Introduction. Adrenal incidentalomas (AI) are adrenal tumors detected by diagnostic imaging not performed for suspected adrenal disease. In the first and the second part of the thesis we focus on the tumors of adrenal cortex – nonfunctional adrenal incidentaloma (NFAI) and adenomas with mild autonomous cortisol excess (MACE), in the third part to the tumors of adrenal medulla – pheochromocytomas (PHEO) and paragangliomas (PGL) and hormonal activity of the adrenal medulla. The aim of the research work was to evaluate the impact of selected clinical features and parametrs influencing the prevalence, growth and hormonal activity of these tumors.
Hypotheses. The research work consists of three interrelated parts. In the first part we investigated the association between the incidence of AI and body mass index (BMI). In the second part we examined whether basline BMI of participants affects the growth and occurrence of hormonal activity of NFAI after long term follow up. In the third part we compared the incidence of PHEO and/or PGL in patients with cyanotic congenital heart defect (CHD) with the incidence in patients with acyanotic CHD and examined whether the incidence of PGL and/or PHEO was associated with chronic hypoxic stress.
Methods. In the first part we conducted a retrospective study including participants hospitalized because of AI from January 2005 to January 2012. In the second part we conducted a 10-year longitudinal observational study, in which we included 67 subjects from the first part. In the third part we compared patients with cyanotic and acyanotic CHD in a cross-sectional study.
Results. In the first part 290 subjects with NFAI and 142 with MACE were identified. The prevalence of AI, including NFAI and MACE was 68-87 % higher in subjects with obesity and overweight compared to subjects with normal body weight across all age groups. In the second part 15 (22.4 %) out of 67 subjects with NFAI developed MACE (p < 0.001) in 10.5 (9.1–11.9) years of follow-up. The incidence of progression was significantly higher in subjects with overweight and obesity than in subjects with baseline BMI < 25 kg/m2 (p = 0.016 in both groups with BMI > 25 kg/m2). The development of NFAI hormonal activity was more common in NFAIs, with baseline cortisol levels after 1 milligram dexamethasone test (DST) of more than 30 nmol/L. An increase in NFAI was recorded in 38 (56.7 %) subjects, a clinically significant increase in tumor size (䁥 10 mm) in 6 subjects (8.9 %). No significant correlations were observed between tumor growth (NFAI) and baseline size or BMI (p > 0.05). No statistically significant association between Homeostatic model assessment for insulin resistance (HOMAIR) and tumor size was found (ρ = -0.079, p = 0.561). No statistically significant association between waist circumference and tumor size was found (ρ = -0.052, p = 0.728). In the third part statistically significantly higher plasma levels of normetanephrine (p = 0.002) were observed in patients with cyanotic CHD compared to patients with acyanotic CHD. Correlation analysis confirmed the association between normetanephrine plasma levels and proBNP (ρ = 0.449, p = 0.002) and saturation (ρ = -0.444, p = 0.003).
Conclusions. We demonstrated a positive association between the incidence of adrenal tumors and higher BMI in NFAI and MACE. We found that BMI of participants at the time of NFAI presentation did not affect adrenal cortex tumor growth and that higher baseline BMI was associated with higher probability for the development of autonomic glucocorticoid AI activity (MACE) over a 10-year observational period. In addition, progress was found to be more frequent when baseline cortisol levels after a 1 mg DST was > 30 nmol/L. Insulin resistance measured by HOMAIR and waist circumference were not related to tumor size. Hormonal activity of adrenal medulla and/or PGL were significantly higher in patients with cyanotic CHD than patients with acyanotic CHD. The association between normetanephrine plasma levels and saturation and proBNP was statistically significant.
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