What is the appropriate assessment and management plan for a patient with hypertension suspected to be secondary to an endocrine disorder?

Assessment and Management of Hypertension Secondary to Endocrine Disorders

Screen all patients with resistant hypertension (BP >140/90 mmHg on ≥3 drugs including a diuretic), early-onset hypertension (<30 years), or sudden BP deterioration for endocrine causes, prioritizing primary aldosteronism as the most common treatable etiology. 1

Clinical Red Flags Requiring Endocrine Evaluation

When to suspect secondary endocrine hypertension:

• Age of onset <30 years without family history of essential hypertension 2, 3
• Resistant hypertension despite optimal triple therapy including a diuretic 1, 2
• Abrupt onset or sudden worsening of previously controlled BP 1, 2
• Severe hypertension (systolic >180 or diastolic >110 mmHg) 2
• Target organ damage disproportionate to duration or severity of hypertension 2

Symptom-Specific Clinical Assessment

Primary Aldosteronism (8-20% of resistant hypertension):

• Muscle weakness, tetany, cramps, or arrhythmias from hypokalemia 1, 2
• Family history of early-onset hypertension or stroke <40 years 2
• Spontaneous or diuretic-induced hypokalemia 1, 2

Pheochromocytoma:

• Episodic sweating, palpitations, and frequent headaches (classic triad) 1, 2
• Labile or paroxysmal hypertension 2

Cushing Syndrome:

• Central obesity with thin extremities, purple striae (>1 cm wide), easy bruising 1
• Proximal muscle weakness, moon facies, buffalo hump, fatty deposits 1

Thyroid Disease:

• Hypothyroidism: dry skin, cold intolerance, constipation, weight gain, delayed ankle reflexes 1
• Hyperthyroidism: warm moist skin, heat intolerance, tremor, weight loss, tachycardia 1

Physical Examination Findings

Cardiovascular signs:

• Radio-femoral delay suggests coarctation of the aorta 1, 2
• Abdominal systolic-diastolic bruits indicate renovascular disease 1, 4

Endocrine-specific signs:

• Neck circumference >40 cm suggests obstructive sleep apnea 1
• Enlarged thyroid gland 1
• Colored striae and fatty deposits (Cushing syndrome) 1
• Acral features with enlarged hands/feet (acromegaly) 1

Initial Laboratory Screening (All Suspected Cases)

Mandatory baseline tests:

• Plasma aldosterone-to-renin ratio (ARR) - Class IIa recommendation for all confirmed hypertension 2
• Serum sodium and potassium (hypokalemia supports primary aldosteronism) 1, 2
• Serum creatinine and eGFR 1, 2
• Urinalysis with albumin-to-creatinine ratio 1, 2
• Fasting glucose or HbA1c 1, 2
• Thyroid-stimulating hormone (TSH) 2, 3
• 12-lead ECG for left ventricular hypertrophy 1, 2

Critical pitfall: ACE inhibitors and ARBs lower aldosterone and raise renin, potentially causing false-negative ARR results; however, do not discontinue these medications before initial screening as the test remains useful 2

Confirmatory Testing Based on Screening Results

Primary Aldosteronism (if ARR >20 with elevated aldosterone and suppressed renin):

• IV saline suppression test or oral sodium loading test for biochemical confirmation 1, 2
• Adrenal CT scan for lesion localization after positive biochemical testing 2, 3
• Adrenal vein sampling when surgical intervention is contemplated to distinguish unilateral from bilateral disease 1, 2

Pheochromocytoma (if episodic symptoms present):

• 24-hour urinary metanephrines/normetanephrines or plasma free metanephrines 1, 2
• Abdominal/adrenal CT or MRI after biochemical confirmation 1

Cushing Syndrome (if cushingoid features present):

• Late-night salivary cortisol or 24-hour urinary free cortisol 1
• Low-dose dexamethasone suppression test 2

Renovascular Disease (if abrupt onset, flash pulmonary edema, or bruits):

• Renal duplex Doppler ultrasound as first-line imaging 2, 3
• CT or MR renal angiography for definitive diagnosis 1, 2

Obstructive Sleep Apnea (if snoring, daytime sleepiness, obesity):

• Overnight polysomnography; apnea-hypopnea index >5 confirms OSA, >30 indicates severe disease 2

Management Algorithm

Step 1: Treat the Underlying Cause

Primary Aldosteronism:

• Unilateral adrenalectomy for unilateral aldosterone-producing adenoma (curative) 2, 3, 5
• Spironolactone 50-100 mg daily for bilateral adrenal hyperplasia or non-surgical candidates 2, 3, 5
• Eplerenone as alternative mineralocorticoid receptor antagonist 1

Pheochromocytoma:

• Careful preoperative alpha-blockade followed by beta-blockade 6
• Laparoscopic adrenalectomy for adrenal tumors; open approach for paragangliomas 6
• Genetic testing for all patients and first-degree relatives 6

Cushing Syndrome:

• Surgical management of underlying cause when possible 1
• Adequate diuretic therapy as cornerstone of BP control due to mineralocorticoid receptor activation 1

Renovascular Disease:

• Medical therapy for atherosclerotic renal artery stenosis 2
• Percutaneous transluminal renal angioplasty without stenting for fibromuscular dysplasia 1

Step 2: Optimize Antihypertensive Therapy While Addressing Underlying Cause

For resistant hypertension after excluding secondary causes:

• Ensure adherence to RAS blocker, calcium channel blocker, and thiazide-like diuretic (chlorthalidone or indapamide, not hydrochlorothiazide) at maximum tolerated doses 1, 2
• Add spironolactone as fourth-line agent if serum potassium <4.5 mmol/L and eGFR >45 mL/min/1.73m² 1, 2, 5
• Use loop diuretics instead of thiazides if eGFR <30 mL/min/1.73m² 1, 2

Step 3: Lifestyle Modifications

• Sodium restriction <2400 mg/day 1
• Weight loss for obese patients, especially those with sleep apnea 2
• CPAP therapy for moderate-severe obstructive sleep apnea 2

Referral Indications

Refer to hypertension specialist or endocrinologist when:

• Positive screening tests require confirmatory testing 2, 3, 4
• Complex cases need specialized procedures (e.g., adrenal vein sampling) 2, 4
• Surgical intervention is being considered 2, 4
• BP remains uncontrolled despite optimal medical therapy 1, 4

Critical Pitfalls to Avoid

• Delayed diagnosis leads to irreversible vascular remodeling and residual hypertension even after treating the underlying cause 2, 3
• Secondary hypertension is underrecognized despite affecting 5-10% of all hypertensive patients and up to 20% of resistant cases 2, 3, 7
• Do not perform expensive imaging before completing basic laboratory screening 2
• Do not combine two RAS blockers (ACE inhibitor plus ARB) 2
• Even after treating the underlying cause, many patients require ongoing antihypertensive therapy 2