Pituitary and adrenal cortex disorders Flashcards Preview

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Flashcards in Pituitary and adrenal cortex disorders Deck (85)
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1
Q

List the hormones produced by the anterior pituitary gland

A
TSH
ACTH
Growth hormone
LH & FSH
Prolactin
2
Q

List the hormones produced by the hypothalamus but stored by the posterior pituitary gland

A

Oxytocin

ADH (vasopressin)

3
Q

List the hormones produced by the adrenal cortex

A

Mineralocorticoids - e.g. aldosterone
Glucocorticoids (major)- e.g. cortiosol and corticosterone
Androgens - e.g. degydorpiandrosterone (small amounts)

4
Q

Describe the structure of adrenaline

A

It is a water-solible catecholamines (amino acid derived hormone) that is synthesised by enzyme-catalysed steps which convert the amino acid -> tyrosine -> dopamine -> noradrenaline -> adrenaline

5
Q

What is the function of adrenaline?

A

Released in response to stressful situations, it stimulates the sympathetic NS. It has effects on:

  1. CVS - increase cardiac output and blood supply
  2. CNS - increases mental alertness
  3. Carbohydrate metabolism - increases glycogenolysis in liver and muscle
  4. Lipid metabolism - increase lipolysis in adipose tissue
6
Q

What is the general structure of steroid hormones?

A

All are lipophilic (hydrophobic) and synthesised from cholesterol via progesterone in a series of enzyme catalysed reactions

7
Q

How do steroid hormones affect their target tissues?

A

Steroid hormones (like cortisol) can cross the plasma membranes of target cells. Cortisol binds to cytoplasmic receptors and then the hormone/receptor complex enter the nucleus and interacts with specific regions of DNA. Other steroid hormones bind to pre-bound receptors on DNA. Steriod hormones change the rate of transcription of specific genes and may take some time to occur

8
Q

What is the effect of ACTH and CRH on cortisol secretion?

A

CRH - corticotropin releasing hormone is produced in the hypothalamus and stimulates the secretion of ACTH
ACTH - is released from the anterior pituitary and is the main factor contolling secretion of cortisol

9
Q

How can ACTH lead to increased pigmentation in certain areas of the body?

A
  1. The alpha-MSH sequence of 13 amino acids is contained within the ACTH sequence in POMC, giving ACTH some MSH-like activity when present in excess
10
Q

What are the main actions of cortisol on target cells?

A

An important component of the stress response - it has a number of effects on metabolism. The major effects are in the starved and stressed states where it affects the availability of all major metabolic substrates by increasing proteolysis, lipolysis and gluconeogenesis.

11
Q

How can cortisol have weak mineralocorticoid and androgen effects?

A

There is approximately 64% sequence homology between the glucocorticoid receptor and the mineralocorticoid receptor and approx. 62% with the androgen receptor. Therefore cortisol will bind these receptors with low affinity. This binding may become significant when high levels of the hormone are present.

12
Q

Where is the pituitary gland located?

A

At the base of the brain suspended from the hypothalamus by a stalk. It lies in a deep recess of the sphenoid bone (pituitary fossa) surrounded by a small bony cavity (sella turcica)

13
Q

What is unusual about the bloody supply to the pituitary gland?

A

It has a portal system - vessel connecting two capillary beds located in separate tissues, one in the hypothalamus and the other in the anterior pituitary

14
Q

What is the arterial blood supply to the pituitary?

A

From the superior and inferior hypophyseal arteries arising from the internal carotid artery

15
Q

From which cells are the anterior lobe of the pituitary derived?

A

Up-growth of ectodermal cells from the roof of the primitive phaarynx

16
Q

From which cells are the posterior lobe of the pituitary derived?

A

Down-growth of neural tissue from the hypothalamus

17
Q

List the hormones produced by the adrenal medulla

A

Adrenaline (epinephrine)

18
Q

What is produced by thyrotropes in the anterior pituitary?

A

TSH - thyroid stimulating hormone

19
Q

What is produced by corticotropes in the anterior pituitary?

A

ACTH - adrenocorticotropic hormone

20
Q

What is produced by somatotropes in the anterior pituitary (represent the largest number of cells)?

A

Growth hormone

21
Q

What is produced by gonadotropes in the anterior pituitary?

A

LH - luteinising hormone

FSH - follicle-stimulating hormone

22
Q

What is produced by lactotropes in the anterior pituitary?

A

Prolactin

23
Q

Underneath the connective tissue capsule with its plexus of blood vessels (capsular plexus) three zones can be recognised. List the three zones from the superficial to deep

A

Zona glomerulosa
Zona fasiculata
Zone reticularis

24
Q

What do the cells in the Zona glomerulosa secrete and what are their functions?

A

Mineralocorticoids (e.g. aldosterone) that regulate body Na+ and K+ levels

25
Q

What do the cells in the Zona fasiculata secrete and what are their functions?

A

Glucocorticoids (e.g. cortisol) that have a number of important functions including the regulation of carbohydrate metabolism

26
Q

What do the cells in the Zona reticularis secrete and what are their functions?

A

Glucocorticoids and small amounts of androgens (e.g. dehydroepiandrosterone)

27
Q

What stimulates the secretion of CRH?

A

Physical stress - pain, temperature
Chemical stress - hypoglycaemia
Emotional stressors

28
Q

What creates negative feedback on the corticotropes of the anterior pituitary and the hypothalalmus release of CRH?

A

glucocorticoids

29
Q

What type of hormone is ACTH and which receptors does it work on?

A

hydrophillic polypeptide hormone that targets G-protein coupled receptors (GPCR) on the plasma membrane of target cells. Specifically the GPCR melanocortin receptor type 2 (MC2), which uses cAMP as a second messenger

30
Q

What is the name of the large protein that is a bio-synthetic precursor to ACTH and what other biologically active peptides does it create?

A

POMC - proopiomelanocortin
Other precursors:
Alpha-MSH - (melanocyte stimulating hormone)
Endorphins

31
Q

Why does ACTH concentration need to measured at specific points of the day?

A

It has a short half-life in circulation (approx. 8 minutes) and is released in pulses that follow a circadian rhythm. Peak plasma levels occur in the early hours of the morning and lowest levels are seen in the late evening

32
Q

What effect does binding of ACTH on the surface receptors of cells in the zona fasiculata and zona reticularis have?

A

Leads to activation of cholesterol esterase increasing the conversion of cholesterol esters to free cholesterol, as well as stimulating other steps in the synthesis of cortisol from cholesterol.

33
Q

What clinical consequences does over-secretion of ACTH have?

A
  1. Effects on tissues - increased pigmentation due to partial MSH activity
  2. Effects on adrenal cortex - adrenal hyperplasia and over-production of cortisol
34
Q

What clinical consequences does under-secretion of ACTH have?

A

Produces symptoms related to the lack of glucocorticoids but not mineralocorticoids as aldosterone release is not simulated by ACTH and therefore its secretion is normal

35
Q

How does cortisol travel in plasma?

A

It is a steroid hormone and therefore is hydrophobic and must be transported bound to a plama protein. The major transport protein is transcortin (or corticosteroid-binding globulin, CBG) which carries approx. 90% of plasma cortisol - the remaining 10% being free and biologically active

36
Q

List the metabolic actions of cortisol

A

Decrease amino acid uptake
Decrease protein synthesis, Increase proteolysis (not liver)
Increase hepatic gluconeogenesis and glycogenolysis
Increase lipolysis in adipose tissue (N.B. high levels of cortisol increase lipogenesis in adipose tissue - think Cushing’s)
Decrease peritheral uptake of glucose (anti-insulin)

37
Q

What direct effects does cortisol have in addition to its general metabolic actions?

A

Direct effects on cardiac muscle, bone and immune system

38
Q

What is synthesised in the adrenal medulla?

A

Adrenal medulla is in essence a modified sympathetic ganglion. It synthesises various catecholamines, which are stored in membrane-limited vesicle in medullary cells:

  1. Hormone - adrenaline (epinephrine)
  2. Neurotransmitters - noradrenaline (norepinephrine) and dopamine
39
Q

What are the clinical consequences of over-secretion of adrenaline?

A
This is usually due to a tumour and may be associated with:
Hypertension
Anxiety
Palpitations
Pallor
Sweating
Glucose intolerance
40
Q

What is Addison’s disease?

A

Decreased activity (hypoactivity) of the adrenal cortex

41
Q

What can be the cause of hypoactivity of the adrenal cortex?

A
  1. Diseases of the adrenal cortex -> auto-immune destruction - reduces glucocorticoids and mineralcorticoids
  2. Disorders of the pituitary of hypothalamus -> decreased secretion of CRH of ACTH - only affects glucocortiocoids
42
Q

What is Cushing’s syndrome?

A

Increased secretion (hyperactivity) of glucocorticoids

43
Q

What may cause Cushing’s disease?

A
  1. Adenoma - adrenal cortex tumour increasing the cortex activity
  2. Disorders in the secretion of ACTH caused by pituitary adenoma (Cushing’s disease) or ectopic secretion of ACTH
44
Q

What is the difference between Cushing’s syndrome and Cushing’s disease?

A

Cushing’s disease is a disease caused by over-secretion of ACTH by a pituitary adenoma. Cushing’s syndrome is a group of disorders which cause symptoms characteristic of Cushing’s and can be caused by adrenal adenoma and ectopic secretion of ACTH by tumours elsewhere in the body

45
Q

What is congenital adrenal hyperplasia?

A

Refers to a number of clinical conditions caused by defects in enzymes that are required for the synthesis of corisol. The corresponding lack of negative feedback from cortisol results in over-secretion of ACTH and enlagement of the adrenal cortex (hyperplasia). The severity and consequences of these conditions depends on which enzyme(s) is affected

46
Q

What are the characteristic signs of Cusing’s syndrome/ excess cortisol secretion?

A
Thin arms and legs
Large amounts of abdominal fat
Moon-shaped face
Purple striae - lower abdomen, upper arms and thighs
Easy bruising
47
Q

Why can steroid diabetes occur from excess cortisol secretion?

A

It stimulates muscle proteolysis and hepatic gluconeogenesis that may lead to hyperglycaemia with associated polyuria and polydipsia.

48
Q

Why are thin arms and legs a sign of excess cortisol secretion?

A

Increased muscle proteolysis leads to wasting of proximal muscles

49
Q

Why is fat deposition in abdomen, neck and face producing a moon-shaped face and weight gain a sign of excess cortisol secretion?

A

Increased lipogenesis causes by high levels of cortisol (cortisol at lower levels causes increased lipolysis)

50
Q

Why are purple striae on lower abdomen, upper arms and thighs, a sign of excess cortisol secretion?

A

Proteolysis in skin leads to easy bruising because of the thinning of skin and subcutaneous tissue

51
Q

Why does excess cortisol secretion cause a susceptibility to bacterial infection and increased acne?

A

Cortisol causes immunosuppressive, anti-inflammatory and anti-allergic reactions

52
Q

Why can excess cortisol secretion cause osteporosis and therefore back pain and collapse of ribs?

A

It can disturb calcium metabolism resulting in loss of bone matrix protein

53
Q

What mineralocorticoid effects can excess cortisol produce?

A

Hypertension due to sodium and fluid retention

54
Q

What can cause exogenous Cushing’s Syndrome?

A

prescribed glucocorticoids e.g. Prednisolone for treatment of inflammatory disorders:

  1. asthma
  2. IBD
  3. rheumatoid arthritis
  4. Other autoimmune conditions
55
Q

What is the name of the acute emergency that can result from the auto-immune destruction of the adrenal gland?

A

Addisonian crisis

56
Q

What is the name of the chronic debilitating disorder that can result from the auto-immune destruction of the adrenal gland?

A

Addison’s Disease

57
Q

What can cause Addison’s disease to be exacerbated leading to an Addisonian crisis?

A

Exacerbation by stress such as trauma or severe infection

58
Q

What are the signs and symptoms of an Addisonian crisis?

A
nausea
vomiting
severe dehydration
hypotension
confusion
fever
and even coma and death
59
Q

Addisonian crisis is a clinical emergency that can lead to coma and death if not correctly diagnose and treated. How is it treated?

A
Intravenous cortisol
Fluid replacement (dextrose in normal saline)
60
Q

What are the signs and symptoms of Addison’s disease?

A
  1. Insiduous onset with non-specific symptoms of tiredness, extreme muscle weakness, anorexia, vague abdominal pain, weight loss and occasional dizziness
  2. Extreme muscular weakness and dehydration
  3. INCREASED PIGMENTATION on exposed areas of the body, points of friction, buccal mucosa, scars and plamar creases due to ACTH-mediated melanocyte stimulation
  4. Decreased blood pressure due to sodium and fluid depletion
  5. Postural hypotension due to fluid depletion
  6. Hypoglycaemic episodes on fasting
61
Q

What is the function of the mineralocorticoid, aldosterone?

A

Aldosterone stimulates Na+ reabsorption in the kidney in exchange for K+ (or H+)

62
Q

What is the effect of oversecretion of the mineralocortiocoid, aldosterone?

A

Oversecretion of aldosterone increases Na+ absorption and water reabsorption and loss of K+ - causing hypertension and muscle weakness (K+ is crucial in heart function and plays a key role in skeletal and cardiac muscle contraction)

63
Q

What is the effect of oversecretion of the mineralocortiocoid aldosterone?

A

Undersecretion of aldosterone decreases Na+ reabsorption and water reabsorption and K+ is retained - causing hypotension

64
Q

What is the function of androgens (male sex hormones)?

A

They stimulate the growth and development of the male genital tract and male secondary sexual characteristics including height, body shape, facial and body hair, lower pitch. They also have anabolic actions especially on muscle protein.

65
Q

What is the effect of oversecretion of androgens?

A

Produces effects in females such as: hair growth, acne, menstrual problems, virilisation, increased muscle bulk, deepening voice

66
Q

What is the effect of oestrogens?

A

Stimulate growth and development of the female genital tract, breasts and female secondary characteristics including broad hips, accumulation of fat in breasts and buttocks, body hair distribution. They are weakly anabolic and decrease circulating cholesterol levels.

67
Q

What are the three endogenous causes of Cushing’s syndrome?

A
  1. Ectopic cause: tumour (e.g. lung tumour) that can secrete ACTH, but is not part of the negative feedback loop
  2. Adrenal cortex tumour: increased cortisol secretion
  3. Pituitary tumour: increased ACTH secretion
68
Q

How do you test for the presence or absence of Cushing’s syndrome?

A
  1. Urine test for cortisol levels (and break-down products) - over 24hrs
    Or
  2. Low dose of Dexamethasone (potent synthetic steroid) at night - a normal response would be a greater that 50% increase in cortisol secretion - if this does not happen you have Cushing’s
69
Q

How do you test where the malfunction that is causing Cushing’s is occuring?

A

Measure plasma ACTH levels:

  1. Low ACTH suggest adrenal problem
  2. High ACTH suggests ectopic or pituitary problem
70
Q

How do you differentiate High ACTH levels in Cusing’s disease that are caused by a pituitary or ectopic problem?

A

Dexamethasone supression test. Give oral dose of Dexamethasone:

  1. Ectopic - expect no response as not part of negative feedback loop
  2. Pituitary - expect some sensitivity and response as Dex is a potent steroid and therefore would expect a drop in ACTH levels and consequently cortisol levels
71
Q

What test can exclude Addinson’s disease?

A

Administration of Synacthen (synthetic analogue of ACTH) intramuscularly - would normally expect an increase in plasma cortisol by >200nmol/L. A normal response can exclude Addinson’s disease.

72
Q

What are the signs and symptoms of Cushing’s disease?

A
Plethoric (flushed)
Moon-shaped face
Abdominal obesity
Purple striae
Acute weight gain
Hyperglycaemia
Hypertension
73
Q

Why should prescribed corticosteroids not be stopped suddenly?

A

They inhibit the release of CRH from the hypothalamus and ACTH from the anterior pituitary by negative feedback. If they are stopped suddenly the body does not have time to immediately synthesis the concentration of CRH and ACTH that is needed to stimulate endogenous corticosteroid release, therefore results in an adrenal crisis (like that of an Addisonian crisis)

74
Q

What are the net effects of increased cortisol secretion?

A

Increased glucose production (gluconeogenesis)
Breadown of protein
Redistribution of fat

75
Q

In Cushing’s syndrome what specific areas show increased fat depostion?

A

Abdomen
Supraclavicular -> fat pads
Dorsocervical -> buffalo hump
On face -> moon-shaped face

76
Q

Why does muscle wastage in the arms and legs occur?

A
  1. Cortisol inhibits insulin induced GLUT4 translocation in muscle which prevents glucose uptake and therefore glucose utilisation
  2. Increase proteolysis and decreased proteogenesis occur
77
Q

What are the signs and symptoms of Addinson’s disease?

A
More common in woman than men
Postural hypotension
Lethargy
Weight loss
Anorexia
Increased skin pigmentation
Hypoglycaemia
78
Q

How would you treat Addinson’s disease?

A

Sometimes underlying cause of AD can be treated e,g, TB with antibioics. Often cause is unknown and is treated with:
Corticosteroid replacement therapy (for cortisol and aldoesterone) - three doses when wake, noon and early eve to mimic natural cycle of corticosteroid release

79
Q

What are causes of Addinson’s disease?

A

Most common: destructive atrophy from autoimmune response
fungal infection
adrenal cancer
adrenal haemorrhage (e.g. following trauma)
tuberculosis

80
Q

What are the symptoms of an Addisonian crisis?

A
Nausea
Vomiting
Pyrexia
Hypotension
Vascular collapse
81
Q

Addisonian crisis is a life threatening emergency due to adrenal insufficiency. What can it be precipitated by?

A
Severe stress
Salt deprivation
Infection
Trauma
Cold exposure
Over exertion
Abrupt steroid drug withdrawal
82
Q

What can cause Cushing’s syndrome?

A

Increased activity of the adrenal cortex due to a tumour (adenoma)

83
Q

What can cause Addinson’s disease?

A

Reduced glucocorticoid and mineralocorticoid secretion due to autoimmune destruction of the adrenal cortex

84
Q

What type of hormone is aldosterone?

A

Steroid hormone

85
Q

List some types of steroid hormone

A

Aldosterone, cortisol, testosterone, oestrogen - all derived from cholesterol