ESPE Abstracts

Endocrine disorders are the most common causes of secondary hypertension. Early diagnosis and treatment is crucial for prevention of cardiovascular complications. Several rare but important entities like Cushing’s syndrome and pheochromocytoma/paraganglioma can cause endocrine hypertension, in contrast to primary aldosteronism, which is quite frequent. Definition, classification and prevalence: With a prevalence of 6% in unselected patients with hypertension, 5 to 12% of hypertensive patients in specialized outpatient clinics and 23% in therapy-refractory patients, primary hyperaldosteronism (PA) is the most common cause of surgically treatable secondary hypertension. The causes of PA are usually a unilateral aldosterone-producing adrenal adenoma (APA) or bilateral (micronodular) idiopatic adrenal cortex hyperplasia (BAH). The "classic" hypokalemic variant occurs more frequently in the case of APA, whereas the normokalemic form is mostly observed in BAH forms. Case finding: PA screening is required in patients with refractory hypertension, younger patients with hypertension, patients with arterial hypertension and hypokalemia, patients with arterial hypertension and obstractive sleep apnoe syndrome, and patients with arterial hypertension and adrenal incidentaloma. Screening is performed using the sensitive, but not very specific, aldosterone to renin ratio (ARR). Subtype differentiation is carried out by means of CT imaging of the adrenal glands in combination with, as a gold standard, adrenal vein catheterization to differentiate between unilateral and bilateral aldosterone production. In the case of a technically unsuccessful catheterization, nuclear medical procedures (e.g. CXCR4-PET/CT, etomidate-PET) are used in individual cases. Genetics: Most cases of PA are sporadic but inherited patterns of the disease have been reported in the literature. Four forms of familial hyperaldosteronism (FH-I- FH-IV) are currently recognized, and the genetic basis has been clarified in recent years. In FH-I patients, aldosterone excess is produced by a CYP11B1/CYP11B2 fusion gene and it is suppressed by glucocorticoid treatment. FH-II is caused by mutations in the inwardly rectifying chloride channel CLCN2. FH-III is caused by mutations in KCNJ5, a gene coding for an inward rectifier K+ channel and mutations in the T-type calcium channel subunit CACNA1H cause FH-IV. A number of somatic mutations have been identified in ion channels and transporters that drive the aldosterone excess in patients with APA. No clinical application has been firmly established although a potential future use may lie in steroid profiling to circumvent AVS in patients with bilateral disease by selection of those patients with a high probability of having an APA or by selecting patients with an APA carrying KCNJ5 mutations using macrolide antibiotics as selective inhibitors. Genetic testing is recommended in patients with a diagnosis of early-onset PA (< 20 years old) or with a family history of PA or stroke at a young age (< 40 years) for the presence of the hybrid CYP11B1/CYP11B2 gene that causes FH type I and in very young patients with a diagnosis of PA (for example, < 20 years) for germline mutations in the KCNJ5 gene that cause FH type III. Genetic testing of patients in these target groups offers the possibility of an early diagnosis of asymptomatic relatives and provides timely treatment when appropriate. Therapy: Patients with PA have an increased risk of stroke, myocardial infarction, atrial fibrillation and renal insufficiency compared to patients with essential hypertension. Early diagnosis and the appropriate targeted initiation of therapy seem all the more important. An adrenalectomy is indicated for unilateral PA. In the case of BAH, therapy with spironolactone (25-50mg/d) should be initiated.

Learning points:

After this lecture, you should:

• Know the prevalence and at risk populations of endocrine hypertension

• Know the target population which should be screened for PA

• Be able to apply appropriate tests to diagnose and subtype PA

• Be able to identify familiar forms of PA

• Be able to initiate individualized treatment depending on subtype of PA

Key Words: primary aldosteronism, aldosterone, cortisol, adrenal vein sampling, endocrine hypertension, secondary hypertension