Management of Langerhans Cell Histiocytosis (LCH)-Induced Central Diabetes Insipidus and Its Associated Endocrinological/Neurological Sequelae

Central diabetes insipidus (CDI) is caused by a deficiency of arginine vasopressin (AVP), also known as antidiuretic hormone. Although CDI is rare in children and young adults, it should be kept in mind that it is associated with rare histiocytic disorders in the central nervous system (CNS), namely Langerhans cell histiocytosis (LCH), xanthogranulomatosis and Erdheim-Chester disease, all of which specifically affect the hypothalamus and pituitary stalk, thereby inducing CDI (1,2). In particular, CDI is the most frequently occurring CNS event in patients with multi-focal LCH, who often have multisystem lesions, including craniofacial bone lesions (3). LCH is a rare disorder that is characterized by the proliferation of cells that bear the activated Langerhans cell phenotype (4). Early studies reported that CDI occurs in 25–50% of LCH patients but this incidence appears to have dropped to 7–20% since the introduction of systemic chemotherapy (5). CDI can develop either before, simultaneously with, or subsequent to a diagnosis of LCH based on the presence of various extracranial lesions. It can also develop during chemotherapy for systemic LCH or after therapy. Patients with LCH-induced CDI show typical clinical symptoms, such as polyuria/polydispsia, in association with abnormal radiographic findings, such as a thickened pituitary stalk or a hypothalamic mass and the loss of a hot signal (T1 weighted) for the pituitary posterior lobe on brain magnetic resonance imaging (MRI) (5-8). Once CDI develops, it becomes irreversible in most patients, who will require life-long desmopressin replacement therapy with 1-desamino-8-D-arginine vasopressin(DDAVP). In addition, 30– 58% of patients with CDI exhibit anterior pituitary hormone deficiencies (APHD) during follow-up (1,7). LCH-associated APHD appears to be linked to a thickening of the pituitary stalk (6,7). In addition, patients with LCH-induced CDI can eventually develop neurodegenerative (ND) disease (9,10). Appropriate management of LCH-induced CDI involves (a) a prompt correct diagnosis; (b) early intervention with chemo/radiotherapy to reverse the CDI, if possible; (c) appropriately treating CDI to prevent the later development of APHD or ND disease; (d) good control of CDI, once it has become permanent, with DDAVP; and ideally (e) exploring future innovative measures that could prevent the occurrence of CDI in patients with LCH.