Azathioprine as an alternative treatment in primary hypophysitis L. Papanastasiou • T. Pappa • V. Tsiavos • E. Tseniklidi • I. Androulakis • G. Kontogeorgos • G. Piaditis Ó Springer Science+Business Media, LLC 2010 Abstract Primary hypophysitis (PH) is an unusual dis- order characterized by inflammatory infiltration of the pituitary gland with various degree of pituitary dysfunc- tion. Glucocorticoids are the treatment of choice in the majority of patients. Still, in patients with poor response in glucocorticoids or when their administration is accompa- nied with serious side effects, the use of alternative agents should be considered; up to now, data on other therapeutic approaches remains scant mainly due to the rarity of the disease. Among them, the immunosuppressant azathioprine could represent an effective and safe alternative. In this article, we present our clinical experience of two cases with PH successfully treated with azathioprine following serious side effects after initial treatment with glucocorticoids and provide a brief review of the existing literature. Keywords Pituitary gland Á Primary hypophysitis Á Azathioprine Á Glucocorticoids Introduction Primary hypophysitis (PH) is an uncommon disorder char- acterized by focal or diffuse inflammatory infiltration of the pituitary gland. It is commonly presented as a sellar mass difficult to differentiate from other space-occupying lesions. In clinical practice, the diagnosis of PH is actually made after excluding all other causes of hypophysitis. Secondary hypophysitis can either occur in patients with systemic disease or infections (sarcoidosis, Wegener granulomatosis, histiocytosis, tuberculosis, syphilis) or it can originate from neighboring lesions (germinomas, Rathke’s cleft cysts, craniopharyngiomas and pituitary adenomas) [1]. Under the term PH three histopathologic subtypes can be recognized: lymphocytic (LH), granulomatous (GH) and xanthomatous hypophysitis (XH), whereas according to some investigators xanthogranulomatous and necrotizing hypophysitis should also be added in the PH classification [2–5]. In histological examination, the adenohypophysis shows a lymphocytic infiltration variably associated with destruction and fibrosis of the parenchyma. As a rule, there is an overlap among different types of hypophysitis [5]. A variety of clinical manifestations has been described including symptoms of sellar compression (headache, visual disturbances and decreased acuity and more rarely diplopia) and of anterior and posterior pituitary deficiency. Interestingly, ACTH deficiency usually occurs first -and in some cases solely- followed by impairment of the thyro- troph and gonadotroph cells, whereas mild hyperprolacti- nemia is also commonly observed. Common features in PH and sometimes adjuncts to the differential diagnosis (DD) are the discordance between the neuroimaging findings and the pituitary hormonal deficiencies, as well as the sudden onset of diabetes insipidus seen in 14–20% of lymphocytic hypophysitis cases [6, 7]. The natural history of PH is incompletely understood and varies from spontaneous partial or total remission of the pituitary function [8, 9] to permanent pituitary failure [10]. For this reason, conservative management with a watch n’ wait strategy is required in subclinical cases or where L. Papanastasiou (&) Á T. Pappa Á V. Tsiavos Á E. Tseniklidi Á I. Androulakis Á G. Piaditis Department of Endocrinology and Diabetes Center, Athens General Hospital ‘‘G. Gennimatas’’, 154 Mesogion Avenue, 11527 Athens, Attika, Greece e-mail: linapapan@yahoo.gr G. Kontogeorgos Department of Pathology, Athens General Hospital ‘‘G. Gennimatas’’, Athens, Greece 123 Pituitary DOI 10.1007/s11102-010-0252-5