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

NCT ID: NCT06068101

Last Updated: 2023-10-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 274 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-03-01
• Study Completion Date: 2023-08-01

Brief Summary

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.

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.

Conditions

Thyroid Cancer, Papillary; Primary Aldosteronism

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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.

Secreening test for primary aldosteronism and Confirmatory Testing

Intervention Type: DIAGNOSTIC_TEST

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.

No interventions assigned to this group

Interventions

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

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role: collaborator

Instituto do Cancer do Estado de São Paulo

OTHER

Sponsor Role: lead

Responsible Party

ANA ALICE WOLF MACIEL

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Ana Alice Wolf Maciel

São Paulo, , Brazil

Countries

Brazil

Other Identifiers

Primary Aldosteronism + Cancer

Identifier Type: -

Identifier Source: org_study_id