to the mean readiness scores after IRAT. Comparative analysis using paired t-test indicated that the mean confidence scores of the respondents in the recognition, diagnosis, and treatment of hyponatremia were significantly higher among the respondents after the IRAT (t=–24.26, p=0.001), TRAT (t=–34.58, p=0.001), and facilitator discussion (t=–42.72, p=0.001) approaches compared to the mean pre-TBL confidence score. The mean knowledge score of the respondents on the creation of a concept map and the formulation of admission orders of patients with hyponatremia was 25.54±1.98 (95% CI 25.26-25.82). Conclusion: Findings of this study are not to be interpreted as demonstrating a causal relationship. Furthermore, the results are only hypothesis-generating at best. The study showed that online TBL has the potential to be an effective method in improving knowledge outcomes and confidence about hyponatremia in its clinical recognition, classification, diagnostic work-up, and management among fourth year medical students. As a preliminary evaluation of TBL, further studies can be conducted to determine its effectiveness as a teaching modality in the medical curricula in comparison to the traditional method before being adopted as a teaching-learning activity. Key words: team-based learning, online learning, COVID-19, hyponatremia, medical education
Education, Distance ; COVID-19 ; Hyponatremia

Adult ; Aged ; Aged, 80 and over ; Betacoronavirus ; Coronavirus Infections ; complications ; Female ; Glomerular Filtration Rate ; Glycosuria ; epidemiology ; Hospitalization ; Humans ; Hyponatremia ; epidemiology ; Kidney Tubules, Proximal ; physiopathology ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; complications ; Retrospective Studies