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Adrenal Glands Flashcards

1
Q

What hormones are produced by the adrenal gland?

A

Mineralocorticoids - aldosterone
Glucocorticoids - cortisol
Androgens

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2
Q

Which system controls the release of aldosterone from the adrenal gland?

A

Renin angiotensin system

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3
Q

Which system controls the release of cortisol and androgens from the adrenal gland?

A

The hypothalamic-pituitary-andrenocortico axis through the release of ACTH

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4
Q

What is adrenal insufficiency?

A

Inadequate adrenocortical function

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5
Q

What can cause primary adrenal insufficiency?

A

Addison’s disease
Adrenal tumours
Congenital adrenal hyperplasia

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6
Q

What can cause secondary adrenal insufficiency?

A

Lack of ACTH stimulation
Pituitary/hypothalamic disorders
iatrogenic

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7
Q

Congenital adrenal hyperplasia is an autosomal recessive condition where there is a lack of which enzyme?

A

21 hydroxyls

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8
Q

All steroid hormones are produced from which substance?

A

Cholesterol

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9
Q

How does a lack of 21-hydroxylase affect the synthesis of adrenal hormones?

A

Cannot synthesise aldosterone and cortisol so there is increased synthesis of androgens

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10
Q

What is the most common cause of primary adrenal insufficiency?

A

Addison’s disease

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11
Q

How much of the adrenal cortex needs to be destroyed in Addison’s disease in order for symptoms to develop?

A

90% of the cortex

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12
Q

What percentage of patient’s with Addison’s disease will have positive autoantibody tests?

A

70%

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13
Q

What other conditions are associated with Addison’s disease?

A

T1DM
Pernicious anaemia
Autoimmune thyroid disease

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14
Q

What are the symptoms of Addison’s disease?

A 
Anorexia
Weight loss
Fatigue / lethargy
Dizziness
Hypotension
Abdominal pain
Vomiting
Diarrhoea
Skin pigmentation
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15
Q

How are serum sodium and potassium concentrations affected by adrenal insufficiency and why is this the case?

A

Decreased aldosterone means less sodium reabsorption and less potassium excretion which can lead to hyponatraemia and hyperkalaemia

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16
Q

Why might a patient with adrenal insufficiency by hypoglycaemic?

A

Because decreased cortisol levels, decreases gluconeogenesis, decreases the effect of glucagon and increases the affect of insulin

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17
Q

Why is skin pigmentation seen in primary but not secondary adrenal insufficiency?

A

Because this is caused by increased ACTH levels which only occurs in primary insufficiency

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18
Q

Why are ACTH levels increased in primary adrenal insufficiency?

A

The lack of production of cortisol and androgens means that these hormones are not exhibiting a negative feedback effect on the hypothalamus and anterior pituitary and so these glands are releasing more CRH and thus more ACTH.

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19
Q

In an acute presentation of primary adrenal insufficiency treatment should not be delayed to confirm the diagnosis. T/F?

A

True

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20
Q

In the treatment of adrenal insufficiency, what drug is used to act as a cortisol replacement?

A

Hydrocortisone

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21
Q

In the treatment of primary insufficiency, what drug is used to act as a replacement for aldosterone?

A

Fludrocortisone

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22
Q

Why is fludrocortisone therapy not required in patients with secondary adrenal insufficiency?

A

Because this is an aldosterone replacement and since, in secondary insufficiency, only the production of cortisol and androgens are affected by the lack of ACTH, this is not needed.

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23
Q

How should treatment of a patient on long-term steroids be changed when they are ill?

A

Double the steroid dose

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24
Q

Steroid medication can be stopped suddenly. T/F?

A

False - this should never happen

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25
Patients who take long-term steroid medication should carry an ID card. T/F?
True
26
What is the most common cause of secondary adrenal insufficiency?
Exogenous steroid use
27
How can exogenous steroid use lead to secondary adrenal insufficiency?
High doses of exogenous steroid act in a negative feedback loop to prevent the release of CRH and ACTH
28
How do the clinical features of secondary adrenal insufficiency differ from primary insufficiency?
In secondary insufficiency there is no skin pigmentation and aldosterone production is intake so there is no hyponatraemia or hyperkalaemia
29
What is the name of the clinical syndrome where there is an excess of cortisol?
Cushing's syndrome
30
What is the annual incidence of Cushing's syndrome?
2 in a million
31
Women are more likely to get Cushing's disease than men. T/F?
True
32
What are the clinical features of Cushing's syndrome?
Abdominal striae, central fat deposition, bruising, thinning of the limbs, buffalo hump, moon face, poor wound healing, red face, euphoria, tendency to avascular necrosis
33
What are the possible causes of ACTH dependent Cushing's syndrome?
Pituitary adenomas Ectopic ACTH Ectopic CRH
34
Ectopic ACTH secretion (from somewhere other than the pituitary) is most commonly caused by a tumour in which tissue?
The lung
35
What are the possible causes of ACTH dependent Cushing's syndrome?
Adrenal adenomas Adrenal carcinomas Nodular hyperplasia
36
What tests can be used to establish cortisol excess in patient's with suspected Cushing's syndrome?
Dexamethasone supression testing measure 24 hr urinary free cortisol measuring late night salivary cortisol
37
In the investigation of Cushing's syndrome, once cortisol excess has been established, the cause of the excess must be determined. This is done by measuring ACTH levels. If ACTH levels are undetectable then what further investigations are required?
Adrenal CT to look for an adrenal tumour
38
In the investigation of Cushing's syndrome, once cortisol excess has been established, the cause of the excess must be determined. This is done by measuring ACTH levels. If ACTH levels are normal or high then what further investigations are required?
Pituitary MRI to look for pituitary ACTH-secreting tumour | If this is negative then a chest/abdominal/pelvic CT can be done to look for an ectopic ACTH secreting tumour
39
What surgical procedures may be used in the management of Cushing's syndrome?
Transphenoidal pituitary surgery | laparoscopic adrenalectomy
40
Cushing's syndrome can be managed medically in the short term. What drugs are used for this purpose?
Metrypaone | Ketoconazole
41
Iatrogenic steroid use is the most common cause of Cushing's syndrome. T/F?
True
42
Prolonged high dose steroid therapy causes chronic suppression of pituitary ACTH which causes adrenal atrophy. T/F?
True
43
What percentage of cases of hypertension are secondary to another condition?
10%
44
What is the most common cause of secondary hypertension?
Primary aldosteronism
45
What can cause primary aldosteronism?
Single adrenal adenoma | Bilateral adrenal nodules
46
What are the clinical features of primary aldosteronism?
Significant hypertension Hypokalaemia Alkalosis
47
In primary aldosteronism, how are renin levels affected?
Renin is supressed
48
Renin suppression is characteristic of primary aldosteronism. How can this be tested for?
By giving an IV saline load
49
If a patient has a single adrenal adenoma causing primary aldosteronism, how can this be managed?
By unilateral laparoscopic adrenalectomy
50
In cases of bilateral adrenal hyperplasia causing primary aldosteronism, surgery cannot be used. How is this managed instead?
Mineralocorticoid receptor blocks such as spironolactone or eplerenone Blockers of sodium reabsorption in the kidney such as amiloride
51
What condition of the adrenal medulla can cause secondary hypertension?
Phaeochtomocytomas
52
What is a phaeochromocytoma?
A catecholamine secreting tumour of the adrenal medulla
53
What symptoms can result from a phaeochromocytoma?
``` Hypertension (may be intermittent) Episodes of headache Palpitations Pallor Sweating ```
54
How is a phaeochromotcytoma diagnosed?
Measuring urinary catecholamines | CT scan of the adrenal glands
55
How is a phaeochromotcytoma managed?
Adrenalectomy with preoperative treatment with alpha one and beta one antagonists
56
Why are steroid hormones not stored but immediately released?
Because they are lipid soluble and freely permeable to the cell membrane
57
Since steroid hormones are not water soluble they are carried by proteins in the blood. What protein carried cortisol?
Corticosteroid binding globulin
58
Where is the cell are steroid hormones produced?
Mitochondria and smooth ER
59
Why are the adrenal glands yellow in colour?
They have a high cholesterol content
60
What is the term for the arrangement of the vessels in the adrenal gland whereby the blood reaches the outer surface of the gland before entering and supplying each layer?
Centripetal blood flow
61
The right suprarenal vein drains to...?
The IVC
62
The left suprarenal vein drains to...?
The left renal vein
63
What type of cells exist in the adrenal medulla?
Chromaffin cells
64
What nerves supply the adrenal cortex?
Nerves from the coeliac plexus and greater splanchnic nerves
65
What is the arrangement of cells in the zona glomerulosa of the adrenal cortex?
Small clusters of cells
66
Which layer of the adrenal cortex produces the mineralocorticoids (aldosterone)?
Zona glomerulosa
67
How are the cells arranged in the zona fasciculata of the adrenal cortex?
Large cells arranged in cords
68
What hormones are produced by the zona reticularis of the adrenal cortex?
DHEA Androstenedione Small amounts of cortisol
69
What enzyme controls the rate limiting step in the process of de novo synthesis of cholesterol for acetyl coA?
HMG-CoA reductase
70
In the pathway of steroid hormone production, what is cholesterol first converted to?
Pregnenolone
71
What is required as a cofactor in the conversion of cholesterol to pregnenolone?
Cytochrome P450
72
Where is the cell does conversion from cholesterol to pregnenolone take place?
Mitochondria
73
What protein carries out the transport of free cholesterol from the cytoplasm into the mitochondria?
Steroidogenic acute regulatory protein (StAR)
74
In the pathway of steroid hormone synthesis from cholesterol, which conversion steps take place in the mitochondria?
Cholesterol to pregnenolone 11-deoxycorticosterone to corticosterone to 18-OH- corticosterone to aldosterone 11- Deoxycotisol to cortisol
75
Which enzyme is responsible for the conversion of cholesterol to pregnenolone?
Side chain cleavage enzyme desmolase
76
Which enzymes is responsible for the conversion of pregnenolone to progesterone?
3beta HSD
77
Which enzyme is responsible for the conversion of progesterone to 11-deoxycorticosterone and also for the conversion of 17-OH progesterone to 11-deoxycortisol?
21-hydroxylase
78
What conversion steps is the enzyme 17 alpha hydroxylase responsible in the steroid hormone synthesis pathway?
pregnenolone to 17-OH- pregnenolone to DHEA Progesterone to 17-OH-progesterone to andostenedione
79
What conversion steps is the enzyme 11 beta hydroxylase responsible in the steroid hormone synthesis pathway?
Conversion of 11-deoxycorticosterone to corticosterone Conversion of 11-deoxycortisol to cortisol
80
What conversion steps is the enzyme aldosterone synthase responsible in the steroid hormone synthesis pathway?
Corticosterone to 18-OH-corticosterone to aldosterone
81
What is the function of the A/B domain of the steroid nucleus receptor superfamily?
Controls which domain is activated
82
D is the hinge region of the steroid nuclear receptor superfamily. What does this do?
Controls movement of the receptor to the nucleus
83
To which domain of the steroid nuclear receptor superfamily does the ligand bind to?
E
84
Describe the binding of a steroid hormone to its receptor and how this causes an effect?
The steroid hormone diffuses through the pm and binds to its intracellular cytosolic receptor and the receptor-hormone complex then enters the nucleus and binds to the glucocorticoid response element which initiates gene transcription to produce mRNA which is translated to proteins which mediate the effects on the target cell
85
Glucocorticoid receptors are widespread throughout the body. T/F?
True
86
Where in the body are mineralocorticoid receptors found?
``` Distal nephron Salivary glands Sweat glands Large intestine Brain vascular tissue Heart ```
87
To which substance is the affinity of glucocorticoid receptors highest?
Dexamethasone
88
To which substance is the affinity of mineralocorticoid receptors highest?
Aldosterone
89
There is a much higher level of circulating cortisol than aldosterone so cortisol will bind to mineralocorticoid receptors (MR). How is illicit occupation by glucocorticoids of the MRs in the kidney stopped?
By the enzyme 11 beta HSD 2 which catalyses the conversion of cortisol to the inactive cortisone
90
What are the effects of cortisol on the body?
Increases gluconeogenesis in the liver Permissive effect on glucagon Acts as an insulin antagonist Increases breakdown of skeletal muscle protein Has a role in memory, learning, mood and immune suppression
91
What are the effects of aldosterone on the body?
Increases sodium and water reabsorption with concomitant potassium and hydrogen excretion in the distal tubule and collecting ducts of the kidney stimulates sodium and water reabsorption form the gut, salivary glands and sweat glands in exchange for potassium
92
Describe how aldosterone is able to exert its action?
It binds to its receptor and is translocated into the nucleus where it binds to HREs to act as a transcription factor which creates mRNA transcripts of SGK-1, ENaC and Na/K-ATPase to promote sodium reabsorption and potasisum secretion
93
Cortisol release follows a circadian rhythm. Thus, when are cortisol levels highest?
In the morning
94
What type of hormone is ACTH?
Peptide hormone
95
ACTH is formed by the cleavage of...?
POMC
96
What other molecules are formed as by-products in the synthesis of ACTH?
Lipotropin Beta endorphin Met-enkephalin Melanoycte stimulating hormone
97
How does ACTH act on the adrenal gland to increase the synthesis of cortisol and androgens?
Binds to a GPCR which stimulates adenylyl cyclase ceasing an increase in cAMP, activation of PKA and a calcium influx. This stimulates cholesterol delivery to the mitochondria and increases transcription go genes coding for steroidogenic enzymes
98
How does angiotensin II act on the adrenal gland to increase the synthesis of aldosterone?
It binds to a GPCR to activate phospholipase C which hydrolyses PIP2 to form IP3 and DAG IP3 causes the release of stored calcium to activate calcium calmodulin dependent protein kinases with stimulate the transcription of StAR and cholesterol uptake into the mitochondria to increase aldosterone production
99
How will an increase in serum potassium concentration affect aldosterone secretion?
It will increase aldosterone secretion
100
Where does the superior suprarenal artery come from?
Inferior phrenic artery
101
Where does the middle suprarenal artery come form?
Direct branch of the abdominal aorta
102
Where does the inferior suprarenal artery come from?
The renal artery
103
Which plasma protein is cortisol bound to?
Corticosteroid binding globulin - transcortin
104
Which plasma protein is aldosterone and dehydroepiandrosterone?
Bound to albumin
105
Cortisol plays a key role is adaptation to stress. How is cortisol secretion affected by stress?
Increased
106
How does cortisol exert anti-inflammatory and immunosuppressive effects?
Blocks production of inflammatory chemokine (prostaglandins and leukotrienes) suppresses the migration of neutrophils to the injured site Inhibits proliferation of fibroblasts Interfere with antibody production in lymphocytes
107
The use of corticosteroid replacement therapy aims to mimic endogenous hormonal secretion. T/F?
True

Endocrine System (12 decks)

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