Practice Recommendations for Diagnosis and Treatment of the Most Common Forms of Secondary Hypertension

Abstract

The vast majority of hypertensive patients are never sought for a cause of their high blood pressure, i.e. for a 'secondary' form of arterial hypertension. This under detection explains why only a tiny percentage of hypertensive patients are ultimately diagnosed with a secondary form of arterial hypertension. The prevalence of these forms is, therefore, markedly underestimated, although, they can involve as many as one-third of the cases among referred patients and up to half of those with difficult to treat hypertension. The early detection of a secondary form is crucial, because if diagnosed in a timely manner, these forms can be cured at long-term, and even when cure cannot be achieved, their diagnosis provides a better control of high blood pressure, and allows prevention of hypertension-mediated organ damage, and related cardiovascular complications. Enormous progress has been made in the understanding, diagnostic work-up, and management of secondary hypertension in the last decades. The aim of this minireview is, therefore, to provide updated concise information on the screening, diagnosis, and management of the most common forms, including primary aldosteronism, renovascular hypertension, pheochromocytoma and paraganglioma, Cushing's syndrome, and obstructive sleep apnea.

Keywords: Cushing’s syndrome; Obstructive sleep apnea; Pheochromocytoma/paraganglioma; Primary aldosteronism; Renovascular hypertension.

Fig. 1

Simplified algorithm for the work-up for primary aldosteronism. Please note the pivotal role of adrenal vein sampling (AVS) for patient’s assignment to surgery or medical treatment. In case of uncertain AVS results or unsuccessful AVS, the indication to unilateral adrenalectomy can be justified by in case of drug-resistant hypertension and/or unbearable side effects with the antihypertensive treatment. *Confirmatory tests are not explained in this simplified algorithm because their accuracy and diagnostic gain over a well-performed baseline ARR has not been proven in studies that fulfilled the Standards for Reporting of Diagnostic Accuracy (STARD) requirements [25]. Moreover, in the largest and only study that followed these requirements, the captopril test was not shown to provide any diagnostic gain over the baseline ARR [26]. PA primary aldosteronism, ARR aldosterone: renin ratio, PRA plasma renin activity, K⁺ potassium, Na⁺ sodium, CT computed tomography, MRI magnetic resonance imaging, AVS adrenal vein sampling, BP blood pressure

Fig. 2

Diagnostic algorithm for identification and treat renovascular hypertension (RVH). As no single test is sensitive and specific enough to detect and ruled out RVH, a comprehensive assessment based on biochemical (↓ K⁺, ↑ renin, ↑ plasma aldosterone concentration) and instrumental tests (Duplex sonography and renal post-captopril scintigraphy) is necessary. Imaging by angio-CT or angio-MR plays a key role to assess the localization of stenosis and multivessel involvement, and to plan revascularization, by angioplasty in FMD-RVH and angioplasty + stenting in case of ATS-RVH. RVH renovascular hypertension, FMD fibromuscular dysplasia, CT computed tomography, MR magnetic resonance, PTRA percutaneous transluminal renal angioplasty, BP blood pressure

Fig. 3.

A schematic algorithm suggested for diagnosis and treatment of hypertensive patients with suspected of pheochromocytoma and paraganglioma. CT has been suggested as the first-choice imaging modality because of its excellent spatial resolution for thorax, abdomen, and pelvis. MRI is recommended in patients with metastatic PPGLs, for detection of skull base and neck paragangliomas. *Biochemical screening should be performed after withdrawing of interfering drugs and substances, including acetaminophen, labetalol, sotalol, α-methyldopa, tricyclic antidepressants, MAO-inhibitors, sympathomimetics, cocaine. **A quarter of patients with PPGLs show borderline biochemical results, likely due to inappropriate sampling. If results remain elevated after repeating the measurement, the clonidine suppression test with detecting of plasma normetanephrine can be used. This test has been claimed to have a 100% diagnostic specificity with a 97% sensitivity; however, it has not been validated in prospective studies. HT hypertension, CT computed tomography, MRI magnetic resonance imaging, MIBG metaiodobenzylguanidine, ¹⁸F-FDG [18F]-fluoro-fluorodeoxyglucose, ¹⁸F-FDOPA 6-[18F]-l-fluoro-l-3,4-dihydroxyphenylalanine, PET positron-emission tomography

Fig. 4

Schematic algorithm summarizing the steps for recognition of obstructive sleep apnea and its diagnostic and therapeutic work-up. *Upper airway surgery and oral appliances are indicated only for specific cases with objective upper airways abnormalities. OSA obstructive sleep apnea, PSG polysomnography, AHI apnea/hypopnea index, PAP positive airway pressure, MRAs mineralocorticoid receptor antagonists