The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is frequent in lung cancer patients. Here, we report a case with persistent hyponatremia, which suggested malignant SIADH and facilitated an early diagnosis of small cell lung cancer (SCLC). A combined radio-chemotherapy led to a partial remission and resolution of SIADH. An early relapse was indicated by reoccurring severe hyponatremia and increased copeptin levels, which were used as surrogate markers for the antidiuretic hormone (ADH). As palliative immunochemotherapy, together with fluid restriction and solute substitution, were unable to control hyponatremia, treatment with the ADH V2-receptor antagonist tolvaptan was initiated. Over time, the dose of tolvaptan needed to be increased, paralleled by a well-documented exponential increase of copeptin levels. In summary and conclusion, this is a rare case of a secondary failure to tolvaptan with unique documentary evidence of increasing copeptin levels. This observation supports the hypothesis that exceedingly high ADH levels may lead to competitive displacement of tolvaptan from the V2 receptor.

Syndrome of inappropriate antidiuresis (SIAD) is one of the most frequent causes of euvolemic hyponatremia (serum sodium levels < 135 mEq/L) and it represents more than 35% of hyponatremia cases in hospitalized patients. It is characterized by an inappropriate vasopressin (AVP)/antidiuretic hormone (ADH) secretion, which occurs independently from effective serum osmolality or circulating volume, leading to water retention via its action on type 2 vasopressin receptor in the distal renal tubules. Corpus callosum agenesis (CCA) is one of the most common congenital brain defects, which can be associated to alterations in serum sodium levels. This report presents a rare case of chronic hyponatremia associated with SIAD in a woman with CCA, whose correction of serum sodium levels only occurred following twice-daily tolvaptan administration.
A 30-year-old female was admitted to our hospital for non-acute hyponatremia with dizziness, headache, distal tremors, and concentration deficits. She had profound hyponatremia (Na 121 mmol/L) with measured plasma hypo-osmolality (259 mOsm/Kg) and urinary osmolality greater than 100 mOsm/Kg (517 mOsm/Kg). She presented clinically as normovolemic. After the exclusion of other causes of normovolemic hyponatremia, such as hypothyroidism and adrenal insufficiency, a diagnosis of SIAD was established. We have ruled out paraneoplastic, inflammatory, and infectious causes, as well as ischemic events. Her medical history showed a CCA and frontal teratoma. We administered tolvaptan initially at a low dosage (15 mg once a day) with persistence of hyponatremia. Therefore, the dosage was first doubled (30 mg once a day) and then increased to 45 mg once a day with an initial improvement in serum sodium levels, although not long-lasting. We therefore tried dividing the 45 mg tolvaptan administration into two doses of 30 mg and 15 mg respectively, using an off-label treatment schedule, thus achieving long-lasting serum sodium levels in the low-normal range associated with a general clinical improvement.
This report underlines the importance of the correct diagnosis, management and treatment of SIAD, as well as the need for further studies about the pharmacokinetics and pharmacodynamics of vasopressin receptor antagonists.

BACKGROUND: Holoprosencephaly (HPE) is a congenital malformation with various degrees of incomplete separation of the cerebral hemispheres due to differentiation disorders of the forebrain. Although HPE with diabetes insipidus due to associated pituitary dysfunction has been reported, HPE with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is very rare. Tolvaptan, a vasopressin V2 receptor antagonist, is effective in adults with SIADH. However, there is no report of its efficacy in infants with SIADH. The purpose of this report is to demonstrate that tolvaptan is effective for SIADH in infants and that administration of tolvaptan eliminates the need for restriction of water intake and sodium administration.
METHODS: A 2414-g female infant was born at 38 wk by normal vaginal delivery. Facial anomalies and head magnetic resonance imaging indicated semilobar HPE. After birth, she had hyponatremia due to SIADH and was treated using water and sodium restriction. However, she developed an exaggerated response to the fluid restrictions, resulting in large fluctuations in serum sodium levels. Subsequent administration of tolvaptan improved the fluctuations in serum sodium levels without the need for adjustment of water or sodium administration. Serum sodium was maintained within the normal range after discontinuation of tolvaptan at 80 d of life. There were no side effects, such as hypernatremia or liver dysfunction, during the administration of tolvaptan.
CONCLUSIONS: This is the first report on the safety and efficacy of tolvaptan in an infant with SIADH associated with HPE.

Ascites in patients with decompensated cirrhosis can lead to abdominal distention and decrease quality of life. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective agent in the treatment of ascites, whereas some patients are refractory to tolvaptan. The efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for these patients is not known. In this study, we performed TIPS for tolvaptan-refractory cirrhotic patients and analysed its efficacy and safety in these patients.
This retrospective analysis included patients with liver cirrhosis who received TIPS for ascites or hydrothorax refractory to tolvaptan therapy along with conventional diuretics between January 2015 and May 2018 at Tokai University Hospital. We evaluated the efficacy and safety of TIPS.
This study included four patients. All patients presented with Child-Pugh class B liver cirrhosis and model for end-stage liver disease-sodium scores were 10/12/14/16. TIPS was generated successfully without any major complications in all patients. The body weight decreased by a mean of 4.7 (SD=1.0) kg and estimated glomerular filtration rate improved from a mean of 38.2 (SD=10.3) to 59.5 (SD=25.0) mL/min/1.73 m2 in a month after TIPS procedure.
TIPS is an effective potential treatment for ascites in patients with tolvaptan refractory condition. In appropriate patients who can tolerate TIPS, the treatment may lead towards renal function improvement.

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BACKGROUND: Polycystic kidney disease (PKD) is a genetic disorder characterized by the growth of numerous cysts within the kidneys. Disease progress of some patients often occurs at the early stage. Thus, managing and controlling disease progress is important to slow the kidney function decline especially for the patient with other disorders.
METHODS: One 80-year-old male autosomal dominant polycystic kidney disease (ADPKD) patient with chronic kidney disease and other clinical disorders was treated with tolvaptan and edoxaban. Estimated glomerular filtration rate, creatinine and uric acid were monitored during the treatment. In addition, the whole exome sequencing was performed to screen ADPKD genetic variants. The kidney function decline was prevented after using tolvaptan and edoxaban treatment and in the meantime, a venous thromboembolism was removed and leg and pedal edema were alleviated. One mutation c.10102G>A /p.D3368N in the PKD1 gene was identified.
CONCLUSIONS: Tolvaptan combined with edoxaban administration could delay kidney function decline and eliminate the edema caused by the thromboembolism.

BACKGROUND: Patients with autosomal dominant polycystic kidney disease (ADPKD) may require specific therapy with vasopressin receptor antagonists to slow the progression of renal disease. Because of its mechanism of action, the most common side effects are polyuria, nocturia, and polydipsia. Elevations of liver enzyme levels can also occur during treatment with Tolvaptan. Temporary drug withdrawal may be indicated if the patient is unable to hydrate adequately or if there are concomitant causes of dehydration, including major infectious events. During the Coronavirus Disease 2019 (COVID-19) pandemic, this should be considered in the management of patients on Tolvaptan therapy.
METHODS: We present the clinical case of a 51-year-old male with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection and ADPKD receiving Tolvaptan therapy with particular reference to the medical management of the patient during the infectious event. The patient was instructed to discontinue promptly Tolvaptan as soon as symptoms appeared. He was treated with forced hydration and symptomatic therapy. Nevertheless, a transient elevation of liver enzyme levels was detected. The timely discontinuation of Tolvaptan therapy avoided the risk of potential hepatotoxicity in a condition of known susceptibility.
CONCLUSIONS: Tolvaptan therapy of patients with ADPKD is safe even during SARS-CoV-2 infection. There is need for appropriate and prompt patient counseling to avoid potentially adverse side effects.

Autosomal dominant polycystic kidney disease (ADPKD) may coexist with other genetic disorders, such as tuberous sclerosis, when deletion in TSC2/PKD1 genes occurs. Recently, the effect of tolvaptan has been explored in ADPKD patients alone, but its safety and efficacy on TSC2/PKD1 contiguous gene syndrome are unknown.
This report describes the case of an asymptomatic patient with TSC2/PKD1 contiguous gene syndrome that fulfills the imaging criteria for initiating the treatment with tolvaptan. After twelve months, the patient did not exhibit severe adverse effects and blood pressure control improved.
In this TSC2/PKD1 contiguous gene syndrome single case report, tolvaptan was safe and well-tolerated. More extensive experimental studies are needed to deeply understand the therapeutic implications of vasopressin V2-receptor inhibition in the TSC2/PKD1 contiguous gene syndrome patients.

We report the case of a 68-year-old man, who presented in emergency care with inarticulate speech. The patient was diagnosed with syndrome of inappropriate antidiuretic hormone (SIADH) associated with pancreatic cancer. All diagnostic criteria for SIADH were met, and cancer of the pancreatic tail was identified by computed tomography. Standard treatment for SIADH includes water restriction, oral NaCl, continuous intravenous infusion of 3% NaCl, and intravenous infusion of furosemide. However, these treatments have varying effectiveness and are difficult for both patients and medical staff. Furthermore, unless treatment of the underlying disease is successful, continued hospitalization is needed and the patient\'s quality of life is significantly impaired. In this case, hyponatremia improved with this standard treatment, but ascites and edema developed. We treated the patient with tolvaptan due to decreased cardiac function, and symptoms improved rapidly. Although surgery and chemotherapy could not be performed for pancreatic cancer, the SIADH was treated for 7 months without relapse. In summary, a case of SIADH complicated by pancreatic cancer was difficult to control with standard treatment, but responded rapidly to tolvaptan, and outpatient treatment could be continued for a long period. Tolvaptan is useful for the treatment of SIADH associated with cancer.

Suprasellar arachnoid cysts represent a rare occurrence in the pediatric population and usually cause symptoms related to mass effect and can occasionally cause endocrine dysfunctions. The association between SAC and the syndrome of inappropriate antidiuretic hormone (SIADH) in the pediatric population has rarely been described previously. In most cases, SIADH is temporary and resolves by treating the underlying cause. The first-line treatment consists of fluid restriction in asymptomatic children. Oral urea and demeclocycline are other effective treatment options. Vaptans are a new class of medication for the management of SIADH. These agents are a nonpeptide vasopressin V2 receptor antagonist that selectively antagonizes the antidiuretic effect of AVP, resulting in excretion of diluted urine or \"aquaresis.\" Their efficacy has been shown in adult patients with euvolemic or hypervolemic hyponatremia. However, evidence is lacking in pediatric patients with SIADH. We report the case of a 9-year-old female child with a SAC, who underwent endoscopic fenestration at the age of 2 years. After surgery she developed chronic hyponatremia due to SIADH. Hyponatremia was refractory to treatment with fluid restriction, oral sodium, and urea. In order to normalize serum sodium levels, tolvaptan treatment was started on a compassionate-use basis; 24-48 h later serum sodium levels returned to normal. To date, tolvaptan has been used regularly for 6 years with no side effects occurring during the treatment period. This is the first case of a child with chronic SIADH secondary to SAC successfully treated with tolvaptan. Further studies are needed to demonstrate its usefulness on a broader case series.