Management of advanced-stage neuroblastoma in a patient with 21-hydroxalase deficiency.

A 2-year-old boy presented with a 21-hydroxylase deficiency, associated with advanced-stage neuroblastoma primarily occurring in the left adrenal gland. He required intensive chemotherapy with polypharmacy, followed by cord blood stem cell transplantation to treat the neuroblastoma. The precise adjustment of cortisol levels was crucial in this patient to prevent adrenal crisis. We administered hydrocortisone by continuous infusion while monitoring blood cortisol levels. As there are no published reports on the target cortisol levels for children, we used two control infants with advanced-stage neuroblastoma, also undergoing chemotherapy and cord blood stem cell transplantation, to guide the continuous hydrocortisone therapy. The daily dose of hydrocortisone during chemotherapy required about threefold the normal treatment to avoid adrenal insufficiency. Continuous hydrocortisone therapy is feasible for preventing adrenal crisis and this report may provide an effective management for hydrocortisone replacement in 21-hydroxylase-deficient patients undergoing chemotherapy and hematopoietic stem cell transplantation.

Adipsic hypernatremia without hypothalamic lesions accompanied by autoantibodies to subfornical organ.

Adipsic (or essential) hypernatremia is a rare hypernatremia caused by a deficiency in thirst regulation and vasopressin release. In 2010, we reported a case in which autoantibodies targeting the sensory circumventricular organs (sCVOs) caused adipsic hypernatremia without hypothalamic structural lesions demonstrable by magnetic resonance imaging (MRI); sCVOs include the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), which are centers for the monitoring of body-fluid conditions and the control of water and salt intakes, and harbor neurons innervating hypothalamic nuclei for vasopressin release. We herein report three newly identified patients (3- to 8-year-old girls on the first visit) with similar symptoms. The common features of the patients were extensive hypernatremia without any sensation of thirst and defects in vasopressin response to serum hypertonicity. Despite these features, we could not detect any hypothalamic structural lesions by MRI. Immunohistochemical analyses using the sera of the three patients revealed that antibodies specifically reactive to the mouse SFO were present in the sera of all cases; in one case, the antibodies also reacted with the mouse OVLT. The immunoglobulin (Ig) fraction of serum obtained from one patient was intravenously injected into wild-type mice to determine whether the mice developed similar symptoms. Mice injected with a patient's Ig showed abnormalities in water/salt intake, vasopressin release, and diuresis, which resultantly developed hypernatremia. Prominent cell death and infiltration of reactive microglia was observed in the SFO of these mice. Thus, autoimmune destruction of the SFO may be the cause of the adipsic hypernatremia. This study provides a possible explanation for the pathogenesis of adipsic hypernatremia without demonstrable hypothalamus-pituitary lesions.