A 38-year-old man was admitted because of transient somnolence. Five weeks previously, he had suffered a subarachnoid hemorrhage from a ruptured aneurysm of the anterior communicating artery (ACOM), which was treated by craniotomy and clipping. He had recovered well, although loss of short-term memory and a forehead paresis on the side of craniotomy persisted. Clinical examination on admission showed no new neurological deficits. Cerebral computed tomography with angiography revealed no bleeding or infarction and correctly positioned clips. Laboratory examination showed severe hypernatremia (179 mmol/L). The patient was admitted to the intensive care unit (ICU) and treated with oral fluids and 5% glucose intravenously. Remarkably, he denied being thirsty and had to be encouraged to drink. Urine osmolality quickly fell to 294 mOsm/kg, polyuria of up to 400 mL/h was measured, and serum sodium remained elevated. Therefore, diabetes insipidus (DI) was obvious. After application of desmopressin acetate, urine output dropped to around 50 mL/h, confirming central DI or vasopressin deficiency (VD). Desmopressin acetate dose and volume management were continuously adjusted to blood sodium to restore euvolemia. Drinking volume needed to be supervised because of persistent lack of thirst and amnesia of being told to drink. Adipsic VD (aAVP-D) is a rare syndrome characterized by the combination of VD and loss of thirst in response to hypernatremia. It usually occurs within days after cell damage of osmoreceptors, for example after disruption of blood supply as in clipping of an ACOM aneurysm. Management includes titrated desmopressin acetate replacement, fixed water intake, weight monitoring, patient education and sodium monitoring. Adipsic vasopressin deficiency (aAVP-D) is a rare form of vasopressin deficiency (VD) characterized by additional loss of thirst in response to hypernatremia due to impaired function of periventricular osmoreceptors. Bleeding from ACOM aneurysm and, possibly, therefore the performed frontal craniectomy with aneurysm clipping are the most frequent causes of aAVP-D. Other causes include craniopharyngioma, head trauma, germinoma or neurosarcoidosis. Management of aAVP-D includes replacement of titrated desmopressin acetate, fixed water intake, daily weight tracking, good patient education and regular sodium monitoring.

Adipsic arginine vasopressin deficiency(aAVP-D) is a rare, high-risk syndrome, particularly difficult to recognize and manage in children and adolescents. This investigation examined the clinical features and management of aAVP-D in children and adolescents with sellar germ cell tumors (GCTs). A retrospective survey was performed on 260 patients with sellar GCTs, categorized into aAVP-D and non-aAVP-D groups based on thirst presence. General characteristics, hypothalamic syndrome, pituitary function, metabolic indicators, and complications were compared. Biochemical indicator changes in the aAVP-D group were analyzed after systematic management, and receiver operating characteristic (ROC) curve analysis established the optimum serum sodium cut-off for predicting the aAVP-D. 25 patients (9.6%) developed aAVP-D. The aAVP-D group had larger tumors with hypothalamic involvement and more surgical resections. They also demonstrated more hypothalamic syndrome, central adrenal insufficiency, central hypogonadism, and insulin-like growth factor-1 levels below norms. Furthermore, aAVP-D patients exhibited significantly higher rates of hypernatremia (100% vs 20.9%, p < 0.001), hyperuricemia (60.0% vs 23.4%, p < 0.001), renal impairment (32.0% vs 1.7%, p < 0.001), and venous thrombosis (4.0% vs 0%, p = 0.002). Following systematic management, aAVP-D patients experienced significant reductions in serum sodium, uric acid, and creatinine levels, although these remained higher than in the non-aAVP-D group. ROC analysis indicated that a serum sodium level above 149.5 mmol/L predicted aAVP-D. Conclusion Patients with aAVP-D had more tumor involvement in the hypothalamic region, surgical resections, hypothalamic syndrome, hypopituitarism, and complications. Serum sodium levels above 149.5 mmol/L necessitated heightened vigilance for aAVP-D. Early identification and systematic management reduced complications, though clinical management remained challenging. What is Known • Adipsic arginine vasopressin deficiency (aAVP-D) is a rare and high-risk syndrome that is difficult to recognize and manage. • There are few reports on aAVP-D, most of which focus on adult patients. • The characteristics and management of aAVP-D in children and adolescents remain unclear. What is New • Children and adolescents with aAVP-D experienced higher rates of hypothalamic region tumor involvement, surgical resections, hypothalamic syndrome, hypopituitarism, and associated complications. • Serum sodium levels above 149.5 mmol/L necessitated heightened vigilance for aAVP-D. • Early recognition and structured management of ADI lowered the risk of complications.

"Adipsic hypernatremia" is clinically characterized by chronic elevation of plasma [Na+] with an inappropriate lack of thirst and upward resetting of the osmotic set point for arginine vasopressin (AVP) secretion, combined with a relative deficiency of AVP, thereby resulting in persistent hypernatremia. Many cases are accompanied by structural lesions in the hypothalamus, pituitary gland, and circumventricular organs (CVOs). On the other hand, cases without structural lesions have been reported since the 1970s, but the pathophysiology was unknown for a long time. In 2010, Hiyama et al. reported that an anti-Nax antibody response caused adipsic hypernatremia in a pediatric case with ganglioblastoma. In recent years, advances in clinical research have led researchers to recognize that an autoimmunological pathogenic mechanism might be associated with periventricular organs such as the subfornical organ (SFO). In addition, in pediatric cases diagnosed as ROHHAD (rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation) syndrome, it has been reported that half of the cases have abnormal serum Na levels, and some research findings indicated an autoimmune mechanism acting on the organs of the hypothalamus and CVOs. Then, anti-ZSCAN1 antibody response was detected in cases diagnosed as ROHHAD-NET in 2022. In this review, by summarizing a series of studies on Nax and ZSCAN1, which are expressed in the hypothalamus, pituitary gland, and SFO, I would like to describe the current findings of the autoimmune pathogenesis of adipsic hypernatremia.

A 16-month-old neutered male domestic shorthair cat weighing 2.7 kg was referred for further evaluation of acute generalized muscle weakness and paraparesis after a long-standing history of polyuria-polydipsia. The diagnosis of hypodipsic/adipsic hypernatremia relied on the key findings of absent spontaneous drinking despite hypernatremia and a hyperosmolar state (444.8 mOsm/kg, reference interval 280 to 310 mOsm/kg). Brain MRI revealed severe multifocal anatomic anomalies of the rostral calvarium and the forebrain, suggestive of encephaloclastic porencephaly. Involvement of the thalamic and hypothalamic regions could have been responsible for the cat's adipsic hypernatremia. The unique aspects of this case were the rare description of central nervous system disease leading to hypodipsia, and the history of chronic polydipsia before the acute onset of hypodipsia. Key clinical message: Multifocal abnormalities of the forebrain can present with polyuria-polydipsia syndrome, hypodipsia/adipsia, or both, depending on the stage of the disease. This likely happens when the hypothalamic and thalamic regions are affected, since they regulate antidiuretic hormone release and thirst, respectively. Hypernatrémie hypodipsique après polydipsie ancienne chez un chat suspect de traumatisme crânien néonatal. Un chat domestique à poil court mâle castré âgé de 16 mois et pesant 2,7 kg a été référé pour une évaluation plus approfondie de faiblesse musculaire aiguë généralisée et de paraparésie après une longue histoire de polyurie-polydipsie. Le diagnostic d’hypernatrémie hypodipsique/adipsique reposait sur les principales conclusions de l’absence d’abreuvement spontané malgré l’hypernatrémie et un état hyperosmolaire (444,8 mOsm/kg, intervalle de référence de 280 à 310 mOsm/kg). L’IRM du cerveau a révélé des anomalies anatomiques multifocales sévères de la calotte crânienne rostrale et du prosencéphale évoquant une porencéphalie encéphaloclastique. L’atteinte des régions thalamique et hypothalamique pourrait être responsable de l’hypernatrémie adipsique du chat. Les aspects uniques de ce cas étaient la description rare d’une maladie du système nerveux central conduisant à l’hypodipsie, et l’histoire de la polydipsie chronique avant l’apparition aiguë de l’hypodipsie.Message clinique clé :Les anomalies multifocales du cerveau antérieur peuvent présenter un syndrome de polyurie-polydipsie, une hypodipsie/adipsie, ou les deux, selon le stade de la maladie. Cela se produit probablement lorsque les régions hypothalamique et thalamique sont affectées, car elles régulent respectivement la libération d’hormone antidiurétique et la soif.(Traduit par Dr Serge Messier).

Specific antibody responses to subfornical organs, including Nax antibody, have been reported in patients with adipsic hypernatremia of unknown etiology who do not have structural lesions in the hypothalamic-pituitary gland. The subfornical organ, also referred to as the window of the brain, is a sensing site that monitors sodium and osmotic pressure levels. On the other hand, ROHHAD syndrome is a rare disease for which the etiology of the hypothalamic disorder is unknown, and there have been some reports in recent years describing its association with autoimmune mechanisms. In addition, abnormal Na levels, including hypernatremia, are likely to occur in this syndrome. When comparing the clinical features of adipsic hypernatremia due to autoimmune mechanisms and ROHHAD syndrome, there are similar hypothalamic-pituitary dysfunction symptoms in addition to abnormal Na levels. Since clinical diagnoses of autoimmunological adipsic hypernatremia and ROHAD syndrome might overlap, we need to understand the essential etiology and carry out precise assessments to accurately diagnose patients and provide effective treatment. In this review, I review the literature on the autoimmune mechanism reported in recent years and describe the findings obtained so far and future directions.