Clinical and Genetic Investigation of the Association Between Primary Aldosteronism and Thyroid Cancer

Aldosterone excess can cause oxidative stress leading to DNA damage in vitro and in vivo. Single case reports demonstrated a coincidence of primary aldosteronism (PA) with different malignancies. A higher prevalence of thyroid nodules and non-toxic multinodular goiter was described in patients with PA compared to those with essential hypertension (EH). A single study showed an association between PA and papillary thyroid cancer (PTC), but without a paired control group. Objective: To assess PA prevalence in a transversal cohort of patients with PTC and EH compared to a paired control group with HT.

Study Overview

• Status: Completed
• Conditions: Thyroid Cancer, Papillary; Primary Aldosteronism
• Intervention / Treatment: Diagnostic test: Secreening test for primary aldosteronism and Confirmatory Testing

Detailed Description

Primary aldosteronism (PA) is the most frequent cause of endocrine hypertension, with an estimated prevalence of 20% among individuals with resistant hypertension. PA is associated with an increased risk of malignancy, probably due to aldosterone effects in promoting cell proliferation. Recently, a high prevalence of PA was demonstrated in patients with essential hypertension (EH) and papillary thyroid cancer (PTC), similarly to the prevalence of PA among individuals with resistant EH. In addition, abnormalities in thyroid ultrasound (non-toxic multinodular goiter) are more common in PA patients when compared to controls. Despite of this initial evidence, the link between PA and PTC remains to be elucidated. Then, the aim of this study is to investigate the clinical and genetic aspects of the association between PA and PTC. The specific aims are: 1) To evaluate the prevalence of PA in a transversal cohort of patients with EH and PCT; 2) To investigate thyroid ultrasonography abnormalities in PA patients; 3) To perform exome sequencing (blood DNA) in patients with PA and PTC paired with tumor tissue; and 4) To conduct functional studies of the novel genetic variants identified by exome sequencing. To achieve this goal, the investigators will employ the following techniques: next-generation sequencing, bioinformatic analysis, real-time PCR and immunohistochemistry. In this project, the investigators expect to establish the prevalence of PA among patients with EH and PTC, and to identify new genetic targets involved in the association between PA in PTC.

• Study Type: Observational
• Enrollment (Actual): 274

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01246-000
    • Ana Alice Wolf Maciel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

In this cross-sectional case-control study, PA was investigated in all patients with PTC and EH (n= 137), regardless of hypertension severity, under active surveillance at a cancer institute from 2019 to 2022. The control group included 137 (1:1) age-, sex- and body mass index (BMI)-matched individuals from a retrospective cohort of EH previously investigated for PA from 2011 to 2022. Serum aldosterone and plasma direct renin concentrations were measured by a chemiluminescent immunoassay. A positive PA screening was defined by aldosterone > or = 10 ng/dL and aldosterone to renin ratio > or = 2 ng/dL/uUI/mL.

Description

Inclusion Criteria:

• All patients with PTC and EH regardless of hypertension severity

Exclusion Criteria:

• Patients who were using medications that secondarily increase blood pressure levels were excluded
• Did not agree to participate

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with papillary thyroid cancer (PTC) and EH (essential hypertension); Primary Aldosteronism was investigated in all patients with PTC and EH (n= 137), regardless of hypertension severity, under active surveillance at a cancer institute from 2019 to 2022.	Diagnostic test: Secreening test for primary aldosteronism and Confirmatory Testing; Serum aldosterone and plasma direct renin concentrations were measured by a chemiluminescent immunoassay. A positive PA screening was defined by aldosterone > or = 10 ng/dL and aldosterone to renin ratio > or = 2 ng/dL/uUI/mL
Patients with EH (essential hypertension) previously investigated for PA (primary aldosteronism); The control group included 137 (1:1) age,sex and body mass index (BMI) matched individuals from a retrospective cohort of EH previously investigated for PA from 2011 to 2022.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PA prevalence in a transversal cohort of patients with PTC and EH	To assess PA prevalence in a transversal cohort of patients with PTC and EH compared to a paired control group with EH	Through study completion, an average of 1,5 year

Collaborators and Investigators

• Sponsor: Instituto do Cancer do Estado de São Paulo
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: August 15, 2023
• First Submitted That Met QC Criteria: October 3, 2023
• First Posted (Actual): October 5, 2023

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Adenocarcinoma, Papillary; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Thyroid Diseases; Thyroid Neoplasms; Thyroid Cancer, Papillary; Hyperaldosteronism
• Other Study ID Numbers: Primary Aldosteronism + Cancer

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No