379 Adrenal Flashcards
1
Q
three classes of corticosteroid hormones produced by the adrenal cortex
A
glucocorticoids, mineralocorticoids and adrenal androgen precursors
2
Q
usual cause of hormone excess
A
neoplasia
3
Q
weight of adrenal glands
A
6-11 g each
4
Q
location of the adrenal glands
A
above the kidneys and have their own blood supply
5
Q
embryonic origin of the adrenals
A
originate from the urogenital ridge and separate from the gonads and kidneys at the sixth week of gestation
6
Q
play a crucial role in the development of the adrenal and regulate a multitude of adrenal genes involved in steroidogenesis
A
SF1 steroidogenic factor 1 and DAX1 dosage sensitive sex reversal gene 1
7
Q
control the production of glucocorticoids and adrenal androgens
A
Hypothalamic-pituitary adrenal axis
8
Q
regulates the mineralocorticoids
A
renin angiotensin aldosterone system
9
Q
acts as the pivotal regular of the adrenal cortisol synthesis with additional short term effects on mineralocorticoid and adrenal androgen synthesis
A
ACTH
10
Q
controls the pulsatile release of CRH and ACTH according to circadian rhythm
A
suprachiasmic nucleus of the hypothalamus
11
Q
if cortisol production is driven by an ACTH producing pituitary adenoma, what is the effect of dexamethasone suppression tests
A
dexamethasone is ineffective at low doses but usually induced suppression at higher doses
12
Q
if cortisol production is driven by an ectopic source, what is result of the dexamethasone suppression test
A
tumors are usually resistant to dexamethasone suppression
13
Q
how to assess glucocorticoid deficiency
A
ACTH stimulation tests
14
Q
how is the standard ACTH stimulation test done
A
0.25 mg IM or IV of cosyntropin is given and serum cortisol collection is done 0, 30 and 60 mins;
15
Q
normal ACTH stimulation test result
A
cortisol more than 20 ug or more than 550 nmmol/L 30-60 min after cosyntropin stimulation
16
Q
alternate test to check adrenal function
A
insulin tolerance test
17
Q
how is the insulin tolerance test done
A
0.1 U/Kg IV regular insulin and then 0, 30, 60, 120 mins blood tests for glucose, cortisol, GH
18
Q
normal response of the Insulin tolerance test
A
normal response is cortisol more than 20 ug/dL or GH more than 5.1 ug/L
19
Q
side effect of insulin tolerance test
A
symptomatic hypoglycemia serum glucose of less than 40 mg/dL may be managed with oral or IV glucose
20
Q
contraindication to insulin tolerance tests
A
coronary disease, cerebrovascular disease, seizure disorder
21
Q
commonly accepted first line test to assess glucocorticoid deficiency
A
cosyntropin test
22
Q
initiates the release of mineralocorticoids
A
renin from the juxtaglomerular cells in the kidney
23
Q
hormone the enhances sodium retention and potassium excretion, increases arterial perfusion pressure, regulates renin release
A
aldosterone
24
Q
True or false. HPA damage does not significantly impact the capacity of the adrenal to synthesize aldosterone
A
True.
25
Required for the initiation of steroidogenesis
ACTH stimulation
26
True or false. Adrenal steroidogenesis occurs in a zone specific fashion
True.
27
Zone of mineralocorticoid synthesis
zona glomerulosa
28
zone of glucocorticoid synthesis
zona fasciculata
29
zone of adrenal androgen synthesis
zona reticularis
30
required for all steroidogenic pathways
cholesterol
31
majority of steroidogenic enzymes
cytochrome P450
32
where are these steroidogenic enzymes located
mitochondrion, endoplasmic reticulum
33
majority of the DHEA form in the adrenal
it's sulfate ester form, DHEAS
34
True or false. Cortisone also exerts glucocorticoid action but much weaker than cortisol itself.
True.
35
True or false. Free cortisol enter the cell directly not requiring active transport
True.
36
what drives aldosterone synthesis in the adrenal zona glomerulosa
aldosterone synthase (CYP11B2)
37
reflects a constellation of clinical features that result from chronic exposure glucocorticoids of any etiology
Cushing syndrome
38
what is Cushing's disease
cushing syndrome caused by a pituitary corticotrope adenoma
39
True or false. Cushing's syndrome is generally considered a rate disease
True.
40
True or false. Majority of Cushing syndrome is caused by ACTH producing corticotrope adenoma of the pituitary
True.
41
How many percent of Cushing syndrome is caused by adrenals
10%
42
Most common cause of Cushing's syndrome
medical use of glucocorticoid for immunosuppresion or for the treatment of inflammatory disorders
43
mutation found in Cushings disease
deubiquitinase USP8
44
Causes predominant ectopic ACTH production
occult carcinoid tumors
45
rare notable cause of adrenal cortisol excess
macronodular adrenal hyperplasia
46
autosomal dominal multiple neoplasia associated with cardiac myxoma, hyperlentiginosis, Sertoli cell tumors, and PPNAD
Carney's complex
47
rare cause of ACTH independent Cushing syndrome associated with polyostotic fibrous dysplasia, unilateral cafe au lait spots and precocious puberty
McCune Albright syndrome
48
most important features of cortisol excess
upregulation of gluconeogenesis, lipolysis, and protein catabolism
49
Algorithm for management of patients suspected with Cushings syndrome. Screening 24 hour urine?
24h urinary free cortisol excretion 3x above normal;
50
Algorithm for management of patients suspected with Cushings syndrome. Screening dexamethasone
dexamethasone overnight test with plasma cortisol more than 5 nmol/L at 8-9 Am after 1 mg dexamethasone at 11 PM
51
Algorithm for management of patients suspected with Cushings syndrome. Screening plasma cortisol
midnight plasma cortisol more than 130 nmol/L or midnight salivary cortisol more than 5 nmol/L
52
Algorithm for management of patients suspected with Cushings syndrome. Screening low DEXA
low dexa plasma cortisol more than 5 nmol/L after 0.5 mg dexamethasone q6hrs for 2 days
53
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. What to do next?
Get plasma ACTH
54
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. ACTH normal or high more than 15 pg/ml.
ACTH dependent Cushing
55
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. ACTH supressed less than 15 pg/ml.
ACTH independent Cushing
56
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. ACTH normal or high. What to do next?
MRI pituitary, CRH ttest, high dexa test
57
values for CRH test
ACTH increase more than 40% at 15-30 min plus cortisol increased more than 20% at 45-60 mins after CRH 100 ug IV
58
values for high DEX test
cortisol suppression more than 50% after q6hrs DEX for 2 days
59
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. ACTH normal or high. CRH and high DEXX positive. What to do next?
Cushing disease. Transphenoidal pituitary surgery
60
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. ACTH normal or high. CRH and high DEXA negative. What to do next?
Inferior petrosal sinus sampling (petrosal/peripheral ACTH ratio more than 2 at baseline, more than 3 at 2-5 mins after CRH 100 ug IV
61
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. ACTH normal or high. CRH and high DEXA negative.Petrosal/Peripheral ACTH ratio more than 2. What to do?
Cushing disease. Transphenoidal pituitary surgery
62
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. ACTH normal or high. CRH and high DEXA equivocal. What to do next?
?
63
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. ACTH normal or high. CRH and high DEXA negative.Petrosal/Peripheral ACTH ratio negative. What to do?
Locate and remove ectopic ACTH source
64
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. ACTH supressed.
Unenhanced CT adrenal.
65
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. ACTH supressed. CT scan of adrenals, unilateral mass. What to do next?
Adrenal tumor workup
66
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. ACTH supressed. CT scan of adrenals, bilateral micro or macronodule adrenal hyperplasia. What to do next?
bilateral adrenalectomy
67
Algorithm for management of patients suspected with Cushings syndrome. Screening positive. ACTH normal or high. CRH and high DEXA negative.Petrosal/Peripheral ACTH ratio negative. No ectopic ACTH source. What to do?
bilateral adrenalectomy
68
can cause rapid inactivation of dexamethasone
concurrent intake of CYP3A4 inducing drugs such antiepileptics, rifampicin
69
True or false. Concurrent intake of oral contraceptives that raise CBG and thus total cortical can cause failure to suppress after dexamethasone
True.
70
How many weeks off estrogen can dexamethasone suppression test done?
4-6 weeks off estrogen
71
investigation of choice for ACTH dependent cortisol excess
MRI
72
What is the prognosis of overt Cushing syndrome
poor prognosis if left untreated
73
treatment of choice of Cushing disease
selective removal of the pituitary corticotrope via endoscopic transphenoidal approach
74
oral agents with established efficacy in Cushing syndrome
metyrapone and ketoconazole
75
inhibits cortisol synthesis at the level of 11B hydroxylase
metyrapone
76
inhibits early tels of steroidogenesis
ketoconazole
77
dose of metyrapone
Metyrapone 500 mg TID max 6 g per day
78
dose of ketoconazole
Ketoconazole 200 mg max 1200
79
derivative of insecticide opDDD, is also effective in reducing cortisol
mitotane
80
an agent that potently blocks 11B hydroxylase and aldosterone synthase
etomidate
81
True or false. After successful removal of an ACTH or cortisol producing tumor, HPA axis will remain suppressed thus hydrocortisone replacement needs to be initiated at the time of surgery and slowly tapered following recovery to allow physiologic adaptation to normal cortisol levels
True.
82
other name for aldosteroe producing adrenal adenoma
Conn's syndrome
83
most common cause of mineralocorticoid excess
primary aldosteronism
84
clinical hallmark of mineralocorticoid excess
hypokalemic hypertension
85
refers to patient with concurrent mild autonomous cortisol excess along with primary aldosteronism
Connshing syndrome
86
accepted screening test for primary aldosteronism
concurrent measurement of plasma renin and aldosterone with subsequent calculation of the aldosterone renin ratio
87
True or false. Serum potassium needs to be normalized prior to calculation the aldosterone renin ratio
True,
88
should MR antagonist be stopped in screening for primary aldosteronism?
Yes for at least 4 weeks prior to ARR testing
89
when is ARR screening positive
if ARR more than 750 pmol/L per ng/ml per hour with concurrently high normal or increased aldosterone
90
how is the saline test done
2L of physiologic saline administered for 4 hr period then serum aldosterone is suppressed to less than 140 nmol/L or 5 ng/dL
91
What does a positive saline test mean
autonomous mineralocorticoid excess
92
how is oral sodium loading test done
300 nmol NaCl/day for 3 days
93
alternative to sodium test
fludrocortisone suppression test 0.1 mg q6hrs with 30 nmmol NaCl q8hrs for 4 days
94
disadvantage of using fludrocoritsone plus Nacl
risk of profound hypokalemia and incrased hypertension
95
next step after the diagnosis of hyperaldosteronism is established
use adrenal imaging to further assess the cause
96
imaging of choice in primary aldosteronism as it provides excellent visualization of adrenal morphology
Fine cut CT scanning of the adrenal region
97
when is adrenal venous sampling done
only be carried out in surgical candidate with either no obvious lesion on CT or evidence of unilateral lesion in patients with more than 40
98
how is lateralization in primary aldosteronism confirmed
aldoserone/cortisol ratio 2x higher on the affected side
99
cortisol gradient between vena cava and each adrenal vein on adrenal venous sampling
cortisol gradient more than 3
100
which is adrenal vein is more difficult to cannulate
right adrenal vein
101
how to avoid postsurgery hypoaldosteronism
MER antagonist spironolactone 12.5 to 50 mg BID and titrated up to maximum of 400 mg/day to control blood pressure and normalize potassium
102
most selective MR antagonist
Eplerenone 25 mg BID titrated up to 200 mg/ day
103
another drug useful in primary aldosteronism, a sodium channel blocker
Amiloride 5-10 mg BID
104
Clinical suspicion of mineralocorticoid excess
severe hypertension despite 3 agents; hypokalemia, adrenal mass or family history of early onsent hypertension or cerebrovascular events at less than 40 years old
105
Screening for mineralocorticoid excess
ARR on current BP medications and hypokalemia corrected
106
what is a positive ARR screen
ARR more than 750 pmol:ng/ml and aldosterone more than 450
107
confirmation of diagnosis of mineralocorticoid excess
saline infusion, oral sodium loading, fludrocortisone suppression
108
what to do if both renin and aldosterone suppressed
24 hr urinary steroid profile
109
True or false. Majority of adrenal nodules are endocrine inactive adrenocortical adenomas
True,
110
True or false. Adrenocortical carcinoma is considered a highly malignant tumor
True,
111
True or false. FNA is not indicated in ACC
True,
112
Why is FNA not indicated in Adrenocortical adenoma
cytology and also histopathology of a core biopsy cannot differentiate between benign and malignant primary adrenal masses; FNA violates th tumor capsule and may even cause needle canal metastasis
113
most common histopathologic classification of ACC
Weiss score
114
Mixed excess production of several corticosteroid classes by an adrenal tumor is generally indicative of malignancy
True.
115
FNA of a pheochromocytoma can cause a life threatening hypertensive crisis
True.
116
Algorithm for the management of patient with incidentally discovered adrenal mass. Screening tests?
plasma metanephrines or 24 hr urine for metanephrine excretion, 24 hr urine for free cortisol, plasma ACTH, dexamethasone 1 mg overnight test, plasma aldosterone and plasma renin in patients with hypertension and or hypokalemia, if tumor more than 4 cm serum 17B hydroxyprogesterone and DHEAS
117
when should serum 17B hydoxyprogesterone and DHEAS taken
patients with incidental adrenal mass of more than 4 cm
118
How many dexamethasone 1 mg overnight tests for a positive result
at least 2 out of 4 tests
119
high sensitive for the detection of malignancy and can be used to detect small metastases or local recurrence that may not be obvious on CT
18 FDG PET
120
Most common metastasis in ACC
liver and lung
121
most important prognostic histopathologic parameter in ACC
Ki67 proliferation index
122
Meaning of Ki67 proliferation index in ACC
less than 10%slow to moderate growth velocity and Ki67 more than 10% means poor prognosis including high risk or recurrence and rapid progression
123
most common cause of primary adrenal insufficiency
autoimmune adrenalitis
124
consequence of dysfunction of the hypothalamic pituitary component of HPA axis
secondary adrenal insufficiency
125
clinical features of primary adrenal insufficiency
loss of both glucocorticoid and mineralocorticoid section
126
other name of primary adrenal insufficiency
Addison's disease
127
Differentiate primary from secondary adrenal insufficiency
secondary adrenal insufficiency only glucocorticoid deficiency is present as the adrenal itself is still intact and still amenable to regulation by RAA system
128
distinguishing feature of primary adrenal insufficiency
hyperpigmentation, which is caused by excess ACTH stimulation of melnocytes
129
where is hyperpigmentation most pronounced in skin primary adrenal insufficiency
in skin areas exposed to increased friction or shear stress and is increased by sunlight
130
characteristic biochemical feature in primary adrenal insufficiency
hyponatremia
131
differentiate primary from secondary adrenal insufficiency as to skin pigmentation
primary adrenal insufficiency: hyperpigmentation; secondary adrenal insufficiency: alabaster due to lack of ACTH stimulation
132
how is adrenal insufficiency established
short cosyntropin test with cortisol levels less than 450-500 nmol/L (16-18 ug/dL) sampled 30-60 min after ACTH stimulation
133
what is the next step once adrenal insufficiency is confirmed
measurement of plasma ACTH
134
initial management of acute adrenal insufficiency
immediate rehydration with saline infusion at rate of 1 L/h with continuous cardiac monitoring
135
how is glucocorticoid replacement done in acute adrenal insufficiency
Hydrocortisone 100 mg bolus IV then 200 mg hydrocortisone over 24 hrs
136
when can mineralocorticoid replacement in acute adrenal insuffiency done
when daily hydrocortisone dose has been reduced to less than 50 mg because higher of hydrocortisone provide sufficient stimulation of mineralocorticoid receptors
137
how glucocorticoid replacement done in chronic adrenal insufficiency
replace physiologic daily cortisol production by oral administration of 15-25 mg hydrocortisone in two or three divided doses
138
True or false. Pregnancy may require an increase in hydrocortisone dose by 50% during the last trimester
True.
139
True or false. In all patients, at least one half of the daily dose should be administered in the morning
True.
140
why are long acting glucocorticoids such as prednisolone or dexamethasone not preferred
they result in increased glucocorticoid exposure
141
equipotency for 1 mg hydrocortisone
1.6 mg cortisone acetate, 0.2 mg prednisolone, 0.25 mg prednisone, 0.025 mg dexamethasone
142
Diagnosis. Low normal ACTH, normal renin, normal aldosterone
secondary adrenal insufficiency
143
Diagnosis. High ACTH, high renin, low aldosterone
primary adrenal insufficiency
144
treatment of primary adrenal insufficiency
mineralocorticoid and glucocorticoid replacement
145
treatment of secondary adrenal insufficiency
glucocorticoid replacement
146
True or false. All patients with adrenal insufficiency need to be instructed about the requirement for stress related glucocorticoid dose adjustment
True. Doubling dose in case of intercurrent illness or stress
147
how is mineralocorticoid replacement done in primary adrenal insufficiency
Fludrocortisone 100-150 ug
148
equivalent of 40 mg hydrocortisone
100 ug fludrocortisone
149
True or false. Fludrocortisone should be increased to by 50-100 ug during the summer and during pregnancy
True,
150
True or false. Pregnancy has antimineralocorticoid activity from progesterone
True
151
caused by mutation in genes encoding steroigenic enzymes involve in glucocorticoid synthesis
congenital adrenal hyperplasia
152
most prevalent cause of CAH
mutations in CYP21A2
153
useful marker for overtreatment in CAH
17OHP
