# Primary Aldosteronism Subtypes: Pathophysiology and Steroid Signatures

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $751,696

## Abstract

ABSTRACT
 Primary aldosteronism (PA) is the most common adrenal disorder and the most common cause of
endocrine hypertension. PA is associated with cardiovascular morbidity and mortality that are disproportionately
higher compared to those observed in patients with similar degree of essential hypertension. The two major
types of PA are unilateral PA (typically an aldosterone producing adenoma, APA, ~40% of PA cases), which can
be cured with surgery, and bilateral hyperaldosteronism (BHA, ~60% of PA cases), which requires life-long
targeted medical therapy. Despite its high prevalence and serious cardio-renal complications, PA is
underdiagnosed, in part because the steps for diagnosis and subtyping are complicated, costly, and invasive.
Adrenal imaging is inaccurate in identifying the source(s) of excessive aldosterone production. Consequently,
the current standard-of-care for PA subtyping is adrenal vein sampling (AVS), which is an invasive, technically
challenging, and poorly standardized procedure, with availability limited to tertiary referral centers.
 The overall objectives of this application are: 1) to define the steroid synthetic capacity of various APAs
by implementing comprehensive histologic, genomic and steroid profiling analyses of APA tissue; 2) combine
baseline and dynamic blood tests to define the steroid signatures of PA subtypes in peripheral blood. This
approach will eliminate the need for AVS in over 60% PA patients (BHA). Two specific aims have been designed
to address critical gaps in the care of PA patients. • In Aim 1, we will probe the working hypothesis that APAs
with distinct underlying aldosterone-driver somatic mutations have specific steroid fingerprints. We will implement
CYP11B2 immunohistochemistry-guided next-generation sequencing (NGS) to characterize the somatic
mutations underlying APAs. In parallel, we will use state-of-the-art mass spectrometry to define the steroid
profiles of APAs from: (a) optimal cutting temperature (OCT)-embedded APA tissue; (b) blood from the adrenal
veins draining these tumors; and (c) peripheral blood. • In Aim 2, we will test the working hypothesis that panels
of steroid biomarkers measured in peripheral blood can distinguish APAs from both BHA and essential
hypertension. We will implement baseline and dynamic testing (ACTH stimulation and Dexamethasone
suppression) to identify differences between the steroid signatures of PA subtypes. Mass spectrometry will be
used to quantify steroids in patients with PA and essential hypertension. This approach will directly address the
critical clinical need to simplify PA diagnosis and subtyping and will take essential steps towards our long-term
goal, of expanding personalized PA treatment and maximizing the number of cured PA cases.

## Key facts

- **NIH application ID:** 10108025
- **Project number:** 1R01HL155834-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Adina F Turcu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $751,696
- **Award type:** 1
- **Project period:** 2021-01-07 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108025

## Citation

> US National Institutes of Health, RePORTER application 10108025, Primary Aldosteronism Subtypes: Pathophysiology and Steroid Signatures (1R01HL155834-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10108025. Licensed CC0.

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