Cushing’s syndrome 一40岁女性，自述近两年体重增加，尤其腹部，但体力却明显下降。到当地医院就诊时发现血压高、血糖高、血脂高、血钾低，对症治疗不见好转来诊。你考虑该患可能得了什么病？线索？为什么？还应做那些检查？ 鉴别：2型糖尿病：类固醇性糖尿病：小剂量地塞米松抑制试验被抑制 代谢综合征：
Effects of glucocorticoid Effects on metabolism Effects on immunologic function and inflammatory Effects on musculoskeletal and connective tissues Effects on fluid and electrolyte homeostasis Neuropsychiatric and behavioral effects Gastrointestinal effects Developmental effects
Clinical features Obesity (The increased fat distribution is not generalized) Moon-shaped face and plethoric Purple striae Hypertension IGT Osteoporosis Hypokalemic alkalosis
The hypothalamic-pituitary-adrenal axis Hypothalamus Nyctohemeral rhythm CRH Neural stimuli Anterior pituitary Negative feedback ACTH Adrenal cortex Cortisol Cortisol (CBG bound) (free) Physiological and Metabolic effects Plasma Inactivation by reduction and conjugation Liver Urine Tetrahydrocortisol Tetrahydrocortisone Cortols,Cortolones (measurd as urinary 17-OHCS) Unchanged cortisol (measured as urinary free cortisol) The hypothalamic-pituitary-adrenal axis
Suspected Cushing’s synd. Suspected Cushing’s synd. Plasma cortisol Urinary free cortisol Urinary 17-OHCS Low dose dexamethasone suppression test 2.0mg/day2days <50% reduce from basal >50% reduce from basal Cushing’s Synd. NORMAL High dose dexamethasone suppression test 8.0mg/day2days >50% reduce from basal <50% reduce from basal Plasma ACTH Adrenal Disease Ectopic ACTH Synd. Probable Cushing’s Disease
Probable Ectopic ACTH Synd. Probable Adrenal Disease Plasma ACTH Increased Low Probable Ectopic ACTH Synd. Probable Adrenal Disease Tumor Search CT /MRI Scan of Adrenals positive negative normal adrenal mass urinary 17-KS Plasma DHEA ECTOPIC ACTH SYNDROME Consider Adrenonodular Hyperplasia, Other Disorders 17-KS DHEA DHEA 17-KS ADRENAL ADENOMA ADRENAL CARCINOMA
hypothalamus pituitary Drugs: Cyproheptadine Metergoline Bromocryptine Surgery Radiation hypothalamus CRH Surgery: Transsphenoidal microsurgery Radiation: 60Co linear accelerator pituitary ACTH 赛更定Cyproheptadine（血清素抑制剂） 麦角苄脂Metergoline 双氯苯二氯乙烷（米托坦）o,p’DDD(mitotane)（束、网状带萎缩） 美替拉酮Metyrapone（抑制CS合成） 氨基导眠能Aninoglutethmide（抑制CS合成） 酮康唑ketokonazole（减少CS合成） Drug: o,p’DDD(mitotane) Metyrapone Aninoglutethmide ketokonazole Adrenalectomy adrenal TREATMENT CS
Oat cell carcinoma of lung A 45-year-old man complaints of severe weakness. He appears chronically wasted and is mildly hyperpigmented. His blood pressure is 160/100mmHg. A high-dose dexamethasone suppression test (2 mg every 6 h) causes no suppression of urinary free cortisol, 17-hydroxycorticosteroids (17-OHCS ,or 17-ketosteroids(17-KS). The most appropriate diagnosis Is Oat cell carcinoma of lung
A 26-year-old woman complaints of irregular menses, obesity, and low back pain. She has mild hypertension, central obesity, broad striae, acne, and mild hirsutism. A low-dose dexamethasone suppression test causes no suppression of urinary free cortisol and 17-OHCS. A high-dose dexamethasone suppression test causes greater than 50 percent suppression of urinary free cortisol and 17-OHCS. The most appropriate diagnosis is Cushing’s disease
3. A 28-year-old woman complaints of weakness, easy bruising, hirsutism, and irregular menses. She exhibits moon face, central obesity, and severe hirsutism involving the face and trunk, but no virilism. A high-dose dexamethasone suppression test causes no suppression of free cortisol, 17-OHCS, or 17-KS. Plasma dehydroepiandrosterone(DHEA) sulfate is fourfold normal. The most appropriate diagnosis is Adrenal carcinoma
Congenital adrenal hyperplasia 4. A 15-year-old boy complaints of short stature.He has history of early sexual development and accelerated growth that ceased 5years ago.He displays hyperpigmentation. A high-dose dexamethasone suppression test causes greater than 50 percent suppression of urinary 17-KS. The most appropriate diagnosis is Congenital adrenal hyperplasia
Laboratory values serum plasma urine Cortisol K+ HCO3 ACTH 17-OHCS at 8 A.M. (ug/100 ml) K+ (mmol/L ) HCO3 (mmol/L ) ACTH (PG/100ML) 17-OHCS (mg/24h) 17-KS (mg/24h) 1. 2. 3. 4. 3.0 3.9 3.2 3.8 35 25 32 40 20 80 13 1000 90 5 250 35 15 4 40 15 70 65 Normal: cortisol:10-24,; ACTH:40-100; 17-OHCS:3-12; 17-KS: 5-20