KULIAH ADRENAL 1

ADRENAL GLAND
Anatomy
A pair of triangular structures
Superomedial of the kidney
Cortex and medulla
The adrenal cortex
from mesodermal splanclic
steroidogenesis
The adrenal medullla
from neural crest cells
cathecolamines

GLOMERULOSA

FASCICULATA

RETICULARIS

Cholesterol

Cholesterol

Cholesterol

Regnenolone

Pregnenolone

Pregnenolone

Progesterone

17-OHpregnenolone

17-OHpregnenolone

Deoxycorticosterone

17-OHprogesterone

Corticosterone

11-deoxycortisol

Dehydroepiandrosterone

aldosterone

cortisol

androstenedione

Glucocorticoid
Steroid adrenal, main effect : carbohydrate metabolism
In human : cortisol (hydrocortison) has a role in almost
all glucorticoid activity
Secretion : 20 mg/day
Corticosterone : a weak glucocorticoid
cortisol has metab effect for almost all tissues

Effect of ACTH
The adrenal cortex :
Activate adenylate cyclase &
cholesterol synthesis;
adrenal;

c-AMP

uptake protein by cortex

RNA. DNA & protein synthesis

Chronic stimmulation of ACTH

hyperthrophic of adrenal cortex

hyperplasia &

Extra adrenal effect :

Secretion MSH

(melanocyte stimmulating hormone)

Cortisol secretion
1. Diurnal variation :
2. Cortisol feed-back :
Blood Glucocorticoid (GCC )

ACTH

Exogenous GCC

ACTH

3. Stress (physical & psychological) :

sress

ACTH

cortisol

GCC effects :
-

Gluconeogenesis
lipid & protein catabolism
redristribution & depostition of body fat in adipose tissue
lysis of lymphoid system
lymphocytes in circulation
eosinophil & basophil suppression
neutrophil
osteoporosis (osteoblast activity)
GCC
: - sufficient amount : normal muscle function
- hypo- / hyper: muscular weakness
- Pharmacological dose : potent effect to inflammatory &
immune respons.
- High dose : suppress the inflammatory & immune response

Cortisol transportation
Mostly bound to CBG = corticosteroid-binding globulin
(-glob, produced by liver) and to albumin.
Small amount : free cortisol
estrogen

CBG

circ. cortisol :
free cortisol : N

CBG

circ. cortisol :
free cortisol : N

liver disease
nephrotic syndr

Cortisol catabolism

Half life

: 90 mnts
its bound to CBG

Catabolism

: in the liver

Excreted

: urine (17- hydroxycorticosteroids)

CUSHING S SYNDROME
Hypercortisolism (cortisol
Cushing disease

: primary hypercortisolism
(from pituitary gland)

Etiology

-Exogen

: administration of supraphysiologic doses of CS

in long term
: - pituitary tumor ( 60-70%)
- adrenal tumor (20%)
- nonendocrine tumors ACTH-like substance :

-Endogen

> Oat cell Ca (lung tumor)

> Carcinoid bronchial adenoma
> Prostat / Ovarium Ca
> Pancreas Ca

Cushings syndrome
Clinical manifestations :
1. Habitus : obesity (trunk, buffalo hump, supracavicular
and abdominal), moon face
2. Hypertension (mineralocorticoid effect & increase sensitivity
to catecholamine)
3. Muscular weakness
4. Easy bruising, skin hyperpigmentation
5. Osteoporosis
6. Glucose intolerance
7. Androgen
acne, hirsutism, amenorrhoe
8. Striae lividae
9. Psychiatric manifestation

Cushings disease
Diagnosis :
Clinical app : habitus, striae, aosteoporosis, hypertension
1. Exogenous : history of usage of CS drugs
blood cortisol & ACTH at 8.0 a.m
2. Endogenous : 2 steps
a) screening test : dexamethasone test
1 mg of dexamethasone at 10 p.m (po)
morning at 8 a.m : blood cortisol level
Normal response : cortisol < 5 g/dl
Cushings disease : no cortisol suppression

Diagnosis :
Liddle test :
0.5 mg (po) dexamethasone every 6-h intervals 48 h
24-h urine samples for 17-OCHS
(before and during dexamethasone administration)
Normal
: urine 17-OCHS
Cushings dis: fail to suppress

b) Definitive test
1. Cortisol & ACTH level without dexamethasone adm
2. Metyrapone test

Diagnosis :
Radiologic diagnosis :
1. X- ray : sella turcica
2. Adrenal angiography & venography :
uni/bilateral ?
3. Scanning
Treatment :
1. Surgery
2. Pituitary irradiation
3. Drugs : metyrapone ( inhibits 11- hydroxylase )
- pre-operative
- inoperable adrenal Ca
- ectopic tumor with unknown sites or has
already metastated