Adrenocortical Function and Dysfunction

Question 1

Describe the embryological origin of the adrenal medulla. What does it secrete?

Answer 1

Modified sympathetic ganglia
Secretes catecholamines (neurohormones)

Question 2

Describe the embryological origin of the adrenal cortex. What does it secrete?

Answer 2

True endocrine gland
Secretes steroids (classical hormones)

Question 3

List the 3 layers of the cortex and the class of steroid hormones secreted by each

Answer 3

Zona reticularis: sex hormones
Zona fasciculata: glucocorticoids
Zona glomerulosa: mineralocorticoids
NB: there is some overlap in secretion between reticularis and fasciculata

Question 4

What sex hormones are secreted by zona reticularis (and fasciculata)?

Answer 4

Androgens
Oestrogens
Dehydroepiandosterone (DHEA)

Question 5

What is the primary glucocorticoid secreted by zona fasiculata (and reticularis)?

Answer 5

Cortisol

Question 6

What is the primary mineralocorticoid secreted by zona glomerulosa?

Answer 6

Aldosterone

Question 7

What stimulates secretion of cortisol?

Answer 7

ACTH

Question 8

What stimulates secretion of aldosterone?

Answer 8

RAAS activation (primarily via ATII, local K+ levels and ACTH

Question 9

Why do cells of the adrenal cortex produce different steroid hormones?

Answer 9

Because they have different enzymes

Question 10

Why are there sometimes crossover effects between different steroid hormones?

Answer 10

Due to their similar chemical structure (e.g. acting on both mineralocorticoid and glucocorticoid receptors)

Question 11

What are the 6 main effects of cortisol?

Answer 11

Gluconeogenesis and glycogenolysis in the liver
Protein catabolism in skeletal muscle
Lipolysis of adipose tissue
Suppresses immune system
Negative Ca2+ balance (decreases absorption, increases excretion, stimulates bone resorption)
Influences brain function (mood, memory, learning)

Question 12

What are the 4 main direct effects of CRH?

Answer 12

Effects inflammation and immune responses
Inhibits appetite
Signals onset of labour
Effects mood (linked to several mood disorders)

Question 13

What is urocortin? What does it do?

Answer 13

A brain neuropeptide in the CRH family

Suppresses appetite

Question 14

What is POMC? What is its role and what enzymes does it produce inside and outside the pituitary?

Answer 14

Pro-opiomelanocortin is a large protein which undergoes proteolysis to produce a number of bioactive peptides, including ACTH and B-endorphins in the anterior pituitary
Outside of pituitary processing, it produces a-MSH (melanocyte-stimulating hormone)

Question 15

What is the role of a-MSH?

Answer 15

Decrease food intake
Increases skin melanin
Modulates the immune response

Question 16

What is the role of B-endorphins?

Answer 16

Reduce pain perception

Question 17

What are melanocortins?

Answer 17

Hormone family including MSH hormones and ACTH

Question 18

For which hormones does cortisol play a permissive role?

Answer 18

Glucagon and catecholamine actions

Question 19

Describe the pattern of cortisol secretion

Answer 19

Follows a diurnal rhythm where secretion peaks in the morning and is at its lowest point as night

Question 20

How can cortisol be used therapeutically? What are the drawbacks?

Answer 20

To inhibit the inflammatory response in e.g. bee stings, poison ivy, pollen allergies, organ transplantation
Long term use results in inhibition of ACTH secretion and atrophy of cortisol-secreting glands, so patients should have their doses tapered gradually when coming off cortisol

Question 21

How is cortisol transported in the blood?

Answer 21

On corticosteroid-binding globulin

Question 22

What is the eponymous name for primary hyperaldosteronism?

Answer 22

Conn’s syndrome

Question 23

What is the cause of secondary hyperaldosteronism?

Answer 23

RAAS hyperactivity

Question 24

What are the 3 main clinical and biochemical findings in hyperaldosteronism?

Answer 24

Hypernatraemia
Hypokalaemia
Hypertension

Question 25

Distinguish between Cushing's syndrome and Cushing's disease

Answer 25

Cushing's syndrome refers to any syndrome caused by excess cortisol Cushing's disease refers to cortisol excess secondary to a pituitary tumour that autonomously secretes ACTH

Question 26

What is the primary cause of Cushing's syndrome and what are the biochemical findings?

Answer 26

Adrenal cortex tumour autonomously secreting cortisol | Increased cortisol, decreased ACTH and CRH

Question 27

List 2 causes of Cushing's syndrome outside of the primary and secondary causes

Answer 27

``` Hyperstimulation of the adrenal cortex by CRH or ACTH Iatrogenic hypercortisolism (treatment with exogenous glucocorticoids) ```

Question 28

What is adrenogenital syndrome and what causes it? How can it be treated?

Answer 28

Excess androgen and oestrogen production, due to hereditary absence of enzyme for cortisol steroidogenic pathway Treated with glucocorticoids (which repair the glucocorticoid deficit and provide negative feedback to reduce androgen production stimulated by ACTH)

Question 29

List 8 symptoms of Cushing's syndrome as well as the mechanism of each

Answer 29

Hyperglycaemia (due to gluconeogenesis/glycogenolysis) Muscle wasting (due to proteolysis) Thin limbs (due to lipolysis) Fat deposits in trunk and face ("moon facies", "buffalo hump", central adiposity; due to increased appetite) Reddish purple striae (due to fat deposits stretching skin) Salt and water retention, hypertension (due to mineralocorticoid action of excess glucocorticoids) Osteoporosis (due to bone resorption) Mood elevation then depression, learning and memory difficulties (due to influence of cortisol on brain function)

Question 30

What are the secondary causes of Cushing's syndrome and what are the biochemical findings?

Answer 30

A pituitary tumour that autonomously secretes ACTH (increased ACTH and cortisol, decreased CRH) Hypothalamic hypersecretion of CRH (increased CRH, ACTH and cortisol)

Question 31

What is more common: adrenal hypersecretion or hyposecretion?

Answer 31

Hyposecretion

Question 32

What is the cause of primary adrenal insufficiency? What are the symptoms and what causes this presentation?

Answer 32

Autoimmune destruction of the adrenal cortex (Addison's disease) K+ retention leading to cardiac arrhythmias, and Na+ depletion leading to hypotension (due to decreased aldosterone secretion) Decreased gluconeogenesis/glycogenolysis leading to hypoglycaemia (due to decreased cortisol)

Question 33

What are the biochemical findings in secondary adrenal insufficiency?

Answer 33

Decreased ACTH, leading to a decrease in cortisol only (not aldosterone)

Question 34

What are the cells in the adrenal medulla responsible for secretion of catecholamines?

Answer 34

Chromaffin cells

Question 35

What are the 3 catecholamines? Which of these are only made in the adrenal medulla?

Answer 35

Epinephrine (made only in the adrenal medulla) Norepinephrine Dopamine

Question 36

Outline the fight-or-flight responses, metabolic effects, central effects, and stress responses produced by the action of catecholamines released from the adrenal medulla

Answer 36

Fight-or-flight: increased HR, contractility, TPR, BP Metabolic: increased glucose, FFAs, BMR Central: increased arousal and alertness Stress responses: physical and psychological responses

Question 37

What disorder produces hyposecretion of catecholamines from the adrenal medulla?

Answer 37

None recognises

Question 38

What disorder produces hypersecretion of catecholamines from the adrenal medulla?

Answer 38

Phaeochromocytoma

Question 39

How is phaeochromocytoma treated?

Answer 39

Surgical removal

Question 40

What is the difference in hormonal response elicited by acute and chronic stress?

Answer 40

Acute: fight-or-flight (catecholamines) Chronic: elevated cortisol (immune suppression)

Question 41

What effect does epinephrine have on the pancreas?

Answer 41

Increases glucagon release, decreases insulin release

Question 42

What effect does stress have on the posterior pituitary?

Answer 42

Stimulates release of vasopressin (ADH)