Seth Politano, Eric Hsieh Essential hypertension is responsible for the majority of patients with hypertension (>90%). There are a number of features, however, that would clue you in to suspect a cause of secondary hypertension: In this younger patient with uncontrolled hypertension on three agents at maximum dosage, and clinical features suggestive of a secondary cause, secondary hypertension should be considered. Table 44.1 summarizes the causes of secondary hypertension and key clinical findings. TABLE 44.1 Causes of Secondary Hypertension and Key Physical Exam/Historical Findings Drugs of abuse (including cocaine or methamphetamine) as well as withdrawal from certain medications (i.e., alcohol and benzodiazepines) should be considered as they can cause both hypertension and anxiety. In addition, medical causes such as pheochromocytoma should be considered in this setting as they induce anxiety as well as hypertension. Pheochromocytomas are rare tumors of the adrenal medulla that derive from neural crest cells. Incidence ranges from 1 to 10 patients per million. They are present in from 0.1 to 1% of hypertensive patients. They usually present in patients between 30 and 40 years of age. Chromaffin cells can produce norepinephrine (most common), epinephrine, dopamine (more common with malignant tumors), and other substances such as vasoactive intestinal peptide and somatostatins. These are responsible for the clinical findings in patients and the variability of clinical presentation. Risk factors for pheochromocytoma include a family history of a genetic syndrome known to be associated with the disease. Table 44.2 lists disease associations with pheochromocytoma. TABLE 44.2 Disease Associations With Pheochromocytoma
A 28-Year-Old Female With Difficult-to-Control Hypertension
When should you be concerned about secondary hypertension?
What are the causes of secondary hypertension? What clues should you look for on history or physical exam?
Condition
Hints to Obtain from History/Exam/Workup
Hyperaldosteronism
Hypokalemia and metabolic alkalosis.
Pheochromocytoma
Palpitations, headache, diaphoresis, anxiety.
Cushing’s syndrome
Dorsocervical fat pad (“buffalo hump”), central obesity, moon facies, striae of the abdomen and thighs. Fatigue, easy bruising, myopathy, amenorrhea. Use of corticosteroids, smoker, and/or chronic lung disease suggesting an ectopic source.
Chronic kidney disease
Elevated potassium, serum creatinine, low serum bicarbonate, uremic symptoms.
Renal artery stenosis
Patient with atherosclerotic risk factors and with other atherosclerotic diseases (coronary artery disease, cerebral vascular accident, peripheral vascular disease). Renal bruit. Hypokalemia. Can present with sudden pulmonary edema and acute renal failure especially after starting angiotensin-converting enzyme in bilateral renal artery stenosis.
Fibromuscular dysplasia
Young female with headache, pulsatile tinnitus. Epigastric, renal, carotid bruits.
Coarctation of the aorta
Systolic blood pressure is >20 mm Hg higher in arms compared to legs. Absent or delayed femoral pulses. Chest radiograph with rib notching and/or “3” sign.
Thyroid diseases (both hyperthyroidism and hypothyroidism)
Fatigue, weight gain/loss, tremor, tachycardia/bradycardia, heat/cold intolerance, menstrual irregularities, bowel irregularities, warm/dry skin.
Obstructive sleep apnea
Excessive daytime somnolence, large neck circumference, snoring and apneic events reported by partner.
Acromegaly
Visual changes, fatigue, headaches. Observed change in appearance including jaw enlargement and coarse facial features. Change in hat/shoe/glove/ring size. Can have visual disturbances, secondary diabetes, sleep apnea.
Hyperparathyroidism
Fatigue, osteoporosis, nephrolithiasis, abdominal pain, constipation, nausea, anorexia, altered mental status, lethargy.
Does this finding increase your suspicion for any causes of the patient’s hypertension?
What is the epidemiology of pheochromocytomas?
What is the pathophysiology of the disease?
What are the risk factors for pheochromocytoma? What other conditions are associated with pheochromocytoma?
Condition
Clinical Hints/Findings
MEN IIA
Pheochromocytoma, hyperparathyroidism, and medullary carcinoma of the thyroid.
MEN IIB
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44 A 28-Year-Old Female With Difficult-to-Control Hypertension
Case 44