Treatment. Surgical resection of the tumor is often curative. For pituitary tumors (Cushing’s disease), transsphenoidal resection is the standard of care.39 For adrenal adenomas, unilateral adrenalectomy is the best option.39
Pheochromocytomas: Most are adrenal, sporadic, and benign
Pheochromocytomas—neuroendocrine, catecholamine-secreting tumors that develop from the adrenal medulla—are another cause of secondary hypertension. Catecholamines include norepinephrine and epinephrine and, rarely, dopamine secreted either intermittently or continuously. The prevalence of pheochromocytoma is 0.1% to 0.3% among patients with hypertension.5,6,28 A “rule of 10” (90:10 ratio) is often applied to pheochromocytomas because of the following:
- 90% of pheochromocytomas are located in the adrenal glands; the remaining 10% are extra-adrenal and can occur anywhere along the sympathetic chain40
- 90% are sporadic; 10% are familial41
- 90% are benign; 10% are malignant40
- 90% are found in adults; 10% affect children.42
Signs and symptoms of pheochromocytomas include palpitations, headache, dyspnea, diaphoresis, and flushing, as well as paroxysmal hypertension.40 Measurement of 24-hour urinary catecholamines and their metabolites has been the screening test of choice,43 but recent evidence suggests that measurement of plasma metanephrine and normetanephrine is a far more sensitive screen.10
Treatment. Surgical resection is the treatment of choice. Alpha blockade is started 7 to 10 days preoperatively;44,45 a beta-blocker is added only after an adequate alpha blockade has been established, as unopposed alpha stimulation could precipitate a hypertensive crisis. Laparoscopic adrenalectomy is routinely performed for small (<5 cm) pheochromocytomas.46,47
Don’t forget these (relatively) common secondary causes
Obstructive sleep apnea (OSA) is one of the most common conditions associated with resistant hypertension.48 Signs and symptoms include snoring, daytime somnolence, and obesity (body mass index ≥30 kg/m2).
OSA involves upper airway collapse during inspiration, causing intermittent hypoxemia with resultant sympathetic nervous system activation.11 The underlying mechanism of OSA-induced hypertension is strongly related to sympathetic activation.49 Overnight polysomnography is required for diagnosis.11
Continuous positive airway pressure is the treatment of choice for patients unable to lose weight.11
Pregnancy-induced hypertension is the most common medical problem encountered in pregnancy. It occurs in up to 15% of pregnancies, either during the pregnancy itself or postpartum. Postpartum hypertension may be related to preexisting chronic hypertension or to the persistence of gestational hypertension or preeclampsia, which usually occurs after 20 weeks’ gestation and is characterized by the presence of hypertension and proteinuria.50 Methyldopa and labetalol are commonly used treatments for hypertension during pregnancy.51
Drug-induced hypertension. Several drugs can cause or exacerbate hypertension, rendering it resistant to therapy. A careful review of the patient’s medication regimen is essential. Generally, drug-induced hypertension falls into 2 broad categories based on mechanism of action: volume overload and sympathetic activity.52,53
Corticosteroids can elevate BP in a dose-dependent manner, as a result of volume overload. Glycyrrhizic acid, the main ingredient in licorice, produces a state of excess mineralocorticoid, with a similar effect. Estrogen-containing oral contraceptives can cause an increased synthesis of angiotensin in the liver, resulting in greater aldosterone secretion and volume overload.
Drugs that stimulate sympathetic activity include cocaine, ephedrine, amphetamine, phenylephrine, phenylpropanolamine, caffeine, and alcohol. Nonsteroidal anti-inflammatory drugs may interfere with the action of ACE inhibitors and cause renal vasoconstriction, leading to sodium and water retention and hypertension.54
Discontinuation of the medication in question is preferable. In many cases, an agent that does not affect BP can be found to replace it.
If the patient is a child
Hypertension is uncommon in young people. However, coarctation of the aorta, a congenital narrowing associated with secondary hypertension, is typically diagnosed in childhood. In rare cases, the condition remains undetected well into adulthood.55 Clinical signs include weak femoral pulses, visible pulsations in the neck, a systolic murmur of the anterior and posterior thorax, and elevated BP in the upper extremities with low BP in the lower extremities.
Thus, once hypertension is confirmed in a young patient, BP should be measured in both arms and legs.56 Delayed or absent femoral pulses and a difference in systolic BP of ≥20 mm Hg between the arms and legs provide evidence of aortic coarctation.57 In adults, stenting is the initial treatment for this condition because of the morbidity associated with surgery.57 Stenting is an option for children with this condition, as well.58
CORRESPONDENCE Bernard M. Karnath, MD, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555; bmkarnat@utmb.edu