Endocrine Abstracts

Context: Acromegaly is associated with several metabolic and cardio-respiratory comorbidities, with a relative increase in the last years of cancer mortality. Although the GH/ IGF-1 axis has long been supposed to play a role on immune modulation, immune function in acromegaly is poorly known.

Objective: This observational, prospective, single site, pilot study (NCT05069324) aims to analyse peripheral blood mononuclear cells (PBMCs) subpopulations in acromegalic patients and the potential impact of disease control and different medical treatments.

Methods: Twenty-nine patients with active acromegaly (16M and 13F, mean age 51.3±15.6 years) (ACRO) have been enrolled - 4 naïve, 15 on somatostatin analogs (SSA), 10 on pegvisomant monotherapy or combined with SSA - and compared with 25 sex- and age-matched control subjects (CTRL). Anthropometric, metabolic, and hormonal parameters were recorded along with full quantification of PBMCs (monocytes, lymphocytes, and natural killer/NK cells) by flow cytometry. Monocytes (MONO) were further divided into classical (CD14++CD16-), intermediate (CD14+CD16+) and non-classical (CD14+CD16++). NK cells were also divided into CD56^dim and CD56^bright, which are respectively characterized by a relatively higher naturally cytotoxic activity or cytokine production. Data are expressed as median (IQR) and non-parametric tests were used for statistical analysis.

Results: Compared with CTRL, ACRO had higher levels of fasting blood glucose (P=0.001), HbA1c (P=0.001) and BMI (P=0.015) and a higher prevalence of cardio-metabolic comorbidities. ACRO had significantly lower total MONO [197 (101-355) vs 334 (279-411) cells/μL, P=0.049], with a lower percentage of intermediate [2.9 (1.5-4.8) vs 7.3 (5.5-10.4) %, P<0.001] but an increased percentage of non-classical MONO [7.9 (5.3-11.37) vs 1.7 (1.0-3.3) %, P<0.001]. Moreover, ACRO had a significantly lower total number of NK [123 (62-261) vs 279 (198-410) cells/μL, P=0.003], with a lower percentage of CD56^bright [0.8 (0.1-2.9) vs 7.8 (6.9-10.2) %, P<0.001] but a higher percentage of CD56^dim [99.0 (97.3-99.8) vs 91.3 (88.2-92.8) %, P<0.001], and similar T and B-lymphocytes. No significant differences were found according to disease control and medical treatment in ACRO.

Conclusions: To the best of our knowledge, this is the first evidence of a peculiar immunological fingerprint in acromegaly, with a reduced number of MONO and NK cells and an imbalance of immune innate cells subsets. No major impact of disease control and treatment was found in this series. This suggests that immune function should be further investigated in acromegalics, particularly in view of their higher oncological risk.