Phd in ENDOCRINOLOGICAL SCIENCES

Thesis title: Exploring sex differences in cardiometabolic complications of females and males with non-aldosterone cortical adrenal adenomas

Nowadays, gender medicine is crucial for personalized healthcare, recognizing and addressing unique health needs based on biological and social differences between males and females, advancing overall clinical understanding and improving patient outcomes. As a result of the widespread use of abdominal imaging adrenal incidentalomas are estimated to be discovered in approximately 5-7% of the general population, making this condition one of the most common in endocrinology. This study represents the first comprehensive examination of sex-related patterns of cardiometabolic comorbidities in a cohort of 107 patients with non-aldosterone cortical adrenal adenomas. The study carefully addressed confounding factors related to menopausal status and age, by selecting a cohort of postmenopausal women and men between 50 and 80 years. The cohort analysis revealed notable sex-specific differences in cardiometabolic comorbidities, particularly in the context of Mild Autonomous Cortisol Secretion (MACS), an asymptomatic condition characterized by mild hypercortisolism without typical signs and symptoms of Cushing’s Syndrome. Females with adrenal incidentaloma and MACS exhibited higher alterations in coagulation pathways, higher total and HDL cholesterol, and a higher frequency of obesity detected with Dual-Energy X-ray Absorptiometry (DXA) compared to males. In terms of body composition, DXA analysis unveiled that dehydroepiandrosterone sulfate (DHEAS) emerged as a potential influencer of body composition, exhibiting an inverse correlation with total fat mass, body fat percentage, and trunk fat percentage in overall cohort. Dividing the population by sex, these correlations remained significant only in females, highlighting a possible role of adrenal androgens in female body composition in menopause. Within the MACS group, females also demonstrated significant disparities in adrenal tumor diameter and cortisol secretion, emphasizing the potential clinical relevance of sexual dimorphism in adrenal tumors. In contrast, males with adrenal incidentaloma showed higher rates of impaired fasting glucose, impaired glucose tolerance, and lower insulin sensitivity than females. Despite limitations in sample size and the observational nature of the study, its strength lies in providing a comprehensive overview of cardiometabolic complications affecting patients with adrenal incidentaloma, considering sex differences and cortisol secretion. The findings underscore the importance of sex-specific considerations in the evaluation and management of adrenal incidentalomas, paving the way for further research to refine risk stratification and tailored treatment approaches.