Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Phase 1b - Endocrinology > Adrenal Disorders > Flashcards

Adrenal Disorders Flashcards

-> Function of endocrine glands: Summarise the function of the key endocrine glands, including the synthesis, regulation and physiological effects of their hormones. -> Endocrine disorders: Describe the clinical features and treatment options of endocrine disorders.

1
Q

What is the steroid precursor?

A
  • Cholesterol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Which part of the adrenal cortex secretes aldosterone (mineralocorticoid)?

A
  • Zona glomerulosa
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which part of the adrenal cortex secretes cortisol (glucocorticoid)?

A
  • Zona fasiculata
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which part of the adrenal cortex secretes androgens and oestrogens (sex steroids)?

A
  • Zona reticularis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the four main enzymes involved in aldosterone synthesis within the adrenal cortex?

A
  • 3-hydroxysteroid dehydrogenase
  • 21-hydroxylase
  • 11-hydroxylase
  • 17-hydroxylase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the overall effect of aldosterone (3)?

A
  • Reduces potassium (Potassium excretion)
  • Regulates sodium (sodium reabsorption)
  • Maintains blood pressure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which adrenal hormones are predominantly insufficient in Addison’s disease (primary adrenocortical failure) (complete or partial 21 hydroxylase deficiency) (2)?

A
  • Aldosterone
  • Cortisol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What type of rhythm is exhibited by cortisol secretion?

A
  • Diurnal rhythm (daily)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the causes of Addison’s disease (primary adrenocortical failure) (3)?

A
  • Tuberculous Addison’s disease (commonest worldwide)
  • Autoimmune Addison’s disease (commonest in UK)
  • Congenital adrenal hyperplasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the main cause of Addison’s disease (primary adrenocortical failure) in the UK?

A
  • Primary adrenocortical failure (destruction of adrenal glands)
    • Autoimmune induced destruction of the adrenal cortex
    • Atrophy of the adrenal glands
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the main cause of Addison’s disease (primary adrenocortical failure) worldwide?

A
  • Tuberculosis of the adrenal gland
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the clinical features of Addison’s disease (primary adrenocortical failure) (8)?

A
  • Increase pigmentation & autoimmune vitilgo
  • Low blood pressure (syncope)
  • Weight loss
  • Fatigue
  • Hyponatremia
  • Hypoglycaemia
  • Hyperkalaemia

Eventual death due to severe hypotension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Why do patients with Addison’s disease (primary adrenocortical failure) have a good tan (5 steps)?

A

1.Increase in pro-opio-melanocortin (POMC)
2. Increase in ACTH & endorphins
3. Increase in MSH
4. Increase in melanin
5. Increase pigmentation & autoimmune vitilgo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the large precursor protein of ACTH?

A
  • Pro-opio-melanocortin (POMC)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the peptides that are formed from the cleavage of POMC (4)?

A
  • ACTH
  • MSH
  • Endorphins
  • Enkephalins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Which peptide is cleaved from POMC subsequently being responsible for hyperpigmentation within patients with Addison’s disease (primary adrenocortical failure)?

A
  • alpha-MSH (Melanocortin-stimulating hormone)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Where is pro-opio melanocortin synthesised?

A
  • Synthesised within the pituitary gland
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What clinical investigations are conducted for a patient suspected with Addison’s disease (primary adrenocortical failure) (3)?

A
  • Low 9am cortisol
  • High ACTH
  • Short synACTHen test to measure the cortisol response (low response)

Short synACTHen test: Give 250 ug synacthen IM & Measure cortisol response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

At what time is cortisol level usually elevated?

A
  • 9am
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is a synACThen test?

A
  • ACTH is administered to patients through intramuscular injections (250ug), and the cortisol response is measured
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What type of injections are administered during an synACTHen test?

A
  • Intramuscular injections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the 3 treatments available for adrenal failure?

A
  • Hydrocortisone
  • Prednisolone
  • Fludrocortisone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the half-life for oral hydrocortisone?

A
  • Short half-life therefore requires more than once daily administration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How often per day is oral hydrocortisone administede?

A
  • Thrice daily
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Which drug replacement therapy in Addison’s disease closely mimics the circadian rhythm?

A
  • Prednisolone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is the stereochemical difference between prednisolone and cortisol?

A
  • There is an additional double bond, subsequently giving a longer half life and potency in comparison to cortisol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the pharmacological advantages of prednisolone to cortisol (3)?

A
  • Longer half life
  • More potent that cortisol
  • x2.3 binding affinity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What 3 doses are available for prednisolone?

A
  • 1mg
  • 2.5mg
  • 5mg
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is the recommended dose for prednisolone replacement therapy?

A
  • 2mg-4mg once daily
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the equivalent dose for an intermediate acting prednisolone?

A
  • 3mg
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the relative glucocoritcoid potency for prednisolone?

A
  • x7
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What pharmacological treatment is available for primary adrenocortical failure?

A
  • Fludrocortisone 50-100mg daily
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How long are the effects of fludrocortisone seen for?

A
  • 18 hours
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Which two receptors are interacted with by fludrocortisone?

A
  • Mineralocorticoid receptors
  • Glucocorticoid receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Which atom is added to fludrocortisone?

A
  • Fluorine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What pharmacodynamic effect does fluorine have in fludrocortisone?

A
  • Fluorine does not exist in natural steroids, so its presence slows metabolism substantially
    • ​Binds to both mineralocorticoid and glucocorticoid receptors
    • Has a longer half life (3.5h and effects seen for 18h)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Which congenital condition is associated with primary adrenocortical failure?

A
  • Congenital adrenal hyperplasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Which adrenal hormones are predominantly insufficient in congenital adrenal hyperplasia (complete or partial 21 hydroxylase deficiency)?

A
  • Aldosterone
  • Cortisol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Which hormones are increased in congenital adrenal hyperplasia (complete or partial 21 hydroxylase deficiency)?

A
  • Sex steroids (androgen production)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is the most common enzyme deficiency in congenital adrenal hyperplasia?

A
  • 21-hydroxylase deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What stage does 21-hydroxylase catalyse in aldosterone synthesis?

A
  • Hydroxylation of progesterone to 11-deoxy corticosterone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What stage does 21-hydroxylase catalyse in cortisol synthesis?

A
  • 17-OH progesterone to 11-deoxycortisol
43
Q

How long can a patient survive with diagnosed congenital adrenal hyperplasia (complete 21 hydroxylase deficiency)?

A
  • Less than 24 hours
44
Q

What is the age of presentation of congenital adrenal hyperplasia (complete 21 hydroxylase deficiency)?

A
  • As a neonate with a salt losing Addisonian crisis
    • Before (while in utero) foetus gets steroids across placenta
    • Girls will be born with ambiguous genitalia due to excess testosterone production
45
Q

Which hormone is concerned with the salt-washing feature of an Addisonian crisis?

A
  • Aldosterone
46
Q

What is the main difference between a partial 21-hydroxylase deficiency and complete deficiency?

A
  • Aldosterone and cortisol is still produced in smaller quantities (responsive to ACTH)
47
Q

What are the clinical features for females with congenital adrenal hyperplasia (complete or partial 21 hydroxylase deficiency) (7)?

A
  • Labial fusion
  • Ambiguous genitalia
  • Ambiguous in physical characteristics
  • Weight loss
  • Vomiting
  • Hypotension
  • Hyperpigmentation
48
Q

What are the main associated symptoms of congenital adrenal hyperplasia (partial 21 hydroxylase deficiency) that present later in life in boys (2)?

A
  • Precocious puberty in boys due to adrenal testosterone
  • Hyperplastic muscles
49
Q

What are the main associated symptoms of congenital adrenal hyperplasia (partial 21 hydroxylase deficiency) that present later in life in girls (5)?

A
  • Hirsutism & virilisation
  • Male pattern baldness
  • Facial hair
  • Clitomegaly
  • Hyperplastic muscles
50
Q

Which 3 hormones are in excess in a congenital adrenal hyperplasia (11 hydroxylase deficiency)?

A
  • Sex steroids
  • Testosterone
  • 11-deoxycorticosterone
51
Q

What are the problems associated with a congenital adrenal hyperplasia (11 hydroxylase deficiency) (3)?

A
  • Virilisation
  • Hypertension
  • Hypokalaemia (due to elevations in 11-deoxycorticosterone)
52
Q

What stages of aldosterone synthesis is catalysed by 11-hydroxylase?

A
  • 11-deoxy-corticosterone hydroxylation into corticosterone
53
Q

What stage of cortisol synthesis is catalysed by 11-hydroxylase?

A
  • 11-deoxycortisol hydroxylation into cortisol
54
Q

Which aldosterone precursor behaves analogous to aldosterone?

A
  • 11 deoxycorticosterone
55
Q

In excess, what effects can be caused by 11 deoxycorticosterone (3)?

A
  • Hypertension
  • Hypokalaemia
  • Virilisation
56
Q

What are the associated problems with a congenital adrenal hyperplasia (17-hydroxylase deficiency) (4)?

A
  • Hypertension
  • Hypokalaemia
  • Sex steroid deficiency
  • Glucocorticoid deficiency (hypoglycaemia)
57
Q

What stage is catalysed by 17-hydroxylase?

A
  • Progesterone hydroxylation into 17-OH-progesterone
58
Q

Which hormones are deficient in a congenital adrenal hyperplasia (17-hydroxylase deficiency) (2)?

A
  • Cortisol
  • Sex steroids
59
Q

Which hormones are in excess in a congenital adrenal hyperplasia (17-hydroxylase deficiency) (2)?

A
  • Aldosterone
  • 11-deoxycorticosterone
60
Q

What are the main causes of Cushing’s syndrome (ACTH dependent 2 / ACTH independent 3)?

A
  • ACTH dependent:
    • Pituitary dependent Cushing’s disease
    • Ectopic ACTH from lung cancer
  • ​ACTH independent:
    • Overdose of oral corticosteroids
    • Adrenal adenoma secreting cortisol
    • Adrenal nodular hyperplasia
61
Q

What are the clinical signs of Cushing’s disease (2)?

A
  • Excess cortisol
  • Hypokalaemia
62
Q

How is ACTH affected in ACTH dependent causes of Cushing’s disease?

A
  • Increase in ACTH
63
Q

How is ACTH affected in ACTH independent causes of Cushing’s disease?

A
  • Decrease in ACTH (due to negative feedback)
64
Q

What are the symptoms of Cushing’s disease (7)?

A
  • Centripetal obesity
  • Moon face and buffalo hump
  • Proximal myopathy
  • Hypertension
  • Red striae, thin skin, and bruising
  • Osteoporosis
  • Diabetes (T2DM)
65
Q

What are the investigations that are conducted to determine the cause of Cushing’s syndrome (3)?

A
  • 24H urine collection for urinary free cortisol
    • Basal (9am) cortisol 800nm
  • Blood diurnal cortisol levels
    • Cortisol usually highest at 9am and lowest at midnight (if asleep)
  • Low dose dexamethasone suppression test (680nM) (dexamethasone is an artificial steroid)
    • 0.5mg 6 hourly for 48 hours
    • Normal will supress Vs Cushing’s disease will fail to suppress
66
Q

What are the treatments available for Cushing’s disease (5)?

A
  • Surgical:
    • Transphenoidal hypoplysectomy
    • Bilateral adrenalectomy
    • Unilateral adrenalectomy
  • Pharmacological:
    • Metryapone
    • Ketoconazole
67
Q

What pharmacological interventions are implemented for patients with hypersecretion of hormones of the adrenal cortex (i.e. Cushing’s Syndrome) (2)?

A
  • Metryapone
  • Ketoconazole

Inhibitors of steroid biosynthesis

68
Q

What is the mechanism of action of metryapone?

A
  • Inhibition of 11B-Hydroxylase, this arrests steroid synthesis within the zona fasciculata at the 11-deoxycortisol stage
69
Q

Does 11-deoxycortisol exert negative feedback on the hypothalamus?

A
  • There is no negative feedback effect on the hypothalamus and pituitary gland
70
Q

How should cortisol be controlled and regulated in patients taking metryapone?

A
  • Adjust oral dose according to cortisol level (aim for mean serum cortisol 150-300nmol/L)
71
Q

What are the advantages of using metryapone preoperatively?

A
  • Improves patient’s symptoms and promotes better post-operative recovery (better wound healing, less infection)
72
Q

What are the adverse actions of metryapone (2)?

A
  • Hypertension on long-term administration
  • Hirsutism (increased adrenal androgen production in women)
73
Q

What are the side effects of using metryapone on aldosterone synthesis?

A
  • Deoxycorticosterone accumulates within the zona glomerulosa, exhibiting aldosterone-like (mineralocorticoid) activity, leading to salt retention & hypertension
74
Q

Where does deoxycorticosterone accumulate in patients taking metryapone?

A
  • Accumulates in the zona glomerulosa
75
Q

What type of effects are exerted by deoxycoticosterone?

A
  • Mineralocorticoid activity
76
Q

Which enzyme is inhibited by ketoconazole?

A
  • 17-alpha hydroxylase
77
Q

What toxic risk is associated with ketoconazole?

A
  • Hepatotoxicity
    • Therefore monitor liver function weekly, clinically and biochemically
78
Q

What follow up investigations should be conducted in patients prescribed with ketoconazole?

A
  • Weekly liver function tests due to hepatotoxicity risks (P450 poison)
79
Q

What are the surgical interventions for the treatment of Cushing’s?

A
  • Transsphenoidal hypophysectomy
  • Bilateral adrenalectomy
  • Unilateral adrenalectomy for adrenal mass
80
Q

What is the 1st line of treatment for a patient with an ACTH-secreting pituitary adenoma?

A
  • Pituitary surgery (transsphenoidal hypophysectomy)
81
Q

What type of hyperaldosteronism is Conn’s syndrome?

A
  • Priamry hyperaldosteronism
82
Q

What is the main cause of Conn’s syndrome?

A
  • Benign adrenal cortical tumour of the zona glomerulosa resulting in an excess production of aldosterone
83
Q

What impact does Conn’s syndrome have on the Renin-angiotensin system?

A
  • RAAS should be suppressed (exclude secondary hyperaldosteronism)
84
Q

What are the associated clinical signs of Conn’s syndrome (3)?

A
  • Hypertension
  • Hypokalaemia
  • Hypernatremia
85
Q

What two main drugs are prescribed in patients with Conn’s syndrome?

A
  • Spironolactone
  • Epleronone

Mineralocorticoid receptor antagonist

86
Q

What is the mechanism of action of spironolactone?

A
  • Converted to several active metabolites, including canrenone, a competitive antagonist of mineralocorticoid receptors (MR)
    • Blocks sodium reabsorption and potassium excretion in the kidney tubules (potassium sparing diuretic)
      • Antihypertensive
87
Q

Which metabolite is formed through the conversion of spironolactone?

A
  • Canrenone
88
Q

Which receptors are antagonised by spironolactone metabolites?

A
  • Mineralocorticoid receptors
89
Q

Describe the pharmacokinetics of spironolactone?

A
  • Orally active
    • Highly protein bound and metabolised in the liver
90
Q

What are the unwanted actions of spironolactone (2)?

A
  • Menstrual irregularities (+progesterone receptor)
  • Gynaecomastia (inhibits androgen receptors)
91
Q

What type of antagonist is epleronone?

A
  • Mineralocorticoid receptor antagonist
92
Q

Which Conn’s syndrome drug is better tolerated?

A
  • Epleronone
93
Q

Why is epleronone better tolerated than spironolactone?

A
  • Less binding to androgen and progesterone receptors compared to spironolactone
94
Q

What is a phaechromocytoma?

A
  • Tumours of the adrenal medulla which secrete catecholamines
95
Q

What are the associated risks with a phaeochromocytoma (4)?

A
  • Family history of endocrine disorders
  • MEN
  • Von-Hippel-Lindau syndrome
  • Germline mutations in the succinate dehydrogenase
96
Q

What is the main clinical feature of a phaeochromocytoma?

A
  • Sustained or paroxysmal hypertension
    • Cases of hypertension may proceed after abdominal pain episodically, in comparison to Conn’s syndrome (smooth secretion of aldosterone)
97
Q

What is the classic triad of symptoms for patients with a phaeocromocytoma?

A
  • Palpitations
  • Headaches
  • Diaphoresis (excessive sweating)
98
Q

What are the potential risks with a phaeochromocytoma?

A
  • Elevations in adrenaline typically manifest as severe hypertension causing potential myocardial infarctions or strokes, as well as ventricular fibrillation within patients becoming a medical emergency
99
Q

Which hormone can be measured in urine and blood as a marker for phaeochromocytoma associated release of adrenaline?

A
  • Metanephrine (has a long half life)
100
Q

What is the first line of treatment of a phaeochromocytoma?

A
  • Anti-hypertensive agents

Alpha-blockade & Beta-blockade

101
Q

Why is an alpha-blockade administered in the management of a phaeochromocytoma?

A
  • Inhibition of alpha-receptors minimises the impact of vasoconstriction induced by noradrenaline/adrenaline, therefore reducing blood pressure
    • IV fluids to compensate for potential hypotensive crisis
102
Q

Why is a beta-blockade administered in the management of a phaeochromocytoma?

A
  • Administer atenolol / metoprolol / propanolol to prevent tachycardia & arrhythmia
103
Q

What are the precautions required for patients with a phaeochromocytoma surgical excision?

A
  • Careful preparation as anaesthetic can precipitate a hypertensive crisis

Phase 1b - Endocrinology (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions