Division of Endocrinology, University of Padua, Padua, Italy.
Neuroendocrinology. 2010;92 Suppl 1:44-9. doi: 10.1159/000314315. Epub 2010 Sep 10.
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.
高血压是内源性库欣综合征（CS）的最显著特征之一，约 80%的成年患者存在高血压，而在儿童中其患病率约为 47%。CS 中的高血压与高皮质醇血症的持续时间显著相关，源于调节血浆容量、外周血管阻力和心输出量的多种病理生理机制的相互作用，所有这些在这种状态下均增加。糖皮质激素通过多种机制引起高血压：其固有盐皮质激素活性；通过激活肾素-血管紧张素系统；通过增强血管活性物质，以及通过引起血管舒张系统抑制。此外，糖皮质激素可能通过中枢神经系统通过糖皮质激素和盐皮质激素受体对心血管调节产生一些高血压作用。CS 中的高血压通常随着肿瘤的手术切除而缓解，但一些患者在术前和术后均需要药物降压治疗。噻嗪类和呋塞米应避免使用，而肾上腺素能阻滞剂和钙通道拮抗剂通常无效。盐皮质激素受体拮抗剂、血管紧张素 II 阻滞剂和 ACE 抑制剂是良好的抗高血压选择；过氧化物酶体增殖物激活受体-γ激动剂可能有助于胰岛素抵抗综合征的许多方面。相对选择性糖皮质激素受体拮抗剂米非司酮（RU 486）可降低 CS 患者的血压。神经调节药物，如 5-羟色胺抑制剂赛庚啶和利坦色林、丙戊酸、多巴胺激动剂、生长抑素类似物偶尔可能有效，以及直接在肾上腺水平作用的药物，如酮康唑和氨基格鲁米特或甚至阿霉素。治疗 CS 中的高血压仍然是一项艰巨的任务和巨大的挑战，以降低与该疾病相关的发病率和死亡率。
