HYPERCORTISOLISM

CUSHING SYNDROME

Shan Zhongyan 单忠艳The Endocrionology Depart

ment,

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?

CapsulaGlomerulosa

Fasciculata

Reticularis

Medulla

Aldosterone

Androgen

Catecholamine

Adrenal Structure

Cortisol

Cortisol Secretion Regulation

ACTH

CRH

Cortisol

Hypothalamus

Pituitary

Adrenal

Causes of Cushing Syndrome

ACTH

CRH

Cortisol

Hypothalamus

Pituitary

Adrenal

Ectopic CRH syndrome

Hypothalamus Cushing syn.

Cushing disease (CD)

Ectopic ACTH syndrome

Adrenal adenoma Adrenal carcinoma Micronodular adrenal disease Massive macronodular adrenal disease

Causes of Cushing syndrome1. Endogenous Cushing syndrome

(1) ACTH-dependent

① Cushing disease (CD)

② Ectopic ACTH syndrome

③ Ectopic CRH syndrome

(2) ACTH-independent

① Adrenal adenoma

② Adrenal carcinoma

③ Micronodular adrenal disease

④ 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

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

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

ObesityLow dose dex. test

YesNo

Cushing Syndrome

Diagnosis Schedules (2)

Cushing Syndrome

ACTH rhythm

Elevated suppressed

Exogenous Cushing

ACTH-dependent

Yes

High dose dex. test

Ectopic ACTH/CRH

No

Cushing Disease

ACTH-independent

Glucocorticoid taken

Yes 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

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

Summary

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

Desoxycorticosterone

Corticosterone

Aldosterone

17-hydroxy pregnenolone

Desoxycortisol

Cortisol

Dehydroepi-androsterone

Androstendione

Estrone

Androstendiol

Testosterone

Estradiol

Cortisol Synthesis Process

胆固醇

孕烯醇酮

去氧皮质酮

皮质酮

醛固酮

17- 羟孕烯醇酮

去氧皮质醇

皮质醇

去氢表雄酮

雄烯二酮

雌 酮

雄烯二醇

睾 酮

雌二醇

孕 酮 17- 羟孕酮