Rationale: Diagnosis of endocrine forms of hypertension (primary aldosteronism, pheochromocytoma/paraganglioma and Cushing syndrome) is a lengthy and tedious process. Recently a multiomics biomarker was developed through machine learning that shows high accuracy in predicting the presence of endocrine hypertension or primary hypertension. Given the propensity to data shift in applications of machine learning derived algorithms validation of this multiomics biomarker in a prospective comparative trial is warranted.

Objective: To determine the diagnostic performance of the new diagnostic biomarker

Study design: A randomized, diagnostic, outcome-based trial

Study population: Hypertensive patients 18-75 yrs, referred to ESH Hypertension Excellence centers, who may suffer from endocrine hypertension.

Intervention (if applicable): One group is diagnosed by classic endocrine tests, the other by the multiomics biomarker. Ensuing treatment depends on diagnosis and subtyping results.

Main study parameters/endpoints:

Primary endpoint is potency of antihypertensive medication to reach a target systolic blood pressure value of 135 mm Hg by home blood pressure measurement or an equivalent value for ambulatory blood pressure measurement, standardized office blood pressure measurement or unattended automatic blood pressure measurement.

Secondary endpoints: Ambulatory blood pressure, biochemical cure of endocrine hypertension (if treated by surgery), costs, quality of life

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: In the control group patients follow the same diagnostic itinerary as in usual care. In the biomarker group, endocrine tests will have been replaced by a blood and urine collection. The risk in both arms consists of missing an endocrine diagnosis. From the preceding accuracy study this risk is low for the use of the biomarker. After 6 months follow-up patients that were diagnosed by the biomarker may switch to a classic analysis.

Inclusion Criteria:

• Age 18-75 years
• Have a properly documented hypertension by abpm, hbpm, unattended office blood pressure measurement or carefully performed office measurement.
• Has a physician who feels an urge to exclude or diagnose EHT for one or more of the following reasons
• resistant hypertension AND/OR
• hypokalemia, spontaneous or diuretic-induced AND/OR
• history or physical examination suggestive of endocrine hypertension
• Willingness and ability to give informed consent

Exclusion Criteria:

• White-coat hypertension
• Known renal artery stenosis
• Known licorice abuse
• Known familial form of endocrine hypertension
• Cardiovascular event (myocardial infarction, cerebrovascular event) < 6 months [Y/N]
• Hypertensive crisis < 6 months
• eGFR < 50 ml/min/1,73m2
• Liver failure
• Known severe valvular or structural heart disease (excluding left ventricular hypertrophy)
• NYHA class III or IV heart failure or known reduced left ventricular function (ejection fraction (EF) <30%)
• EKG demonstrating significant pathology (e.g. myocardial infarction, atrial fibrillation, or any other cardial condition prohibiting start of study medication)
• Life expancy < 1 year
• For women, current pregnancy or unprotected intercourse