Pheochromocytomas are rare catecholamine-producing tumors of the adrenal chromaffin cells. Paragangliomas are even rarer extra-adrenal catecholamine-producing or nonfunctional tumors of sympathetic and parasympathetic ganglia. The diagnosis should be suggested when hypertension is accompanied by paroxysms of headaches, palpitations, pallor, or diaphoresis. However, the most common presentation of pheochromocytoma is an adrenal inci- dentaloma, an incidental adrenal mass discovered unexpectedly on abdominal imaging for another indication. In some patients, 16:000
BP mm Hg
50 100 150 200 250
Sleep
24:00 16:00
hr:min
0 50 100 150 200 250
Office visits
15:00 24:00 15:00
hr:min
Fig. 12.9 Twenty-four hour ambulatory blood pressure (BP) monitor tracings in two different patients. (A) Optimal blood pressure (BP) in a healthy 37-year-old woman. The normal variability in BP, the nocturnal dip in BP during sleep, and the sharp increase in BP on awakening are noted. (B) Pronounced white coat effect in an 80-year-old woman referred for evaluation of medically refractory hypertension. Documentation of the white coat effect prevented overtreatment of the patient’s isolated systolic hypertension.
11:000
BP mm Hg
50 100 150 200
250 Masked
hypertension Office
BP
Nocturnal hypertension
24:00 11:00
hr:min
Fig. 12.10 Twenty-four hour ambulatory blood pressure (BP) monitor tracing shows both masked hypertension and nocturnal hypertension in a 55-year-old man with stage 3 chronic kidney disease. Treatment with three different antihypertensive medications in this patient produced an office BP of 125/75 mm Hg, which seems to be at goal. However, progressive hypertensive heart disease and deterioration of renal func- tion suggested masked hypertension. Ambulatory monitoring revealed that the patient’s treated BP was much higher out of the office, docu- menting both masked hypertension (ambulatory BP of 175/95 mm Hg) and sustained nocturnal hypertension (BP of 175/90 mm Hg). Additional medication was added. (Courtesy of Ronald G. Victor, MD, Hyperten- sion Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.)
pheochromocytoma is misdiagnosed as panic disorder. A family his- tory of early-onset hypertension may suggest pheochromocytoma as part of the multiple endocrine neoplasia syndromes or familial para- ganglioma. If the diagnosis is missed, then outpouring of catechol- amines from the tumor can cause an unsuspected hypertensive crisis during unrelated radiologic or surgical procedures; the perioperative mortality exceeds 80% in such patients.
Laboratory confirmation of pheochromocytoma is made by demonstrating elevated levels of plasma or urinary metanephrines;
these are methylated derivatives of norepinephrine and epinephrine that are made in the adrenal medulla and continually leak out into
the plasma even between blood pressure spikes. Pheochromocytomas are typically large adrenal tumors that can usually be localized by CT or MR imaging, although nuclear scanning with specific isotopes that localize to chromaffin tissue is occasionally needed to identify smaller tumors and paragangliomas.
Treatment of these tumors is surgical resection. Patients must receive adequate preoperative management with α-blockade followed by β-blockade and volume expansion to prevent the hemodynamic swings that can occur during surgical manipulation of the tumor. For unresectable tumors, chronic therapy with the α-adrenergic blocker phenoxybenzamine is usually effective.
A
Proximal stenosis
B
“String of beads”
Fig. 12.11 Computed tomography (CT) angiogram with three-dimensional reconstruction. (A) Classic string- of-beads lesion of fibromuscular dysplasia. (B) Severe proximal atherosclerotic stenosis of the right renal artery. (Courtesy of Bart Domatch, MD, Radiology Department, University of Texas Southwestern Medical Center, Dallas, Texas.)
TABLE 12.6
Guide to Evaluation of Secondary Hypertension
Probable Diagnosis Clinical Clues Diagnostic Testing
Renal parenchymal hypertension Estimated GFR <60 mL/min/1.73 m2 Urine albumin:creatinine >30 mg/g
Renal ultrasound Renovascular disease New elevation in serum creatinine, significant
elevation in serum creatinine with initiation of ACEI or ARBs, refractory hypertension, flash pulmonary edema, abdominal bruit
MR or CT angiography, invasive angiogram
Coarctation of the aorta pulses, arm BP >leg Arm pulses >leg chest MR or CT, aortogram BP, chest bruits, rib notching on chest radiograph
Primary aldosteronism Hypokalemia, refractory hypertension Plasma renin and aldosterone, 24-hr urine potassium, 24-hr urine aldosterone and potassium after salt loading, adrenal CT scan, adrenal vein sampling Cushing’s syndrome Truncal obesity, wide and blanching 24-hr urine cortisol, purple striae, muscle weakness,
dexamethasone suppression test, adrenal CT scan Pheochromocytoma Spells of paroxysmal hypertension, palpitations,
perspiration, pallor
Plasma and 24-hr urine metanephrines and catechol- amines, adrenal CT scan
Pain in the head Diabetes
Obstructive sleep apnea Loud snoring, daytime somnolence, obesity, large neck Sleep study
ACEI, Angiotensin-converting enzyme inhibitor; ARBs, angiotensin-receptor blockers; BP, blood pressure; CT, computed tomography; GFR, glomer- ular filtration rate; MR, magnetic resonance.
153 CHAPTER 12 Vascular Diseases and Hypertension
TABLE 12.7
Oral Antihypertensive Agents
Drug
Dose Range, Total mg/day (Doses Per Day)
Diuretics
Thiazide Diuretics
Hydrochlorothiazide (HCTZ) 6.25-50 (1)
Chlorthalidone 12.5-25 (1)
Indapamide 1.25-5 (1)
Metolazone 2.5-5 (1)
Loop Diuretics
Furosemide 20-160 (2)
Torsemide 2.5-20 (1-2)
Bumetanide 0.5-2 (2)
Ethacrynic acid 25-100 (2)
Potassium-Sparing
Amiloride 5-20 (1)
Triamterene 25-100 (1)
Spironolactone 12.5-400 (1-2)
Eplerenone 25-100 (1-2)
β-Blockers
Acebutolol 200-800 (2)
Atenolol 25-100 (1)
Betaxolol 5-20 (1)
Bisoprolol 2.5-20 (1)
Carteolol 2.5-10 (1)
Metoprolol 50-450 (2)
Metoprolol XL 50-200 (1-2)
Nadolol 20-320 (1)
Nebivolol 5-40 (1)
Penbutolol 10-80 (1)
Pindolol 10-60 (2)
Propranolol 40-180 (2)
Propranolol LA 60-180 (1-2)
Timolol 20-60 (2)
β/α-Blockers
Labetalol 200-2400 (2)
Carvedilol 6.25-50 (2)
Calcium-Channel Blockers Dihydropyridines
Amlodipine 2.5-10 (1)
Felodipine 2.5-20 (1-2)
Isradipine CR 2.5-20 (2)
Nicardipine SR 30-120 (2)
Nifedipine XL 30-120 (1)
Nisoldipine 10-40 (12)
Nondihydropyridines
Diltiazem CD 120-540 (1)
Verapamil HS 120-480 (1)
Angiotensin-Converting Enzyme Inhibitors
Benazepril 10-80 (12)
Captopril 25-150 (2)
Enalapril 2.5-40 (2)
Fosinopril 10-80 (1-2)
Lisinopril 5-80 (1-2)
Moexipril 7.5-30 (1)
Perindopril 4-16 (1)
Quinapril 5-80 (1-2)
Drug
Dose Range, Total mg/day (Doses Per Day)
Ramipril 2.5-20 (1)
Trandolapril 1-8 (1)
Angiotensin-Receptor Blockers
Azilsartan 40-80 mg (1)
Candesartan 8-32 (1)
Eprosartan 400-800 (1-2)
Irbesartan 150-300 (1)
Losartan 25-100 (2)
Olmesartan 5-40 (1)
Telmisartan 20-80 (1)
Valsartan 80-320 (1-2)
Direct Renin Inhibitor
Aliskiren 75-300 (1)
α-Blockers
Doxazosin 1-16 (1)
Prazosin 1-40 (2-3)
Terazosin 1-20 (1)
Phenoxybenzamine 20-120 (2) for pheochromocytoma Central Sympatholytics
Clonidine 0.2-1.2 (2-3)
Clonidine patch 0.1-0.6 (weekly)
Guanabenz 2-32 (2)
Guanfacine 1-3 (1) (q hs)
Methyldopa 250-1000 (2)
Reserpine 0.05-0.25 (1)
Direct Vasodilators
Hydralazine 10-200 (2)
Minoxidil 2.5-100 (1)
Fixed-Dose Combinations
Aliskiren/HCTZ 75-300/12.5-25 (1)
Amiloride/HCTZ 5/50 (1)
Amlodipine/benazepril 2.5-5/10-20 (1) Amlodipine/valsartan 5-10/160-320 (1) Amlodipine/olmesartan 5-10/20-40 (1) Atenolol/chlorthalidone 50-100/25 (1) Azilsartan/chlorthalidone 40-80/12.5-25 (1)
Benazepril/HCTZ 5-20/6.25-25 (1)
Bisoprolol/HCTZ 2.5-10/6.25 (1)
Candesartan/HCTZ 16-32/12.5-25 (1)
Enalapril/HCTZ 5-10/25 (1-2)
Eprosartan/HCTZ 600/12.5-25 (1)
Fosinopril/HCTZ 10-20/12.5 (1)
Irbesartan/HCTZ 15-30/12.5-25 (1)
Losartan/HCTZ 50-100/12.5-25 (1)
Olmesartan/amlodipine 20-40/5-10 (1)
Olmesartan/HCTZ 20-40/12.5-25 (1)
Olmesartan/amlodipine/HCTZ 20-40/5-10/12.5-25 (1) Spironolactone/HCTZ 25/25 (1/2-1)
Telmisartan/HCTZ 40-80/12.5-25 (1)
Trandolapril/verapamil 2-4/180-240 (1)
Triamterene/HCTZ 37.5/25 (1/2-1)
Valsartan/HCTZ 80-160/12.5-25 (1)
Valsartan/amlodipine/HCTZ 80-160/5-10/12.5-25 (1)
Pheochromocytoma is a great masquerader and the large differ- ential diagnosis includes causes of neurogenic hypertension such as sympathomimetic agents (cocaine, methamphetamine), baroreflex failure, and obstructive sleep apnea. A history of surgery and radi- ation therapy for head-and-neck tumors suggests the possibility of baroreceptor damage. Loud snoring, obesity, and somnolence sug- gest obstructive sleep apnea. Weight loss, continuous positive airway pressure, and corrective surgery improve BP control in some patients with sleep apnea.
Other causes of secondary hypertension include nonsteroidal anti-inflammatory drugs (NSAIDs), hypothyroidism, hyperthyroid- ism coarctation of the aorta, and immunosuppressive drugs, especially cyclosporine and tacrolimus.