Validation of nanoparticle-based steroid biosensor for diagnosis of primary hyperaldosteronism.

• Grant number: 25/03865-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2025
• End date: April 30, 2027
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Madson Queiroz Almeida
• Grantee: Daniel Temponi Lebre
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 24/04349-2 - Continuous steroid monitoring in interstitial fluid with wearable and nanoparticle-enhanced biosensors for improved management of adrenal disorders, AP.TEM

Abstract

The adrenal steroids cortisol and aldosterone are critical components of the endocrine system. Deficiency of these hormones can cause life-threatening adrenal crisis, while excess production of cortisol or aldosterone leads to cardiovascular complications (e.g., hypertension and heart failure), metabolic and psychological disorders. These complications are potentially preventable if adrenal diseases are diagnosed and treated early. However, currently available diagnostic methods are often inefficient, as they rely on occasional and often random measurements of steroids, which have limited diagnostic and prognostic value, since serum steroid concentrations fluctuate throughout the day (circadian rhythm). We recently demonstrated high intra-individual variability in aldosterone measurements in a large cohort of patients with primary hyperaldosteronism, which directly impacts the diagnosis of aldosterone excess1. The high intraindividual coefficient of variation of aldosterone resulted in a high rate of false-negative tests in a single blood collection. Increasing the number of aldosterone/renin ratio measurements improved the sensitivity of diagnosing primary aldosteronism from 86% to 98.4%. More promising for steroid monitoring is interstitial fluid as it reflects the composition of the blood due to continuous mass transfer. Recently, Uptonet al.2 evaluated steroid concentrations in interstitial fluid using a microdialysis catheter implanted subcutaneously to collect interstitial fluid with an infusion pump in 214 healthy volunteers. Steroid analysis was performed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). There was a significant correlation between serum and interstitial aldosterone concentrations. However, the dynamics of aldosterone secretion in interstitial fluid has not been evaluated in patients with primary hyperaldosteronism. In phase 3 of this proposal, biosensors based on nanoparticles functionalized by aptamers will be developed for continuous and real-time quantification of cortisol and aldosterone in interstitial fluid. The objective of this project is to validate the continuous monitoring of interstitial cortisol through this biosensor for the diagnosis of primary hyperaldosteronism. Continuous measurement of interstitial cortisol concentrations via the wearable biosensor will be evaluated over a 48h period in 32 healthy controls and 32 patients with primary hyperaldosteronism. On the second day of continuous monitoring with the biosensor, exogenous ACTH stimulation test and saline infusion test will be performed on all individuals. The total area under the curve (AUC) of aldosterone concentrations, morning peak and evening nadir of continuous interstitial aldosterone measurements will be calculated for each patient during the 48h period of biosensor use. These measurements will be compared between patients with primary hyperaldosteronism and healthy controls to determine the diagnostic applications of continuous aldosterone monitoring.