Cushing’s syndrome

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 plethoricPurple striaeHypertensionIGT OsteoporosisHypokalemic alkalosis

Nyctohemeral rhythm

Neural stimuliCRH

ACTH

Cortisol Cortisol(CBG bound) (free)

Physiological andMetabolic effects

Negativefeedback

Plasma

Hypothalamus

Anterior pituitary

Adrenal cortex

Inactivation by reduction and conjugation

Liver

Unchanged cortisol(measured as urinary free cortisol)

TetrahydrocortisolTetrahydrocortisoneCortols,Cortolones(measurd as urinary 17-OHCS)

Urine

The hypothalamic-pituitary-adrenal axis

Suspected Cushing’s synd.

Plasma cortisolUrinary free cortisolUrinary 17-OHCS

Low dose dexamethasone suppression test2.0mg/day2days

>50% reduce from basal<50% reduce from basal

NORMALCushing’s Synd.

High dose dexamethasone suppression test8.0mg/day2days

<50% reduce from basal >50% reduce from basal

ProbableCushing’s Disease

Adrenal DiseaseEctopic ACTH Synd.

Suspected Cushing’s synd.

Plasma ACTH

Adrenal DiseaseEctopic ACTH Synd

Adrenal DiseaseEctopic ACTH Synd

Plasma ACTH

Increased Low

Probable Ectopic ACTH Synd. Probable Adrenal Disease

Tumor Search CT /MRI Scan of Adrenals

positive negative

ECTOPICACTH

SYNDROME

normal adrenal mass

ConsiderAdrenonodular

Hyperplasia,Other Disorders

urinary 17-KSPlasma DHEA

17-KS DHEA

ADRENALCARCINOMA

DHEA 17-KS

ADRENALADENOMA

hypothalamushypothalamus

pituitary

adrenal

Drugs: Cyproheptadine Metergoline Bromocryptine

Adrenalectomy

Surgery:Transsphenoidal microsurgeryRadiation: 60Co linear accelerator

Drug: o,p’DDD(mitotane) Metyrapone Aninoglutethmide ketokonazole

CRH

ACTH

CS

SurgeryRadiation

TREATMENT

1. 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

2. 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

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

K+

(mmol/L )HCO3

(mmol/L )

Cortisolat 8 A.M.

(ug/100 ml)

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

25

40

20

80

13

1000

90

5

250

35

15

35

4

40

15

70

65

Normal: cortisol:10-24,; ACTH:40-100; 17-OHCS:3-12; 17-KS: 5-20