Cushing syndrome Cushing 综合症 武汉大学第一临床学院 包艳

Definition Cushing syndrome, the constellation of clinical signs and symptoms resulting form chronic glucocorticoid excess, was probably first described in 1899 Cushing syndrome, the constellation of clinical signs and symptoms resulting form chronic glucocorticoid excess, was probably first described in 1899

定 义 为各种病因造成肾上腺分泌过多的 糖皮质激素（主要是皮质醇）所致 病症的总称 主要临床表现为满月脸，多血质外 貌，向心性肥胖、痤疮、皮肤紫纹 高血压和骨质疏松等

Aetiology Clinical presentation laboratory examination Diagnosis and differential diagnosis Treatment ( principle) Prognosis

病因分类 临床表现 实验室检查 诊断及鉴别诊断 治疗 ( 原则 ) 预后

Aetiology 病因分类

Hypothalamus 下丘脑 （ CRH ） pituitary gland 垂体 （ ACTH ） adrenal cortex 肾上腺皮质 zona glomerulosa zona fasciculata zona reticularis （ Aldosterone ）（ cortisol ）（ gonadal hormone ）

Aetiology ACTH-dependent Cushing syndrome Cushing disease Ectopic ACTH syndrome ACTH- independent Cushing syndrome Adrenocortical adenoma Adrenocortical adenocarcinoma Micronodular adrenal disease Massive macronodular adrenal disease

病因分类 依赖 ACTH 的 cushing 综合症 cushing 病 异位 ACTH 综合症 非依赖 ACTH 的 cushing 综合症 肾上腺皮质腺瘤 肾上腺皮质癌 原发性色素结节性肾上腺病 大结节性巨大肾上腺病

Clinical feature 各型临床特征

Cushing Disease It is the most common type of Cushing syndrome, and accounts for about 70% of the syndrome Pathogenesis Most patients have ACTH-secreting anterior pituitary corticortrope microadenomas( ＜ 10mm in diameter), but a small number have diffuse corticotrope hyperplasia and pituitary macroadenoma

Cushing 病 最常见，约占 cushing 综合症的 70%, 多见于 成人，女性多于男性，是由于垂体分泌过 多的 ACTH 所致 病因 垂体微腺瘤－ 80% 垂体大腺瘤－ 10 ％：压迫、侵袭等症状 下丘脑功能紊乱

Ectopic ACTH syndrome The majority of patients with ectopic ACTH syndrome have outside pituitary tumor Other sites are, Other sites are pulmonary carcinosis, carcinoid of bronchus, thymic carcinoma pancreatic cancer, chromaffin tumor, medullary carcinoma of thyroid and so on

异位 ACTH 综合症 继发于垂体以外的恶性肿瘤 小细胞肺癌、支气管类癌、胸腺癌、胰腺 癌、嗜铬细胞瘤、神经母细胞瘤 等等 临床上分两型 缓慢进展型 迅速进展型

Adrenocortical adenoma Patients with adrenal adenoma usually have gradual onset of sign of hypercortisolism, accounts for about 15-20% of the syndrome Adenoma is round or ellipse, diameter is 3- 4cm, weight is about 40g

肾上腺皮质腺瘤 多见于成人，男性多于女性－ 15%-20% 腺瘤呈圆形或椭圆形，直径约 3-4cm ，重 40g 左右，包膜完整 其病缓慢，病情中等，多毛及雄激素增多 少见

Adrenocortical adenocarcinoma It occurs in lower than 5% patients of cushing syndrome Patients with Patients with adenocarcinoma tend to have a more acute and progressive course and virilizing effects may predominate The The bulk of tumor is larger

肾上腺皮质腺癌 占 cushing 综合症的 5 ％以下 瘤体积大（直径 5-6cm) ，肿瘤可浸润包膜 病情重，进展快，重度 cushing 综合症的表现 ( 低钾性碱中毒、女性男性化）

Micronodular adrenal disease The disease is also known as Meador ’ s syndrome About half of patients with this disorder have no distinctive clinical presentation other than being young-always younger than 30 years of age, half younger than 15 years and some infants

原发性色素结节性肾上腺病 此病又称这为 Meador 综合症或原发性色素 性结节性肾上腺疾病 患者多为儿童和青少年 临床表现：一部分同一般的临床表现 一部分为家族性，呈显性遗传 (Carney 综合症）

Massive macronodular adrenal disease 大结节性巨大肾上腺病

Clinical presentation 临床表现

典型病例 重型 cushing 综合症 早期病例 以并发症为主者 周期性或间歇性

Typical cases 典 型 病 例

Clinical presentation1 Progressive obesity is the most common sign. It is usually central, involving the face, neck trunk and abdomen All over the body and nervous system: weakness, change of emotion and so on The skin is atrophic, the stratum corneum is thinned, and there is loss of subcutaneous fat allowing subcutaneous blood vessels to been seen

Clinical presentation2 Cardiovascular complication is a major cause of morbidity and death in untreated Cushing syndrome Moderate hypertension is common Moderate hypertension is common Glucocorticoid suppress immune function Inflammatory and febrile responses to bacterial infection are suppressed Dysbolism and sexual disturbance sometimes occur

临床表现 1 满月脸、多血 质外貌、向心 性肥胖

临床表现 2 全身和神经系统症状：肌无力，常有不同 程度的精神、情绪变化 皮肤表现：皮肤薄，微血管脆性增加，易 出现淤斑、紫纹, 易合并真菌感染, 有时可出 现皮肤色素沉着

临床表现 2 心血管表现： 高血压－心衰、脑血管意外 凝血功能异常 ( 血小板，纤维蛋白原 ），脂代谢 紊乱，动静脉血栓 对感染的抵抗力减弱 使达到炎症病灶的单核细胞减少 巨噬细胞对抗原的固定、吞噬和杀伤力减弱 中性粒细胞运动能力，吞噬作用减弱 抗体的形成受到阻抑

临床表现 3 性功能障碍： 月经减少、不规则、停经、痤疮等 明显男性化（警惕肾上腺癌） 代谢障碍： 脂、蛋白、糖代谢 低钾性碱中毒 ，低钙 骨质疏松，伤口愈合不良，生长发育延迟

重型 cushing 综合症 多由癌肿所致，病情严重，进展迅速 体重减轻 高血压、浮肿、低钾性碱中毒

早期病例 全身情况较好 以高血压为主 肥胖、向心性的特点不够显著

以并发症为主者 Cushing 综合症本身不明显 多以并发症就诊：心衰、脑卒中 病理性骨折、精神症状、肺部感 染等等

周期性或间歇性

Laboratory examination 实验室检查

Laboratory examination The laboratory examination of Cushing syndrome is cortisol hypersecretion. Increased urinary excretion of cortisol and urinary 17-OH Loss of rhythm of plasma cortisol, ACTH Loss of normal suppressibility of cortisol by low-dose dexamethasone

实验室检查 皮质醇分泌增多，失去昼夜分泌节律，且 不能被小剂量地塞米松抑制试验所抑制 尿 17 －羟皮质类固醇、游离皮质醇增高 血浆皮质醇浓度增高 小剂量地塞米松抑制试验

皮质醇分泌增多，失去昼夜节律， 不能被小剂量地塞米松抑制

Diagnosis and Differential diagnosis 诊断和鉴别诊断

Diagnosis The clinical diagnosis of Cushing ’ s syndrome is confirmed by clinical presentation, cortisol hypersecretion, loss of normal rhythm in cortisol and loss of normal suppressibility of cortisol by low- dose dexamethasone

诊 断诊 断 临床表现 皮质醇分泌增多，失去昼夜分泌节律 尿 17- 羟皮质醇和游离皮质醇增高 不能被小剂量地塞米松所抑制

病 因 诊 断病 因 诊 断

Cushing ’ s disease adeno ma adenocarc inoma Ectopic ACTH syndrome Urinary 17-OH, 17-KS, Urinary 17-OH, 17-KS, cortisol ↑ ↑ ↑ ↑ ↑ ↑ ↑ ↑ ↑ High-dose dex suppression test YNNN ACTH↑↓↓ ↑ ↑ ↑ Hypokalemia alkali poisoning Y(sometimes)NYY CT of sella turcica YNNN CT, MRI of CT, MRI of Adrenal Bilateral hyperplasia tumourtumour

Differential diagnosis Cushing ’ s syndrome needs to identify with the following diseases Simple obesity Type 2 diabetes Alcoholism and hepatic lesion Depressive disorder

鉴别诊断 2 型糖尿病：临床表现、皮质醇节律正常 单纯性肥胖：地米抑制试验、皮质醇节律正常 酗酒兼有肝损害者，出现假性 cushing 综合症 抑郁症：临床表现

Treatment Treatment of Cushing syndrome is aimed at following goals: Cure of the syndrome by reduction of cortisol secretion to normal Eradication of any tumor threatening the health of patients Prevention of permanent dependency on medications Avoidance of permanent hormone deficiency

Treatment-cushing disease Transsphenoidal microadenomectomy is the most rational current treatment for Cushing disease In patients who are not cured by this treatment, three options remain Reoperate on the pituitary gland Radiate the pituitary gland Perform surgical adrenalectomy and corticoid antagonist

cushing 病的治疗 经蝶窦切除微腺瘤，是本病的首选方法 一侧肾上腺全切，另一侧肾上腺全部或大部分 切除，术后可能并发 Nelson 综合症 开颅手术治疗，如不能全部切除，可在术后辅 以放疗 阻滞肾上腺皮质激素合成的药物

Treatment-Adrenocortical adenoma and adenocarcinoma Small adenomas can be removed by laparascopy Large adenomas and carcinomas require an open flank or transabdominal approach The cure with surgical removal of adrenal adenoma is virtually 100%

肾上腺腺瘤、腺癌的治疗 肾上腺腺瘤手术可获根治，术后采用氢化 可的松替代 腺癌应尽可能早作手术，如不能，采用药 物治疗

Treatment- Ectopic ACTH syndrome When possible, the tumor should be surgically excised, removing the source of ectopic ACTH and thereby curing the metabolic disorder In most patients, however, the tumor is nonresectable at the time of diagnosis. Chemotherapy or radiation therapy, or both may be helpful

异位 ACTH 综合症的治疗 治疗原发性的恶性肿瘤 手术、 放疗、化疗 使用肾上腺皮质激素合成阻滞药

Adrenal enzyme inhibitors O, p ’ -DDD Aminoglutethimide SU4885 Ketoconazole

肾上腺皮质激素合成阻滞药 米托坦 氨鲁米能 美替拉酮 酮康唑

手术前后的处理 患者血浆皮质醇浓度很高，一旦切除相 关肿瘤，皮质醇分泌量锐减，有可能发 生急性肾上腺皮质功能不全的危险 手术前后均需补充糖皮质激素

Prognosis Cushing disease will be better after virtually treatment The prognosis with adrenal adenoma is excellent because surgery is usually curative The prognosis with adrenal carcinoma is poor because most patients have distant metastases at diagnosis

预 后 经过有效的治疗，病情好转，症状减轻 癌的预后取决于是否早期发现及能否完全切除 肾上腺腺瘤的预后最好 Cushing 病疗效不一，应定期观察

如需鉴别库欣综合征与单纯性肥胖，下列 各项中最有意义的检验或试验是： A 血皮质醇测定 B 24 小时尿 17- 羟、 17- 酮 C 24 小时尿游离皮质醇 D 小剂量地塞米松抑制试验 E 大剂量地塞米松抑制试验

为确定库欣综合征的病变部位，下列各项 中最有意义的检验或试验是： A 血皮质醇测定 B 24 小时尿 17- 羟、 17- 酮 C 24 小时尿游离皮质醇 D 小剂量地塞米松抑制试验 E 大剂量地塞米松抑制试验

为明确诊断哪项检查最为重要： A 再次 OGTT 试验 B 血浆皮质醇测定 C 血浆醛固酮测定 D 血儿茶酚胺测定

讨 论 题讨 论 题 在 Cushing 综合征的诊断过程中，行 小剂量地塞米松抑制试验和大剂量地 塞米松抑制试验的意义何在