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Hypertension in Cushing's syndrome: from pathogenesis to treatment
Maria Verena Cicala1, Franco Mantero
1Division of Endocrinology, University of Padua, Padua, Italy.
Insights
Hypertension is common in Cushing's syndrome (CS) due to excess cortisol. Effective treatments focus on mineralocorticoid receptor antagonists, Ang II blockers, and ACE inhibitors, while some drugs are ineffective.
Area of Science:
- Endocrinology
- Cardiovascular Medicine
Background:
- Hypertension is a hallmark of endogenous Cushing's syndrome (CS), affecting 80% of adults and 47% of children.
- Hypertension in CS is linked to hypercortisolism duration and involves complex mechanisms affecting plasma volume, vascular resistance, and cardiac output.
Purpose of the Study:
- To review the pathophysiological mechanisms of hypertension in Cushing's syndrome.
- To discuss effective and ineffective pharmacological treatments for hypertension in CS patients.
Main Methods:
- Literature review of studies on hypertension in Cushing's syndrome.
- Analysis of the mechanisms by which glucocorticoids induce hypertension.
- Evaluation of antihypertensive drug efficacy in CS.
Main Results:
- Glucocorticoids cause hypertension via mineralocorticoid activity, renin-angiotensin system activation, enhanced vasoactive substances, and suppressed vasodilatory systems.
- Mineralocorticoid receptor antagonists, Ang II blockers, and ACE inhibitors are effective antihypertensive options in CS.
- Thiazides, furosemide, adrenergic blockade, and calcium channel antagonists are generally ineffective.
Conclusions:
- Treating hypertension in CS is challenging, requiring tailored pharmacological approaches.
- Mineralocorticoid receptor antagonists, Ang II blockers, and ACE inhibitors represent key therapeutic options.
- Further research is needed to optimize management and reduce associated morbidity and mortality.
Abstract:
Hypertension is one of the most distinguishing features of endogenous Cushing's syndrome (CS), as it is present in about 80% of adult patients whereas in children its prevalence is about 47%. Hypertension in CS is significantly correlated with the duration of hypercortisolism and results from the interplay between several pathophysiological mechanisms regulating plasma volume, peripheral vascular resistance and cardiac output, all of which are increased in this state. Glucocorticoids cause hypertension through several mechanisms: their intrinsic mineralocorticoid activity; through activation of the renin-angiotensin system; by enhancement of vasoactive substances, and by causing suppression of the vasodilatory systems. In addition, glucocorticoids may exert some hypertensive effects on cardiovascular regulation through the CNS via both glucocorticoid and mineralocorticoid receptors. Hypertension in CS usually resolves with surgical removal of the tumor, but some patients require pharmacological antihypertensive treatment both pre- and postoperatively. Thiazides and furosemide should be avoided, while adrenergic blockade and calcium channel antagonists are usually ineffective. Mineralocorticoid receptor antagonists, Ang II blockers and ACE inhibitors are good anti-hypertensive options; PPAR-γ agonists may help in many aspects of the insulin resistance syndrome. The relatively selective glucocorticoid receptor antagonist Mifepristone (RU 486) could reduce blood pressure in patients with CS. Neuromodulatory agents such as the serotonin inhibitors cyproheptadine and ritanserin, valproid acid, dopamine agonists, somatostatin analogs may occasionally be effective, as well as drugs acting directly at the adrenal levels, such as Ketoconazole and aminoglutetimide or even opDDD. Treating hypertension in CS remains a difficult task and a big challenge, in order to decrease the morbidity and mortality associated with the disease.
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