Circulating immune cell profile in patients with acromegaly: results from the PROMISE, a prospective clinical trial

Objective: Although GH and IGF-1 have long been proposed to play a role in immune-modulation, the circulating immune cell phenotype in acromegaly (ACRO) is poorly understood. Design: This observational, prospective, single-site clinical trial (NCT05069324) analyzed peripheral blood mononuclear cell (PBMC) subpopulations in ACRO, investigating the role of disease control, pharmacological treatments, and metabolic profile. Methods: Sixty consecutive patients with ACRO (34 males, mean age 54.7 ± 15) attending an outpatient visit between July 2020 and December 2024 were enrolled. Patients were compared with two populations: 40 healthy controls (CTRL) and 40 patients with type 2 diabetes (T2DM), with no significant differences in age or sex. An 8-week follow-up evaluation was performed and compared among patients according to the introduction or changes in their pharmacological treatment. Results: Compared with CTRL, ACRO patients had lower total monocytes with a decreased percentage of classical and an increased proportion of non-classical subsets. There were fewer NK cells, with higher CD56dim and lower CD56bright subpopulations, and similar T and B lymphocytes. Compared with T2DM, ACRO showed lower total monocytes, with higher classical and lower non-classical subsets, as well as lower NK cells and B lymphocytes. In the short-term, treatment appeared unable to restore immune cell profile but partially affected the distributions of innate immune cells subpopulations. Conclusions: This is the first evidence of a distinct immunological pattern in ACRO that is independent of glucose metabolism. The immune signature may contribute to the persistence of cardio-metabolic and oncological risk observed in ACRO, even when the disease is adequately controlled by medical treatment.