Transcript HYPERCORTISOLISM CUSHING SYNDROME

HYPERCORTISOLISM
CUSHING SYNDROME
Shan Zhongyan
单忠艳
The Endocrionology
Department,
Contents
1. What is Cushing syndrome?
2. What is the causes?
3. How to diagnose?
 Clinical Features
 Hormone levels
 Functional test
 Localization
4. How to treatment?
Contents
1. What is Cushing syndrome?
2. What is the causes?
3. How to diagnose?
 Clinical Features
 Hormone levels
 Functional test
 Localization
4. 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
Contents
1. What is Cushing syndrome?
2. What is the causes?
3. How to diagnose?
 Clinical Features
 Hormone levels
 Functional test
 Localization
4. How to treatment?
Adrenal Structure
Capsula
Glomerulosa
Aldosterone
Fasciculata
Cortisol
Reticularis
Androgen
Medulla
Catecholamine
Cortisol Secretion Regulation
CRH
Hypothalamus
ACTH
Pituitary
Cortisol
Adrenal
Causes of Cushing Syndrome
Hypothalamus Cushing syn.
CRH
Ectopic CRH syndrome
Hypothalamus
Cushing disease (CD)
ACTH
Ectopic ACTH syndrome
Pituitary
Cortisol
Adrenal
Adrenal adenoma
Adrenal carcinoma
Micronodular adrenal disease
Massive macronodular adrenal
disease
Causes of Cushing syndrome
1. Endogenous Cushing syndrome
(1) ACTH-dependent
①
Cushing disease (CD)
②
Ectopic ACTH syndrome
③
Ectopic CRH syndrome
(2) ACTH-independent
①
②
③
④
Adrenal adenoma
Adrenal carcinoma
Micronodular adrenal disease
Massive macronodular adrenal disease
(3) Pseudocushing syndrome
2. Exogenous Cushing syndrome
Contents
1. What is Cushing syndrome?
2. What is the causes?
3. How to diagnose?
 Clinical Features
 Hormone levels
 Functional test
 Localization
4. How to treatment?
Function
Clinical Features
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
Hormone Level
1. Cortisol levels
① Plasma cortisol rhythm (8Am, 4Pm, midnight)
② 24h Urinary free cortisol, 17-OHCS, 17-KS
③ Plasma ACTH rhythm
2. Functional Tests
① Low dose dexamethasone suppression test
② High dose dexamethasone suppression test
③ 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
No
Cushing
Syndrome
Yes
Obesity
Diagnosis Schedules (2)
Cushing Syndrome
ACTH rhythm
Elevated
suppressed
ACTH-dependent
ACTH-independent
High dose dex. test
Glucocorticoid taken
No
Yes
Yes
Ectopic
ACTH/CRH
Cushing
Disease
Exogenous
Cushing
No
Adrenal
Tumor/Nodule
Contents
1. What is Cushing syndrome?
2. What is the causes?
3. How to diagnose?
 Clinical Features
 Hormone levels
 Functional test
 Localization
4. How to treatment?
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.
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
Yes
Yes
Diet + exercise
Obesity
Treatment
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？
Cortisol Synthesis Process
Cholesterol
Pregnenolone
17-hydroxy
pregnenolone
Dehydroepiandrosterone
Androsten
diol
Desoxycortic
osterone
Desoxycortisol
Androstend
ione
Testosterone
Cortisol
Estrone
Estradiol
Corticosterone
Aldosterone
Cortisol Synthesis Process
胆固醇
孕烯醇酮
17-羟孕烯醇酮
去氢表雄酮
孕 酮
17-羟孕酮
雄烯二酮
去氧皮质酮
去氧皮质醇
皮质酮
皮质醇
醛固酮
雌 酮
雄烯二醇
睾
酮
雌二醇