Secondary Hypertension

Renal hypertension due to renal parenchymal disease

• Consider renal disease as the cause of hypertension in patients with increased plasma creatinine, proteinuria and/or haematuria. If the patient has none of the aforementioned (not even microalbuminuria) and ultrasonography shows normal renal anatomy, a parenchymal disease is unlikely. Normal creatinine concentration alone does thus not rule out renal hypertension (see Increased Blood Creatinine Concentration, Egfr and Renal Function Tests).
• If the diagnosis is not evident, such as diabetic nephropathy, chronic glomerulonephritis, polycystic renal disease or secondary amyloidosis, refer the patient to a nephrologist. If necessary, the diagnosis is confirmed by renal biopsy.
• Long-term hypertension may also cause renal disease (so-called hypertensive nephrosclerosis).

Renovascular hypertension

• Suspect renovascular hypertension when
  • the patient has therapy-resistant hypertension or the response to therapy declines
  • the patient has clinical signs of general arteriosclerosis; especially peripheral arterial disease increases the probability of renal artery stenosis
  • an ACE inhibitor or an angiotensin receptor blocker causes an unexpectedly large increase in plasma creatinine concentration.
• Investigations at hospital in case of suspicion: primarily Doppler ultrasonography; if necessary, an MR angiography or a CT scan is performed (the choice of investigation depends on the degree of renal insufficiency).
  • Captopril-enhanced nephrography is of no benefit in patients with renal failure.

Causes and initial investigations

1. Primary aldosteronism (Conn's syndrome Primary Hyperaldosteronism (Pha)) is the most common cause of endocrine hypertension and clearly more common than earlier thought.
   • The prevalence may be as high as 20% in patients with treatment-resistant hypertension.
   • The condition is a typical diagnosis by exclusion, since according to current knowledge only 9-37% of the patients have hypokalaemia.
   • Consider the diagnosis if the patient has a low plasma potassium concentration at onset (< 3.5 mmol/l) or persistent hypokalaemia on a small dose of diuretics (plasma potassium < 3 mmol/l).
   • High serum aldosterone concentration in association with low plasma renin concentration suggests primary hyperaldosteronism. For diagnostics: see Primary Hyperaldosteronism (Pha).
   • The cause is either a cortical adenoma or bilateral cortical hyperplasia (micro- or macronodular).
     • An adenoma is usually managed surgically.
     • Hyperplasia is more common than earlier thought because up to 50% of adenoma patients remain hypertensive after surgery.
   • Treatment aims at normotension, normokalaemia and normalization of excessive aldosterone secretion.
   • Spironolactone is the primary drug. It binds to mineralocorticoid receptors, thus inhibiting the effect of aldosterone. Alternatives include eplerenone or amiloride.
2. Hyperparathyroidism Hypercalcaemia and Hyperparathyroidism
   • Four times more common in women than in men. Prevalence increases with age.
   • Traditionally the syndrome has had a many-faceted clinical picture: urinary tract stones, osteopenia/osteoporosis, general weakness, nausea, constipation, abdominal pains, changes of mood. Nowadays, the disease is more often diagnosed in symptomless patients on the basis of high plasma calcium concentration.
   • The cause is an adenoma of the parathyroid gland.
   • Investigations
     • Initially, plasma ionized calcium (or plasma calcium and albumin)
     • In the next phase, plasma PTH (increased also in secondary hyperparathyroidism caused by renal failure, in which plasma calcium concentration usually is low)
   • The mechanism behind hypertension is unclear; it is possibly caused by hypercalcaemia.
   • The choice of treatment depends on other possible symptoms.
   • The adenoma can be surgically removed.
   • Hypertension in a patient with mild hypercalcaemia and only few symptoms is treated pharmacologically and the patient is monitored.
3. Cushing's syndrome Cushing's Syndrome
   • Typical clinical manifestations are the most important diagnostic clue.
   • Do not forget to ask about the patient's use of glucocorticoids.
   • Investigation in primary care: short 1 or 1.5 mg dexamethason test Cushing's Syndrome
   • The treatment is surgical.
4. Pheochromocytoma Rare Endocrine Tumours
   • Typical clinical manifestations are the most important diagnostic clue. Blood pressure rises paroxysmally (40%) or permanently.
   • Rare (< 1% of all cases of secondary hypertension)
   • Caused by an adenoma that produces catecholamines
     • 90% located in the adrenal gland
     • 90% benign
   • Diagnosis by exclusion; symptoms are various
     • serum metanephrine and normetanephrine
   • The treatment is usually surgical.
5. Hyperthyroidism Hyperthyroidism or hypothyroidism Hypothyroidism
   • Both hyper- and hypothyroidism are associated with hypertension. In hypothyroidism, the diastolic blood pressure more commonly increases, while in hyperthyroidism more commonly the systolic blood pressure.

Exogenous causes

• Exogenous causes are first to be excluded.
• Drugs
  • Cyclosporin
  • Tacrolimus
  • NSAIDs
  • Oral contraceptives
    • Always ask the method of contraception from women under 40 years of age. Hypertension is a cause for changing to another method of contraception Hormonal Contraception. Hormone replacement therapy does not elevate blood pressure.
  • Glucocorticoids, mineralocorticoids, anabolic steroids
  • Sympathomimetic-containing drugs for rhinits, cough and allergy in long-term use
  • Some psychotropic drugs (e.g. venlafaxine, duloxetine)
  • Erythropoietin
• Heavy alcohol use
• Illicit drugs (cocaine, amphetamine)
• Liquorice
  • Hypertension, hypokalaemia, low concentrations of plasma renin and serum aldosterone
  • Glycyrrhetinic acid is a metabolite of liquorice. It inhibits the enzyme (11-beta hydroxysteroid dehydrogenase, 11β-OHSD) that inactivates cortisol. This leads to increased binding of cortisol to mineralocorticoid receptors and causes a state that resembles hyperaldosteronism.
  • The enzyme inhibition lasts up to 2-3 weeks after ingestion of liquorice.
  • Deficiency of 11β-OHSD enzyme may also be congenital.

Endogenous causes