Secondary Hypertension

~10% of cases of hypertension are secondary to another disease process (1). Secondary hypertension should be evaluated in young patients with otherwise-unexplained hypertension or patients with difficult-to-control hypertension.

The most common etiologies are:

  • Hyperthyroidism
  • Hyperaldosteronism
  • Hypercalcemia
  • Obstructive Sleep Apnea
  • Renovascular Hypertension
  • Chronic Kidney Disease
  • Coarctation of the Aorta
  • Cushing Syndrome
  • PheoChromocytoma

One mnemonic to remember these is: HHH OR CCCC

Hyperthyroidism

  • Typically manifests as systolic hypertension through thyroid hormone-mediated increase in cardiac output and decrease in peripheral vascular resistance (2)
  • Screen by checking TSH with reflex T4
  • For more, see Hyperthyroidism

Hyperaldosteronism

  • Classic triad: Resistant hypertension, metabolic alkalosis, hypokalemia
  • Secondary to either adrenal hyperplasia or functional adenoma (Conn Syndrome)
  • Screening: plasma aldosterone concentration:plasma renin activity ratio
  • Over 90% sensitive and specific if BOTH ratio > 30 AND plasma aldosterone consentration > 20 ng/dL (3)
  • Imaging (if plasma aldosterone concentration:plasma renin activity ratio is elevated)
    • CT abdomen/pelvis with contrast to evaluate for source (Adrenal hyperplasia and adenomas secreting excess aldosterone may not always be visualized)
  • Adrenal vein sampling
    • Confirms source (ensures an adenoma on imaging is functioning, rather than an incidental, non-functioning adenoma)
  • Treatment
    • Hyperfunctioning adenoma: Unilateral adrenalectomy
      • Consider ACTH stimulation test post-operatively to assess for adrenal insufficiency (4)
    • Bilateral adrenal hyperplasia: Aldosterone receptor antagonist such as spironolactone or eplerenone

Hypercalcemia

  • Mechanism: Increased calcium levels act directly on vascular smooth muscle to increase peripheral vascular resistance. Calcium also indirectly affects blood pressure by causing an increased level of catecholamine secretion from the adrenal glands (5)
  • Screening test is a simple serum calcium level or ionized calcium level
  • see Hypercalcemia for further workup and treatment if calcium level is elevated

Obstructive Sleep Apnea

  • Mechanism: Intermittent hypoxia likely causes sustained, increased sympathetic activation leading to hypertension (6)
  • Screening: History (STOP BANG) (7)
    • Snoring
    • Tiredness during the day
    • Observation of apnea by someone else
    • Pressure (blood pressure elevation)
    • Body mass index >35
    • Age older than 50 years
    • Neck circumference >40 cm
    • Gender (males are at higher risk)
  • Diagnosed by polysomnography (sleep study) showing apnea/hypopnea index of >15 (8)
  • Treatment: Continuous positive airway pressure (CPAP) while sleeping, nocturnal oral airway appliance, surgery

Renovascular Hypertension

  • Mechanism: Decreased perfusion of kidneys -> increased secretion of renin, activating RAAS system –> Increase in intravascular volume and SVR
  • Diagnosis: Renal artery ultrasound
  • Treatment
    • Medical optimization (ACE-Inhibitors/ARBs, unless bilateral renal artery stenosis)
    • Revascularization (if new-onset, severe, or medical therapy insufficient)
      • Three randomized controlled trials (STAR, ASTRAL, and CORAL) failed to show that renal artery angioplasty confers additional benefit above optimal medical therapy for patients with atherosclerotic renovascular disease who have stable kidney function
      • Percutaneous angioplasty and stenting
      • Surgical revascularization (if complex anatomic lesions)

Chronic Kidney Disease

  • Mechanism (9)
    • Causes endothelial dysfunction -> increases SVR
    • Increases sodium retention -> increases intravascular volume
    • Increases sympathetic activation -> increases SVR
    • Increases renin secretion -> increases intravascular volume and SVR
  • see CKD regarding management

Coarctation of the Aorta

  • Pressure increases proximal to the coarctation. May create a pressure discrepancy in the upper extremities if the coarctation is proximal to the left subclavian artery
  • Measure blood pressure in BOTH arms as well as lower extremities
  • Diagnosis by echocardiography/ultrasound
  • Indications for intervention (surgical or transcatheter intervention) (10)
    • Peak to peak coarctation gradient ≥ 20 mmHg (as measured via catheterization)
    • Radiographic evidence of significant collateral flow
    • Hypertension is attributable to the coarctation
    • Heart failure attributable to coarctation
    • Lower extremity claudication

Cushing Syndrome

  • Cortisol-Induced Hypertension Mechanism (11)
    • Mineralocorticoid effects (cortisol saturates the cortisol receptor, leading to “spillover” to the mineralocorticoid receptor)
    • Increased angiotensin II receptors
    • Inhibition of vasodilators (decreasing activity of ANP and decreasing production of nitric oxide synthase)
    • Increased vascular sensitivity to vasopressors
  • See Cushing Syndrome regarding diagnosis and treatment

Pheochromocytoma (/Paraganglioma)

  • Tumors of neural crest cell origin that secrete catecholamines
  • Classic symptoms: Hypertension, headache, palpitations, diaphoresis
  • Diagnosis: Serum metanephrine and normetanephrine levels (which are metabolites of epinephrine and norepinephrine, respectively) followed by imaging and biopsy
  • Treatment: Surgical resection. Preoperatively, patients should be treated with an alpha blockade (typically, phenoxybenzamine)

References:

  1. Berta, E., Lengyel, I., Halmi, S., Zrínyi, M., Erdei, A., Harangi, M., . . . Bodor, M. (2019, July 17). Hypertension in thyroid disorders. Retrieved March 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652798/
  2. Iglesias P;Acosta M;Sánchez R;Fernández-Reyes MJ;Mon C;Díez JJ;. (n.d.). Ambulatory blood pressure monitoring in patients with hyperthyroidism before and after control of thyroid function. Retrieved March 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/15963064/
  3. Dominguez, A. (2020, November 21). Hyperaldosteronism. Retrieved March 24, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK499983/
  4. Heinrich, D., Adolf, C., Holler, F., Lechner, B., Schneider, H., Riester, A., . . . Reincke, M. (2019, June 21). Adrenal insufficiency AFTER Unilateral adrenalectomy in Primary Aldosteronism: Long-term outcome and clinical impact. Retrieved March 24, 2021, from https://academic.oup.com/jcem/article/104/11/5658/5520803
  5. Eiam-Ong S;Eiam-Ong S;Punsin P;Sitprija V;Chaiyabutr N;. (n.d.). Acute hypercalcemia-induced hypertension: The roles of calcium channel and alpha-1 adrenergic receptor. Retrieved March 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/15217180/
  6. Phillips, C., & O’Driscoll, D. (2013, May 10). Hypertension and obstructive sleep apnea. Retrieved March 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666153/
  7. Semelka, M., Wilson, J., & Floyd, R. (2016, September 01). Diagnosis and treatment of obstructive sleep apnea in adults. Retrieved March 24, 2021, from https://www.aafp.org/afp/2016/0901/p355.html
  8. Goyal, M., MD, & Johnson, J., DO. (2017, March). Obstructive Sleep Apnea Diagnosis and Management. Retrieved March 23, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140019/
  9. Lee, B J., Wei, J, Weir, M R. Hypertension in CKD: Core Curriculum 2019. (2019, July 1). Retrieved April 20, 2021, from https://www.ajkd.org/article/S0272-6386(19)30094-0/fulltext
  10. Agasthi, P., Pujari, S., Tseng, A., Graziano, J., Marcotte, F., Majdalany, D., . . . Arsanjani, R. (2020, May 26). Management of adults with coarctation of aorta. Retrieved April 20, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284000/
  11. Singh, Y., Kotwal, N., & Menon, A. (2011, October). Endocrine hypertension – Cushing’s syndrome. Retrieved April 20, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230089/

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