Secondary hypertension: screening tests and causes

In most people with hypertension the exact cause remains unknown, but in a minority there is an identifiable cause that can be treated.^[1][2] This page covers who to screen, which tests to use and what each held guideline says about the main causes. How hypertension is first diagnosed and staged is in Hypertension: diagnosis and staging. The patient whose BP stays high on three drugs is in Resistant hypertension and renal denervation.

What secondary hypertension is

ESC 2024 says most patients with hypertension have essential or primary hypertension, where the exact cause remains unknown, while an estimated 10% have secondary hypertension with an identifiable cause.^[1] It adds that some studies indicate the prevalence may be substantially higher with modern systematic screening.^[1]

The point of finding the cause is that it can change treatment.^[1][2] ESC 2024 says that, by definition, secondary hypertension should be, for the most part, cured when the underlying cause has been unambiguously identified and removed, but in clinical practice this is not always the case.^[1] Vascular remodelling, a common feature of delayed diagnosis, affects renal function and can account for residual high BP in some patients (ESC 2024).^[1] The rate of cure is higher when the diagnosis is made early.^[1] AHA/ACC 2025 says that if a cause can be correctly diagnosed and treated, patients may experience a marked improvement in BP control with a reduction in cardiovascular disease (CVD) risk.^[2]

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AHA/ACC 2025 names primary aldosteronism and obstructive sleep apnoea (OSA) as common forms of secondary hypertension.^[2] ESC 2024 calls primary aldosteronism the most common form.^[1]

Who to screen

Both guidelines tie most screening to clinical suspicion.^[1][2] ESC 2024 also recommends comprehensive screening for the main causes when hypertension is diagnosed before the age of 40 years, except in obese young adults, in whom it recommends starting with an obstructive sleep apnoea evaluation.^[1] For primary aldosteronism, ESC 2024 says screening should be considered in all adults with confirmed hypertension, and the Endocrine Society suggests screening all individuals with hypertension.^[1][4]

Screening rows

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Clues that should raise suspicion

AHA/ACC 2025 lists the settings where secondary hypertension is more common.^[2] They are stage 2 hypertension, treatment-resistant hypertension, sudden onset, increased BP in patients previously controlled on drug therapy, and early-onset hypertension (age <30 years).^[2] Diastolic hypertension in older adults and target organ damage disproportionate to the duration or severity of the hypertension complete the list.^[2] Its Figure 5 is titled "Screening for Features Suggesting Secondary Hypertension".^[2]

• Young adults (ESC 2024): secondary hypertension is more frequent in younger than in later-onset hypertension; major causes include drug-induced hypertension (for example oestrogen-progesterone oral contraceptives and cold medication) and primary aldosteronism, and the use of recreational drugs or substances, supplements and energy drinks should be investigated.^[1]
• Young women (ESC 2024): fibromuscular dysplasia should be considered as a cause, whereas primary aldosteronism is equally common in different age classes; in obese young adults primary hypertension is more common, though OSA should also be considered.^[1]
• Resistant hypertension (ESC 2024): secondary causes are more likely when hypertension is resistant.^[1]
• Night-time BP (ESC 2024): nocturnal hypertension and an absent night-time dipping pattern are more common in secondary hypertension.^[1]
• Adrenal incidentaloma (ESC 2024): people with an incidental adrenal nodule warrant screening for elevated BP and hypertension, and those with an adrenal incidentaloma and hypertension warrant a basic work-up for secondary hypertension to include screening for primary aldosteronism, Cushing's syndrome and phaeochromocytoma.^[1]
• After a hypertensive emergency (ESC 2024): these patients remain at high risk and should be screened for secondary hypertension.^[1]
• Pregnancy (ESC 2024): the most common cause of secondary hypertension during pregnancy is chronic kidney disease (CKD); onset of hypertension in the first trimester should prompt consideration of primary aldosteronism.^[1]

ESC 2024 says that in most healthcare systems general practitioners are typically the gatekeepers of access to specialised care and should be involved in screening for common causes of secondary hypertension, especially sleep apnoea and primary aldosteronism.^[1]

What the routine work-up already screens

ESC 2024 Table 8 (Routine tests recommended in the initial work-up of a patient with elevated blood pressure or hypertension) builds some screening into every new patient.^[1] Blood sodium and potassium, haemoglobin and/or haematocrit, calcium and TSH are listed for screening secondary hypertension (primary aldosteronism, Cushing's disease, polycythaemia, hyperparathyroidism and hyperthyroidism).^[1] Blood creatinine and eGFR, urinalysis and urinary albumin-to-creatinine ratio are listed for, among other purposes, screening for renoparenchymal and renovascular secondary hypertension.^[1] Beyond these, ESC 2024 calls the investigations aimed at screening for secondary hypertension additional optional tests.^[1]

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Screening tests by cause

ESC 2024 Table 13 gives one screening test set per cause, to be used in the presence of suggestive signs, symptoms or medical history.^[1]

Optional tests that should be used to screen for secondary hypertension in the presence of suggestive signs, symptoms, or medical history (ESC 2024 Table 13)

^[1]

AHA/ACC 2025 Table 10 (Causes of Secondary Hypertension With Indications for Additional Testing and Diagnostic Screening Tests) adds prevalence, clinical clues and confirmatory tests, and splits the causes into common and uncommon.^[2]

AHA/ACC 2025 Table 10: prevalence, screening and confirmation

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AHA/ACC 2025 Table 10 also lists three rare causes: congenital adrenal hyperplasia, mineralocorticoid excess syndromes other than primary aldosteronism, and acromegaly.^[2] For Cushing syndrome the two guidelines file the tests differently.^[1][2] ESC 2024 lists 24 h urinary free cortisol and a low-dose dexamethasone suppression test as screening tests.^[1] AHA/ACC 2025 screens with the overnight 1-mg dexamethasone suppression test and lists 24-h urinary free cortisol (preferably multiple) and midnight salivary cortisol as confirmatory.^[2]

^[1]

Primary aldosteronism

What it is and why it matters

AHA/ACC 2025 defines primary aldosteronism as a group of disorders in which aldosterone production is inappropriately high for sodium and volume status.^[2] Production is relatively autonomous of the major regulators of aldosterone secretion (angiotensin II and potassium) and cannot be completely suppressed with sodium loading.^[2] The excess aldosterone induces intravascular volume expansion, suppressed plasma renin activity, sodium retention, increased potassium excretion, hypertension, and cardiovascular and kidney damage.^[2] Hypokalaemia can follow if the potassium loss is prolonged and severe, but it is absent in the majority of cases, and normokalaemia has a low negative predictive value for the diagnosis (AHA/ACC 2025).^[2]

AHA/ACC 2025 says bilateral adrenal hyperplasia causes the excess aldosterone in two-thirds of patients.^[2] In about one-third it comes from unilateral production: an aldosterone-producing adenoma, less commonly unilateral adrenal hyperplasia, or, rarely, adrenal carcinoma.^[2] ESC 2024 adds that management depends on the subtype, particularly whether adrenal lesions are unilateral or bilateral, because unilateral forms are amenable to surgery while bilateral forms require lifelong medical treatment.^[1]

^{[2] [1]}

AHA/ACC 2025 reports meta-analyses of studies that matched patients with primary aldosteronism to those with primary hypertension.^[2] Primary aldosteronism carried a 2.0-fold increased risk of heart failure, 2.8-fold of stroke, 1.7-fold of coronary artery disease and 4.0-fold of atrial fibrillation (AF), with increased kidney damage.^[2] ESC 2024 says primary aldosteronism is associated with an increased risk of CVD events, which may be partly independent of BP.^[1] The 2025 Endocrine Society guideline, quoted here from its PubMed abstract, says primary aldosteronism remains markedly underdiagnosed and undertreated despite effective methods for diagnosing and treating it.^[4]

Screening rates bear this out.^[1][2] ESC 2024 puts them at around 2% of eligible patients with resistant hypertension and 4% of those with hypokalaemia, and AHA/ACC 2025 says rates of screening for primary aldosteronism in appropriate patients are exceptionally low (1% to 2%).^[1][2]

Who to screen for primary aldosteronism

Primary aldosteronism screening rows

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AHA/ACC 2025 explains its targeted list.^[2] Patients with resistant hypertension, hypertension with hypokalaemia (spontaneous or diuretic induced) and hypertension with OSA have a relatively high prevalence of primary aldosteronism (about 20%-35%).^[2] Patients with early-onset hypertension and/or a cerebrovascular accident at a young age may have primary aldosteronism due to glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type 1) and therefore also warrant screening.^[2]

For stage 2 hypertension, AHA/ACC 2025 gives the prevalence of primary aldosteronism as approximately 5% to 10% in stage 1 and 11% to 22% in stage 2 hypertension, varying with the modality of testing and the thresholds used.^[2] It adds that the potential burden of additional testing outside resistant hypertension, to confirm the diagnosis and determine optimal therapy, may be taken into consideration before screening.^[2]

Do not wait for low potassium.^[1][2] ESC 2024 says spontaneous or diuretic-induced hypokalaemia is strongly suggestive, but a history of hypokalaemia is not present in most patients diagnosed with the condition, so the ARR is recommended for screening.^[1] AHA/ACC 2025 says the decision to screen should not rely on a history of hypokalaemia alone.^[2]

The aldosterone-to-renin ratio

AHA/ACC 2025 rows on testing and referral

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AHA/ACC 2025 gives the numbers.^[2] Patients with primary aldosteronism typically have suppressed renin activity (<1 ng/mL/h).^[2] Most data support a plasma aldosterone concentration of at least 10 ng/dL to call the test positive, but additional evaluation may be indicated if renin activity is suppressed.^[2] The most commonly used ARR cut-off is 30 with aldosterone in ng/dL and renin activity in ng/mL/h, although some data support alternative thresholds (20 or 40).^[2] ESC 2024 notes that ARR cut-offs vary with the unit of measurement and by local laboratory.^[1]

Preparation matters (AHA/ACC 2025): unrestricted salt intake, serum potassium in the normal range (to avoid false-negative testing) and, ideally, an MRA (for example spironolactone or eplerenone) withdrawn for at least 4 weeks before testing.^[2] ESC 2024 adds that assessing sodium intake (preferably 24 h urinary sodium, or the sodium-to-creatinine ratio in the morning urine sample) is important for interpreting the ARR, as is time in the menstrual cycle in females.^[1]

Interfering drugs: test on treatment or switch first?

ESC 2024 notes that the ARR is easy in treatment-naive patients but far more often considered in people already on treatment, and the drugs being taken at the time of testing can influence it.^[1] It describes 2 approaches for treated patients.^[1]

^[1]

AHA/ACC 2025 recommends continuing most antihypertensive medications (other than MRAs) before initial screening (COR 1, LOE C-EO).^[2] It says initial screening can typically be interpreted in the context of most medications that affect renin and aldosterone.^[2] Sometimes screening is negative or borderline despite a high level of suspicion, and confirmation would change management.^[2] Then potentially interfering drugs may be temporarily replaced with noninterfering ones (nondihydropyridine CCBs, vasodilators, peripheral alpha-blockers and potentially dihydropyridine CCBs) for at least 2 to 4 weeks before repeat testing.^[2] When an MRA cannot be stopped for safety reasons (severe hypokalaemia, or severe hypertension in severe hyperaldosteronism), ESC 2024 says recent evidence suggests ARR accuracy is only marginally affected, particularly in florid primary aldosteronism.^[1]

Drugs and conditions that affect aldosterone, renin, and aldosterone-to-renin ratio (ESC 2024 Table 12)

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Read the table by direction: ESC 2024 marks beta-blockers, alpha-2 agonists, NSAIDs, steroids, drospirenone and sodium loading as false-positive risks, and ACE inhibitors, ARBs, diuretics, hypokalaemia, sodium restriction and short-acting dihydropyridine CCBs as false-negative risks.^[1] AHA/ACC 2025 describes the same pattern.^[2] Beta-blockers and central alpha agonists can suppress both renin and aldosterone, and ACE inhibitors and ARBs may stimulate renin and suppress aldosterone.^[2] Thiazide-type and loop diuretics, MRAs and potassium-sparing diuretics can stimulate both.^[2]

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Confirmation and subtyping

AHA/ACC 2025 says the diagnosis may require an aldosterone suppression test such as an intravenous (IV) saline suppression test or oral salt-loading test.^[2] Its Section 3.2.3 adds that screening may require sodium loading to induce aldosterone suppression if plasma screening by the ARR is inconclusive.^[2] Its Table 10 lists three confirmatory tests: an oral sodium loading test (with 24-h urine aldosterone), an IV saline infusion test with plasma aldosterone at 4 h, or a captopril suppression test (in patients not on ACE inhibitor or ARB treatment).^[2] Adrenal CT and adrenal vein sampling sit in the same column.^[2]

AHA/ACC 2025 then describes a sequence.^[2] If the diagnosis is confirmed and the patient agrees that surgery would be desirable, the patient is referred for adrenal venous sampling to determine whether aldosterone production is unilateral or bilateral.^[2] Unilateral excess on sampling leads to referral for unilateral laparoscopic adrenalectomy.^[2] Bilateral excess, unsuitability for surgery or no interest in surgery leads to treatment with an MRA (for example spironolactone or eplerenone).^[2] Once primary aldosteronism is confirmed, imaging of the adrenal glands should be considered even if treatment will be medical.^[2] The aim is to exclude a large adrenal mass that may need adrenalectomy if features suggest malignancy (size >4 cm, imaging characteristics).^[2]

ESC 2024 says that in sporadic forms, unilateral and bilateral primary aldosteronism are distinguished by adrenal vein sampling or functional imaging with radiolabelled tracers.^[1] In the much less common familial forms, which make a family history necessary, genetic testing for germline mutations is necessary.^[1]

The Australian and New Zealand Adrenal Vein Sampling Working Group developed practical consensus recommendations based on evidence, expertise and previous consensus statements, without using the GRADE framework; they are quoted here from the full text in PubMed Central.^[6] The working group calls adrenal vein sampling the current recommended procedure for identifying unilateral subtypes, which are amenable to surgery with the potential for cure.^[6] It describes the procedure as technically challenging and usually undertaken by interventional radiologists at tertiary centres.^[6] It recommends that people with a confirmed diagnosis of primary aldosteronism who are considering the option of adrenalectomy and are appropriate surgical candidates be referred for adrenal vein sampling irrespective of adrenal imaging findings; the exceptions it lists include:^[6]

• people aged under 35 years with florid primary aldosteronism (aldosterone >550 pmol/L, suppressed renin, spontaneous hypokalaemia) and a solitary unilateral adrenal nodule on imaging, who may proceed to imaging-guided surgery without sampling with a very high likelihood of biochemical cure; some centres extend this exception to age under 45 years, or to any age, if there is a normal contralateral gland on imaging^[6]
• those with certain confirmed germline mutations (rare, under 5% of cases), listed as the chimeric CYP11B1/CYP11B2 gene (familial hyperaldosteronism type I) and germline mutations of CLCN2 (type II), KCNJ5 (type III) and CACNA1H (type IV)^[6]
• an adrenal lesion suspicious for adrenal cortical carcinoma.^[6]

The working group adds that there should be no upper age limit to offering adrenal vein sampling if surgery is considered a feasible therapeutic option.^[6]

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Treatment

ESC 2024 says surgical removal of the affected adrenal gland is typically considered for unilateral disease, unless the patient is older or has comorbidities of concern; surgery is not an option for bilateral disease.^[1] Medical treatment is based on MRAs, and spironolactone is the most widely available.^[1] Its effective dose is usually 50–100 mg once daily and can be titrated up to 300–400 mg once daily if necessary (ESC 2024).^[1] Eplerenone is less potent than spironolactone and needs twice-daily dosing, but causes less gynaecomastia and erectile dysfunction in men (ESC 2024).^[1]

• Endocrine Society 2025 (abstract): suggests primary aldosteronism-specific therapy, medical or surgical, for people with primary aldosteronism.^[4]
• MRA versus ENaC inhibitor (Endocrine Society 2025): suggests MRAs over epithelial sodium-channel (ENaC) inhibitors in medical treatment.^[4]
• Which MRA (Endocrine Society 2025): suggests spironolactone over other MRAs given its lower cost and greater availability; all MRAs titrated to equivalent potencies are anticipated to have similar efficacy, so MRAs with greater mineralocorticoid receptor specificity and fewer androgen- and progesterone-receptor side effects may be preferred in some situations.^[4]
• Titration (Endocrine Society 2025): in people on an MRA, suggests monitoring renin and, when hypertension remains uncontrolled with suppressed renin, titrating the MRA to increase renin.^[4]
• Familial hyperaldosteronism type 1 (ESC 2024): of the familial forms, only glucocorticoid-remediable primary aldosteronism can be corrected with dexamethasone, usually at low doses free of glucocorticoid effects that can be used safely in pregnancy.^[1]
• Newer agents (ESC 2024): newer agents, such as the non-steroidal MRA finerenone and the aldosterone synthase inhibitor baxdrostat, which lower BP in resistant hypertension, are also being tested for treating primary aldosteronism.^[1]

AHA/ACC 2025 says treating primary aldosteronism, with an MRA or with unilateral adrenalectomy if indicated, is associated with resolution of hypokalaemia, lower BP, fewer antihypertensive drugs required and improved parameters of impaired cardiac and kidney function.^[2] It reports that a meta-analysis of observational data suggests adrenalectomy may be associated with a lower risk of major adverse cardiovascular events and all-cause mortality than medical therapy.^[2]

Renovascular disease and fibromuscular dysplasia

ESC 2024 defines renovascular hypertension as renal artery occlusion or stenosis that lowers renal perfusion pressure enough to activate the renin–angiotensin–aldosterone system and raise BP.^[1] Its major causes are atherosclerosis and fibromuscular dysplasia (FMD).^[1] Atherosclerosis is the most common form, especially in older adults.^[1] FMD is a systemic non-atherosclerotic disease of medium-sized muscular arteries, and when the renal arteries are involved it may cause renovascular hypertension, especially in children and younger women (ESC 2024).^[1]

AHA/ACC 2025 says renal artery stenosis can cause a haemodynamically significant restriction of blood flow, usually by >75%.^[2] Atherosclerosis causes about 90% of it, whereas non-atherosclerotic disease, most commonly FMD, is much less prevalent and tends to occur in younger, otherwise healthier patients, with a predilection for women.^[2] Atherosclerotic renovascular disease may be present in 14% to 40% of adults with hypertension, but only a small fraction (0.1%-5%) is considered haemodynamically significant enough to cause renovascular hypertension.^[2] It adds that FMD is most common in women (90%), may present at a younger age (mean age 53 years), and affects the renal and carotid circulations with almost equal frequency.^[2]

That gap matters.^[1][2] ESC 2024 warns that bystander renal artery stenosis may be present in essential hypertension without causing renovascular hypertension.^[1]

When to suspect it

The 2024 ESC peripheral arterial and aortic diseases guideline says the clinical presentation comprises renovascular hypertension, renal function impairment and eventually flash pulmonary oedema, and it lists the clinical signs in its Table 13.^[3]

• Hypertension onset before 30 years of age^[3]
• Severe hypertension after the age of 55 years, when associated with CKD or heart failure^[3]
• Hypertension and abdominal bruit; rapid and persistent worsening of previously controlled hypertension^[3]
• Resistant hypertension (three antihypertensive drugs including a diuretic agent, or ≥4 antihypertensive drugs, and another secondary form unlikely)^[3]
• Hypertensive crisis (acute renal failure, acute heart failure, hypertensive encephalopathy, or grade 3–4 retinopathy)^[3]
• New azotaemia or worsening of renal function after treatment with RAAS blockers^[3]
• Unexplained atrophic kidney or discrepancy in kidney size, or unexplained renal failure; flash pulmonary oedema^[3]

AHA/ACC 2025 Table 10 lists similar indications: resistant hypertension; hypertension of abrupt onset or worsening or increasingly difficult to control; flash pulmonary oedema (atherosclerotic); and early-onset hypertension, especially in women (fibromuscular hyperplasia), with abdominal systolic-diastolic bruit or bruits over other arteries on examination.^[2]

Imaging

Diagnostic rows for renal artery disease

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The same guideline says renal scintigraphy, plasma renin measurements before and after ACE-inhibitor provocation, and venous renin measurements are not considered for renal artery stenosis evaluation.^[3] The 2024 ESC hypertension guideline says very elevated renin levels raise the suspicion, though they are not highly sensitive.^[1] It bases the work-up on imaging tests such as renal artery Doppler ultrasound with bilateral assessment of the renal arterial resistive index, abdominal CT angiography or MRI.^[1] Because FMD is a systemic disease, it says CT or MRI angiography from head to pelvis is recommended in patients with FMD-related renovascular hypertension.^[1]

Treatment rows

ESC 2024 says patients with renovascular hypertension should receive medical therapy to reduce BP in the first instance.^[1] Percutaneous transluminal renal angioplasty (PTRA) without stenting is the treatment of choice for FMD and can restore renal perfusion pressure and lower BP.^[1] When this is not feasible, renin–angiotensin system (RAS) blockers are the drugs of choice, but they need careful monitoring of renal function because they can cause acute renal failure with tight bilateral stenoses or a stenosed solitary functioning kidney (ESC 2024).^[1] ESC 2024 adds that possible involvement of the carotid, coronary and other major arteries, possibly leading to dissection if BP is not controlled, should be considered, as FMD is recognised as a systemic disease affecting multiple vascular beds.^[1]

Antihypertensive drug rows for renal artery stenosis

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ESC 2024 hypertension guideline: renovascular hypertension rows

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ESC 2024 defines a haemodynamically relevant stenosis as usually a luminal narrowing of >70%, or 50%–70% with post-stenotic dilatation.^[1]

ESC 2024 peripheral arterial and aortic diseases guideline: treatment rows for renal artery disease

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Its Figure 19 (Diagnostic and treatment algorithm for renal artery stenosis) defines the terms these rows use.^[3] High-risk features are rapidly progressive, treatment-resistant arterial hypertension; rapidly declining renal function; flash pulmonary oedema; and a solitary kidney.^[3] Signs of kidney viability are a renal size >8 cm, a distinct cortex (>0.5 cm), an albumin-creatinine ratio <20 mg/mmol and a renal resistance index <0.8.^[3] Signs of non-viability are a size <7 cm, loss of corticomedullary differentiation, an albumin-creatinine ratio >30 mg/mmol and a resistance index >0.8.^[3]

AHA/ACC 2025: renal artery stenosis rows

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The two ESC documents published in 2024 word the FMD row differently.^[1][3] For hypertension with haemodynamically significant renal artery stenosis due to FMD, the hypertension guideline says angioplasty without stenting should be considered (Class IIa, Level C).^[1] For hypertension and/or signs of renal dysfunction due to renal artery stenosis caused by FMD, with concomitant high-risk features and signs of kidney viability, the peripheral arterial and aortic diseases guideline says primary balloon angioplasty with bailout stenting should be considered (Class IIa, Level B).^[3] They also differ on open surgery: may be considered after technically unfeasible or failed angioplasty and stenting (hypertension guideline, Class IIb, Level C) versus should be considered with complex anatomy or after failed endovascular revascularisation (peripheral arterial and aortic diseases guideline, Class IIa, Level B).^[1][3]

For atherosclerotic disease, AHA/ACC 2025 says no randomised controlled trial (RCT) to date has shown a clear clinical advantage of renal artery revascularisation over medical therapy in people with hypertension.^[2] Trials comparing these procedures with medical therapy suggested no benefit over aggressive medical therapy alone, though there may be benefit in subgroups not represented in the trials, including progressively worsening kidney function or sudden-onset pulmonary oedema (AHA/ACC 2025).^[2] On the basis of the CORAL trial, AHA/ACC 2025 describes the medical approach as optimal BP management with a regimen that includes a RAS blocker, plus LDL cholesterol lowering with a high-intensity statin, smoking cessation, HbA1c reduction in diabetes, and antiplatelet therapy.^[2] ESC 2024 says patients with significant atherosclerotic renal artery stenosis are at very high risk of CVD and renal events, and it recommends that PTRA and stenting be performed in experienced centres because of the high risk of restenosis.^[1] It notes that some null trials, which did not solely recruit patients with true significant atherosclerotic renovascular hypertension, have reduced enthusiasm for investigating atherosclerotic stenosis.^[1] It warns this could result in more uncontrolled hypertension, recurrent flash pulmonary oedema (Pickering syndrome) and worsening renal function ultimately leading to end-stage renal disease.^[1]

For non-atherosclerotic disease, AHA/ACC 2025 says renal artery angioplasty may cure hypertension in some adults.^[2] It says revascularisation may be considered for non-atherosclerotic renal artery disease (for example FMD, or Takayasu arteritis in select cases) with hypertension and may be curative.^[2] It adds that angioplasty alone without stenting can improve and even normalise BP, especially with recent-onset or resistant hypertension.^[2]

^{[2] [1] [3]}

Phaeochromocytoma and paraganglioma

ESC 2024 calls PPGLs a rare form of secondary hypertension with a highly heterogeneous clinical presentation, usually discovered incidentally.^[1] Phaeochromocytomas are present in <0.2% of patients with hypertension, and a small percentage (<10%) of catecholamine-producing tumours are extra-adrenal (ESC 2024).^[1] AHA/ACC 2025 Table 10 gives a prevalence of <0.6%.^[2]

ESC 2024 says a PPGL should be suspected with signs and symptoms of catecholamine excess, in syndromic PPGL, with a family history of PPGL, and in carriers of a germline mutation in a PPGL-causing gene.^[1] AHA/ACC 2025 Table 10 lists resistant hypertension; paroxysmal hypertension or crisis superimposed on sustained hypertension; "spells", BP lability, headache, sweating, palpitations and piloerection; a positive family history; and adrenal incidentaloma, with skin stigmata of neurofibromatosis or orthostatic hypotension on examination.^[2] Sympathetic PPGLs are usually secreting and present with chronic, episodic or labile hypertension (ESC 2024).^[1]

Biochemistry, imaging and genetics

• ESC 2024: because normetanephrine and metanephrine are secreted constitutively, as opposed to the highly variable catecholamine secretion, they are preferred as screening tests; Table 13 gives 24 h urinary and/or plasma metanephrine and normetanephrine.^[1]
• AHA/ACC 2025 (Table 10): screen with 24-h urinary fractionated metanephrines or plasma metanephrines under standard conditions (supine position with an indwelling IV cannula); confirm with CT or MRI of abdomen and pelvis, or Ga-DOTATATE PET/CT.^[2]
• Endocrine Society 2014 (abstract): the task force recommends that initial biochemical testing include plasma free or urinary fractionated metanephrines, that preanalytical factors causing false-positive or false-negative results be considered, and that all positive results be followed up.^[5]
• Imaging (Endocrine Society 2014): CT is suggested for initial imaging, but MRI is a better option in metastatic disease or when radiation exposure must be limited.^[5]
• Genetics (ESC 2024): more than 35% of non-syndromic PPGLs are due to germline mutations, which should be screened for because they can drive management of the proband and family and inform the choice of functional imaging; some, such as those involving succinate dehydrogenase B, carry a risk of malignant adrenal tumours.^[1]
• Genetics (Endocrine Society 2014): consider genetic testing in all patients, by accredited laboratories; test patients with paraganglioma for SDHx mutations and those with metastatic disease for SDHB mutations.^[5]
• Genetic testing row (ESC 2024 Recommendation Table 11): genetic testing should be considered in specialist centres for patients with phaeochromocytoma/paraganglioma (Class IIa, Level B).^[1]

Preparation, surgery and crises

ESC 2024 says identifying a single tumour mandates surgical excision after adequate pharmacological preparation, because secreting PPGLs can cause fatal events with no warning.^[1] Doxazosin or terazosin, followed by a beta-blocker, usually controls BP and adrenergic crises.^[1] Because PPGLs redistribute volume from the periphery to the cardiopulmonary system, patients have peripheral hypovolaemia that exposes them to profound hypotension, particularly right after tumour excision, so fluid administration should be carefully managed (ESC 2024).^[1] Adrenergic crises cause hypertensive emergencies and should be treated with an IV alpha-1-blocker such as phentolamine, doxazosin or terazosin, or labetalol (ESC 2024).^[1]

• Blockade (Endocrine Society 2014): all patients with functional PPGLs should undergo preoperative blockade to prevent perioperative complications, with a high-sodium diet and fluid intake to prevent postoperative hypotension.^[5]
• Surgery (Endocrine Society 2014): minimally invasive adrenalectomy is recommended for most phaeochromocytomas and open resection for most paragangliomas; partial adrenalectomy is an option for selected patients.^[5]
• Follow-up (Endocrine Society 2014): lifelong follow-up is suggested to detect recurrent or metastatic disease.^[5]
• Pregnancy (ESC 2024): phaeochromocytoma in pregnancy is rare (0.002% of all pregnancies) but highly morbid.^[1]

Cushing's syndrome, thyroid disease and rarer causes

ESC 2024 groups genetic causes (Liddle's syndrome, glucocorticoid-remediable aldosteronism), excess liquorice, Cushing's syndrome, thyroid disease, hyperparathyroidism, aortic coarctation and acromegaly as rare forms and says affected patients should be referred to specialised centres for treatment.^[1] For the rarer forms in general, it says patients should be referred to specialised hypertension centres.^[1]

Endocrine and rare causes: clues and tests

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Two of these sit in the routine work-up: ESC 2024 Table 8 lists TSH and calcium among the routine blood tests for screening secondary hypertension, naming Cushing's disease, hyperparathyroidism and hyperthyroidism among the targets.^[1] ESC 2024 also lists Cushing's syndrome in the basic work-up for people with an adrenal incidentaloma and hypertension.^[1] AHA/ACC 2025 names Cushing syndrome among the secondary forms where clinical expertise is practical for prognosis and treatment plans.^[2]

Obstructive sleep apnoea

AHA/ACC 2025 describes OSA as a chronic condition of recurring upper airway obstruction during sleep, causing hypoxia and disrupted sleep, and says moderate-to-severe OSA is associated with an increased risk of hypertension, CVD events and mortality.^[2] ESC 2024 says OSA syndrome is prevalent in hypertension and particularly in resistant hypertension, with studies indicating that up to 60% of patients with resistant hypertension have features of it.^[1]

ESC 2024 says OSA should be suspected in hypertension with suggestive symptoms, in all patients with resistant hypertension, and with a non-dipping or reverse-dipping pattern on 24 h BP monitoring, especially if obese.^[1] Validated questionnaires may help identify patients at high risk, but lack of suggestive symptoms does not rule it out (ESC 2024).^[1] A simplified polysomnogram confirms the diagnosis (apnoea–hypopnoea index, AHI, >5) and grades severity: mild AHI <15, moderate 15–30, severe >30 (ESC 2024).^[1] AHA/ACC 2025 Table 10 gives a prevalence of 25%-50% and lists snoring, choking or gasping during sleep, daytime sleepiness and resistant hypertension as indications for testing.^[2] It screens with the STOP-Bang or Berlin questionnaire or overnight oximetry.^[2] It confirms by referral for polysomnography or home sleep apnoea testing if there is no suspicion of a nonrespiratory sleep disorder (eg, narcolepsy).^[2]

ESC 2024 says management should be driven by polysomnography, which should give the AHI and the sleep position in which the episodes occur.^[1] For mild OSA (AHI <15), weight loss and sleep hygiene advice are usually sufficient; for moderate (AHI 15–30) and severe (AHI >30) OSA, continuous positive airway pressure (CPAP) is indicated and usually improves BP control and helps to resolve resistant hypertension.^[1] If CPAP is not tolerated, the site of upper airway obstruction should be determined by an ear, nose and throat evaluation with drug-induced sleep endoscopy as a potential step to corrective surgery (ESC 2024).^[1]

AHA/ACC 2025: obstructive sleep apnoea rows

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AHA/ACC 2025 reports that several RCTs have shown short-term CPAP can reduce high office and ambulatory BP by 2 to 5 mm Hg, including in resistant hypertension.^[2] It also says that, although CPAP is an effective therapy for OSA, data do not support its use to prevent CVD events or mortality in moderate-to-severe OSA.^[2]

Drug-induced hypertension

ESC 2024 says over-the-counter medications, prescribed drugs and drug abuse (recreational substances and misuse of drugs) can cause hypertension; its list of such agents (supplementary Table S4) is not held for this topic.^[1] AHA/ACC 2025 Table 10 puts drug- or alcohol-induced hypertension at 2%-20%, screens with a urinary drug screen for illicit drugs, and confirms by the response to withdrawal of the suspected agent.^[2] AHA/ACC 2025 says a careful history should pay close attention to prescription and over-the-counter medications, illicit drugs and herbal products, and that, when feasible, drugs associated with increased BP should be reduced or discontinued and alternative agents used.^[2]

Selected List of Frequently Used Medications and Other Substances That May Cause Elevated Blood Pressure With Recommendations for Management (AHA/ACC 2025 Table 11)

^[2]

• Contraception (ESC 2024): combined oestrogen-progesterone contraceptives are among the most common causes of drug-induced hypertension in young women and should not be used in hypertensive women unless no other method is available or acceptable; progestin-only contraceptives are generally considered safe in women with hypertension.^[1]
• Cancer therapy (ESC 2024): anticancer and anti-angiogenic drugs can cause hypertension, especially vascular endothelial growth factor inhibitors, with which BP increases in 80%–90%; tyrosine kinase inhibitors, proteasome inhibitors and adjuvant therapies (corticosteroids, calcineurin inhibitors, NSAIDs and anti-androgen hormone therapy) also raise BP, and the hypertension is often dose limiting and may be reversible after therapy interruption or discontinuation.^[1]
• Managing cancer-therapy hypertension (ESC 2024): management is recommended to follow that for the general population.^[1]
• Drospirenone and the ARR (ESC 2024 Table 12): contraceptive agents containing drospirenone raise aldosterone, renin and the ARR, giving a false positive.^[1]

Renal parenchymal disease and coarctation

For renal parenchymal disease, ESC 2024 Table 13 screens with plasma creatinine, sodium and potassium, eGFR, a urine dipstick for blood and protein, the urinary albumin-to-creatinine ratio and renal ultrasound.^[1] AHA/ACC 2025 Table 10 gives CKD a prevalence of 14% and lists diabetes, obstruction, haematuria, urinary frequency and nocturia, analgesic abuse, a family history of polycystic kidney disease, elevated serum creatinine and abnormal urinalysis among the indications for testing.^[2]

Pitfalls

Prognosis, referral and follow-up

ESC 2024 says the rate of cure is higher when the diagnosis is made early, and that vascular remodelling can account for residual high BP in some patients.^[1] In patients with secondary hypertension, the underlying cause (OSA, primary aldosteronism) should be treated (ESC 2024).^[1]

Referral is built into the rows.^[2] AHA/ACC 2025 says referral to a clinician with expertise in that form of hypertension is reasonable after a positive screen (COR 2a, LOE C-EO).^[2] After a positive primary aldosteronism screen, or with continued suspicion based on suppressed renin or disproportionate target organ damage, it recommends referral to a hypertension specialist or endocrinologist (COR 1, LOE C-EO).^[2] AHA/ACC 2025 says diagnosis of many secondary causes requires a complex set of tests combined with specialised expertise in interpretation.^[2]

After PPGL surgery, the 2014 Endocrine Society guideline suggests lifelong follow-up to detect recurrent or metastatic disease.^[5] On MRA treatment for primary aldosteronism, the 2025 Endocrine Society guideline suggests monitoring renin.^[4]

Special populations

• Young adults (ESC 2024, Class I, Level B): comprehensive screening for the main causes in adults diagnosed with hypertension before the age of 40 years, except obese young adults, in whom an OSA evaluation comes first.^[1]
• Children and younger women (ESC 2024): FMD may cause renovascular hypertension, especially in children and younger women.^[1]
• Older adults (ESC 2024): atherosclerosis is the most common form of renovascular hypertension, especially in older adults.^[1]
• Pregnancy (ESC 2024): in one study, 10% of pregnant women with chronic hypertension had secondary hypertension; CKD is the most common cause, onset in the first trimester should prompt consideration of primary aldosteronism, and phaeochromocytoma is rare but highly morbid.^[1]
• Pregnancy and familial hyperaldosteronism type 1 (ESC 2024): dexamethasone, usually at low doses free of glucocorticoid effects, can be used safely in pregnancy.^[1]
• Women and contraception (ESC 2024; AHA/ACC 2025 Table 11): combined oestrogen-progesterone pills are among the commonest causes of drug-induced hypertension in young women, and AHA/ACC 2025 advises avoiding oral contraceptives in women with uncontrolled hypertension.^[1][2]

Evidence, guidelines and regional differences

^{[1] [2] [4]}

The three primary aldosteronism positions differ in reach.^[1][2][4] ESC 2024 says screening should be considered in all adults with confirmed hypertension (Class IIa, Level B), and the Endocrine Society suggests screening all individuals with hypertension.^[1][4] AHA/ACC 2025 instead recommends screening for defined indications (COR 1) and says it may be considered in stage 2 hypertension (COR 2b).^[2]

In Australia and New Zealand

No Australian or New Zealand guideline on secondary hypertension was found in the census for this topic (PubMed, 2026-10-09), so the screening and treatment rows above are from the ESC, AHA/ACC and Endocrine Society guidelines. The Australian and New Zealand Adrenal Vein Sampling Working Group published expert consensus recommendations on the preparation, performance and interpretation of adrenal vein sampling; it calls the procedure the current recommended way to identify unilateral subtypes of primary aldosteronism.^[6]

Guidelines checked for this topic

Rows on this page come from the 2024 ESC hypertension guideline, the 2025 AHA/ACC high blood pressure guideline and the renal artery rows of the 2024 ESC peripheral arterial and aortic diseases guideline.^[1][2][3] The 2025 Endocrine Society primary aldosteronism guideline and the 2014 Endocrine Society phaeochromocytoma and paraganglioma guideline are quoted from their PubMed abstracts.^[4][5] The two hypertension guidelines are the newest ESC and AHA/ACC hypertension guidelines, and the two Endocrine Society documents the newest Endocrine Society guidelines on these conditions, among the guidelines checked for this topic (census 2026-10-09). A correction to the 2025 Endocrine Society guideline was published in October 2025; its text is not held for this topic. The ESC 2026 cardiovascular disease and CKD guideline (PMID 42661426) is not held (version of record unreachable); none of its rows are used.

Exam pearls

• ESC 2024: screen with suggestive features (Class I, Level B); screen everyone diagnosed with hypertension before 40 years comprehensively, but start with an OSA evaluation if obese (Class I, Level B).^[1]
• Primary aldosteronism: 5% to 10% of patients with hypertension and 20% of those with resistant hypertension; spontaneous hypokalaemia in only 20% to 50% (AHA/ACC 2025).^[2]
• ARR (AHA/ACC 2025): patients with primary aldosteronism typically have renin activity <1 ng/mL/h; most data support aldosterone of at least 10 ng/dL for a positive test; the most commonly used cut-off is 30 (ng/dL per ng/mL/h), with some data supporting 20 or 40.^[2]
• ARR false positives (ESC 2024 Table 12): beta-blockers, alpha-2 agonists, NSAIDs, steroids, drospirenone and sodium loading; false negatives: ACE inhibitors, ARBs, diuretics, hypokalaemia, sodium restriction and short-acting dihydropyridine CCBs.^[1]
• Non-interfering drugs for a clean screen (ESC 2024): long-acting CCBs and alpha-receptor antagonists.^[1]
• Subtype in sporadic forms: adrenal vein sampling or functional imaging with radiolabelled tracers (ESC 2024); spironolactone usually 50–100 mg once daily, up to 300–400 mg once daily if necessary.^[1]
• FMD-related renovascular hypertension: for hypertension with haemodynamically significant renal artery stenosis due to FMD, renal artery angioplasty without stenting should be considered (ESC 2024 hypertension guideline, Class IIa, Level C), and CT or MRI angiography from head to pelvis is recommended.^[1]
• PPGL: metanephrines, not catecholamines (ESC 2024); alpha-blockade (doxazosin or terazosin) before a beta-blocker.^[1]
• OSA: a simplified polysomnogram with AHI >5 confirms it; CPAP is indicated for moderate (AHI 15–30) and severe (AHI >30) OSA (ESC 2024); CPAP can be useful in reducing BP in resistant hypertension with moderate-to-severe OSA, COR 2a, LOE B-R (AHA/ACC 2025).^[1][2]

References6ShowHide

1. [1]McEvoy JW, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J, 2024.PMID 39210715
2. [2]Jones DW, et al. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol, 2025.PMID 40815242
3. [3]Mazzolai L, et al. 2024 ESC Guidelines for the management of peripheral arterial and aortic diseases. Eur Heart J, 2024.PMID 39210722
4. [4]Adler GK, et al. Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2025.PMID 40658480
5. [5]Lenders JW, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab, 2014.PMID 24893135
6. [6]Yang J, et al. Adrenal Vein Sampling for Primary Aldosteronism: Recommendations From the Australian and New Zealand Working Group. Clin Endocrinol (Oxf), 2025.PMID 39360599