Cushing
Syndrome
Epidemiology and Etiology:
- Etiologies:
- Exogenous glucocorticoids
(most)
- Hypersecretion of
ACTH by pituitary (Cushing disease) (70-80% of endogenous Cushing
syndrome)
- F:M = 5:1
- 20s-30s
- pituitary
microadenoma (vast majority)
- corticotroph cell
hyperplasia
- primary
- CRH-prodcing
hypothalamic tumour
- Hypersecretion of
cortisol by adrenal (10-20% of endogenous Cushing syndrome)
- Adrenal adenoma
- More common
in women, 30-50s
- Adrenal carcinoma
(about as common as adenoma)
- more common
in children and women 30-50s
- more
marked hypercortisolism than adenomas or hyperplasia
- Hyperplasia
- Diffuse
hyperplasia
- Nodular
hyperplasia
- usually
secondary
- uncommon
cause of primary adrenal Cushing
- massive
macronodular adrenocortical disease (MMAD)
- older
adults
- >3mm
nodules
- primary
pigmented nodular adrenal disease (PPNAD)
- children
more often
- familial
- <3mm
nodules, darkly pigmented
- Ectopic ACTH
secretion (~10% of endogenous Cushing syndrome)
- neoplasms
- Small cell
carcinoma of lung (most)
- Carcinoid
- Medullary carcinoma
- Pancreatic adenomas
- Some release CRH
rather than ACTH
Common sites:
Gross features:
- diffuse
hyperplasia:
- enlarged glands
(up to 25-40g)
- cortex diffusely
thickened, yellow
- nodular
hyperplasia:
- combined weight up
to 30-50g
- nodularity of
cortex (0.5-2.0cm nodules scattered throughout
- intervening areas
of thickend cortex
- bilateral
- adrenal adenoma:
- yellow
- thin or well
developed capsule
- usually < 30g
- adrenal carcinoma:
- unencapsulated
- larger than
adenoma usually (frequently > 200-300g)
- Stigmata of Cushing’s:
- Overweight
- Central / truncal
obesity
- Buffalo hump
- Moon facies
- Decreased muscle
mass
- Thin skin
- Easily bruise
- Cutaneous striae
- hirsuitism
Histologic features:
- Pituitary:
- Adrenal (morphology
depends on cause):
- Cortical atrophy
(exogenous Cushing)
- Diffuse hyperplasia
(60-70% of endogenous Cushing)
- Nodular hyperplasia
- Adenoma
- Cells similar
to those in zona fasciculata
- Identical
morphology in Cushing and Hyperaldosteronism
- Adjacent
atrophic gland if functioning
- Carcinoma
- Anaplastic
features
- Adjacent
atrophic gland if functioning
Immunophenotype:
Marker:
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Sensitivity:
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Specificity:
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Molecular features:
Other features:
- clinical
signs / symptoms:
- hypertension
- hyperglycemia
- glucosuria
- polydipsia
- osteoporosis
- suppressed immune
system
- psychiatric:
- mood
swings
- depression
- psychosis
- menstrual
abnormalities
References:
- Robbins &
Cotran Pathologic Basis of Disease (2005)