HYPERCORTISOLISM CUSHING SYNDROME

HYPERCORTISOLISM CUSHING SYNDROME Shan Zhongyan 单忠艳 The Endocrionology Department,

Contents • What is Cushing syndrome? • What is the causes? • How to diagnose? • Clinical Features • Hormone levels • Functional test • Localization • How to treatment?

Definition • Cushing Syndrome A diverse symptom complex resulting from excess steroid hormone (cortisol) production • Cushing Disease A hypercortisolism resulting from pituitary ACTH hypersecretion

Adrenal Structure Capsula Glomerulosa Aldosterone Fasciculata Cortisol Reticularis Androgen Medulla Catecholamine

CRH Hypothalamus ACTH Pituitary Cortisol Adrenal Cortisol Secretion Regulation

Causes of Cushing Syndrome Hypothalamus Cushing syn. CRH Ectopic CRH syndrome Hypothalamus Cushing disease (CD) ACTH Ectopic ACTH syndrome Pituitary • Adrenal adenoma • Adrenal carcinoma • Micronodular adrenal disease • Massive macronodular adrenal • disease Cortisol Adrenal

Causes of Cushing syndrome 1. Endogenous Cushing syndrome • (1) ACTH-dependent • Cushing disease (CD) • Ectopic ACTH syndrome • Ectopic CRH syndrome • (2) ACTH-independent • Adrenal adenoma • Adrenal carcinoma • Micronodular adrenal disease • Massive macronodular adrenal disease (3) Pseudocushing syndrome 2. Exogenous Cushing syndrome

Functions Clinical Features Fat Central obesity, “moon face” “buffalo hump” Protein Thin extremities, muscle weakness, Purple striae, bruising, osteoporosis Glucose IGT, DM Electrolyte Hypertension, hypokalemia, alkalosis Function Clinical Features

Functions Clinical Features Immunity Infection, impaired wound healing Sex gland Hirsutism, acne, menstrual dysfunction, Erectile dysfunction Bone marrow Increased RBC and WBC，plethoric Mental Increased lability Skin Hyperpigmentation Function Clinical Features

Hormone Level • 1. Cortisol levels • Plasma cortisol rhythm (8Am, 4Pm, midnight) • 24h Urinary free cortisol, 17-OHCS, 17-KS • Plasma ACTH rhythm • 2.Functional Tests • Low dose dexamethasone suppression test • High dose dexamethasone suppression test • Metyrapone test

Localization Adrenal CT

Localization Pituitary MRI

Diagnosis 1. Confirmation of hypercortisolism (Y/N) Plasma cortisol rhythm (8Am, 4Pm, midnight) 24h Urinary free cortisol, 17-OHCS, 17-KS Low dose dexamethasone suppression test 2. Differentiation of Cushing syndrome (What) Plasma ACTH level High dose dexamethasone suppression test Metyrapone test CRH stimulation test 3. Localization (Where) Adrenal CT, Pituitary MRI

Diagnosis Schedules (1) Cushing Syndrome suspected Cortisol rhythm, UFC, 17-OHCS, 17-KS Elevated Normal Low dose dex. test Obesity Yes No Cushing Syndrome

Diagnosis Schedules (2) Cushing Syndrome ACTH rhythm Elevated suppressed ACTH-dependent ACTH-independent High dose dex. test Glucocorticoid taken No Yes Yes No Ectopic ACTH/CRH Cushing Disease Exogenous Cushing Adrenal Tumor/Nodule

Treatment Cause Treatment Cushing D Transsphenoidal Ectopic ACTH Surgery+drug Ectopic CRH Surgery +drug Adrenal Aden. Surgery Adrenal Carc. Surgery +drug Micronodular Surgery +replace Macronodular Surgery +replace Nelson Syndrome

Summary Cause incidence Cor. ACTH Low-Dex. High-Dex. Treatment Cushing D 80 No Yes Transsphenoidal Ectopic ACTH 20 No No Surgery+drug Ectopic CRH Rare No No Surgery +drug Adrenal Aden. 40-50 No No Surgery Adrenal Carc. 40-50 No No Surgery +drug Micronodular Less No No Surgery +replace Macronodular Rare No No Surgery +replace Exogenous More No No Stop taking Obesity Yes Yes Diet + exercise

病例分析 张**，女，27岁主述：体重增加2年现病史：病人2年来体重逐渐增加，尤近半年明显，由60公斤增至76公斤。伴疲乏无力，头迷，近3个月未来月经，觉汗毛加重，长胡须，面部经常起痤疮。病来无明显多食，活动量未减少，无多饮多尿，睡眠正常，无视物障碍及缺损，无怕冷少汗，无软瘫。体格检查：Bp 190/110mmHg ， P 86次/分， T 36.8℃，H 1.58m，BW 76Kg。神志清晰，腹型肥胖。皮肤菲薄，满月脸，多血质面容，毛发浓密多油腻，发际下移，可见胡须，颜面可见痤疮。背部毛囊角化明显，下腹部及双下肢近端多条粉红色紫纹，呈梭型，四肢均可见片状瘀斑。甲状腺不大，心律规整，腹部未扪及包块。锁骨上、肾区均未闻及血管杂音。问题：1、根据病人临床症状，你的初步诊断是什么？ 2、如何检查明确诊断？

病例分析 检查结果：尿pH 6.0，尿蛋白阴性。血WBC 8.6 X109/L, Hb 12g/L。血pH 7.42，血钾3.32mmol/L，BUN、Cr正常。血皮质醇 8 Am 2084 nmol/L，3pm 2162 nmol/L。 ACTH 8 Am <10 pmol/L, 3pm < 10pmol/L。 OGTT BG 0’ 5.6 mmol/L，120’ 8.9 mmol/L。小剂量地塞米松抑制试验：皮质醇前2284 ，后 2146 nmol/L。大剂量地塞米松抑制试验：皮质醇前2146 ，后 1984 nmol/L。肾上腺增强CT：左侧肾上腺占位病变。问题：3、该病人完整的诊断包括什么？ 4、如何选择治疗方案？　

Cholesterol 17-hydroxy pregnenolone Dehydroepi-androsterone Androstendiol Pregnenolone Desoxycorticosterone Androstendione Desoxycortisol Testosterone Corticosterone Cortisol Estrone Estradiol Aldosterone Cortisol Synthesis Process

胆固醇 孕烯醇酮 17-羟孕烯醇酮去氢表雄酮雄烯二醇孕酮雄烯二酮睾酮 17-羟孕酮去氧皮质酮去氧皮质醇雌二醇皮质酮皮质醇雌酮醛固酮 Cortisol Synthesis Process

HYPERCORTISOLISM CUSHING SYNDROME