adrenal gland Flashcards
1
Q
what are the 3 zones of the adrenal cortex
A
glomerulosa
fasiculata
reticularis
2
Q
what is made in the zona glomerulosa
A
mineralocorticoids
aldosterone
3
Q
what is made in the zona fasiculata
A
glucocorticoids
cortisol
4
Q
what is made in the zona reticularis
A
sex steroids
glucocortioids
5
Q
what is the medulla of the adrenal gland innervated by
A
presynaptic fibres from sympathetic system (splanchnic nerves)
6
Q
what are the neuroendocrine cells in the medulla of the adrenal gland called and what do they secrete
A
chromaffin cells
secrete catecholamines - adrenaline and noradrenaline
7
Q
how is the release of cortisol and androgen from the adrenal gland controlled
A
HPA axis
8
Q
how is the release of aldosterone from the adrenal gland regulated
A
RAAS and plasma potassium
activated in response to fall in BP
9
Q
where are mineralocorticoid receptors for aldosterone found
A
kidneys
salivary glands
sweat glands
gut
10
Q
what are the effects of aldosterone via mineralocorticoid receptors
A
sodium reabsorption
K+/H+ excretion
–> BP regulation, ECFV regulation and sodium/potassium balance
11
Q
what is the cause of CAH
A
deficiency of enzymes required for steroid biosynthesis
12
Q
what is the enzyme most commonly deficient in CAH
A
alpha-21-hydroxylase
13
Q
what is the inheritance pattern of CAH
A
autosomal recessive
14
Q
how does a lack of alpha-21-hydroxylase cause cortical hyperplasia
A
lack of cortisol causes release of ACTH from hypothalamus causing hyperplasia of the adrenal gland
15
Q
what are the 2 main presentations of CAH
A
classical - simple virilising/salt wasting
non-classical - hyperandrogenaemia
16
Q
how does classical CAH present
A
salt wasting crisis at 2-3 weeks age
female genital ambiguity
poor weight gain
high potassium low sodium
17
Q
how does non-classical CAH present
A
hirsute acne oligomenorrhoea precocious puberty masculinisation infertility/subfertility
18
Q
does non-classical or classical present earlier
A
classical
19
Q
how can CAH be diagnosed
A
basal or stimulated 17-OH progesterone
genetic mutation analysis
synacthen
20
Q
what is the treatment for CAH
A
replace glucocorticoid
replace aldosterone (in some)
surgical correction
in older - correct androgen excess
21
Q
true/false
adrenocortical tumours are more common in females
A
false - equal men and women
22
Q
what are the 2 main types of adrenocortical tumours
A
adrenocortical adenoma
adrenocortical carcinoma
23
Q
how would you describe an adrenocortical adenoma
A
well circumscribed encapsulated lesion buried within gland
24
Q
what colour are adrenocortical adenomas
A
yellow/yellow-brown surface (lipid)
25
what size are adrenocortical adenomas?
| do they cause a mass lesion?
usually small 2-3cm
| no
26
do adrenocortical adenomas usually occur alone or multiple
solitary
27
adrenocortical adenomas are composed of cells resembling ----
adrenocortical cells
28
what may been seen in adrenocortical adenomas
spironolactone bodies
29
what are the nuclei like in adrenocortical adenomas
small
30
are mitoses rare or common in adrenocortical adenomas
rare
31
are adrenocortical adenomas usually functional or non-functional
can be functional but usually not
| Can cause Conn's syndrome
32
is the adjacent and contralateral tissue in adrenocortical adenomas atrophic
no - ACTH not suppressed so adjacent and contralateral tissue not atrophic
33
are adrenocortical carcinomas functional
more likely to be
34
although adrenocortical carcinomas can resemble adrenocortical adenomas, what are some features suggestive of a carcinoma
```
large size
haemorrhage and necrosis
frequent, atypical mitoses
lack of clear cells
capsular or vascular invasion
```
35
what is the 5 year survival rate of adrenocortical carcinomas
20-30%
| 50% dead in 2 years
36
what is an example of a functional adrenocortical carcinoma
androgen secreting tumour
37
how would an androgen secreting adrenocortical carcinoma be diagnosed
MRI of adrenals and ovaries
38
what would happen with an androgen secreting adrenocortical carcinoma
rapid onset symptoms
virilisation
high levels testosterone
39
where would an adrenocortical carcinoma spread locally
retroperitoneum
| kidney
40
where would mets of an adrenocortical carcinoma tend to go/spread
haem spread
| liver, lung, bone
41
where else might an adrenocortical carcinoma spread
peritoneum
| pleura
42
what is primary hyperaldosteronism
autonomous production of aldosterone independent of its regulation
43
primary hyperaldosteronism is the commonest secondary cause of what
hypertension
44
what is the most common cause of primary hyperaldosteronism
adrenal adenoma (Conn's syndrome)
45
what is the second commonest cause of primary hyperaldosteronism
bilateral adrenal hyperplasia
46
what is a genetic mutation that can cause Conn's syndrome
mutation in the KCNJ5 channel
47
what is the KCNJ5 channel
rectifying selective channel that maintains membrane hyperpolarisation - mutations lead to loss of selectivity and Na+ entry and depolarisation
48
give 2 other rare causes of primary hyperaldosteronism
adrenal carcinoma
| unilateral hyperplasia
49
what is the main s/s of primary hyperaldosteronism
significant hypertension
50
what happens to potassium levels in primary hyperaldosteronism
hypokalaemia
51
do you get acidosis or alkalosis with primary hyperaldosteronism
alkalosis
52
what causes hypertension in primary hyperaldosteronism
Na reabsorption - water retention
53
what would the renin levels be like in primary hyperaldosteronism
decreased renin
54
what are the 2 stages in diagnosing primary hyperaldosteronism
confirm aldosterone excess
| confirm subtype
55
how do you confirm aldosterone excess in primary hyperaldosteronism
measure of aldosterone to renin plasma ratio
| if raised, further investigate with a saline suppression test
56
what would happen in a saline suppression test with primary hyperaldosteronism
failure of plasma aldosterone to suppress by >50% with 2L normal saline - primary hyperaldosteronism
57
how do you confirm the subtype of primary hyperaldosteronism
adrenal CT/adrenal vein sampling for adenoma
58
what is the treatment of Conn's
unilateral laparoscopic adrenalectomy
59
what is the treatment of bilateral adrenal hyperplasia
MR antagonists
60
give 2 examples of MR antagonists
spironolactone
| eplerenone
61
what can cause secondary hyperaldosteronism
high renin from decreased renal perfusion
62
what are some causes of acute primary adrenocortical hypofunction
Waterhouse-friderichsen (bilateral adrenal cortex haemorrhage) - commonly after infection
rapid withdrawal of steroid treatment
adrenal crisis in patient with chronic adrenocortical insufficiency due to stress
63
what is the most common cause of primary adrenal insufficiency
addisons
64
what is a cause of secondary adrenocortical hypofunction
lack of ACTH stimulation
- hypopituitarism
- suppression of adrenal cortex (exogenous steroids)
65
what is addisons disease
autoimmune destruction of the adrenal cortex leading to glucocorticoid and mineralocorticoid deficiency
66
what percentage of people with addisons are antibody positive
70%
67
what are some s/s of addisons
```
weakness
fatigue
anorexia
N+V
weight loss
craving salty food
tearful/depression
vitiligo
diarrhoea
constipation
skin pigmentation
dizzy/faint
low BP
abdominal pain
myalgia
arthralgia
postural hypotension
```
68
what causes the skin pigmentation in addisons
ACTH cross reacts with melanin receptors
69
what would the Na and K levels be like in addisons
low Na
| high K
70
would someone with addisons by hypo or hypertensive
hypotensive
71
would someone with addisons by hypo or hyper glycaemia
hypogylcaemia
72
what other biochemistry might be seen in someone with addisons
uraemia
increased calcium
eosinophilia
anaemia
73
how is addisons diagnosed
biochemistry
short synacthen test
adrenal autoantibodies
74
describe a short synacthen test and what results would be normal as baseline cortisol and after the test
measure plasma cortisol before and 30 mins after IV/IM ACTH injection
normal:
cortisol baseline > 250 nmol/L
cortisol after ACTH > 550nmol/L
75
what would the levels of ACTH and renin be like in addisons
raised
76
what is the treatment for addisons
hydrocortisone + fludrocortisone
77
how should dosage be changed in a person with addisons if they are ill/injured/stressed
double dose
78
should you wait until a diagnosis before starting treatment?
no - start treatment before disgnosis
79
what is the treatment for an adrenal crisis
hydrocortisone 100mg IV
IV fluid bolus
monitor blood glucose - risk of hypo
if high K - calcium gluconate
80
would someone with secondary adrenal insufficiency have tinted skin
no - no increased ACTH
81
what are the 2 main tumours of the adrenal medulla
neuroblastoma
| phaeochromocytoma
82
when are neuroblastomas usually diagnosed
around 18 months
83
40% of neuroblastomas arise in the adrenal medulla - where do the rest arise?
along sympathetic chain
84
how do the cells in a neuroblastoma appear
primitive but can show maturation/differentiation towards ganglion cells
85
what 2 genetic features predict a poor outcome of neuroblastoma
amplification of n-myc
| expression of telomerase
86
what is a phaechromocytoma
neoplasm derived from chromaffin cells of adrenal medulla that secretes catecholamines
87
where do phaeochromocytoma mets go
skeletal, regional lymph nodes, liver, lung
88
what is the appearance of a phaeochromocytoma
necrotic tumour mass and may see adrenal remnants on surface
yellow/red-brown
necrotic
haemorrhagic
89
why will potassium chromate turn tumour dark brown
oxidation of catecholamines in tumour cells
90
tumour cells in phaeochromocytoma form nests what are these called
zellballen
91
what are the 6 10% rules of phaeochromocytoma
```
10% extra adrenal
10% bilateral
10% malignant
10% not assoc. hypertension
10% familial
10% assoc. hyperglycaemia
```
92
where do extra-adrenal phaeochromocytoma occur
along sympathetic chain
93
when phaeochromocytomas occur extra adrenally what are they called
paraganglioma
94
where exactly do paragangliomas occur
organs of Zuckerkandl (aortic bifurcation)
| carotid body
95
what is the only definitive evidence of malignancy with phaeochromocytoma
mets
96
if a phaeochromocytoma is familial, is it more or less likely to occur in someone who is younger and is it more or less likely to be bilateral
more likely to be younger and bilateral
97
phaeochromocytoma is more often malignant if assoc. with what germline mutation
germline mutation of beta subunit of succinate dehydrogenase
98
what is the classic presenting triad of phaeochromocytoma
hypertension (50% paroxysmal)/tachycardia/palpitations
headache
sweating
99
what other s/s may be seen in phaeochromocytoma
```
palpitations
breathlessness
constipation
anxiety
weight loss
flushing
pallor
pyrexia
```
100
what are some complications of phaeochromocytoma
```
paralytic ileus of bowel
LV failure
myocardial necrosis
stroke
shock
```
101
what would K and Ca levels look like in phaeochromocytoma
low K
| mild hypercalcaemia
102
what would to the WCC in phaeochromocytoma
increased
103
what would happen to the haematocrit in phaeochromocytoma
high
104
would people with phaeochromocytoma be more likely to be acidotic or alkalotic
lactic acidosis
105
who should be investigated for phaeochromocytoma
```
family members with syndromes
resistant HT
HT < 50
classical symptoms
HT with hyperglycaemia
```
106
what is an investigation for phaeochromocytoma
urine analysis of vanillymandelic acid (VMA) - may be false +ves
107
what are the 2 stages in diagnosing phaechromocytoma
confirm catecholamine excess
| identify source of catecholamine excess
108
how can you confirm catecholamine excess
urine - 2 x 24 hr catecholamines or metanephrines
| plasma - ideally at time of symptoms
109
how can you confirm the source of catecolamines
MRI/CT
MIBG scan
PET scan
110
what is an MIBG scan
meta-iodobenzylguanidine scan - looks for extra adrenal tumours
111
what is the treatment of phaeochromocytoma
full alpha and beta blockade
laparoscopic total excision if possible/tumour debulking
chemo if malignant - radio labelled MIBG
112
what comes first alpha or beta blockade in phaeochromocytoma
alpha before beta
113
what is an example of an alpha blocker
phenoxybenzamine
114
what is an example of a beta blocker used in phaeochromocytoma
propranolol, atenolol, metoprolol
115
if someone has borderline catecholamine excess what test can be done
clonidine suppression test
116
give 5 syndromes where phaeochromocytoma may be seen
```
MEN2A/2B
VHL syndrome
succinate dehydrogenase mutations
neurofibromatosis
tuberose sclerosis
```
117
what else might cause catecholamines to be raised
heart failure
118
why might someone with phaeochromocytoma have normal catecholamine levels
episodic secretion
119
what is cushings syndrome
excess cortisol
120
what is cushings disease
cushings syndrome caused by pituitary adenoma
121
are men or women more likely to get cushings
women
122
what is the most common cause of cushings
pituitary adenoma
123
what is a pituitary adenoma and how does it cause cushings
tumour arising from corticotroph cells of anterior pituitary - secretes ACTH
124
is a pituitary adenoma an ACTH dependent or indepentent cause of cushings
ACTH dependent
125
is adrenal adenoma/carcinoma an ACTH dependent or indepentent cause of cushings
ACTH independent
126
is ectopic CRH from medullary thyroid cancer/prostate cancer an ACTH dependent or indepentent cause of cushings
ACTH dependent
127
is an adrenal nodular hyperplasia an ACTH dependent or indepentent cause of cushings
ACTH independent
128
is ectopic ACTH from a paraneoplastic syndrome an ACTH dependent or indepentent cause of cushings
ACTH dependent
129
what paraneoplastic syndrome causes ectopic ACTH release
small cell lung carcinoma
130
what 3 things can cause pseudocushings
alcohol
depression
prolonged steroid medication
131
what 2 genetic syndromes can cause cushings
Carney complex
Mccune Albright
both ACTH independent
132
what is the first step in diagnosing cushings
confirm raised plasma cortisol - overnight dexamethasone suppression test
133
describe the overnight dexamethasone suppression test
1mg PO at midnight and measure serum cortisol at 8am
normal: cortisol suppressed to < 50
cushings: no suppression
134
what is a normal level for 24hr urinary free cortisol
< 250
135
what is a normal value for cortisol/creatinine ratio
< 25
136
what is another easy test to do to measure serum cortisol
late night salivary cortisol
137
describe a 48hr low dose dexamethasone suppression test and the findings
0.5mg/6hr PO for 2 days
normal: cortisol suppressed to < 50 (6hrs after last dose)
cushings syndrome: no suppression
138
how would you find out if the cause of cushings was pituitary after discovering that the person does have cushings using 48hr low dose dexamethasone suppression test
48 hour high dose dexamethasone suppression test
- 2mg/6hr
pituitary cause - suppression
other cause - no/part suppression
139
what are 2 other localising tests
plasma ACTH
| CRH test
140
if plasma ACTH is undetectable what is likely
adrenal tumour
141
if you suspected an adrenal tumour what tests would you carry out
CT adrenals
| or adrenal vein sampling or adrenal scintigraphy (if no mass found)
142
would plasma ACTH be higher in ectopic ACTH or a pituitary adenoma
ectopic ACTH
143
describe a CRH test
100 ug CRH IV and measure cortisol at 120 mins
144
what would the results of a CRH test show if cushings was caused by pituitary disease
cortisol rises
145
what would you do if you suspected pituitary disease
MRI pituitary
146
in ectopic ACTH production what would the CRH test show
cortisol doesnt rise
147
if you suspected ectopic production of ACTH what tests would you carry out
IV CT contrast of chest,abdo,pelvis
| +/- MRI neck, thorax, abdomen
148
pituitary cause LDDT
no suppression
149
pituitary cause ACTH
< 300
150
pituitary cause HDDT
suppression
151
pituitary cause CRH
cortisol rises
152
adrenal cause LDDT
no suppression
153
adrenal cause ACTH
<1
154
adrenal cause HDDT
no suppression
155
ectopic LDDT
no suppression
156
ectopic ACTH
> 300
157
ectopic HDDT
no suppression
158
ectopic CRH
cortisol doesnt rise
