Adrenal Glands

Where are adrenal glands found

Outer cortex (80%)

Inner Medulla (20%)

Location & structure of the adrenal glands

Hormones produced by medulla & % of each

Adrenaline (80%)

Nor-Adrenaline (20%)

Precursor of adrenaline

Tyrosine

As you produce adrenaline you also produce what other hormone

Dopamine

Blood conc. of adrenaline

10^-10M

Effects of adrenal medulla hormones on the CVS

Effects of adrenal medulla hormones on the GIT

Decreased motility

Effects of adrenal medulla hormones on the skin

Increased sweating

Effects of adrenal medulla hormones on the skeletal muscle

Increased tension generation

Effects of adrenal medulla hormones on the nervous tissue

Increased brain arousal, reflex speed, aggression, anxiety

Metabolic effects of adrenal medulla hormones on muscle, pancreatic islets, liver & fat

What is pheochromocytoma

Rare catecholamine producing tumour

What do pheochromocytomas arise from

chromaffin cells of adrenal medulla or from sympathetic ganglia

Symptoms of pheochromocytomas

Pressure - sudden major increase in blood pressure

Pain - abrupt throbbing headache, chest, abdominal pain

Perspiration - generalized diffuse diaphoresis

Palpitations usually with true tachycardia often with feelings of panic or anxiety

Pallor of the skin from vasoconstriction

3 types of steroid hormones produced int he adrenal cortex

Mineralocorticoids

Glucocorticoids

Weak Androgens

Give an example of each type of steroid hormone produced int he adrenal cortex

Mineralocorticoids

Glucocorticoids

Weak Androgens

Mineralocorticoids - Aldosterone

Glucocorticoids - Cortisol

Weak Androgens - Weak Sex Steroids (Androstenedione & Dehydroepiandrosterone)

Mineralocorticoids

1. What are they derived from

2. Are they stored

3. Are they synthesised on command

Mineralocorticoids are:

Derived From Cholesterol

Not Stored

Synthesised on Demand

How are glucocorticoids found in the body

glucocorticoids are found bound to plasma

How are weak androgens found in the body

Bound to intracellular receptors in the cytoplasm / nucleus

Role of weak androgens

Alter gene activity

What are the layers from outside to inside in the adrenal gland

Capsule - Adrenal cortex (zona glomerulosa, zona fasciculata, zona reticularis) - Adrenal medulla

What will a problem in each of the zones present as

zona glomerulosa: sodium imbalance

zona fasciculata: cortisol imbalance (causes high/low blood sugar)

zona reticularis: androgenic effects (or deficiency)

Remembered as GFR - salt, sugar, sex!

A deficiency in cholesterol causes a deficiency in what types of steroid hormone (mineralocorticoids, glucocorticoids, androgens)

all 3: mineralocorticoids, glucocorticoids, androgens

A deficiency in progesterone causes a deficiency in what types of steroid hormone (mineralocorticoids, glucocorticoids, androgens)

mineralocorticoids

glucocorticoids

Some androgens - would have an effect on androstenedione production but not dehydroepiandrosterone

A deficiency in 17-hydroxypregnenolone causes a deficiency in what types of steroid hormone (mineralocorticoids, glucocorticoids, androgens)

glucocorticoids & androgens

What zones in the adrenal gland secrete glucocorticoids

Zona Fasiculata and Reticularis

Most common glucocorticoid

Cortisol

Why is cortisone prescribed more than cortisol

Fewer side effects

Normal Cortisol Blood Concentration

5-25µg/100mls

In what zone of the adrenal gland is cortisol mainly produced

zona fasciculata (contains enzymes for cortisol synthesis)

(small amounts in zona reticularis)

What hormones are required for cortisol synthesis

Corticotropin-Releasing Hormone (CRH)

Adrenocorticotropic Hormone (ACTH)

How is cortisol release regulated

Hypothalamic-Pituitary-Adrenal (HPA) Axis regulates cortisol release through a negative feedback loop

Hypothalamus releases CRH (Corticotropin-Releasing Hormone) → stimulates the pituitary.

Anterior Pituitary releases ACTH (Adrenocorticotropic Hormone) → stimulates the adrenal cortex.

Adrenal Cortex (Zona Fasciculata) releases Cortisol into the bloodstream.

Cortisol provides negative feedback to suppress CRH and ACTH production, preventing excess cortisol release.

What is the Dexamethasone Suppression Test (DST) used for

Diagnose the cause of hypercortisolemia (high cortisol levels)

Based on the negative feedback mechanism

When is cortisol highest & lowest

Highest @ 8am

Lowest @ 2am

Is adrenocroticotrophin (ACTH) an anterior/posterior pituitary hormone

anterior

Precursor of adrenocroticotrophin (ACTH)

Pro-Opio-Melano-Corticotrophin (POMC)

What other hormones is Pro-Opio-Melano-Corticotrophin (POMC) a precursor for

MSH (Melanocyte-Stimulating Hormones)

Lipotropins

Endorphins

CLIP

How is cortisol transported

Mainly Bound in Plasma

How is cortisol transported

Mainly Bound in Plasma to transcortin

What synthesises transcortin

Liver

In the equilibrium between free & bound cortisol, what balance is there between the 2

Mostly bound, some free (active)

What influences free cortisol levels

Increased transcortin decreases free cortisol

Increased oestrogen (pregnancy / oral contraceptives) decreases free cortisol by increasing transcortin

Role of cortisol

Stabilise glucose between meals

• Spares glucose

• Promotes breakdown of protein & fat

(overall catabolic & diabetogenic)

What are the metabolic effects of cortisol on muscle, liver & fat

How do you tell if someone is having an excess of cortisol or glucagon

Cortisol promotes glycogen storage in the liver

Glucagon breaks down glycogen in the liver

Anti-inflammatory & immunosuppressive effects of cortisol

Cortisol inhibits every part of inflammation

• Reduction in inflammation

• Reduction in autoimmune reactions

• Decreased healing

• Decreased immune protection

(synthetic glucocorticoids are used to treat inflammatory disorders - eczema, asthma, prevent transplant rejection)

Effect of cortisol on cardiovascular system

Increases cardiac potential by making you more sensitive to adrenaline

Potentiates Effects of Adrenaline - increases β-adrenergic Sensitivity

Effect of cortisol on bones

Decreased osteoblast production and decreased Ca2+ production

(weakens bones)

Effect of cortisol on the liver

Increased Amino Acid Uptake by Liver

Increased Plasma Hepatic Proteins

What are the Mineralocorticoid Like Effects of Cortisol

Only Significant At Prolonged High Levels

Increased Sodium and Water Re-absorption, increased Potassium Excretion

Maintain Blood Volume in Dehydration, Hemorrhagic Stress

Cortisol effect on RBC production

Increases RBC production

Effect of cortisol & stress on metabolism

Increased energy substrates

Effect of cortisol & stress on mineralocorticoids

Dehydration

Haemorrhagic stress

Effect of cortisol & stress on cardiovascular system

Increased cardiac potential

Effect of cortisol & stress on hepatics

Slows tissue repair done by hepatic AA

Effect of cortisol & stress on immune response

Prevents over stimulation of the immune system

Effect of cortisol & stress on RBCs

Increases oxygen carriage

Effect of cortisol & stress on platelets

Prevents blood loss

What causes Cushing’s Syndrome

Caused by excess endogenous or exogenous glucocorticoids

Primarily at adrenal level

What causes Cushing’s disease

Overproduction of ACTH and cortisol

Metabolic symptoms of Cushing’s syndrome

What is Addison’s disease

Primary adrenocortical insufficiency

The adrenal cortex is destroyed

Insufficient production of cortisol, often accompanied by aldosterone and adrenal androgen deficiency

What causes Addison’s disease

The result of an infection (TB / autoimmune disease)

Can be caused by another treatment (e.g. chemo)

Effects of under secretion of cortisol (Addison’s disease) on each of these (arrow up/down)

& other effects of low cortisol

Leads to an inability to maintain blood glucose between meals

Inability to deal with stress

Susceptibility to inflammation & allergies

Increased pigmentation

Increased ACTH, POMC and MSH

Which of these are affected by increased ACTH: Mineralocorticoids (aldosterone), glucocorticoids (cortisol), androgens (dehydroepiandrosterone & androstenedione)

What would the effect be

All

Increased production

Which of these are affected by a lack of 21 β-hydroxylase: Mineralocorticoids (aldosterone), glucocorticoids (cortisol), androgens (dehydroepiandrosterone & androstenedione)

What would the effect be

All

Mineral corticoids & Glucocorticoids production would decrease

Androgens production would increase due to a build up of its precursors

What causes 21 β-hydroxylase deficiency

Congenital abnormality

adrenogenital syndrome or congenital adrenal hyperplasia

What are the results of a 21 β-hydroxylase deficiency

Unable to produce mineralocorticoids or glucocorticoids

Produce adrenal androgens – virilisation of females

In utero – cause masculinisation of external genitalia

In children – increase growth, suppression of gonadal function

Which of these are affected by a lack of 17α-hydroxylase: Mineralocorticoids (aldosterone), glucocorticoids (cortisol), androgens (dehydroepiandrosterone & androstenedione)

What would the effect be

No glucocorticoids or adrenal androgens

What is the result of a deficiency in 17α-hydroxylase

Overproduction of corticosterone but inhibits aldosterone levels

(inhibitory feedback)

Which is more common: 21 β-hydroxylase deficiency or deficiency in 17α-hydroxylase

21 β-hydroxylase deficiency