ORIGINAL ARTICLE Anterior hypopituitarism is rare and autoimmune disease is common in adults with idiopathic central diabetes insipidus M. J. Hannon*, C. Orr*, C. Moran*, L. A. Behan*, A. Agha*, S. G. Ball† and C. J. Thompson* *Academic Department of Endocrinology, Beaumont Hospital/RCSI Medical School, Dublin, Ireland and †Endocrine Unit, Royal Victoria Infirmary, Newcastle Hospitals NHS Trust and University of Newcastle, Newcastle-Upon-Tyne, UK Summary Objective Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, although many of these are thought to have an autoim- mune basis. Published data have suggested that anterior hypopitu- itarism is common in childhood-onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituita- rism in a cohort of adult patients with idiopathic diabetes insipidus. Design and patients We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone magnetic resonance imaging scanning and dynamic pituitary test- ing (either insulin tolerance testing or GHRH/arginine and short synacthen testing) to assess anterior pituitary function. Results One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. Thirty-three percent had at least one autoimmune disease in addition to central diabetes insipidus. Conclusions Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not, therefore, be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology. (Received 13 July 2011; returned for revision 3 August 2011; finally revised 20 October 2011; accepted 20 October 2011) Introduction Central diabetes insipidus (CDI) (also known as neurogenic, cra- nial or hypothalamic diabetes insipidus) is attributed to insufficient arginine vasopressin (AVP) secretion from the posterior pituitary gland. 1 There are many causes of CDI. Up to 40% of patients have been traditionally labelled as idiopathic diabetes insipidus (DI), 2 although there are data to suggest that a significant proportion of these cases are autoimmune in aetiology. In a large cohort of patients with idiopathic DI, recruited from a number of academic centres in London, approximately 30% were shown to have plasma antibodies to vasopressin-secreting neurones. 3 Subsequent studies showed that a significant proportion of these patients had associ- ated autoimmune endocrine disease, most commonly thyroid dis- ease and pernicious anaemia. 4 Furthermore, open biopsy of the infundibulum and neurohypophysis in two patients with idio- pathic CDI revealed inflammatory infiltrates, T lymphocytes and plasma cells, changes typical of autoimmune disease. 5 These studies have led to the understanding that some cases of idiopathic CDI are autoimmune in nature. Radiographic studies have defined abnormalities characteristic of autoimmune DI, including a thick- ened pituitary stalk and loss of the posterior pituitary hyperintensi- ty on T1-weighted magnetic resonance imaging (MRI). 6 However, MRI appearances are nonspecific, as the intensity of the posterior pituitary signal decreases with age in normal subjects. 7 The results of a study of a paediatric cohort with idiopathic DI showed that nine of 12 children demonstrated plasma anti-AVP antibodies, 8 with the authors suggesting an autoimmune aetiology for DI in these patients. A further study in a cohort of childhood- onset DI, of autoimmune or idiopathic aetiology, reported a high incidence of anterior pituitary hormone deficiencies, particularly growth hormone (GH) deficiency. 9 This prompted the suggestion that, in children, autoimmune DI might be one manifestation of a more widespread autoimmune process including autoimmune anterior pituitary failure. The authors also suggested that children with DI should be routinely screened for anterior pituitary hor- mone deficiencies. Our clinical impression was that anterior hypopituitarism was rare in adults with idiopathic DI, although other autoimmune diseases such as thyroid dysfunction were common. However, as the implica- tions for investigation of adult patients with DI were significant, we, therefore, tested this hypothesis by retrospectively reviewing the results of dynamic anterior pituitary hormone testing in a large cohort of adults with idiopathic CDI from two centres with a special interest in disorders of water balance. We also retrospectively exam- ined our cohort for the presence of autoimmune endocrine disease. Correspondence: Mark J. Hannon, Academic Department of Endocrinol- ogy, Beaumont Hospital/RCSI Medical School, Dublin 9, Ireland. Tel.: 00353 86 8641152; Fax: 00353 1 8376501; E-mail: markjhannon2002@ yahoo.co.uk Clinical Endocrinology (2012) 76, 725–728 doi: 10.1111/j.1365-2265.2011.04270.x Ó 2012 Blackwell Publishing Ltd 725