Análise do fluxo salivar e do perfil de citocinas inflamatórias em adultos com acromegalia

Abstract

Introduction: Acromegaly is a rare endocrine disorder caused by the hypersecretion of growth hormone and insulin-like growth factor 1, resulting from a pituitary tumor. Chronic exposure to excessive levels of these hormones leads to physical, body, and orofacial changes, as well as systemic, cardiological, metabolic, respiratory, musculoskeletal, neurological, neoplastic, and immunological alterations. Despite the significant negative impact on the quality of life of these individuals, little is known about how these changes affect the oral health of acromegalic patients. Objectives: Therefore, this study aimed to evaluate the salivary flow and inflammatory biomarkers present in the saliva of patients with acromegaly. In Chapter I, the goal was to investigate the levels of unstimulated (USF) and stimulated salivary flow (SSF) in acromegalic patients and identify possible clinical factors associated with increased salivary flow in this population. In Chapter II, the objective was to investigate the levels of pro- and anti-inflammatory cytokines in the saliva of adults with acromegaly. Method: A case-control study was conducted with two groups: one consisting of patients diagnosed with acromegaly and the other as a control group. Sociodemographic variables, lifestyle habits, and diabetes diagnosis were collected. Anthropometric measurements, including body mass index (BMI), cervical circumference (CC), and abdominal circumference (AC), were also recorded, along with saliva samples for cytokine quantification (IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-22, TGF-α, and TNF-α). USF and SSF were measured and analyzed as outcome variables. Independent T-tests, Pearson's correlation, and multivariate regression models were used in statistical analysis, adopting a significance level of 5%. For the analysis of inflammatory biomarkers, Mann-Whitney tests, Spearman’s correlation, and ROC curve analysis were performed. Results: When evaluating salivary flow, it was observed that the USF level was significantly higher in the acromegaly group compared to the controls (0.50 ml/min vs. 0.22 ml/min, P < 0.001). SSF showed a direct correlation with CC measurements (r = 0.470, P = 0.010). Acromegaly was associated with higher USF even after adjusting for confounding factors (Coefficient = 0.903, P < 0.001). Regarding inflammatory biomarkers, the results showed that acromegalic patients had significantly higher levels of IL-4, IL-6, IL-10, IL-17A, TGF-α, and TNF-α in their saliva compared to controls (P < 0.001). No significant differences were observed for IL-1β and IL-22 levels. The analysis of cytokine ratios, such as IL-

22/IL-4 (P < 0.001), IL-1β/IL-10 (P = 0.023), and IL-22/IL-10 (P = 0.003), indicated a more pronounced inflammatory profile in patients with acromegaly compared to controls. A strong positive correlation was also observed between IL-4 and IL-22 (Rho = 0.933; P < 0.001) and between IL-6 and TNF-α (Rho = 0.826; P < 0.001) in the acromegaly group. The differences in anti-inflammatory cytokine levels remained significant after adjusting for confounding variables such as age, gender, and diabetes. Conclusion: Quantitative and qualitative changes in the saliva of patients with acromegaly were observed, which may have implications for their oral and general health. Therefore, further studies are needed so that this information can serve as a strategy for more effective clinical monitoring of these patients.