60 SURGICAL HYPERTENSION
Thomas A. Whitehill M.D.

1. What are the surgically correctable causes of hypertension?

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Renovascular hypertension, pheochromocytoma, Cushing’s syndrome, primary hyperaldosteronism (Conn’s syndrome), coarctation of the aorta, and unilateral renal parenchymal disease. Surgical hypertension accounts for 5% of all hypertensive patients.

2. Which form of surgical hypertension is most common?

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Renovascular hypertension is most common. Although the overall frequency of renovascular hypertension among patients with elevated diastolic blood pressure is about 3%, moderate or severe diastolic hypertension may be caused by renal artery occlusive disease in as many as 25% of cases. Pheochromocytoma, hyperaldosteronism, Cushing’s disease, and coarctation of the aorta each are found in only 0.1% of all hypertensive patients.

3. What are the most common causes of renovascular hypertension?

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Atherosclerosis causes 70% of cases; it affects men twice as often as women. The second most common cause is fibromuscular dysplasia (25%). Of the many pathologic subtypes, the most common is medial fibrodysplasia (85%); it invariably affects women. Last is developmental renal artery stenosis (10%), which is often associated with neurofibromatosis and abdominal aortic coarctation.

4. What clinical criteria support the pursuit of investigative studies for suspected renovascular hypertension?

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Although no clinical characteristics are pathognomonic of renovascular hypertension, the following findings strongly suggest the presence of an underlying renal artery stenotic lesion:

* Hypertension in very young individuals or in women younger than 50 years of age
* Rapid onset of severe hypertension after age 50 years
* Hypertension refractory to three-drug regimens
* Initial presentation with diastolic blood pressure > 115 mmHg or sudden worsening of presumed preexisting hypertension
* Accelerated or malignant hypertension
* Deterioration of renal function after the initiation of antihypertensive agents, especially angiotensin-converting enzyme (ACE) inhibitors
* Systolic or diastolic upper abdominal or flank bruits

5. What is the renin-angiotensin-aldosterone system (RAAS)?

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Renin is released from the juxtaglomerular apparatus of the kidney in response to changes in renal cortical afferent arteriolar perfusion pressure. Renin acts locally and in the systemic circulation on renin substrate (angiotensinogen), a nonvasoactive alpha2 globulin is produced in the liver to form angiotensin I. Angiotensin I undergoes enzymatic cleavage by ACE in the pulmonary circulation to produce angiotensin II, a potent vasopressor responsible for the vasoconstrictive element of renovascular hypertension. Angiotensin II increases adrenal gland production of aldosterone with subsequent retention of sodium and water; this process establishes the volume element of renovascular hypertension.

6. How do ACE inhibitors work?

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Direct inhibition of ACE decreases concentrations of angiotensin II, which leads to decreased vasopressor activity and decreased aldosterone secretion. Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.

7. Should patients with renovascular hypertension be treated medically or surgically?

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Although prospective randomized studies comparing drug and interventional therapy have not been published, surgical treatment and percutaneous transluminal renal angioplasty (PTRA) have been favored over drug therapy by most clinicians. The key is early recognition of the problem.

8. When should patients with renovascular hypertension be treated with PTRA?

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Clear indications for PTRA include nonorificial atherosclerotic lesions and medial fibrodysplastic lesions limited to the main renal artery.

9. What findings on history and physical examination should lead to a suspicion of pheochromocytoma?

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Pheochromocytomas are tumors primarily of the adrenal medulla and extraadrenal paraganglia cells. Approximately 90% of them are found within the adrenal gland, and the remaining 10% are scattered along the abdominal paravertebral sympathetic chain or in ganglia located remotely (e.g., urinary bladder, pelvic nerves). Tumors are classified as functioning when they produce catecholamines, always autonomously and usually in great excess. The predictable clinical effects of increased endogenous cathecholamine outpouring is sustained hypertension with episodes of increased blood pressure, tachycardia, headache, palpitations, or flushing. Rarely, patients maintain periods of normotension with infrequent and unpredictable paroxysmal episodes of hypertension.

10. How is pheochromocytoma diagnosed?

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Diagnosis is best confirmed by 24-hour urine collection for excreted catecholamines, metanephrines, and vanillylmandelic acid. The best single test to confirm the diagnosis of pheochromocytoma is still debated; some believe that the metanephrine level is the most precise (85%). Plasma catecholamines are also a specific test, but given the variability of results in individual patients and in many assays, the current approach should continue to emphasize the use of urinary catecholamines. Eighty percent of patients with pheochromocytoma have at least one urinary metabolite greater than twice the normal value. The diagnosis of pheochromocytoma should be followed by studies to localize the tumor.
KEY POINTS: SURGICAL HYPERTENSION

1. The causes of surgically correctable hypertension include renovascular hypertension, pheochromocytoma, Cushing’s syndrome, Conn’s syndrome, coarctation of the aorta, and unilateral renal parenchymal disease.
2. The most common cause of renovascular hypertension is atherosclerosis.
3. The diagnosis of pheochromocytoma is confirmed by 24-hour urine collection for excreted catecholamines, metanephrines, and vanillylmandelic acid.
4. Conn’s syndrome is characterized by hypertension, hypokalemia, hypernatremia, metabolic alkalosis, and periodic muscle weakness and paralysis.

11. What is the best test to localize a pheochromocytoma?

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Computed tomography (CT) scanning, magnetic resonance imaging (MRI), and 131I-metaiodobenzylguanidine (MIBG) scanning are three available imaging modalitites. Because 97% of pheochromocytomas are intraabdominal and almost always > 2 cm, an abdominal CT scan (thin cuts through the adrenal bed from the diaphragm to the aortic bifurcation) rarely misses a lesion and provides good anatomic detail. MRI has been increasingly used because 90% of pheochromocytomas are characteristically bright on T2 weighted images. MIBG is best used in patients who are suspected to have extraadrenal, multifocal, or recurrent pheochromocytoma. It is less sensitive than CT and MRI. MIBG is best reserved for patients at higher risk for multiple or extra-adrenal tumors and malignant pheochromocytoma.

12. Describe the immediate antihypertensive treatment in patients with pheochromocytoma.

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Hypertension from pheochromocytoma is caused by activation of vascular smooth muscle alpha1-receptors, which results in vasoconstriction. Thus, the best acute treatment is intravenous administration of an alpha1-antagonist or -blocker; options include phenoxybenzamine, prazosin, or terazosin. Second-line agents include calcium channel blockers and ACE inhibitors. Antiarrhythmic beta-blockade should be avoided initially because these agents cause both unopposed peripheral alpha1-receptor stimulation and decreased cardiac output (secondary to high vascular resistance). Congestive heart failure may be precipitated by beta-blocking the heart before lowering the blood pressure.

13. How is primary hyperaldosteronism (Conn’s syndrome) diagnosed?

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Conn’s syndrome, which results from autonomous mineralocorticoid hypersecretion, is characterized by hypertension, hypokalemia, hypernatremia, metabolic alkalosis, and periodic muscle weakness and paralysis, often caused by an aldosterone-secreting adenoma. The syndrome is now identified by the combined findings of hypokalemia, suppressed plasma renin activity despite sodium restriction, and high urinary and plasma aldosterone levels after sodium repletion in hypertensive patients.

14. Why does Cushing’s syndrome or Cushing’s disease cause hypertension?

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Both cause hypercortisolism or excessive amounts of glucocorticoids. In the cardiovascular system, glucocorticoids produce increased cardiac chronotropic and inotropic effects, along with an increased peripheral vascular resistance. Receptors in the distal renal tubules respond to glucocorticoids by increasing tubular resorption of sodium. These receptors belong to a different class from receptors that mediate the more potent actions of aldosterone.

15. What findings suggest aortic coarctation?

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Lower blood pressure in the legs than in the arms and diminished or absent femoral pulses. Rib notching may be evident on chest radiograph in patients with long-standing, hemodynamically significant coarctation. Bruits may be heard over the chest or abdominal wall. Adults may even develop congestive heart failure and renal failure.

16. How does aortic coarctation cause hypertension?

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No single cause has been identified. Mechanical obstruction to ventricular ejection is one component that leads to upper extremity hytertension. Hypoperfusion of the kidneys with resulting activation of the RAAS probably contributes. Abnormal aortic compliance, variable capacity of collateral vessels, and abnormal setting of baroreceptors also have been implicated.

References
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