Severe Hyponatremia During First Cycle of Cyclophosphamide/Doxorubicin Chemotherapy.

Syndrome of inappropriate anti-diuretic hormone release (SIDAH) is a condition characterized by an unregulated release of anti-diuretic hormone (ADH) resulting in increased water retention and decreased plasma osmolarity. Without regulation, ADH release will cause a significant decrease in plasma sodium concentration and can present with cramping, nausea, vomiting, and in severe cases, seizures, and potentially falling into a comatose state. The causes of SIADH are variable and range from infections, some malignancies to some medications. We report a rare case of SIADH resulting from a single cycle of doxorubicin and cyclophosphamide chemotherapy in a 66-year-old female with left and right, estrogen receptor positive breast cancer who experienced seizures resulting from a dramatic drop in sodium levels.

Ketamine-precipitated syndrome of inappropriate antidiuretic hormone secretion in a patient with persistent lumbar pain: a case report.

PURPOSE: To report on an unusual case of ketamine-precipitated syndrome of inappropriate antidiuretic hormone secretion (SIADH) in an individual managed by an outpatient pain specialty team. CLINICAL FEATURES: A 78-yr-old male presented to the emergency department with lethargy, malaise, nausea, and abdominal bloating three days following intravenous ketamine infusion for intractable postsurgical lumbar radicular pain with neuropathic features. The patient had a history of resected prostate cancer, hyperlipidemia, chronic kidney disease, and spinal stenosis and the cause of his symptoms was investigated. He was found to be hyponatremic and the treating team excluded reversible surgical and medical causes. A Naranjo score of 7 was calculated, suggesting that the correlation between ketamine and hyponatremia was "likely." Hence, a diagnosis of ketamine-precipitated SIADH was made. The patient was treated with fluid restriction and symptoms were controlled with antiemetics. He returned to baseline function with resolution of the hyponatremia within three days of discharge. CONCLUSION: This case is of clinical importance for providers using ketamine in the field of pain management as the effect of this medication reaction can be profound. Clinicians should develop an awareness that ketamine can potentiate adverse effects such as SIADH and they should monitor, detect, and manage as appropriate.

RéSUMé: OBJECTIF: Nous signalons un cas inhabituel de syndrome de sécrétion inappropriée d'hormones antidiurétiques (SIADH - syndrome of inappropriate antidiuretic hormone secretion) précipité par la kétamine chez une personne prise en charge par une équipe spécialisée en douleur en soins ambulatoires. CARACTéRISTIQUES CLINIQUES: Un homme de 78 ans s'est présenté à l'urgence souffrant de léthargie, de malaise, de nausées et de ballonnements abdominaux trois jours après avoir reçu une perfusion intraveineuse de kétamine pour le traitement d'une douleur radiculaire lombaire postopératoire rebelle avec des caractéristiques neuropathiques. Le patient avait des antécédents de résection de cancer de la prostate, d'hyperlipidémie, d'insuffisance rénale chronique et de sténose du canal rachidien, et la cause de ses symptômes a été évaluée. Il s'est avéré hyponatrémique et l'équipe soignante a exclu les causes chirurgicales et médicales réversibles. Un score Naranjo de 7 a été calculé, suggérant que la corrélation entre la kétamine et l'hyponatrémie était « probable ¼. Par conséquent, un diagnostic de SIADH précipité par la kétamine a été posé. Le patient a été traité par restriction hydrique et les symptômes ont été contrôlés par des antiémétiques. Il est revenu à son fonctionnement de référence avec la résolution de l'hyponatrémie dans les trois jours suivant son congé. CONCLUSION: Ce cas est important d'un point de vue clinique pour les praticiens qui utilisent la kétamine pour la prise en charge de la douleur, car l'effet de cette réaction médicamenteuse peut être profond. Les cliniciens devraient prendre conscience que la kétamine peut augmenter des effets indésirables tels que le SIADH et ils devraient monitorer, dépister et prendre en charge le patient, le cas échéant.

Folinic Acid, Fluorouracil, and Oxaliplatin Therapy for Recurrent Esophageal Cancer with Syndrome of Inadequate Antidiuretic Hormone Secretion (SIADH) After Preoperative Cisplatin/5-Fluorouracil Therapy.

BACKGROUND Cisplatin/5-fluorouracil therapy is the standard therapy for unresectable and recurrent esophageal cancer. Cisplatin-based chemotherapy often causes adverse effects, such as nausea, vomiting, and renal dysfunction, which may necessitate dose modification or treatment prolongation. Therefore, novel combination therapies are urgently needed to improve the efficacy and overcome drug toxicity in this setting. CASE REPORT A 77-year-old man with advanced esophageal cancer received cisplatin/5-fluorouracil therapy as neoadjuvant chemotherapy. On day 8 of administration, the patient had lightheadedness, diaphoresis, and nausea and became unconscious and developed severe hyponatremia. We diagnosed the patient with cisplatin-induced syndrome of inadequate antidiuretic hormone secretion (SIADH). Subsequently, water restriction was started, and treatment with a salt-added diet and 3% hypertonic saline infusion was initiated. The hyponatremia improved and the patient was discharged on day 16 of administration. Therefore, neoadjuvant chemotherapy was discontinued, and surgical treatment was performed. However, the tumor recurred and chemotherapy was required. The patient developed severe hyponatremia while receiving neoadjuvant chemotherapy; hence, folinic acid, fluorouracil, and oxaliplatin therapy (FOLFOX) were administered as an alternative treatment. The patient completed the FOLFOX therapy without developing SIADH. CONCLUSIONS The cisplatin/5-fluorouracil therapy is currently the standard chemotherapy regimen for esophageal cancer. However, SIADH is a known adverse effect when using cisplatin. In patients with esophageal cancer, oxaliplatin appears to have a lower risk of SIADH than cisplatin, suggesting that oxaliplatin can be a therapeutic option for patients with esophageal cancer who are at high risk of SIADH.

Red urine and a red herring - diagnosing rare diseases in the light of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has occupied the time and resources of health care professionals for more than 1 year. The risk of missed diagnoses has been discussed in the medical literature, mainly for common diseases such as cancer and cardiovascular events. However, rare diseases also need appropriate attention in times of a pandemic. CASE REPORT: We report a 34-year-old woman with fever, pinprick sensation in her chest and thoracic spine, and dizziness after receiving the first dose of ChAdOx1 nCoV-19 vaccination. The patient's condition worsened with abdominal pain, red urine, and hyponatremia, needing intensive care admission. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) was diagnosed. Vaccine-induced thrombocytopenia and thrombosis were ruled out. Acute hepatic porphyria was finally diagnosed, and the patient recovered completely after treatment with hemin. CONCLUSION: Currently, the focus of physicians is on COVID-19 and associated medical problems, such as vaccine side effects. However, it is important to be vigilant for other uncommon medical emergencies in medically exceptional situations that may shift our perception.

Hyponatremia and Fever in a Patient on Ipilimumab and Nivolumab (Immune Checkpoint Inhibitors): A Case Report.

Immune checkpoint inhibitors (ICIs) are novel anticancer therapy approved in multiple tumors and their use is rapidly increasing. They are associated with various systemic side effects that are immune-mediated and clinically coined as "immune-related adverse effects" (irAE). Hyponatremia is a possible side effect in patients receiving ICIs. Fever is another side effect that is mostly non-infectious. There are different mechanisms leading to hyponatremia in patients on ICIs, which could be (1) hypovolemic hyponatremia due to hemodynamic disturbance secondary to volume depletion (eg, from irAE like colitis and enteritis) or hypervolemia due to congestive heart failure, cirrhosis, or nephrosis; (2) syndrome of inappropriate antidiuretic hormone (SIADH) secretion (especially from underlying lung cancer or neurological irAE like encephalitis and meningitis) with elevated urine sodium and urine osmolarity; and (3) irAE-related endocrinopathies such as hypophysitis, adrenal insufficiency, and hypothyroidism leading to euvolemic hyponatremia. We describe an interesting case of hyponatremia and fever in a patient receiving Ipilimumab and Nivolumab. The possible etiology of hyponatremia, in this case, was hypovolemia and volume depletion secondary to fever.

[SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION AS A SIDE EFFECT OF CHEMOTHERAPY FOR URACHAL CARCINOMA: A CASE REPORT].

A 54-year-old woman was admitted to our hospital complaining of gross hematuria and difficulty urinating. Cystoscopy revealed a tumor 4 cm in size with calcification on top of the bladder. After diagnosis of urachal carcinoma by transurethral resection of the bladder, partial cystectomy with en bloc resection of the median umbilical ligament and pelvic lymphadenectomy was performed. Pathological diagnosis confirmed urachal carcinoma, pT3b, ly1, v0, pN1, RM0. TS-1 and cisplatin chemotherapy (TS-1 at 100 mg/day on days 1-21, CDDP at 60 mg/m2 on day 8) was administered. On day 13, the patient was admitted because of consciousness disorder (Glasgow Coma Scale E2V1M4). Hyponatremia (Na 109 mEq/l) and renal excretion of sodium were present and the patient was diagnosed with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by chemotherapy. Serum sodium level and her consciousness level gradually improved after administration of 3% saline. SIADH caused by chemotherapy containing cisplatin is a relatively rare, but potentially serious adverse effect that requires close attention.

Symptomatic hyponatremia induced by low-dose cyclophosphamide in patient with systemic lupus erythematosus: A case report.

RATIONALE: Cyclophosphamide (CY) is an alkylating agent used widely to treat cancer and autoimmune diseases. Hyponatremia is a common adverse effect of high-dose and moderate-dose of intravenous CY, but is rare in patients treated with low-dose (<15 mg/kg). PATIENT CONCERNS: A 52-year-old woman with new-onset systemic lupus erythematosus (SLE) was treated with low-dose cyclophosphamide (8 mg/kg, CY), but showed sudden headaches, disorientation and weakness. Laboratory examinations revealed severe isovolumic hyponatremia along with low-serum osmolality and high urine osmolality. DIAGNOSIS: The acute hyponatremia was consistent with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and was an adverse event of low-dose CY, with no evidence of endocrine, cancer, pulmonary, or cerebral abnormalities relevant to the SIADH. INTERVENTION: The hyponatremia was resolved after the supplementation of NaCl solution. OUTCOMES: The hyponatremia was resolved without any complications. LESSONS: Hyponatremia induced by low-dose CY should be recognized as an underlying life-threatening complication in clinical practice.

[Syndrome of inappropriate secretion of antidiuretic hormone in multiple myeloma patients treated with bortezomib, lenalidomide, and dexamethasone combination therapy].

Hyponatremia occurs while receiving bortezomib-containing combination therapy in multiple myeloma (MM) ; however, the mechanism of hyponatremia remains unclear. A 65-year-old female with MM was treated with bortezomib, lenalidomide, and dexamethasone. Fourteen days after chemotherapy initiation, she developed hyponatremia (serum sodium, 127 mEq/l, compared with 136 mEq/l before chemotherapy) with plasma hypo-osmolality and urine hyper-osmolality. She exhibited neither dehydration nor adrenal insufficiency. Her serum arginine vasopressin peptide (AVP) level was 1.5 pg/ml. She was diagnosed with syndrome of inappropriate secretion of antidiuretic hormone (SIADH), wherein causative roles of inflammatory cytokines were strongly suggested in the development because (1) SIADH was triggered by the cessation of the dexamethasone treatment and (2) hyponatremia was successfully treated with prednisolone, which was administered for the complication of drug eruption. Perhaps, bortezomib-induced immune reactions could be involved in a subset of hyponatremia during bortezomib-containing antimyeloma chemotherapy.

Rapid-onset hyponatremia and delirium following duloxetine treatment for postherpetic neuralgia: Case report and literature review.

RATIONALE: Hyponatremia following duloxetine treatment has been reported in patients with major depressive disorder, fibromyalgia, diabetic neuropathy, or sciatic pain. The manifestations of duloxetine-induced hyponatremia are varying in different individuals. The overall prognosis for this type of hyponatremia is favorable if properly managed. PATIENT CONCERNS AND DIAGNOSES: Herein, we reported rapid-onset hyponatremia and delirium in an older patient after 2 doses of duloxetine, which was used to control his postherpetic neuralgia. Laboratory examinations revealed a rapid decline in serum sodium level and indicated the possibility of syndrome of inappropriate antidiuretic hormone (SIADH). INTERVENTIONS: Discontinuation of duloxetine, restriction of water intake, and intravenous supplement of normal saline were adopted to manage the hyponatremia. OUTCOMES: Serum concentration of sodium gradually normalized following aforementioned strategies. LESSONS: Special attention to the electrolyte abnormality is recommended in old patients undergoing duloxetine treatment.

Hyponatremia in patients with esophageal cancer treated with chemotherapy including cisplatin.

BACKGROUND: Little is known about hyponatremia in patients with esophageal cancer treated with cisplatin-based chemotherapy. The aim of this study was to analyze the risk factors for hyponatremia and its effect on outcomes in patients with esophageal cancer treated with chemotherapy including cisplatin. METHODS: We retrospectively analyzed the records of 137 patients with esophageal cancer who received chemotherapy including cisplatin for the first time between January 2011 and December 2014. RESULTS: Hyponatremia (Na < 135 mEq/L) was seen in 77 patients (59%), of whom 29 had Grade 3 (120 ≤ Na < 130 mEq/L) or Grade 4 (Na < 120 mEq/L) hyponatremia. We divided patients into the hyponatremia group (patients with Na < 130 mEq/L) and the control group (patients with Na ≥ 130 mEq/L), and compared the results between the two groups. Three patients (2%) were diagnosed with the syndrome of inappropriate secretion of antidiuretic hormone. The serum sodium level before starting chemotherapy was significantly lower and white blood cell count was significantly higher in the hyponatremia group. Appetite loss was seen significantly more often in the hyponatremia group as the chemotherapy-related adverse effect. There was no significant difference in overall survival between the two groups. CONCLUSIONS: Hyponatremia is a common adverse effect induced by cisplatin. Caution should be exercised with patients with a low sodium level before starting chemotherapy. Hyponatremia can be associated with other chemotherapy-related adverse effects, and it should therefore be treated correctly.

Walking hyponatremia syndrome of inappropriate antidiuretic hormone secretion secondary to carbamazepine use: a case report.

BACKGROUND: Severe hyponatremia is rare when carbamazepine is used as monotherapy. It is common to encounter this imbalance in the hospital setting, but rare in the ambulatory one. Here, we present a case of hyponatremia secondary to carbamazepine use in an otherwise asymptomatic patient. CASE PRESENTATION: A 44-year-old Guatemalan woman presented to our outpatient clinic with a chief complaint of left knee pain. One month prior, our patient had previously consulted with an outside physician, who prescribed her with 300 mg of carbamazepine, 5 mg of prednisone every 24 hours, and ibuprofen every 8 hours as needed. The symptoms did not resolve and our patient had increased the dose to 600 mg of carbamazepine and 20 mg of prednisone 7 days prior. Our patient complained of left knee pain, fatigue, and bilateral lower limb cramps. No pertinent medical history was recorded and her vital signs were within normal limits. A physical examination was non-contributory, only multiple port-wine stains in the upper and lower extremities associated with mild hypertrophy of the calves, more prominent on the right side. Laboratory studies revealed: a serum sodium level of 119 mmol/L, potassium level of 2.9 mmol/L, thyroid-secreting hormone of 1.76 mIU/m, thyroxine of 14.5 ng/dL, and serum osmolality at 247 mmol/kg. No neurologic or physical disabilities were recorded. In the emergency department, her electrolyte imbalance was corrected and other diagnostic studies revealed: a urinary sodium level of 164 mmol/L and osmolality at 328 mmol/kg. Our patient was diagnosed with syndrome of inappropriate antidiuretic hormone secretion secondary to carbamazepine use, hypokalemia secondary to corticosteroid therapy, and Klippel-Trénaunay-Weber syndrome. Carbamazepine was discontinued, fluid restriction ordered, and hypokalemia was corrected. One week after discharge, our patient no longer felt fatigued, the cramps were not present, and her left knee pain had mildly improved with acetaminophen use and local nonsteroidal anti-inflammatory cream. Electrolyte studies revealed a sodium level of 138 mmol/L, potassium level of 4.6 mmol/L, and serum osmolality at 276 mmol/L. CONCLUSIONS: Hyponatremia can be misdiagnosed if not recognized promptly; suspicion should be high when risk factors are present and the patient has been prescribed antiepileptic drugs. Presence of mild symptoms such as fatigue or dizziness should lead to suspicion and subsequent laboratory testing. Patients can suffer from neurologic complications if the imbalance is not corrected.

Cisplatin-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH) with life-threatening hyponatraemia.

We present a case of cisplatin-induced syndrome of inappropriate antidiuretic hormone (SIADH) in a patient with metastatic recurrent urothelial carcinoma. Cisplatin-induced SIADH is an uncommon but potentially life-threatening toxicity. Pharmacogenetic characteristics may result in different toxicity profiles in different populations. With such widespread use of cisplatin in a diverse range of cancers, prompt recognition is crucial to detect and prevent severe neurological sequelae.

Syndrome of inappropriate antidiuretic hormone secretion from concomitant use of itraconazole and vindesine.

WHAT IS KNOWN AND OBJECTIVE: Several studies have reported that itraconazole-induced inhibition of vincristine (VCR) metabolism might result in neurological impairment and syndrome of inappropriate antidiuretic hormone (SIADH). However, there are few reports concerning adverse drug reactions (ADRs) resulting from concomitant use of vindesine (VDS) and itraconazole. Here, we report the first case of adverse drug interactions (ADIs) between itraconazole and VDS in a Chinese child with acute lymphocytic leukaemia (ALL). CASE SUMMARY: A 4-year-old boy was diagnosed with standard-risk ALL and was receiving VDS (3 mg/m2 ) for maintenance therapy and itraconazole for IFI recurrence. Severe neurotoxicity, consisting mainly of trismus and SIADH, was noticed after 7 days of VDS administration. After discontinuation of itraconazole and its replacement with caspofungin, the patient recovered from neurological signs and symptoms. The ADIs can be explained by VDS accumulation owing to inherent loss of CYP3A5 (*3/*3) function, and inhibition of CYP3A4 activity by itraconazole. WHAT IS NEW AND CONCLUSION: Syndrome of inappropriate antidiuretic hormone from co-administration of itraconazole and VDS has not previously been reported to our knowledge. We suggest that the concomitant use of these drugs should be avoided if possible. The use of alternative antifungal drugs (AFDs) should be considered, and ADRs should be closely monitored when the combination of itraconazole and VDS is unavoidable.

Pirfenidone-induced hyponatraemia: insight in mechanism, risk factor and management.

Pirfenidone was approved in October 2014 in the USA for the treatment of idiopathic pulmonary fibrosis. Although not included in the adverse events published in the CAPACITY-1 and CAPACITY-2 or ASCEND trials, hyponatraemia was reported in supplementary data with rate of 3.4% in the active therapy arm versus 0.3% in the placebo arm. We performed a retrospective analysis of patients who were initiated on pirfenidone or nintedanib for the treatment of pulmonary fibrosis at our centre. Of the 52 patients who were started on pirfenidone, three (5.8%) developed severe hyponatraemia. Of the 29 patients who were started on nintedanib, none developed hyponatraemia. Laboratory data suggested syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by pirfenidone and the medication was discontinued. Hyponatraemia is a possible significant adverse effect of pirfenidone, able to induce SIADH in patients taking the medication.

Bortezomib-induced syndrome of inappropriate antidiuresis in a patient with multiple myeloma: A case report and literature review
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Bortezomib is a landmark drug in the therapeutic history of multiple myeloma as the first-generation proteasome inhibitor. It is widely used clinically, and its common adverse reaction is peripheral nerve lesion. We observed a severe syndrome of inappropriate antidiuresis (SIAD) in a female patient with multiple myeloma treated with bortezomib. This paper reviews the treatment process and relevant research progress regarding SIAD through a case report so as to improve the clinicians' ability to recognize and diagnose this rare complication.
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Post-cytokine-release Salt Wasting as Inverse Tumor Lysis Syndrome in a Non-cerebral Natural Killer-cell Neoplasm.

The pathogenesis of cerebral/renal salt-wasting syndrome remains unknown. We herein present a case of salt-wasting syndrome with a natural killer-cell neoplasm without cerebral invasion. A 78-year-old man with hemophagocytic syndrome received two cycles of chemotherapy that did not induce tumor lysis syndrome, but repeatedly caused polyuria and natriuresis. The expression of tumor necrosis factor-α in the neoplasm led us to hypothesize that an oncolysis-induced cytokine storm may have caused renal tubular damage and salt wasting. Our theory may explain the pathogenic mechanism of cerebral/renal salt-wasting syndrome associated with other entities, including cerebral disorders, owing to the elevation of cytokine levels after subarachnoid hemorrhage.