Endocrine Abstracts

Central diabetes insipidus (CDI) is a rare condition caused by various underlying diseases including inflammatory and autoimmune diseases, neoplasms (such as germinomas and craniopharyngiomas), infiltrative diseases (such as Langerhans cell histiocytosis), neurosurgery, trauma, and genetic defects in vasopressin synthesis. However, up to 15% of CDI causes remain idiopathic, although, a recent report showed idiopathic CDI is a very uncommon condition. An autoimmune process involving destruction of the neurohypophysis may be involved in many patients with idiopathic CDI. When a definitive cause of CDI is not found, most cases of CDI will be labeled idiopathic, but an autoimmune process should always be considered. Lymphocytic hypophysitis, including Lymphocytic infundibuloneurohypophysitis (LINH) accounts for a substantial subset of autoimmune CDI cases and is characterized by lymphocytic inflammation of the posterior pituitary and infundibular stalk. Obtaining an accurate definitive diagnosis of the underlying cause of CDI is difficult. Pathological examination is required for a definitive diagnosis. Recently, anti-rabphilin-3A antibodies were demonstrated to be a highly sensitive and specific marker of LINH. Here, we report a detailed case series, and evaluated the significance of anti-rabphilin-3A antibodies in differentiating the etiologies of CDI. A prospective analysis was conducted in 15 consecutive patients with CDI from 2013 to 2020 at a single referral center. All patients presenting with polyuria and polydipsia underwent endocrinological tests, including the hypertonic saline infusion test, and cranial magnetic resonance imaging. Anti-rabphilin-3A antibodies were measured and the relationship between antibody positivity and the clinical/histopathological diagnoses was evaluated. Among 15 CDI patients, the positive anti-rabphilin-3A antibodies were found in 4 of 5 LINH cases, 3 of 4 lymphocytic panhypophysitis (LPH) cases (including 2 of the 3 biopsy-proven samples), a subtype of lymphocytic hypophysitis that affects both of the anterior and posterior pituitary gland and causes CDI. The positive anti-rabphilin-3A antibodies were found in one intracranial germinoma case, and were negative in two Rathke cleft cyst cases and one craniopharyngioma case. After the treatment with steroid in patient with LPH who were positive for anti-rabphilin-3A antibodies, GH and/or gonadotropin levels were restored. In conclusion, this is the first case series to evaluate the presence of anti-rabphilin-3A antibodies in consecutive patients with CDI. We found that anti-rabphilin-3A antibodies positivity in CDI patients with biopsy-proven LPH and confirm that measurement of anti-rabphilin-3A antibodies may be valuable for differentiating CDI etiologies.