Diagnóstico precoz de secreción autónoma de cortisol en pacientes con incidentalomas adrenales "no funcionantes"

Résumé

Adrenal incidentalomas (AI) are one of the most frequent consultations in Endocrinology. In all patients with a newly diagnosed AI, two fundamental aspects should be assessed: a) its benign or malignant nature; and b) its functionality. Autonomous cortisol secretion (ACS) is present in up to 50% of Ais and it is associated with increased morbidity and mortality. However, currently available hormonal tests to establish ACS diagnosis present multiple limitations. Moreover, a higher cardio-metabolic and mortality risk has been observed in apparently non-functioning AIs than in the general population. This could be justified by incipient alterations in cortisol metabolism undetected by classical tests. Over time, these alterations may progress, thus becoming detectable. This possibility requires reassessing the autonomous cortisol secretion periodically in patients with non-functioning AIs (NFAIs). Therefore, it would be desirable to identify precise markers of early alterations in cortisol secretion with possible cardio-metabolic repercussions; and clinical, radiological and/or biochemical markers associated with an increased risk of ACS development in patients with NFAIs. This thesis found that some clinical, biochemical, and radiological characteristics allow stratifying the risk of developing ACS in NFAI. The best predictive model for the development of ACS during follow-up combined the variables age, serum cortisol level after a 1 mg dexamethasone suppression test (DST), and the bilaterality of the AI at the time of diagnosis. Patients under 50 years of age with unilateral tumors and post-DST cortisol values <0.45 µg/dl had the lowest risk for developing ACS during follow-up (2%). Moreover, the study of the urinary steroid profile found a lower excretion of androgen metabolites and a higher excretion of urinary free cortisol in patients with NFAI than in patients without adrenal tumors. These findings suggest that NFAI have subtle abnormalities in the steroid secretion, detected by urinary metabolites, which could explain the observed increased cardiometabolic risk of these patients. The results of this thesis suggest that clinical, biochemical, and radiological information can be integrated to improve diagnosis and to individualize management of patients with NFAI, according to the risk for developing ACS.