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Purpose: This publication reviews the accepted knowledges and the findings still discussed on several features of autoimmune hypophysitis, including the most recently described forms, such as IgG4 and cancer immunotherapy- related hypophysitis. Methods: The most characteristic findings and the pending controversies were derived from a literature review and previous personal experiences. A single paragraph focused on some atypical examples of the disease presenting under confounding pretences. Results: Headache, visual field alterations and impaired pituitary secretion are the most frequent clinical findings of the disease. Pituitary biopsy, still considered the gold diagnostic standard, does not always receive consent from the patients. The role of magnetic resonance imaging is limited, as this disease may generate images similar to those of other diseases. The role of antipituitary and antihypothalamus antibodies is still discussed owing to methodological difficulties and also because the findings on the true pituitary antigen(s) are still debated. However, the low sensitivity and specificity of immunofluorescence, one of the more widely employed methods to detect these antibodies, may be improved, considering a predetermined cut-off titre and a particular kind of immunostaining. Conclusion: Autoimmune hypophysitis is a multifaceted disease, which may certainly be diagnosed by pituitary biopsy. However, the possible different clinical, laboratory and imaging features must be considered by the physician to avoid a misdiagnosis when examining a possibly affected patient. Therapeutic choice has to be made taking into account the clinical conditions and the degree of hypothalamic-pituitary involvement, but also considering that spontaneous remissions can occur.

The interrelationship between prolactin (PRL) and the immune system have been elucitaded in the last decade, opening new important horizons in the field of the immunoendocrinology. PRL is secreted not only by anterior pituitary gland but also by many extrapituitary sites including the immune cells. The endocrine/paracrine PRL has been shown to stimulate the immune cells by binding to PRL receptors. Increased PRL levels, frequently described in autoimmune diseases, could depend on the enhancement of coordinated bi-directional communications between PRL and the immune system observed in these diseases. Hyperprolactinemia has been described in the active phase of some non organ-specific autoimmune diseases, as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and organ-specific autoimmune diseases, as celiac disease, type 1 diabetes mellitus, Addison's disease, autoimmune thyroid diseases. In these diseases PRL increases the syntesis of IFNgamma and IL-2 by Th1 lymphocytes. Moreover, PRL activates Th2 lymphocytes with autoantibody production. Of particular interest is the association between hyperprolactinemia and levels of anti DNA antibodies, islet cell antibodies (ICA), thyreoglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb), adrenocortical antibodies (ACA), transglutaminase antibodies (tTGAb) in SLE, in type 1 diabetes mellitus, in Hashimoto's thyroiditis, in Addison's disease and in celiac disease, respectively. High levels of PRL have been also frequently detected in patients with lymphocytic hypophysitis (LYH). Several mechanisms have been invoked to explain the hyperprolactinemia in LYH. The PRL increase could be secondary to the inflammatory process of the pituitary gland but, on the other hand, this increase could have a role in enhancing the activity of the immune process in LYH. Moreover, the detection of antipituitary antibodies targeting PRL-secreting cells in some patients with idiopathic hyperprolactinemia suggests the occurrence of a possible silent LYH in these patients. Finally, the role of anti-prolactinemic drugs to inactivate the immune process in LYH is still discussed.