Evaluation of Plasma ACTH Concentration in Patients with Adrenal Incidentaloma: A Predictor of Hypothalamic-Pituitary-Adrenal Axis Suppression following the 1 mg Dexamethasone Suppression Test

• Grant number: 24/14841-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2024
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Maria Candida Barisson Villares Fragoso
• Grantee: Yolanda Maria Teixeira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Adrenal incidentalomas (AI) are adrenal masses larger than 1 cm, incidentally discovered during imaging studies conducted to investigate conditions unrelated to the adrenal glands. Most of these masses are composed of benign adrenocortical adenomas, which can be non-functioning or associated with autonomous cortisol secretion, ranging from clinically evident Cushing's syndrome to subclinical autonomous cortisol secretion (MACS). The prevalence of AI increases with age, being more common in white women and in patients over 50 years old. These adenomas account for 80% to 96% of AI, and MACS is the most common hormonal abnormality, occurring in 19% to 50% of cases.Given the increased detection of these incidentalomas and their potential complications, it is crucial to advance the understanding of the diagnostic and therapeutic characteristics associated with hypercortisolism. The proposed research primarily aims to evaluate the response to the 1 mg dexamethasone suppression test (1 mg-DST), a crucial examination in AI investigation and in confirming autonomous cortisol secretion. The study seeks to understand the variability of results and establish reference intervals for post-DST cortisol concentrations, as well as assess whether ACTH levels can reliably indicate that the patient took dexamethasone correctly.Furthermore, the research aims to verify if the cortisol suppression test is a reliable method to assess adrenal function in response to ACTH, and describe the clinical implications of these results. Another important goal is to identify the patient population in which post-DST cortisol measurement offers greater diagnostic value, particularly concerning the confirmation of hypercortisolism. The study also intends to explore the relationship between the cortisol/cortisone ratio in 24-hour urine, measured by mass spectrometry, and the clinical status of the patients.Data collection will be carried out retrospectively and prospectively through the analysis of medical records from patients at the Hospital das Clínicas Complex of the University of São Paulo School of Medicine (HC FMUSP) and the Cancer Institute of the State of São Paulo (ICESP), who have undergone the 1 mg-DST since 2016. The analysis will include demographic parameters such as age group, sex, body mass index (BMI), weight, and race, to assess the prevalence of AI and its diagnosis of hypercortisolism according to the criteria of the European Society of Endocrinology (ESE). The methodology includes administering 1 mg of oral dexamethasone at 11 p.m., with serum cortisol measurement at 8 a.m. the following day. Other hormonal markers, such as ACTH, dehydroepiandrosterone sulfate (DHEAS), renin, aldosterone, and 24-hour urinary cortisol will also be analyzed.Expected outcomes include improved diagnosis of conditions related to hypercortisolism, allowing for more accurate identification of disorders such as Cushing's syndrome or adrenal insufficiency. Understanding the relationships between ACTH and cortisol can contribute to the development of more effective and individualized protocols and tests, promoting a more personalized diagnostic and therapeutic approach tailored to the needs of patients.Another expected impact is a deeper understanding of the mechanisms regulating cortisol in response to ACTH, expanding the understanding of stress physiology and its implications for human health. This could influence the clinical management of patients with AI, providing valuable insights for research in endocrinology and adrenal pathophysiology. The research intends to disseminate the findings at conferences and submit them to scientific publications, contributing to the advancement of knowledge in the field of endocrinology.