title: Central diabetes insipidus and autoimmunity: relationship between the occurrence of antibodies to arginine vasopressin-secreting cells and clinical, immunological, and radiological features in a large cohort of patients with central diabetes insipidus of known and unknown etiology.
abstract: Central diabetes insipidus (CDI) is a rare hypothalamus-pituitary disease due to the deficiency of arginine vasopressin (AVP) synthesis from the hypothalamus and/or secretion from the neurohypophysis. The etiology of CDI is unknown in over one third of cases, classified as idiopathic CDI. The aim of this study was 2-fold: 1) to evaluate the occurrence of circulating autoantibodies to AVP-secreting cells (AVPcAb), and 2) to correlate it to clinical (sex, age of disease onset, disease duration, and degree), immunological (clinical history of autoimmune diseases and presence of related organ-specific autoantibodies), and radiological features (neurohypophyseal bright spot, pituitary stalk thickening, and empty sella) in a large cohort of patients with apparently idiopathic CDI or CDI of known etiology. To this purpose, 150 patients with CDI were studied: 64 idiopathic, 6 familial, 12 associated to granulomatous diseases, and 68 secondary to cranial trauma, tumor, or surgery. AVPcAb were measured by an indirect immunofluorescence method. AVPcAb were found in 23.3% of CDI patients: 21 idiopathic (32.8%) and 14 nonidiopathic (16.3%; chi(2) = 13.1; P < 0.001). AVPcAb were independently associated with age less than 30 yr at disease onset (P = 0.001) in patients with idiopathic CDI and with history of autoimmune diseases (P = 0.006 and P = 0.02, respectively) and radiological evidence of pituitary stalk thickening (P = 0.02 and P = 0.003, respectively) in both idiopathic and nonidiopathic CDI. The likelihood of autoimmunity in one patient with apparently idiopathic CDI with age of disease onset less than 30 yr was 53%, it increased to 91% when history of autoimmune diseases was associated and to 99% when pituitary stalk thickening was further associated. In conclusion, autoimmunity is associated with one third of patients with apparently idiopathic CDI, which should therefore be classified as autoimmune CDI. Autoimmune CDI is highly likely in young patients with a clinical history of autoimmune diseases and radiological evidence of pituitary stalk thickening. Conversely, autoimmunity probably represents an epiphenomenon in patients with nonidiopathic CDI.
authors.affiliation: Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Italy. rpivone@tin.it
authors.forename: Rosario
authors.initials: R
authors.lastname: Pivonello
authors.forename: Annamaria
authors.initials: A
authors.lastname: De Bellis
authors.forename: Antongiulio
authors.initials: A
authors.lastname: Faggiano
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Salle
authors.forename: Mario
authors.initials: M
authors.lastname: Petretta
authors.forename: Carolina
authors.initials: C
authors.lastname: Di Somma
authors.forename: Silvia
authors.initials: S
authors.lastname: Perrino
authors.forename: Paolo
authors.initials: P
authors.lastname: Altucci
authors.forename: Antonio
authors.initials: A
authors.lastname: Bizzarro
authors.forename: Antonio
authors.initials: A
authors.lastname: Bellastella
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lombardi
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
mesh_terms: D000328:Adult; D000367:Age Factors; D001127:Arginine Vasopressin / Q000378:metabolism*; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000276:immunology; D015551:Autoimmunity; D020790:Diabetes Insipidus, Neurogenic / Q000000981:diagnostic imaging* / Q000209:etiology / Q000276:immunology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000000981:diagnostic imaging; D010904:Pituitary Gland, Posterior / Q000000981:diagnostic imaging / Q000276:immunology* / Q000378:metabolism; D011859:Radiography; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D001127:Arginine Vasopressin