What is the differential diagnosis for a patient with fluctuating blood pressure between hypotension and hypertensive crisis, considering their demographic and medical history, including age, cardiovascular disease, kidney disease, endocrine disorders, and medication adherence?

Differential Diagnosis for Fluctuating Blood Pressure Between Hypotension and Hypertensive Crisis

Primary Differential Considerations

The most critical differential for blood pressure fluctuating between hypotension and hypertensive crisis is pheochromocytoma, followed by medication non-adherence with rebound phenomena, autonomic dysfunction, and illicit drug use. 1

Endocrine Causes

Pheochromocytoma represents the classic cause of episodic severe hypertension alternating with hypotension and should be the primary consideration in this presentation 1:

• Characterized by episodic hypertension with palpitations, diaphoresis, and headache 1
• Can cause dramatic BP swings from catecholamine surges followed by depletion 1
• Screen with plasma or 24-hour urine metanephrines 1
• Secondary causes are found in 20-40% of patients presenting with malignant hypertension, with endocrine causes being relatively rare but critical to identify 1

Cushing's syndrome can cause severe hypertension with periods of relative hypotension 1:

• Look for moon facies, central obesity, abdominal striae, and interscapular fat deposition 1
• Screen with dexamethasone suppression test 1

Medication-Related Causes

Medication non-adherence is the most common trigger for hypertensive emergencies and can create fluctuating BP patterns 1, 2:

• Intermittent use of antihypertensives causes rebound hypertension alternating with periods of medication effect 1
• Limited access to healthcare and non-adherence frequently contribute to hypertensive emergencies 1
• Many patients presenting with hypertensive emergency have not received antihypertensive medication 1

Drug-induced hypertension with withdrawal periods 1, 2:

• Sympathomimetics (cocaine, amphetamines) cause acute severe hypertension followed by hypotension during withdrawal 2
• NSAIDs, steroids, immunosuppressants, and antiangiogenic therapy can cause BP fluctuations 2
• Interaction between tyramine-containing foods or drugs and monoamine oxidase inhibitors 3

Autonomic Dysfunction

Autonomic failure syndromes cause dramatic orthostatic hypotension with supine hypertension 1:

• Patients with autonomic dysfunction are at increased risk for exaggerated BP responses 4
• Measure supine and upright blood pressures to detect orthostatic changes 1

Baroreflex failure following neck surgery or radiation causes labile hypertension 1:

• Results in loss of normal BP buffering mechanisms
• Can present with severe BP swings throughout the day

Renal and Renovascular Causes

Renal artery stenosis can cause severe hypertension with episodes of flash pulmonary edema and relative hypotension 1:

• More common in young females and patients with known atherosclerotic disease 1
• Worsening renal function with ACE inhibitor use suggests this diagnosis 1
• Screen with duplex ultrasound or CT/MR angiography 1

Renal parenchymal disease is among the most common secondary causes 1:

• Check creatinine clearance and urinalysis 1
• Renal parenchymal disease and renal artery stenosis are the most frequent secondary causes in malignant hypertension 1

Cardiovascular Causes

Aortic coarctation causes upper extremity hypertension with lower extremity hypotension 1:

• Check for differential in brachial versus femoral pulses 1
• Listen for systolic bruit 1

Acute aortic dissection presents with severe hypertension that may alternate with hypotension if rupture occurs 1, 2:

• Requires immediate CT-angiography 2
• Represents a true hypertensive emergency requiring immediate BP reduction to <120 mmHg 2

Other Secondary Causes

Primary aldosteronism causes resistant hypertension with hypokalemia 1:

• Screen with elevated aldosterone/renin ratio 1
• Can cause muscle weakness, tetany, cramps, and arrhythmias from hypokalemia 1

Obstructive sleep apnea contributes to difficult-to-control hypertension 1:

• Look for snoring, witnessed apnea, excessive daytime sleepiness 1
• Neck circumference >40 cm suggests this diagnosis 1

Thyroid disease can cause BP fluctuations 1:

• Hyperthyroidism causes systolic hypertension with wide pulse pressure
• Check TSH as part of basic screening 1

Critical Diagnostic Approach

Immediate Assessment

Determine if acute target organ damage is present to differentiate hypertensive emergency from urgency 1, 2:

• Neurologic: altered mental status, headache with vomiting, visual disturbances, seizures, stroke 2
• Cardiac: chest pain, acute MI, pulmonary edema, acute heart failure 2
• Renal: acute kidney injury, hematuria 1
• Vascular: aortic dissection 2
• Ophthalmologic: bilateral retinal hemorrhages, cotton wool spots, papilledema 2

Essential Laboratory Evaluation

Basic screening should include 1, 2:

• Complete blood count (hemoglobin, platelets) to assess for microangiopathic hemolytic anemia 2
• Basic metabolic panel including creatinine, sodium, potassium 2
• Lactate dehydrogenase (LDH) and haptoglobin to detect hemolysis 2
• Urinalysis for protein and urine sediment 2
• TSH 1
• ECG 2

Screening for Secondary Hypertension

Consider further workup based on clinical clues 1:

• Plasma or urine metanephrines if episodic symptoms suggest pheochromocytoma 1
• Aldosterone/renin ratio if hypokalemia present 1
• Renal artery imaging if flash pulmonary edema or worsening renal function 1
• Sleep study if obstructive sleep apnea suspected 1

Common Pitfalls to Avoid

Do not assume all BP fluctuations represent poor medication adherence without screening for secondary causes, as 20-40% of malignant hypertension cases have identifiable secondary causes 1, 2

Do not overlook pheochromocytoma in patients with episodic severe hypertension, palpitations, and diaphoresis, as this is the classic presentation requiring specific diagnostic workup 1

Do not treat the BP number alone without assessing for true hypertensive emergency versus transient elevations from pain or distress 2

Avoid rapid BP normalization in patients with chronic hypertension, as altered autoregulation can cause cerebral, renal, or coronary ischemia with excessive acute drops >70 mmHg systolic 2, 5

Remember that patients with autonomic dysfunction are at increased risk for exaggerated BP responses to vasopressor agents 4