Adrenal

Pathophysiology
Frank Vuitch, MD

Adrenal
Pathophysiology
Learning
Objectives
Describe three syndromes of hyperadrenalism:
Hypercortisolism - Cushing Syndrome
Hyperaldosteronism - Conn Syndrome
Adrenogenital (virilizing) Syndromes
Causes and features of adrenocortical
insufficiency:
Primary Acute Adrenocortical Insufficiency
Waterhouse-Friderichsen Syndrome
Primary Chronic Adrenocortical Insufficiency Addison Disease
Pathophysiology of adrenocortical neoplasms
Pathophysiology of pheochromocytoma
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Normal Adrenal Gland

Each gland weighs about 4 gms

Cortex: three zones
Glomerulosa (outside) Aldosterone
Potassium, Renin, Angiotensin control
Fasciculata: 75% of cortex cortisol
Feedback loop with pituitary ACTH control
Reticularis (inside) cortisol (small),
estrogen and androgen
Medulla: composed of chromaffin cells
catecholamines (mainly epinephrine)
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Three Syndromes of
Hyperadrenalism

Hypercortisolism - Cushing Syndrome

Hyperaldosteronism - Conn Syndrome
Adrenogenital (virilizing) syndromes

Cushings Syndrome
Truncal obesity, buffalo hump
& moon facies
Weakness (destruction of
proximal muscle mass)
Hirsutism, amenorrhea
Hyperglycemia: Interferes
with glucose uptake &
stimulates
gluconeogenesis
Collagen loss Skin fragility
easy bruising, striae
Bone resorption
osteoporosis
Mental abnormalities
mood swings, depression,
psychosis
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Causes of Cushing
Syndrome

Exogenous Iatrogenic Cortisol

Endogenous Cushing Syndrome:
Primary pituitary hypersecretion of ACTH: 70%
- Cushings disease. Affects women 3.5x
more than men, 3rd-4th decade peak
Adrenal cortical adenoma, carcinoma, or
nodular cortical hyperplasia cortisol: 20%.
Adenoma 10% (females 4:1),
carcinoma 5%
Secretion of ectopic ACTH from neoplasms:
10% Small cell Ca of lung, carcinoid tumor,
medullary Ca of thyroid, etc
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Cushing Syndrome
ACTH

High dose
Dexamethasone
Suppression

Pituitary Adenoma

Elevated

Suppressed

Ectopic ACTH

Markedly
Elevated

Not Suppressed

Primary Adrenal
Neoplasm

Very Low

Not Suppressed

Adrenal Pathology
Large solitary yellow
nodule with adjacent
residual nonneoplastic
adrenal cortex thinned
and atrophic.
Clear lipid-containing
cells in nests. Note the
delicate vascular
network
Could this be carcinoma ?
Could this be adenoma ?
Could this be normal?
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Adrenocortical
Hyperplasia

Primary
Hyperaldosteronism

Caused by:
Adrenal cortical adenoma: 35% - usually <2
cm
Bilateral adrenal hyperplasia: 60%
Clinical:
Excessive levels of aldosterone secretion
Sodium retention, potassium excretion
hypertension with hypokalemia
Women more than men: 4th and 5th decades
Resect adenoma, spironolactone for
hyperplasia
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Adrenogenital
Syndromes
AGS caused by congenital adrenal hyperplasia
(90%) Due to defective conversion of
progesterone to 11-deoxycorticosterone by 21hydroxylase deficiency. This produces:
Salt wasting adrenogenitalism: Total lack of
hydroxylase, no mineralocorticoids, salt wasting
and virilization. Females recognized at birth or in
utero, males at 5-15 days because of salt wasting
Simple virilizing adrenogenitalism: genital
ambiguity, some hydroxylase activity no salt
wasting
Nonclassic or late onset: virtually asymptomatic or
mild manifestation e.g. hirsutism, acne,
menstrual
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Adrenogenital
Syndromes

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Primary Acute Adrenal

Cortical Insufficiency

90% reserve
In crisis: precipitated by stress, especially in
patients with chronic insufficiency (Addison)
Exogenous corticosteroids with rapid withdrawal
Massive adrenal hemorrhage:
Newborns: with prolonged and difficult delivery
Anticoagulants, disseminated intravascular
coagulopathy
Waterhouse-Friderichsen Syndrome:
Overwhelming sepsis - Meningococcemia, others
Purpuric rash, progressive hypotension shock

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Adrenal Insufficiency
Primary chronic adrenocortical insufficiency
(Addison Disease) - 90% functional reserve
Hypotension, hyperkalemia, hyponatremia, GI
sx, hypoglycemia, weakness, pigmentation
Autoimmune adrenalitis, 60-70%
Autoimmune polyendocrine syndromes 1 & 2
APS1: mutated autoimmune regulator gene
Infections - TB, fungi, AIDS
Metastases - especially lung and breast CA
Secondary insufficiency - low ACTH
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Pheochromocytoma

Surgically correctable cause of hypertension

(Name another neoplasm?), measure urinary
catecholamines
0.1 to 0.3% of patients with hypertension
90% in adrenal medulla; others in paraganglia
90% are functional (hypertension, 2/3 paroxysmal)
Up to 25% occur in familial setting
Mutations MEN-2, NF1, VHL, SDH
Nonfamilial tumors:
10% are bilateral
10% are malignant
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Pheochromocytoma

Gross: Small lesions to large hemorrhagic

masses 1 to 4000 gms (average 100 gms).
Cut surface is tan with areas of hemorrhage
Micro: Polygonal to spindle cell shaped cells
clustered in small nests (zellballen).
Malignancy is based solely on metastasis.
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Neurosecretory
granules

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