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| Author(s): |
Ana Alice Wolf Maciel
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2024-06-07 |
| Examining board members: |
Madson Queiroz de Almeida;
Debora Lucia Seguro Danilovic;
Leonardo Vieira Neto;
Laura Sterian Ward
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| Advisor: | Madson Queiroz de Almeida; Ana Amélia Fialho de Oliveira Hoff |
| Abstract | |
Introduction: Primary aldosteronism (PA) is a common cause of secondary hypertension, affecting approximately 6-8% of individuals with hypertension (HT), but it is an underdiagnosed disease. Aldosterone excess can cause oxidative stress leading to DNA damage in vitro and in vivo. The coincidence of primary hyperaldosteronism (PH) with different malignancies has been demonstrated in isolated case reports. A higher prevalence of thyroid nodules and non-toxic multinodular goiter was described in patients with PA compared to those with essential hypertension or normotension. A single study showed a 18% frequency of PA in papillary thyroid cancer (PTC) patients, but without a paired control group. Objective: 1) To assess PA prevalence in a transversal cohort of patients with PTC and HT without prior investigation; 2) Investigate the prevalence of thyroid diseases in patients with PA; and 3) Study the mineralocorticoid receptor expression in PTC patients with and without PA. Methods: In this cross-sectional case-control study, PA was investigated in all patients with PTC and HT (n= 137), regardless of HT severity, under active surveillance at the Cancer Institute of São Paulo State (ICESP) from 2019 to 2023. The control group included 137 (1:1) age-, sex- and body mass index (BMI)-matched individuals from a retrospective cohort of HT previously investigated for PA from 2011 to 2022 at the HT outpatient clinic in the Heart Institute (InCor). Serum aldosterone and plasma direct renin concentrations were measured by a chemiluminescent immunoassay. A positive PA screening was defined by aldosterone 10 ng/dL and aldosterone to renin ratio 2 ng/dL/UI/mL. Mineralocorticoid receptor protein expression was investigated by immunohistochemistry. Results: Results: Age, sex and BMI were not statistically different between PTC and HT control groups. The prevalence of PA was 29.20% (95% CI: 21.91% - 37.68%) in the PTC group and 20.44% (95% CI: 14.22% - 28.35%) in the control group with HT. The prevalence of PA was not statistically different between the two groups (p = 0.093). Although the prevalence of PA was not different, the frequency of severe HT (stage III or resistant) was significantly lower in the PTC group with HT (23%) when compared to controls with HT (73%, p< 0.001). Additionally, the number of antihypertensive medications used was significantly lower in the PTC group compared to HT controls (p <0.001). When analyzing PA patients from both groups, the frequency of stage 3/resistant HT and the number of anti-hypertensive medications were significantly lower in the PTC group (p = 0.006 and p < 0.001, respectively). Although HT was more severe in PA patients from control group, aldosterone and renin levels were not different in both groups, respectively (p = 0.40 and p = 0.26). In the multivariable analysis, PTC was associated with an odds ratio of 4.74 (CI 95% 2.26-10.55, p < 0.001) for PA diagnosis when adjusted for age, sex, stage of HT and BMI. A weak immunoreactivity (+ or ++) for the mineralocorticoid receptor was evidenced in 44% and 41% of the PTC from patients with and without PA, respectively (p= 0.976). Conclusion: PA prevalence in patients with PTC with HT was unexpectedly high (approximately 30%) and similar to the control group with more severe HT when matched for sex, age and BMI. PTC was an independent predictive factor for PA diagnosis in hypertensive individuals. Based on our findings, we propose the association of PTC with HT (regardless of severity) as a novel recommendation for PA screening (AU) | |
| FAPESP's process: | 21/09879-1 - Clinical and genetic investigation of the association between Primary Aldosteronism and Papillary Thyroid Cancer |
| Grantee: | Ana Alice Wolf Maciel |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |