Disorders of Adenocorticol Function

Question 1

What is characterised by decreased activity of the adrenal cortex?

Answer 1

Addisons disease

Question 2

What may Addison’s disease be due to?

Answer 2

NAME?

Question 3

What can cause disease of the adrenal cortex?

Answer 3

Autoimmune destruction

Question 4

What is the result of reduction in activity of the adrenal cortex?

Answer 4

Reduces glucocorticoids and mineralocorticoid secretion

Question 5

What do disorders of the pituitary and hypothalamus leading to decreased secretion of ACTH affect?

Answer 5

Glucocorticoids only

Question 6

What is characterised by increased secretion of glucocorticoids?

Answer 6

Cushing’s syndrome

Question 7

What may Cushing’s syndrome be due to?

Answer 7

• Increased activity of the adrenal cortex due to tumour (adenoma)
• Disorders in secretion of ACTH caused by pituitary adenoma
• Ectopic secretion of ACTH

Question 8

What is the disease caused by pituitary adenoma causing increased ACTH secretion?

Answer 8

Cushing’s disease

Question 9

What is congenital adrenal hyperplasia?

Answer 9

A number of clinical conditions that arise as a consequence of a genetic defect in one or more of the enzymes required for synthesis of cortisol

Question 10

What happens due to the lack of cortisol in congenital adrenal hyperplasia?

Answer 10

The pituitary is not subjected to negative feedback control

Question 11

What is the result of the pituitary not being subject to negative feedback?

Answer 11

It secretes large amounts of ACTH

Question 12

What does excess ACTH secretion in congenital adrenal hyperplasia’s cause?

Answer 12

An enlargement of the adrenal cortex (hyperplasia)

Question 13

What does the severity of the consequences of congenital adrenal hyperplasias depend on?

Answer 13

Which enzyme(s) is affected

Question 14

What are the effects of excess cortisol secretion?

Answer 14

• Increased muscle proteolysis and hepatic gluconeogenesis
• Increased lipogenesis in adipose tissue
• Purple striae on lower abdomen, upper arms and thighs
• Immuno-suppressive, anti-inflammatory and anti-allergic reactions of cortisol
• Back pain and collapse of ribs
• Hypertension

Question 15

What can increased muscle proteolysis and hepatic gluconeogenesis lead to?

Answer 15

Hyperglycaemia, and associated polyuria and polydipsia

Question 16

What is hyperglycaemia due to excess cortisol secretion called?

Answer 16

Steroid diabetes

Question 17

What does increased muscle proteolysis cause?

Answer 17

Wasting of proximal muscle

Question 18

What is the result of proximal muscle wastage?

Answer 18

NAME?

Question 19

What does the increased lipogenesis in adipose tissue on excess cortisol secretion lead to?

Answer 19

Deposition of fate in abdomen, neck and face

Question 20

What does the deposition of fat in excess cortisol secretion lead to?

Answer 20

The characteristic body shape, moon-shaped face and weight gain

Question 21

What do the purple striae caused by excess cortisol secretion reflect?

Answer 21

The catabolic effects of protein structures in skin

Question 22

What does the decreased protein integrity in skin caused by excess cortisol secretion lead to?

Answer 22

Easy bruising

Question 23

Why does excess cortisol secretion lead to easy bruising?

Answer 23

Because there is thinning of the skin and subcutaneous tissue

Question 24

What does the immunological effects of excess cortisol secretion lead to?

Answer 24

Increased susceptibility to bacterial infections, anda cne

Question 25

Why may excess cortisol secretion cause back pain and rib collapse?

Answer 25

Due to osteoporosis

Question 26

Why does excess cortisol production lead to osteoporosis?

Answer 26

Because of disturbances to calcium metabolism, and loss of bone matrix proteins

Question 27

Why may mineralocorticoid effects of excess cortisol lead to hypertension?

Answer 27

Due to sodium and fluid retention

Question 28

Where else may the symptoms of excess cortisol secretion occur?

Answer 28

In patients receiving long-term treatment with glucocorticoids for various chronic conditions

Question 29

What would autoimmune destruction of the adrenal gland?

Answer 29

Involve loss of cortisol and mineralocorticoids

Question 30

How does the loss of cortisol and mineralocorticoids present?

Answer 30

It is a complex situation, that may present as an acute emergency (Addisonian Crisis), or as a chronic debilitating disorder (Addison’s disease)

Question 31

How does Addison’s disease onset?

Answer 31

Insidious onset, with initial non-specific symptoms of tiredness, extreme muscular weakness, anorexia, vague abdominal pain, weight loss and occasional dizziness

Question 32

What symptoms of Addison’s disease are extreme?

Answer 32

The muscular weakness and dehydration

Question 33

What is a more specific sign of Addison’s disease?

Answer 33

Increased pigmentation

Question 34

Where does increased pigmentation occur especially in Addison’s disease?

Answer 34

- Exposed areas of the body  - Points of friction  - Buccal mucosa  - Scars  - Palmar creases

Question 35

Why does Addison’s disease cause increased pigmentation?

Answer 35

Due to ACTH-mediated melanocyte stimulation

Question 36

What happens to blood pressure in Addison’s disease?

Answer 36

It decreases

Question 37

Why does Addison’s disease decrease blood pressure?

Answer 37

Due to sodium and fluid depletion

Question 38

What causes postural hypotension in Addison’s disease?

Answer 38

Fluid depletion

Question 39

What kind of episodes does Addison’s disease cause?

Answer 39

Hypoglycamic

Question 40

When do the hypoglycaemic episodes caused by Addisons disease particularly occur?

Answer 40

On fasting

Question 41

What can exacerbate the effects of Addison’s disease?

Answer 41

Stress, such as trauma of severe infection

Question 42

What can the exacerbation of the symptoms of Addison’s disease with stress cause?

Answer 42

- Nausea - Vomiting - Extreme dehydration - Hypotension  - Confusion  - Fever - Coma

Question 43

What is the exacerbation of the symptoms of Addison’s disease with stress called?

Answer 43

An Addisonian crisis

Question 44

What does an Addisonian crisis constitute?

Answer 44

A clinical emergency

Question 45

How is an Addisonian crisis treated?

Answer 45

IV cortisol and fluid replacement

Question 46

How is adrenocortisol function measured clinically?

Answer 46

- Plasma cortisol  - ACTH levels  - 24hr urinary secretion of cortisol and its breakdown products  - Dynamic function tests

Question 47

What are the breakdown products of cortisol?

Answer 47

17-hydroxysteroids

Question 48

Give 2 examples of dynamic function tests

Answer 48

- Dexomethasone surpression tests  | - ACTH stimulation tests

Question 49

What can clinical tests of adrenocortisol function be used in?

Answer 49

Differential diagnosis of adrenocortisol disease

Question 50

What is dexamethasone?

Answer 50

A potent steroid

Question 51

What would normally happen when dexamethasone is given orally?

Answer 51

Would suppress the secretion of ACTH and therefore cortisol

Question 52

How does dexamethasone suppress?

Answer 52

Feedback inhibition

Question 53

What dexamethasone suppression of plasma cortisol is characteristic of Cushing’s disease?

Answer 53

>50%

Question 54

Why is a dexamethasone suppression of >50% characteristic of Cushing’s disease?

Answer 54

Because for the diseases pituitary, even though its relatively insensitive to cortisol, it does retain some sensitivity to potent synthetic steroids

Question 55

Where does dexamethasone suppression not normally occur?

Answer 55

In adrenal tumours or ectopic ACTH production

Question 56

What is the result of dexamethasone suppression not normally occurring in adrenal tumours or ectopic ACTH production mean?

Answer 56

Rules them out, suggesting the result is due to a pituitary tumour

Question 57

What is Synacthen?

Answer 57

A synthetic analogue of ACTH

Question 58

What does the intramuscular administration of Synacthen normally cause?

Answer 58

An increase in plasma cortisol by >200nmol/L

Question 59

What does a normal response to Synacthen achieve?

Answer 59

The exclusion of Addison’s disease

Question 60

What do the steroid receptors form?

Answer 60

Part of a family of nuclear DNA-binding proteins

Question 61

What does the family of nuclear DNA-binding proteins formed by steroid receptors include?

Answer 61

The thyroid and vitamin D receptors

Question 62

What do all steroid receptors have?

Answer 62

3 main regions

Question 63

What are the 3 main regions of a steroid receptor?

Answer 63

- A hydrophobic hormone-binding region  - A DNA binding region  - A variable region

Question 64

What is the DNA binding region of a steroid receptor rich in?

Answer 64

Cysteine and basic amino acids

Question 65

What exists in the hormone binding regions of steroid receptors?

Answer 65

Sequence homology

Question 66

What is the % homology of the hormone bind region of the glucocorticoid receptor with the mineralocorticoid receptor?

Answer 66

64%

Question 67

What is the % homology of the hormone bind region of the glucocorticoid receptor with the androgen receptor?

Answer 67

62%

Question 68

What is the % homology of the hormone bind region of the glucocorticoid receptor with the oestrogen receptor?

Answer 68

31%

Question 69

What is the % homology of the hormone bind region of the glucocorticoid receptor with the thyroid receptor?

Answer 69

24%

Question 70

What is the result of the sequence homology of steroid receptors?

Answer 70

Cortisol will bind to the mineralocorticoid and androgen receptors with low affinity

Question 71

When may cortisol binding to mineralocorticoid and androgen receptors be significant?

Answer 71

When high levels of hormone present

Question 72

What does aldosterone do?

Answer 72

- Stimulates Na + reabsorption in exchange for K + (or H + ) - Stimulates growth and development of male genital tract and male secondary sexual characteristics, including height, body shape, facial and body hair, lower voice pitch - Anabolic effects on muscle protein

Question 73

What does over-secretion of aldosterone cause?

Answer 73

- Increases Na +  and water retention  - Loss of K + - In females-  - Hair growth (hirsutism) - Acne - Menstrual problems - Virilisation - Increased muscle bulk  - Deepening voice

Question 74

What does an increased Na +  and water retention, and loss of K + cause?

Answer 74

Hypertension and muscle weakness

Question 75

What does under secretion of aldosterone cause?

Answer 75

Hypotension

Question 76

What does oestrogen do?

Answer 76

- Stimulates growth and development of female genital tract, breasts and female secondary characteristics, including broad hips, accumulation of fat in breasts and buttocks, body hair distribution  - Weakly anabolic  - Decrease circulating cholesterol levels