1. Besides renovascular and the traditional endocrine causes of hypertension, what are eight uncommon, but important, causes of secondary hypertension?

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  Obstructive sleep apnea (typically causing hyperaldosteronism)

  
  
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  Drug-induced hypertension (especially nonsteroidal antiinflammatory drugs, steroids, and/or other immunosuppressants)

  
  
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  Thyroid disorders (hypothyroidism more commonly than hyperthyroidism)

  
  
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  Coarctation of the aorta (typically manifested as different blood pressures in the arms or a lower blood pressure in the legs)

  
  
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  Hyperparathyroidism (hypertension is found in only 10% of patients with hyperparathyroidism in the general population and up to 60% of those with additional endocrinopathies, especially multiple endocrine neoplasia syndrome. Removal of the parathyroid adenoma does not always lower blood pressure

  
  
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  Acromegaly (18% to 60% [increasing with age at diagnosis] of patients with acromegaly have hypertension; many have left ventricular hypertrophy; most respond well to antihypertensive drugs; and some have blood pressures that revert to normal when the acromegaly is cured)

  
  
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  “Neurogenic” hypertension

  
  
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  Liddle syndrome (a rare genetic disorder that is also called pseudohyperaldosteronism)

2. What is the usual sequence of diagnostic and therapeutic steps for patients with sleep apnea?

Most such patients are overweight or obese, and many have bed partners who note snoring and/or witness apneic episodes during sleep. The Berlin questionnaire may be useful in screening, but a polysomnographic sleep study is typically required for diagnosis. Cohort studies have shown a significant improvement in survival if continuous positive airway pressure (CPAP) is used during sleep; a meta-analysis of 18 randomized, clinical trials suggests that CPAP significantly lowers 24-hour ambulatory blood pressures (by about 2/2 mm Hg) but not cardiovascular events (odds ratio [OR] = 0.84, 95% confidence interval [CI]: 0.62 to 1.13) or death (OR = 0.85, 95% CI: 0.35 to 2.06). In patients with hyperaldosteronism and sleep apnea, CPAP is recommended primarily for its improvement in quality of life; blood pressure can typically be reduced even further by adding spironolactone or eplerenone; a serum aldosterone/renin ratio is often measured before starting such treatment.

3. What are the most common drug-induced causes of hypertension?

Nonsteroidal antiinflammatory drugs (including agents that are more selective for the second isoform of cyclooxygenase, e.g., celecoxib) are probably the most common cause of drug-induced hypertension due to their widespread, unregulated use. The mechanism is not well worked out, although alteration in intrarenal prostaglandin metabolism, sodium retention, and edema formation is likely.

Anabolic steroids, glucocorticoids, and mineralocorticoids all raise blood pressure, and the usual recommendation is to use the lowest possible dose for the shortest possible time to decrease the risk of long-term consequences (including hypertension and its sequelae).

Patients with chronic kidney disease or transplant recipients often take drugs that raise blood pressure, including cyclosporine, erythropoietin, and tacrolimus. Elevated blood pressures after use of tyrosine kinase inhibitors (given for various cancers) are associated with a favorable tumor response. These drugs are so important for the patient’s overall health that they are continued, and more antihypertensive agents are added.

Many “street” drugs can raise blood pressure acutely; acute withdrawal from nicotine, heroin, or other opioids can have the same effect. The drugs most often causing hypertension in an Emergency Department setting are cocaine, methylphenidate (or other stimulants), gamma-hydroxybutyrate, ketamine, and ergotamine. Chronic ingestion of alcohol increases the risk of hypertension; a meta-analysis of 36 trials involving 2865 participants showed a dose-dependent, significant reduction in blood pressure (by 5.5/3.0 mm Hg, on average) in those who reduced their consumption from >2 drinks/day.

A large variety of other prescription drugs (e.g., phenylpropanolamines, oral contraceptive pills, venlafaxine) can raise blood pressure. A wide variety of other drugs can interfere with antihypertensive medications either directly or via inhibition of metabolic pathways (typically hepatic cytochrome P ₄₅₀ or CYP oxidoreductases). Stimulants used in the treatment of ADHD can cause hypertension. methylphenidate, dextroamphetamine, and lisdexamfetamine can cause hypertension.

4. What are the “usual and customary” antihypertensive treatment strategies for patients who have drug-induced hypertension?

See Table 66.1 .

5. What are three primary diseases of the thyroid that can affect blood pressure?

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  Hypothyroidism is the most common thyroid disease that is associated with hypertension (3% of newly diagnosed hypertensives), although the mechanism is unclear. After appropriate thyroid replacement, blood pressure typically falls without specific antihypertensive therapy. Because hypothyroidism is a rare cause of secondary hypertension, a serum-ultrasensitive thyroid-stimulating hormone was not generally recommended as an initial test for all patients newly diagnosed with hypertension until the 2017 American College of Cardiology/American Heart Association hypertension guidelines (although other historical and physical findings might justify it).

  
  
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  Hyperthyroidism typically presents in younger patients with tachycardia, hypertension, a wide pulse pressure, and other traditional signs, but older people sometimes lack one or more of these typical features. The now-standard initial test is a serum-ultrasensitive thyroid-stimulating hormone level. Therapy is usually propranolol, which treats the hypertension, tachycardia, and (at least according to traditional pharmacologic teachings, now widely challenged) inhibits the peripheral conversion of thyroxine (T ₄ ) to triiodothyronine (T ₃ ).