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

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.

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.

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.

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.

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.