Adrenal Cortex

Introduction
Anatomy – zonation
Z. Glomerulosa,
Z. Fasciculata,
Z. Reticularis
 Hormones Produced – Glucocorticoids (cortisol);
Mineralocorticoids (aldosterone), Androgens (DHEA)

Steroids Secreted by the Human Adrenal Cortex

Steroid Secretion rate
(mg/day)
Cortisol 12-30
Aldosterone 0.05-0.15
DHEA 7-15
DHEA-sulfate 10-25
Hormone Biosynthesis
 Role and Sources of
Cholesterol
 Pathways of Hormone
Production
1. Mineralocorticoid Synthesis
2. Glucocorticoid Synthesis
3. Androgen Synthesis
Steroidogenic pathways in the zona glomerulosa (within broken lines) and zona
fasciculata-zona reticularis (within solid lines) of the human adrenal cortex. The major
secretory products are shaded.
 Zona reticularis
and fasciculata

Zona
glomerulosa
 Secretion and Distribution of
Adrenal Hormones
 Secretion – Determined by
rate of synthesis
 Circulation – Extensive protein
binding (transcortin, CBG)
 Actions of Adrenal Hormones
 Mechanism of Action –
lipophilic hormones
 Glucocorticoids

1. Physiological
2. Pharmacological
 Glucocorticoid Effects and Target Tissues
Effect Site of Action
Stimulates gluconeogenesis Liver
Increases hepatic glycogen Liver
Increases blood glucose Liver
Increases lipolysis Adipose tissue
Catabolic (negative nitrogen balance) Muscle, liver

Blocks inflammatory response Multiple sites

Suppresses immune system Multiple sites
Carb ohy dr ate and pr otei n
meta bol is m
 Corticosteroids protect dependent tissues, e.g.,
brain and heart from starvation.
 Stimulates the liver to form glucose and…
 Net result: increase glucose levels
 Mechanism: translocation of the glucose
transporter from the plasma membrane to an
intracellular location.

 Problem: glucocorticoids can worsen glycemic

control in patients with diabetes
Lip ids

 Redistribution of body fat (Cushing’s

syndrome) back of the neck (buffalo
bump), face (moon facies)
 Truncal adipocytes respond
predominantly to insulin and
Glucocorticoids-induced hyperglycemia.
CNS
Acute
 Mood elevation
 Euphoria
 Insomnia
 Increase motor activity
Chronic
 Anxious
 Depressed
 Psychosis
Neurosteroids regulate neural excitability
Mineralocorticoids
Bl ood pr essur e r e gul atio n
El ectr ol yte bal ance

Mineralocorticoid Effects and Target Tissues

Effect Site of Action
Stimulates Na+ reabsorption Kidney, salivary glands, sweat glands
Stimulates K+ excretion Kidney, salivary glands, sweat glands
Stimulates H+ excretion Kidney
Regulation of Hormone Secretion
Glucocorticoid (Cortisol)
Negative feedback system
 Diurnal rhythm

Diurnal rhythm of plasma cortisol concentrations

 Stress
 Mechanism of action of ACTH
 cAMP
B. Mineralocorticoid (Aldosterone)
1. Reni n - Angi otensi n Sys tem
2. Pl asma Potassi um

Regulation of aldosterone secretion by the zona glomerulosa of the adrenal cortex (+,
stimulation; -, inhibition; ECF, extracellular fluid)
Pathophysiology of Adrenal Cortex
Cushing’s Syndrome -
Hypercortisolism
1. Symptoms
Symptom Frequency of Occurrence (%)
Centripetal obesity 95
Hypertension 82
Hyperglycemia 80
Amenorrhea 75
Hirsutism 75
Purple striae 65
“Moon” facies 60
Osteoporosis 60
Personality change 55
2. Causes
B. Adrenocortical Insufficiency
1. 1°(Addison’s Disease) vs. 2°
 2. Symptoms of Addison’s Disease

Symptom Frequency of Occurrence (%)

Weakness and fatigability 100
Weight loss 100
Hyperpigmentation 92
Hypotension 88
Hyponatremia 88
Hyperkalemia 65

3. Differential Diagnosis – 1°vs. 2°

 Hyperaldosteronism

1° (Conn’s Syndrome) –
adrenal tumor

2° - many causes

3. Symptoms

4. Differential
Diagnosis
Pathogenesis of Primary vs. Secondary Hyperaldosteronism

Primary Hyperaldosteronism
↑ ECF volume
↑ Aldosterone → ↑ Na+ retention → + → ↓ Renin
↑ Renal perfusion pressure

Secondary Hyperaldosteronism
↑ Na+ retention
↓ Renal perfusion pressure → ↑ Renin → ↑ Aldosterone → +
↑ ECF volume
Congenital Adrenal Hyperplasia
(Adrenogenital Syndrome)
 1. Cause – enzymatic defect in
adrenal gland
 2. Symptoms - varied

 3. Treatment – replace missing

hormones
Consequences of a 21-hydroxylase (enzyme number 3) deficiency on adrenocortical
steroidogenesis. The shaded area contains the hormones that cannot be synthesized as a
result of the defect.