METABOLIC DISORDER

IN CUSHING SYNDROME

RONDANG R. SOEGIANTO

2012
Adrenocortical Disorder

A. Excessive secretion of glucocorticoid

Cushing Syndrome:
- Moonface - Osteoporosis
- Truncal obesity - Mental aberrations
- Purple striae - Protein depletion
- Hypertension - Glucose intolerance
B. Deficient secretion of glucocorticoid

Addison disease

Increased skin pigmentation

Weakness, fatigue, anorexia, nausea
Weight loss, hypotension
HPA axis =

Hypothalamic – Pituitary – Adrenal axis

Major hypothalamic regulator:

Peptide CRH =
Corticotropin Releasing Hormone

Major pituitary H that stimulates adrenocortical

endocrine function:
ACTH = Adrenocorticotropic H (39 AA peptide)
ACTH  Blood stream  triggers synthesis
and secretion of - corticosteroids
- adrenal androgens

Effect of hormones to protect tissues from

stress
- Blood pressure >>
- Blood glucose >>
- Immuno system responsiveness
Cortisol = Glucose elevating hormone

Actions: Metabolism of

A. Glycogen

B. Protein

C Lipid
Metabolic Pathway

Gluconeogenesis   Glucose   Glycogen

Glucose released into blood or stored as glycogen

Gluconeogenesis precursors:
Non-carbohydrate substances: - Glycerol
- Lactic acid
- Amino acid
Glycerol  Glycerol-3P (activation by glycerol kinase}
I
Dihydroxyacetone P +Glyceraldeh 3-P

І
Fruct 1,6-bisphosphate
Fruct-1,6-bisphosphatase І
Fruct 6-P
І
Glucose 6-P
Glucose-6-phosphatase І
Glucose (Blood)
Alternative:
G 6-P   Glycogen (Glycogenesis)

Glycogenolysis   G 1-P  G 6-P

Key enzyme: Phosphorylase
Cortisol increases glycogenolysis probably
thru key enzyme
Lactic Acid  Pyruvate
Lactate dehydrogenase (LDH)

Pyruvate enters mitochondria to

bypass non-reversible pyruvate kinase

Leaves mitokondria as malate

Malate  Phosphoenolpyruvate (PEP)
Phosphoenolpyruvatecarboxykinase (PEPCK)
PEP   Glyceraldehyde 3-P
+ F-1,6-bisP
Di-OH- acetone P

Continued as in gluconeogenesis from glycerol

Major aimino acid for gluconeogenesis (gng) is

Alanine CH3-NH2-COOH
І Transaminase
CH3-C=O -COOH (pyruvate)

Proceeds to gng as pyruvate from lactate

Cortisol incr activity of gng enzymes,
principally G6Pase and PEPCK

Overall effect of glucocorticoid is

catabolic effect leading to glucose elevaton
A. Glycogen  glycogenolysis  G1-P
G1-P  G6-P  Glucose
B. Protein  tissue degradation 
release of AA (alanin major AA)
Alanin  pyruvate   glucose
C. Lipid: Fat lipolysis by lipase
TAG  Glycerol + FA
Glycerol  gluconeogenesis
A, B, and C increased in Cushing syndrome
Glucocorticoids effect on catecholamines
(epinephrine and norepinephrine) and
glucagon  Insulin resistance
Also: catabolic changes in muscle, skin
and connective tissue (purple striae)

Cushing: bone formation reduced, less

Ca absorbed than excreted  Osteoporosis