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Growth hormone (GH), mostly through its peripheral mediator, the insulin-like growth factor 1(IGF1), in addition to carrying out its fundamental action to promote linear bone growth, plays an important role throughout life in the regulation of intermediate metabolism, trophism and function of various organs, especially the cardiovascular, muscular and skeletal systems. Therefore, if a prepubertal GH secretory deficiency (GHD) is responsible for short stature, then a deficiency in adulthood identifies a nosographic picture classified as adult GHD syndrome, which is characterized by heart, muscle, bone, metabolic and psychic abnormalities. A GHD may occur in patients with pituitary autoimmunity; moreover, GHD may also be one of the features of some genetic syndromes in association with other neurological, somatic and immune alterations. This review will discuss the impact of pituitary autoimmunity on GHD and the occurrence of GHD in the context of some genetic disorders. Moreover, we will discuss some genetic alterations that cause GH and IGF-1 insensitivity and the arguments in favor and against the influence of GH/IGF-1 on longevity and cancer in the light of the papers on these issues that so far appear in the literature.

Background: Autoimmune hypophysitis is a frequent immune-related adverse event (irAE) in cancer patients treated with immunecheckpoint inhibitors. Studies seeking anti-pituitary (APA) and anti-hypothalamus (AHA) antibodies in patients treated with anti-PD-1 and anti-PD-L1 are scarce. The aim of this study is to search for APA and AHA and related pituitary dysfunction in patients treated with these agents. Methods:Cross-sectional and preliminary longitudinal studies were conducted at the Medical Oncology Unit and Endocrinology and Metabolic Diseases Unit of the University of Campania “Luigi Vanvitelli”. Fifty-four cancer patients on treatments with anti-PD-1 or anti-PD-L1 (Group 1) and 50 healthy controls were enrolled for a cross-sectional study, 13 cancer patients (Group 2) were enrolled for our preliminary longitudinal study. APA/AHA titers and changes in biochemical and hormonal profile were evaluated in Group 1, in Group 2, they were evaluated before and after nine weeks from the start of immunotherapy. Results: Patients of Group 1 showed a higher prevalence of APA and AHA than controls: 21 of them had APA, 16 had AHA, and 11 had both autoantibodies. In total, 7 of 13 patients in Group 2 became APA-positive and 3 became AHA-positive after nine weeks of immunotherapy, showing an increase in prolactin and a decrease in ACTH and IGF-1 levels compared with basal values. Conclusions:Anti-pituitary and anti-hypothalamus antibodies seem to play a pivotal role in hypothalamic–pituitary autoimmunity and secondary endocrine-related alterations evoked by anti-PD-1 and PD-L1 antibodies.

The role of antipituitary antibodies in the pathophysiology of pituitary hormone deficiency has been increasingly elucidated over the last decade. Prader-Willi syndrome is a genetic disorder which includes hypothalamic/pituitary dysfunction as one of its main features. We looked for autoimmune pituitary involvement in 55 adults with Prader-Willi syndrome, discovering that about 30% of them have a positive titer of antipituitary antibodies. Although the presence of these autoantibodies could only be an "epiphenomenon", our results suggest that autoimmune mechanisms might contribute, at least in part, to the pituitary impairment of Prader-Willi syndrome, and in addition to genetically determined dysfunction of the central nervous system. This paper provides a new perspective on pituitary impairment in these patients, suggesting that the search for hypophisitis could be a reasonable and interesting field for further research.

Hyperprolactinemia is often observed in lymphocytic hy- pophysitis (LYH). To clarify the possible autoimmune pituitary involve- ment in patients with apparently idiopathic hyperprolactinemia we inves- tigated the presence of antipituitary antibodies (APA) in hyperprolactine- mic patients with idiopathic hyperprolactinemia and in those with pro- lactinoma. Sixty-six hyperprolactinemic patients (52 F, 14 M age range 28-42 years, group1) were studied. Of them, 34 out of 66 showed clinical features of hyperprolactinemia and subsequently underwent cabergoline therapy; the 32 out of 66 patients without symptoms of hyperprolactine- mia did not receive cabergoline therapy. Moreover, 32 patients (24 F/8M, age range 23-44 years) with hyperprolactinemia due to microprolacti- noma (group 2) were also studied. APA, by immunofluorescence method, and anterior pituitary function were evaluated in both groups of patients. APA were present in 17 out of 66 (25.7%) patients in group 1 with titers ranging from 1/16 to 1/64. All patients of group 2 were considered APA negative because these antibodies were found at low titer (≤1:4) only in five of them. With regard to the function of other pituitary hormones, all APA-negative patients in group 1 and in group 2 showed a normal pituitary function; instead, a partial anterior pituitary impairment was observed in 6 out of 17 (35.3%) APA-positive patients. In asymptomatic patients with apparently idiopathic hyperprolactinemia, APA detection could be useful to disclose forms of potential/subclinical stage of LYH. A future longitudinal study of these patients submitted to cabergoline therapy or free of therapy may be helpful to clarify this assumption.