PATHOPHYSIOLOGY DIAGNOSTIC APPROACH

Cortisol Pathway Cortisol Target Organs and Effects Screening Tests (2/3+) ACTH Level Imaging Studies
1
Hypothalamus CVS CNS Endocrine/Metabolic Low-dose Dexamethasone
Pituitary MRI
Suppression Test
CRH ↑Cortisol ↑Cortisol
Pituitary Dexamethasone ↑ACTH Cushing’s Dx Adrenal CT/MRI
NE NE + + COO-
(1 mg)
D.M. Pit.
post. ant. NE +
β1-AR↑ ↑Cortisol +
NH3 ↓ACTH Ectopic
↑ACTH NE
↑Activity ↑↑Glucose
Adrenal α1-AR↑ Proteolysis CT CAP
+ Cushing’s Synd. ↑↑Cortisol
gland ↑Cortisol FFA + Glycerol ↓ACTH
Z.F. β1-AR Sensitivity of SNS Collagen synthesis Adrenal tumor
Lipolysis Cushing’s ↓Cortisol
↑HR Iatrogenic
↑CO ↑Insulin (extremities) ↑↑Cortisol (normal)
↑SV Atrophy
↑Cortisol α1-AR 2°HTN Gluconeogenesis Fat redistrib. (peripheral)
Glycogenolysis (central)
↑SVR ↑BP Osteopenia 2
Diabetogenic Effect • Moon face Osteoporosis
Urinary Cortisol (24 hrs) High-dose Dexamethasone TREATMENT
Immune System • Buffalo hump Suppression → Which 2°cause?
Fractures
• Abdominal obesity
Dexamethasone 1
Neutrophils Thin skin (8 mg) Pit. tumor Transsphenoidal Resection
↑↑Cortisol margination Striae
GNRH
(abdomen)
T cell T-cell ↑ACTH ↑Cortisol ↓ACTH ↓Cortisol 2
proliferation ↓FSH/LH Ecchymosis
a. Ketoconazole
↑↑Risk for Antibody Slow wound b. Adrenalectomy
Infections production healing Cushing’s ↑Cortisol
↑↑Cortisol ↑ACTH ↑Cortisol
(fungal) 3
Plasma cell
↓Libido Amenorrhea a. Chemoradiation/Removal
Ectopic site (SCLC)
b. Ketoconazole

3 3
Cushing Syndrome VS Cushing Disease Exceptions Late-night Salivary CRH Stimulation Test
Cortisol Test Alternative to ↑Dose Dex. test Iatrogenic Cushing's
1°↑Cortisol a. Taper Steroid Dosage

CRH
Tumor pituatry ↑CRH CRH↑
Adenoma* ↑↑Cortisol Tumor
↑Cortisol Pituitary
Carcinoma ↑MSH Pit. tumor
↑↑↑Cortisol
Adenoma
↑ACTH ↑ACTH Saliva Pit.
Iatrogenic ACTH↑↑↑
↑Cortisol ↑ACTH ↑Cortisol
Chronic ↓ACTH ↑ACTH
Steroids ↑Melanin Cushings ↑Cortisol
CRH
↑Cortisol
(ex. Autoimmune)
(Ectopic) SCLC ↑Androgens (♀) Ectopic
SCLC
↑Corticosteroid = Cortisol
small lung cancer
Acne Hirsutism Hyperpigmentation

CUSHING’S SYNDROME