Abstract
Purpose: To detect the presence of antipituitary (APA) and antihypothalamus antibodies (AHA) in subjects treated for brain cancers, and to evaluate their potential association with pituitary dysfunction.Methods: We evaluated 63 patients with craniopharyngioma, glioma, and germinoma treated with surgery and/or radiotherapy and/or chemotherapy at a median age of 13 years. Forty-one had multiple pituitary hormone deficiencies (MPHD), six had a single pituitary defect. GH was the most common defect (65.1%), followed by AVP (61.9%), TSH (57.1%), ACTH (49.2%), and gonadotropin (38.1%). APA and AHA were evaluated by simple indirect immunofluorescence method indirect immunofluorescence in patients and in 50 healthy controls.Results: Circulating APA and/or AHA were found in 31 subjects (49.2%) and in none of the healthy controls. In particular, 25 subjects out of 31 were APA (80.6%), 26 were AHA (83.90%), and 20 were both APA and AHA (64.5%). Nine patients APA and/or AHA have craniopharyngioma (29%), seven (22.6%) have glioma, and 15 (48.4%) have germinoma. Patients with craniopharyngioma were positive for at least one antibody in 39.1% compared to 33.3% of patients with glioma and to 78.9% of those with germinoma with an analogous distribution for APA and AHA between the three tumors. The presence of APA or AHA and of both APA and AHA was significantly increased in patients with germinoma. The presence of APA (P = 0.001) and their titers (P = 0.001) was significantly associated with the type of tumor in the following order: germinomas, craniopharyngiomas, and gliomas; an analogous distribution was observed for the presence of AHA (P = 0.002) and their titers (P = 0.012). In addition, we found a significant association between radiotherapy and APA (P = 0.03).Conclusions: Brain tumors especially germinoma are associated with the development of hypothalamic–pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.
Highlights
Hypothalamic–pituitary (HP) dysfunction in subjects with intracranial mass involving the sellar and parasellar region may be due to several causes including the local compressive effect, inflammation, and or infiltration by the primary lesion, neurosurgery, and or radiotherapy [1]
Both lymphocytic hypophysitis with central diabetes insipidus (CDI) and subsequent hypopituitarism masking a suprasellar germinoma, and isolated lymphocyte infiltration of pituitary stalk preceding the diagnosis of germinoma were reported [2,3,4]
Antipituitary antibodies (APA) and antihypothalamus (AHA) are often seen in patients with different pituitary pathologies including hypopituitarism, central hypothyroidism, acromegaly, adenomas, CDI, and in patients with Prader–Willi syndrome associated with hypothalamic dysfunction [13,14,15,16,17,18,19,20,21]
Summary
Hypothalamic–pituitary (HP) dysfunction in subjects with intracranial mass involving the sellar and parasellar region may be due to several causes including the local compressive effect, inflammation, and or infiltration by the primary lesion, neurosurgery, and or radiotherapy [1]. Inflammatory lesions of the pituitary/pituitary stalk/hypothalamus including the chronic lymphoplasmacytic process known as lymphocytic infundibulo-hypophysitis, autoimmune hypophysitis, granulomatous inflammation, and xanthomatous hypophysitis [1, 11, 12] may raise diagnostic difficulties with tumors like germinomas. Both lymphocytic hypophysitis with central diabetes insipidus (CDI) and subsequent hypopituitarism masking a suprasellar germinoma, and isolated lymphocyte infiltration of pituitary stalk preceding the diagnosis of germinoma were reported [2,3,4]. A mouse model of autoimmune hypophysitis showed endocrine dysfunction and disease progression associated with pituitary expansion followed by pituitary atrophy, suggesting the existence of a relationship between autoimmunity and endocrinopathy [22]
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