Central diabetes insipidus in infancy with or without hypothalamic adipsic hypernatremia syndrome: early identification and outcome

Context: Neonatal central diabetes insipidus (CDI) with or without adipsia is a very rare complication of various complex hypothalamic disorders. It is associated with greater morbidity and a high risk of developing both hypernatremia and hyponatremia, due to the condition itself or secondary to treatment with vasopressin analogs or fluid administration. Its outcomes have yet to be evaluated. Objective: To investigate the clinical outcomes of patients with neonatal-onset CDI or adipsic CDI with hypernatremia. Design, Setting, and Participants: All patients diagnosed with neonatal CDI in a university hospital-based observational study and followed between 2005 and 2015 were included and analyzed retrospectively. Main Outcome Measures: The various causes of CDI were grouped. Clinical outcome and comorbidities were analyzed. Results: Ten of the 12 patients had an underlying condition with brain malformations: optic nerve hypoplasia (n = 3), septo-optic dysplasia (n = 2), semilobar holoprosencephaly (n = 1), ectopic neurohypophysis (n = 3), and unilateral absence of the internal carotid artery (n = 1). The other two were idiopathic cases. During the median follow-up period of 7.8 (4.9-16.8) years, all but one patient displayed anterior pituitary deficiency. Transient CDI was found in three (25%) patients for whom a posterior pituitary hyperintense signal was observed with (n = 2) and without (n = 1) structural hypothalamic pituitary abnormalities, and with no other underlying cerebral malformations. Patients with permanent CDI with persistent adipsia (n = 4) and without adipsia (n = 5) required adequate fluid intake and various doses of desamino-D-arginine-8-vasopressin. Those with adipsia were more likely to develop hypernatremia (45 vs 33%), hyponatremia (16 vs 4%) (P < .0001), and severe neurodevelopmental delay (P < .05) than those without adipsia. Comorbidities were common. The underlying cause remains unknown at the age of 23 years for one patient with CDI and normal thirst. Conclusion: Neonatal CDI may be transient or permanent. These vulnerable patients have high rates of comorbidity and require careful monitoring.