Hypertension is the Primary Risk in Hypercorticism, Not Adrenal Crisis or Hyperkalemia
Patients with hypercorticism are at significantly higher risk for hypertension compared to adrenal crisis or hyperkalemia. 1 Hypercorticism, also known as Cushing syndrome, is characterized by chronic excessive glucocorticoid exposure that leads to a constellation of symptoms including hypertension, which is present in approximately 80% of adult patients with the condition.
Pathophysiological Mechanisms of Hypertension in Hypercorticism
Hypercorticism causes hypertension through several mechanisms:
- Mineralocorticoid activity: Excess cortisol overwhelms the enzyme that normally prevents cortisol from binding to mineralocorticoid receptors, leading to sodium retention and potassium excretion 2
- Activation of the renin-angiotensin system 2
- Enhancement of vasoactive substances and increased peripheral vascular resistance 2
- Suppression of vasodilatory systems 2
- Central nervous system effects through both glucocorticoid and mineralocorticoid receptors 2
Clinical Presentation and Diagnosis
Patients with hypercorticism typically present with:
- Central obesity, "moon" face, dorsal and supraclavicular fat pads
- Wide (1-cm) violaceous striae
- Hirsutism
- Proximal muscle weakness
- Depression
- Hyperglycemia 1
Diagnostic testing includes:
- Overnight 1-mg dexamethasone suppression test
- 24-hour urinary free cortisol excretion (preferably multiple measurements)
- Midnight salivary cortisol 1
Risk of Adrenal Crisis and Hyperkalemia
While hypertension is a predominant feature of hypercorticism, adrenal crisis and hyperkalemia are not typically associated with this condition:
Adrenal crisis: This is characterized by acute adrenal insufficiency with hypocortisolism, not hypercorticism. Adrenal crisis presents with hypotension, not hypertension 1
Hyperkalemia: Hypercorticism actually tends to cause hypokalemia rather than hyperkalemia due to the mineralocorticoid effects of excess cortisol, which promotes potassium excretion 1, 2
Cardiovascular Impact of Hypercorticism
The cardiovascular impact of hypercorticism is significant:
- Patients with hypercorticism demonstrate high cardiovascular morbidity and mortality 3
- Hypercorticism-induced cardiovascular comorbidities include hypertension, impaired glucose metabolism, dyslipidemia, and obesity 3
- These cardiovascular risk factors lead to increased rates of cardiovascular events and mortality 3
- This risk is reduced, but not completely reversed, even after successful treatment of hypercorticism 3
Treatment Considerations
Treatment of hypertension in hypercorticism requires careful medication selection:
- Avoid thiazides and furosemide as they may worsen metabolic abnormalities 2
- Mineralocorticoid receptor antagonists (spironolactone, eplerenone) are effective options 2
- Angiotensin II blockers and ACE inhibitors are good antihypertensive choices 2
- PPAR-γ agonists may help address insulin resistance aspects 2
The definitive treatment is addressing the underlying cause of hypercorticism, which may include:
- Surgical removal of adrenal or pituitary tumors
- Medication to block cortisol production or effects
- Discontinuation of exogenous glucocorticoids if that is the cause 1
Special Considerations
In patients with subclinical hypercorticism (elevated cortisol without full clinical syndrome), aldosterone may play a significant role in hypertension development. Higher plasma aldosterone concentrations have been associated with elevated systolic blood pressure in these patients 4.
Effective management of adrenocortical hormone excess can lead to complete resolution of arterial hypertension and metabolic disorders, particularly in younger patients without pre-existing cardiovascular conditions 5.