Primary Aldosteronism: Screening and Genetic Risk in Focus

Expanding screening for primary aldosteronism (PA) and tailoring the management of pheochromocytomas and paragangliomas according to genetic risk were among the recommendations discussed at a symposium organized by the French Society of Endocrinology (SFE) and FIRENDO, the French rare endocrine diseases healthcare network, held on October 7, 2026, during the 42nd SFE annual congress in Bordeaux, France.Maria-Christina Zennaro, MD, PhD, professor at the Paris Cardiovascular Research Center, French National Institute of Health and Medical Research, Université Paris Cité, and associated investigator at the Genetics Department, European Hospital Georges Pompidou, both in Paris, France, discussed the diagnosis of PA, while Charlotte Lussey Lepoutre, MD, PhD, professor of nuclear medicine at the Pitié-Salpêtrière University Hospital, Assistance Publique-Hôpitaux de Paris, and Sorbonne University, Paris, reviewed recommendations for managing pheochromocytomas and paragangliomas.Expanded ScreeningThe Endocrine Society recommends screening all patients with hypertension for PA. This conditional recommendation extends screening to patients without specific risk profiles. Its implementation will depend on the available resources, local expertise, and capacity of the healthcare system.PA is the most common endocrine cause of secondary hypertension. The 2025 Endocrine Society guideline estimated its prevalence at approximately 5.9% among patients with hypertension in primary care and at 7.2% among those seen in referral centers, although estimates vary across studies. Despite its prevalence, PA is substantially underdiagnosed.PA is associated with an increased risk for cardiovascular complications, including myocardial infarction, atrial fibrillation, heart failure, and stroke. Identifying the condition allows clinicians to offer targeted medical or surgical treatment.Screening involves measuring serum or plasma aldosterone and plasma renin levels and calculating the aldosterone-to-renin ratio. PA is suggested when renin is suppressed, aldosterone is inappropriately high relative to renin, and the aldosterone-to-renin ratio is elevated.Serum potassium levels help with interpretation; however, the absence of hypokalemia does not rule out PA. Low potassium levels can lead to falsely low aldosterone measurements. Therefore, potassium should be corrected before screening is repeated when an initially negative result is inconsistent with clinical suspicion.Antihypertensive medications that may interfere with screening can be continued or selectively withdrawn, depending on individual safety and feasibility. The guidelines described minimal-withdrawal and no-withdrawal approaches to reduce barriers to screening.Recommendations for screening have also evolved. Aldosterone suppression tests, which assess aldosterone levels after an intervention intended to reduce its secretion, are no longer routinely recommended. Further testing may be unnecessary when biochemical findings strongly suggest PA. Suppression tests are now mainly considered when the likelihood of unilateral disease is intermediate and the patient is willing and able to undergo surgery.However, imaging alone cannot establish which adrenal gland produces excess aldosterone. Adrenal vein sampling addresses this limitation by comparing aldosterone secretion between the two glands. These results help distinguish unilateral disease, which may be treated with surgery, from bilateral diseases.When an adrenal adenoma is present, a dexamethasone suppression test is performed to assess coexisting autonomous cortisol secretion. This is important because excess cortisol production could affect the interpretation of adrenal vein sampling results and subsequent postoperative management.Targeted Treatment and MonitoringThe Endocrine Society recommends unilateral adrenalectomy for patients with unilateral disease who wish to undergo surgery. Patients with bilateral disease and those who do not undergo surgery are generally treated with mineralocorticoid receptor antagonists.Spironolactone is the preferred treatment because it is inexpensive and widely available. However, medication selection may be adjusted according to patient tolerance and contraindications. Monitoring should include blood pressure, serum potassium, renal function, and renin levels.If blood pressure remains uncontrolled and renin levels are suppressed, PA-specific treatment should be intensified to increase renin levels. However, the benefit of increasing medication doses solely to raise renin levels is uncertain when blood pressure is already controlled.Paraganglioma GeneticsApproximately 40% of patients with pheochromocytoma or paraganglioma have a germline genetic predisposition. Succinate dehydrogenase (SDH) gene variants are important because they increase the risk for multiple tumors, both secretory and nonsecretory, which can occur from the skull base to the pelvis.The SDH subunit D (SDHD) gene variant typically manifests when inherited from the father. These variants are commonly associated with head and neck paragangliomas, which may occur at multiple sites, according to the 2023 international consensus. SDHB gene variants are more commonly associated with abdominal or pelvic paragangliomas and a higher risk for metastasis, according to the 2024 consensus.Evaluation includes clinical examination, metanephrine measurement, and appropriate imaging. The measurement of 3-methoxytyramine may provide additional information. Functional imaging targeting somatostatin receptors, particularly gallium-68 PET, may help characterize the disease. Management decisions should be discussed by a specialized, multidisciplinary team.Long-Term RisksFor head and neck paragangliomas associated with the SDHD gene variant, the international consensus recommends an initial period of observation before treatment. Surgery carries a risk for cranial nerve damage, particularly when tumors are multiple or bilateral. If a tumor grows, compresses adjacent structures, or causes symptoms, surgery or radiation therapy may be considered according to its location and the potential treatment risks.In SDHB gene variant-associated tumors, the risk for metastasis warrants specialized surgical evaluation. However, the decision depends on the tumor location and benefit-risk ratio.Pediatric ConsiderationsAn international consensus statement on the diagnosis and management of pheochromocytoma and paraganglioma in children and adolescents highlighted the high proportion of hereditary cases and the possibility of metastatic or multifocal tumors in this population. The presentation may be atypical, without hypertension or the classic triad of headache, palpitations, and sweating.Close collaboration among specialists from different disciplines is essential. After tumor removal, patients with hereditary diseases require lifelong follow-up because recurrent or new tumors and metastases may occur years later.Surveillance for relatives who carry a pathogenic SDH gene variant should begin in childhood, with the starting age and frequency of clinical assessments, biochemical testing, and imaging determined by the specific gene involved in the disease.This story was translated from Univadis France, part of the Medscape Professional Network.