We present a case of small-cell lung cancer (SCLC) with syndrome of inappropriate antidiuretic hormone secretion (SIADH) in which serum sodium gradually normalized with the onset of hypertension, refractory hypokalemia, and chloride-resistant metabolic alkalosis due to ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS). In this case report, we discuss the diagnostic challenges of dual paraneoplastic syndromes with SIADH and EAS, management of SCLC with paraneoplastic endocrinopathies, and their prognostic impact on SCLC. In addition, we discuss neuroendocrine differentiation and ectopic hormone production in relation to intratumoral heterogeneity in SCLC and propose tumor microenvironment and hormonal and metabolic dependence as important determinants of tumor growth and survival.

Tolvaptan is an orally active antagonist of vasopressin (antidiuretic hormone [ADH]) V2 receptors. By blocking water reabsorption in kidney collecting ducts, it prompts renal free-water excretion and has been used for the treatment of hyponatremia, both euvolemic due to the syndrome of inappropriate ADH secretion, and hypervolemic due to liver cirrhosis and congestive heart failure. In the past few years, it has been shown that vasopressin and its second messenger cyclic adenosine monophosphate (cAMP) play an important role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This has been the rationale for the use of tolvaptan to halt the progression of ADPKD, mainly through slowing kidney growth and decline in renal function. Two major randomized clinical trials have demonstrated the benefits of tolvaptan in slowing the progression of ADPKD in terms of kidney growth and decline in renal function at 1 and 3 years (REPRISE and TEMPO). However, the long-term effectiveness of treatment with tolvaptan remains to be determined.

Inappropriate ADH syndrome (SIADH) may develop after intracranial surgery. SIADH in pediatric age is mostly seen in intracranial mass and not only after surgery. The management of these clinical conditions in patients is important for the clinical course of the patient. Fluid restriction is standard therapy in SIADH. Resistant hyponatremic pattern may be encountered in some cases. Vaptans have recently started to be used in hyponatremia due to SIADH. A patient with SIADH of triphasic episode presented to our clinical practice after surgery of craniopharyngioma. Resistant hyponatremia was not resolved despite fluid restriction and hypertonic saline support. The patient responded to single dose of tolvaptan fast and well and thus the clinical condition of the patient was successfully under control. There is inadequate data about tolvaptan treatment in pediatric patients. Our case report will contribute to the literature in this regard.

After a 34-year-old female developed a headache and high fever, she was diagnosed with aseptic meningitis. On admission, neurological examinations revealed cerebellar limb ataxia, horizontal gaze paretic nystagmus, and pyramidal tract signs. Laboratory tests showed hyponatremia (129 mEq/l). Five days after admission, convulsions in the upper limbs due to the severe hyponatremia (108 mEq/l) were noted. In addition, serum antidiuretic hormone levels were markedly increased to 18.5 pg/ml. Brain MRI showed multiple small inflammatory lesions in the subcortical cerebral white matter, thalamus, and around the third ventricular diencephalic regions. Pulse corticosteroid treatment promptly improved her symptoms. Although tests for serum anti-aquaporin 4, anti-myelin oligodendrocyte glycoprotein, and anti-voltage-gated potassium channel antibodies were negative, cerebrospinal fluid samples tested positive for anti-N-methyl-D-aspartate (NMDA) receptor antibodies. Oral prednisolone administration was continued, but she developed paresthesia in her upper and lower extremities and gaze-evoked nystagmus three months after the first attack. MRI showed that the previously observed high-intensity regions were decreased, but a new area of high intensity was observed in ventral regions through the lower midbrain to the pons. Because pulse corticosteroid treatment was again effective, we continued the oral prednisolone treatment. This case presented none of the characteristic symptoms of anti-NMDA receptor antibody encephalitis during the clinical course other than repeated demyelinating encephalitis and severe syndrome of inappropriate antidiuretic hormone secretion (SIADH). Additional clinical observations are needed to better understand the underlying pathology of the NMDA receptor antibodies in the cerebrospinal fluid in this case.

A 79-year-old woman without any cerebral hernia symptoms was hospitalized with hyponatremia. After syndrome of inappropriate antidiuretic hormone induced by drugs was diagnosed and water restriction implemented, the patient became comatose during overcorrection caused by the generation of a large volume of electrolyte-free urine. Once the serum sodium concentration was immediately relowered by the administration of desmopressin and 5% glucose solution, the patient's level of consciousness improved dramatically without osmotic demyelination syndrome (ODS) developing. This outcome suggests that, similar to the findings in rat models, relowering the serum sodium concentration as early as possible to counter a disturbance of consciousness during the overcorrection of hyponatremia prevents ODS.