What tests should be ordered to rule out an endocrine cause of hypertension?

Diagnostic Tests to Rule Out Endocrine Causes of Hypertension

To rule out endocrine causes of hypertension, a comprehensive panel of tests should be ordered including aldosterone-renin ratio, plasma free metanephrines, late-night salivary cortisol, and thyroid function tests, along with appropriate imaging studies based on clinical suspicion. 1, 2

Initial Laboratory Investigations

• Serum electrolytes (sodium, potassium) - hypokalemia may suggest primary aldosteronism 1
• Serum creatinine and estimated glomerular filtration rate (eGFR) to assess renal function 1
• Fasting blood glucose - to screen for diabetes which may coexist with endocrine hypertension 1
• Lipid profile - dyslipidemia often accompanies endocrine hypertension 1
• Urinalysis - to detect proteinuria or hematuria 1
• 12-lead ECG - to detect left ventricular hypertrophy or arrhythmias 1

Specific Endocrine Tests

Primary Aldosteronism (Most Common Endocrine Cause)

• Aldosterone-renin ratio (ARR) - primary screening test 1, 2
• Ensure proper preparation: discontinue interfering medications (if possible), correct hypokalemia, and maintain adequate sodium intake before testing 3, 4
• If ARR is elevated, proceed with confirmatory testing (saline suppression test, captopril challenge, or fludrocortisone suppression test) 2, 4

Pheochromocytoma/Paraganglioma

• Plasma free metanephrines or 24-hour urinary fractionated metanephrines and catecholamines 1, 2
• Testing should be performed while the patient is supine and relaxed for at least 30 minutes 2, 5

Cushing's Syndrome

• Late-night salivary cortisol or overnight dexamethasone suppression test 1, 2
• 24-hour urinary free cortisol if clinical suspicion is high 2, 5

Thyroid Dysfunction

• Thyroid function tests (TSH, free T4) - both hyperthyroidism and hypothyroidism can cause hypertension 2, 3

Hyperparathyroidism

• Serum calcium and parathyroid hormone (PTH) levels 5, 3

Imaging Studies

• Adrenal imaging (CT or MRI) - for suspected primary aldosteronism, Cushing's syndrome, or pheochromocytoma 1, 2
• Renal ultrasound/renal artery duplex - to evaluate renal parenchymal disease or renal artery stenosis 1
• CT/MR angiography - if renovascular hypertension is suspected 1
• Echocardiography - to assess for left ventricular hypertrophy and cardiac function 1

Advanced Testing (Based on Initial Results)

• Adrenal vein sampling - to determine laterality in primary aldosteronism when surgical intervention is considered 2, 4
• Genetic testing - for suspected familial forms of endocrine hypertension 6, 3
• MIBG scan or PET imaging - for localization of pheochromocytoma/paraganglioma 2, 5

Clinical Clues That Warrant Endocrine Testing

• Age of onset <30 years or sudden onset of hypertension in patients >50 years 2, 6
• Resistant hypertension (requiring >3 medications from different classes) 2, 3
• Hypokalemia (spontaneous or diuretic-induced) 1, 4
• Presence of specific symptoms:
  • Muscle weakness, tetany, cramps (primary aldosteronism) 1, 2
  • Episodic sweating, palpitations, headaches (pheochromocytoma) 1, 2
  • Central obesity, facial plethora, purple striae (Cushing's syndrome) 1, 5
  • Enlarged thyroid, tachycardia or bradycardia (thyroid disorders) 2, 3

Common Pitfalls to Avoid

• Failure to discontinue interfering medications before endocrine testing (particularly antihypertensives for aldosterone testing) 2, 4
• Not recognizing drug-induced hypertension before extensive workup 2
• Inadequate preparation for specialized endocrine tests leading to false results 3, 4
• Overlooking primary aldosteronism due to absence of hypokalemia (present in only 9-37% of cases) 3, 4

Early identification and appropriate management of endocrine hypertension can significantly reduce morbidity and mortality associated with these conditions 6, 3.