The frequency and natural history of diabetes insipidus in children with Langerhans-cell histiocytosis

Diabetes insipidus is a well-recognized complication of Langerhans-cell histiocytosis (histiocytosis X), but its frequency and natural history are not well defined. Of 52 children with histiocytosis whom we studied, 12 (23 percent) had diabetes insipidus. Only two children had diabetes insipidus at presentation with histiocytosis, but the cumulative risk that it would develop during the first four years after the presentation and diagnosis of histiocytosis was found to be 42 percent. Diabetes insipidus occurred most often among children with multisystem disease and those with proptosis. To determine the natural history of diabetes insipidus in children with histiocytosis, we measured the response of urinary arginine vasopressin to water deprivation every six months in 21 children who did not have diabetes insipidus and who had had histiocytosis for less than four years. Five of the 21 children (24 percent) had subnormal responses during the initial test. One subsequently had spontaneous improvement in the functioning of the posterior pituitary, and diabetes insipidus subsequently developed in two, as it did in one of the children who initially had normal function of the posterior pituitary. Two of the children received irradiation to the pituitary within two to four weeks after diabetes insipidus developed, but they had no improvement in pituitary function. However, diabetes insipidus improved transiently during prednisolone therapy in one of these children and improved permanently after etoposide therapy in another child. We conclude that prospective study with the use of a simple water-deprivation test will allow partial defects of posterior-pituitary function to be detected in patients with histiocytosis and will permit a more appropriate evaluation of the effects of therapeutic intervention.