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.

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.

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

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.