Hypertension in patients with cushing’s disease: Pathophysiology, diagnosis, and management

Sacerdote, Alan; Weiss, Karolina; Tran, Tri H.; Noor, Begum Rokeya; McFarlane, Samy I.

doi:10.1007/s11906-005-0013-4

Cited by 43 publications

(22 citation statements)

References 41 publications

(81 reference statements)

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“…76 Although the main mechanism of hypertension in Cushing's syndrome is overstimulation of the nonselective mineralocorticoid receptor by cortisol, 77 other factors such as sleep apnea and the insulin resistance syndrome are major contributors to hypertension in this disease. 78,79 Although the exact prevalence of resistant hypertension in patients with Cushing's syndrome is unknown, one group found that 17% had severe hypertension. 80 Furthermore, it is well documented that target organ damage in Cushing's syndrome is more severe than in primary hypertension.…”

Section: Cushing's Syndromementioning

confidence: 99%

“…82 Because the pathogenesis of hypertension in Cushing's syndrome involves activation of mineralocorticoid receptors, the usual antihypertensive agents employed in treating primary hypertension (renin-angiotensin system blockers, calcium channel antagonists, adrenergic blockers, diuretics) may not be effective in lowering blood pressure to goal. 79 Surgical excision of an adrenocorticotropic hormone (ACTH)-or cortisol-producing tumor-effectively lowers blood pressure. 79 The most effective antihypertensive pharmacological agent in Cushing's syndrome is a mineralocorticoid receptor antagonist (spironolactone or eplerenone).…”

Section: Cushing's Syndromementioning

confidence: 99%

“…79 Surgical excision of an adrenocorticotropic hormone (ACTH)-or cortisol-producing tumor-effectively lowers blood pressure. 79 The most effective antihypertensive pharmacological agent in Cushing's syndrome is a mineralocorticoid receptor antagonist (spironolactone or eplerenone). 79 …”

Section: Cushing's Syndromementioning

confidence: 99%

See 2 more Smart Citations

Resistant Hypertension: Diagnosis, Evaluation, and Treatment

Calhoun¹,

Jones²,

Textor³

et al. 2008

Circulation

1,237

401

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Abstract-Resistant hypertension is a common clinical problem faced by both primary care clinicians and specialists. While the exact prevalence of resistant hypertension is unknown, clinical trials suggest that it is not rare, involving perhaps 20% to 30% of study participants. As older age and obesity are 2 of the strongest risk factors for uncontrolled hypertension, the incidence of resistant hypertension will likely increase as the population becomes more elderly and heavier. The prognosis of resistant hypertension is unknown, but cardiovascular risk is undoubtedly increased as patients often have a history of long-standing, severe hypertension complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease. The diagnosis of resistant hypertension requires use of good blood pressure technique to confirm persistently elevated blood pressure levels. Pseudoresistance, including lack of blood pressure control secondary to poor medication adherence or white coat hypertension, must be excluded. Resistant hypertension is almost always multifactorial in etiology. Successful treatment requires identification and reversal of lifestyle factors contributing to treatment resistance; diagnosis and appropriate treatment of secondary causes of hypertension; and use of effective multidrug regimens. As a subgroup, patients with resistant hypertension have not been widely studied. Observational assessments have allowed for identification of demographic and lifestyle characteristics associated with resistant hypertension, and the role of secondary causes of hypertension in promoting treatment resistance is well documented; however, identification of broader mechanisms of treatment resistance is lacking. In particular, attempts to elucidate potential genetic causes of resistant hypertension have been limited. Recommendations for the pharmacological treatment of resistant hypertension remain largely empiric due to the lack of systematic assessments of 3 or 4 drug combinations. Studies of resistant hypertension are limited by the high cardiovascular risk of patients within this subgroup, which generally precludes safe withdrawal of medications; the presence of multiple disease processes (eg, sleep apnea, diabetes, chronic kidney disease, atherosclerotic disease) and their associated medical therapies, which confound interpretation of study results; and the difficulty in enrolling large numbers of study participants. Expanding our understanding of the causes of resistant hypertension and thereby potentially allowing for more effective prevention and/or treatment will be essential to improve the long-term clinical management of this disorder. (Circulation. 2008;117:e510-e526.)

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Section: Cushing's Syndromementioning

confidence: 99%

Section: Cushing's Syndromementioning

confidence: 99%

See 1 more Smart Citation

Resistant Hypertension: Diagnosis, Evaluation, and Treatment

Calhoun¹,

Jones²,

Textor³

et al. 2008

Circulation

1,237

401

View full text Add to dashboard Cite

show abstract

“…Compression of the left renal artery by the tumor visualized by CT-scan and hypercortisolism could have favored renin hypersecretion by juxtaglomerular apparatus (Sacerdote et al 2005, Magiakou et al 2006. It was also conceivable that carcinoma may have synthesized and secreted substantial amounts of renin, as formerly reported (Iimura et al 1986, Racz et al 1992, Yamanaka et al 2000.…”

Section: E Louiset Et Al: 5-ht 7 Receptors In Adrenocortical Carcinomamentioning

confidence: 92%

Ectopic expression of serotonin7 receptors in an adrenocortical carcinoma co-secreting renin and cortisol

Louiset¹,

Isvi²,

Gasc³

et al. 2008

Endocrine Related Cancer

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Abnormal expression of membrane receptors has been previously described in benign adrenocortical neoplasms causing Cushing's syndrome. In particular, we have observed that, in some adreno corticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia tissues, cortisol secretion is controlled by ectopic serotonin 7 (5-HT 7 ) receptors. The objective of the present study was to investigate in vitro the effect of serotonin (5-hydroxy tryptamine; 5-HT) on cortisol and renin production by a left adrenocortical carcinoma removed from a 48-year-old female patient with severe Cushing's syndrome and elevated plasma renin levels. Tumor explants were obtained at surgery and processed for immunohistochemistry, in situ hybridization and cell culture studies. 5-HT-like immunoreactivity was observed in mast cells and steroidogenic cells disseminated in the tissue. 5-HT stimulated cortisol release by cultured cells. The stimulatory effect of 5-HT on cortisol secretion was suppressed by the 5-HT 7 receptor antagonist SB269970. In addition, immunohistochemistry showed the occurrence of 5-HT 7 receptor-like immunoreactivity in carcinoma cells. mRNAs encoding renin as well as renin-like immunoreactivity were detected in endothelial and tumor cells. Cell incubation studies revealed that the adrenocortical tissue also released renin. Renin production was inhibited by 5-HT but was not influenced by ACTH and angiotensin II (Ang II). In conclusion, the present report provides the first demonstration of ectopic serotonin receptors, i.e. 5-HT 7 receptors, in an adrenocortical carcinoma. Our results also indicate that 5-HT can influence the secretory activity of malignant adrenocortical tumors in an autocrine/paracrine manner. The effects of 5-HT on adrenocortical tumor cells included a paradoxical inhibitory action on renin production and a stimulatory action on cortisol secretion involving 5-HT 7 receptors.

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“…The most effective antihypertensive agents are mineralocorticoid receptor antagonists (such as spironolactone or eplerenone), but frequently only surgical removal of an adrenocorticotropic hormone (ACTH) or another cortisol-producing tumor allows effective blood pressure control. Target organ damage and overall cardiovascular risk in Cushing's syndrome is more severe than in primary hypertension, because the disease is associated with other cardiovascular risk factors such as metabolic syndrome, diabetes mellitus, obesity, sleep apnea syndrome, and dyslipidemia (Sacerdote et al, 2005).…”

Section: Cushing's Syndromementioning

confidence: 99%