Endocrinology Part 3 (Adrenal Gland) Flashcards
1
Q
multifunctional organ that produces steroid hormones and neuropeptides essential for life
A
Adrenal gland
2
Q
pyramid-like shaped gland composed to 2 conjoined gland
A
Adrenal gland
3
Q
location of adrenal gland
A
superior and medial to the kidneys
4
Q
outer part of adrenal gland
A
ADRENAL CORTEX
5
Q
% composition of adrenal cortex with the total adrenal gland
A
90%
6
Q
% composition of adrenal medulla with the total adrenal gland
A
10%
7
Q
color of adrenal cortex in cross section
A
Yellowish
8
Q
color of adrenal medulla in cross section
A
dark mahogany
9
Q
adrenal cortex is derived from
A
Mesenchymal cells
10
Q
Major site of STEROID HORMONE production
A
adrenal cortex
11
Q
3 zones of Adrenal Cortex, each with distinct tissues
A
Zona glomerulosa (G-zone)
Zona fasciculata (F-zone)
Zona reticularis (R-zone)
12
Q
loc and % of Zona glomerulosa (G-zone) in total adrenal cortex
A
Outer; 10%
13
Q
loc and % of Zona fasciculata (F-zone) in total adrenal cortex
A
Middle; 75%
14
Q
loc and % of Zona reticularis (R-zone) in total adrenal cortex
A
Inner; 15%
15
Q
Hormone produced by G-zone
A
Aldosterone
16
Q
Hormone produced by F-zone
A
Glucocorticoids (cortisol and cortisone)
Adrenal androgens: dehydroepiandrosterone (DHEA)
17
Q
Hormone produced by R-zone
A
DHEA-S
18
Q
a mineralocorticoid (regulates Na2+)
A
Aldosterone
19
Q
stored form of cortisol
A
cortisone
20
Q
critical for glucose homeostasis and BP
A
glucocorticoids
21
Q
precursor for other active androgen or sex hormones, which is sulfated in innermost zona reticularis (R-zone)
A
dehydroepiandrosterone (DHEA)
22
Q
main adrenal androgen
A
DHEA-S (dehydroepiandrosterone sulfate)
23
Q
major active precursor for androgens and estrogen
A
DHEA-S (dehydroepiandrosterone sulfate)
24
Q
inner part of adrenal gland
A
ADRENAL MEDULLA
25
Adrenal medulla is derived from
Neural crest
26
hormones produced by adrenal medulla
amine hormones: CATECHOLAMINES
27
Composed of Chromaffin Cells
adrenal medulla
paraganglia
28
Function of chromaffin cells
secretes catecholamines
29
enumerate conversion of chole to pregnenolone
CRH (hypothalamus)
ACTH (pituitary) - promotes entry of chole into mitochondria
Mitochondria: chole --> pregnenolone by cytochrome P450
30
Major regulator of adrenal hormone regulation
Corticotropin-releasing hormone (CRH)
31
produced by hypothalamus; stimulate pituitary gland to secrete ACTH
Corticotropin-releasing hormone (CRH)
32
Corticotropin-releasing hormone (CRH) production is in response to:
1. ↓ cortisol level
2. Stress
3. Circadian Rhythm
33
peak in CRH is seen during
6-8 AM
34
lowest CRH level is seen during
10-12 MN
35
Produced by pituitary gland
Adrenocorticotropic Hormone (ACTH)
36
Stimulates the adrenal cortex to produce STEROID HORMONES
Adrenocorticotropic Hormone (ACTH)
37
main precursor of steroid hormones
cholesterol
38
Stimulates transport of free cholesterol inside the mitochondria of adrenal cortex, initiating STEROIDOGENESIS
Adrenocorticotropic Hormone (ACTH)
39
1st product produced in steroidogenesis
PREGNENOLONE
40
serves as a substrate for ALL adrenal cortex hormones
PREGNENOLONE
41
FEEDBACK SYSTEM/MECHANISM followed by adrenal cortex hormones production
NEGATIVE
↓ cortisol will stimulate ↑ CRH
42
T/F
decrease in cholesterol will stimulate G-zone (hormone produced: aldosterone)
F
↓ chole and cortisol will not increase aldosterone (unstimulated G-zone) since aldosterone is only dependent to RAAS
43
produced by kidneys in response to ↓ BP, ↓ BV
renin
44
stimulate Aldosterone production by G-zone
renin
45
Adrenal cortex hormone (steroid hormone) synthesis
STEROIDOGENESIS
46
event that takes place in mitochondria during steroidogenesis
Cholesterol --> Pregnenolone by cytochrome P450 (CYP450)
47
what happens next when chole is converted to pregnenolone?
Newly synthesized Pregnenolone is then returned to the cytosol
(further conversions of Pregnenolone to various adrenal cortex hormone )
48
event that takes place in G-zone
Pregnenolone --> Aldosterone
*in response to RAAS
49
event that takes place in F-zone
17a-hydroxypregnenolone --> Cortisol --> cortisone
*in response to CRH & ACTH
50
enzyme that converts Pregnenolone --> 17a-hydroxypregnenolone
17-a-hydroxylase
51
17-a-hydroxypregnenolone in F-zone may migrate to the R-zone to form
dehydroepiandrosterone (DHEA) which are sulfated –> DHEAS
52
major substrate for androgen production such as testosterone and estradiol
DHEAS
53
Associated with absent or deficient enzyme required for steroidogenesis
CONGENITAL ADRENAL HYPERPLASIA (CAH)
54
Inherited family of enzyme disorders
CONGENITAL ADRENAL HYPERPLASIA (CAH)
55
Required steroidogenesis enzymes
21ß-hydroxylase
11ß-hydroxylase
3ß-hydroxysteroid isomerase
17α-hydroxylase
56
cortisol and aldosterone levels in CAH
decreased
57
high lab value caused by deficient 3ß-hydroxysteroid isomerase
DHEA
58
high lab value caused by deficient 17α-hydroxylase
Aldosterone
59
high lab value caused by deficient 11ß-hydroxylase
11-deoxycorticosterone
60
high lab value caused by deficient 21ß-hydroxylase
17a-hydroxyprogesterone
61
effect in hypertension and virilization if 3ß-hydroxysteroid isomerase is deficient
HTN: no
Virilization: slight
62
effect in hypertension and virilization if 17α-hydroxylase is deficient
HTN: yes
virilization: no
63
effect in hypertension and virilization if 11ß-hydroxylase is deficient
HTN: yes
virilization: marked
64
effect in hypertension and virilization if 21ß-hydroxylase is deficient
HTN: no
virilization: marked
65
dev’t of masculine physical traits among women –e.g. Hirsutism (usually with PCOS)
Virilization
66
T/F
Enzyme deficient will increased the substrate in the pathway it convert.
T
67
reason why ALDOSTERONE is increased if 17α-hydroxylase is deficient
Pathway continues until aldosterone is produced (In enzyme deficiency, when pathway is blocked, it will continue the other pathway)
68
most common enzyme deficient that contributes to CAH
21 beta-hydroxylase
69
type of CAH with marked virilization
21ß-hydroxylase
11ß-hydroxylase
70
type of CAH with hypertension
17α-hydroxylase
11ß-hydroxylase
71
Most potent mineralocorticoid (electroregulating hormone)
ALDOSTERONE
72
regulated by aldosterone
H+ and K+ excretion
Na2+ reabsorption
73
effect of aldosterone in BP
↑ BP through volume expansion by ↑ sodium reabsorption
74
secrete renin
Juxtaglomerular cells (JG cells) of nephrons (kidneys)
75
converted by renin
Angiotensinogen -----------> Angiotensin I
76
converted by ACE
Angiotensin I -------> Angiotensin II
77
angiotensin precursor produced by liver
Angiotensinogen
78
enzyme produced by lungs
ACE
79
4 functions of angiotensin II
* stimulate adrenal cortex to produce aldosterone (Aldosterone – Na2+reabsorption in DCT)
* stimulates hypothalamus to produce ADH (ADH – water reabsorption in collecting duct)
* ↑ arterial pressure by vasoconstriction
* ↑ absorption of Na2+ in PCT
80
Aldosterone Secretion is stimulated by
Low BP
Angiotensin II
ACTH
Elevated serum K+
Progesterone
Dopamine
81
Aldosterone Secretion is inhibited by
Atrial Natriuretic Peptide
Intracellular Calcium
Certain Drugs (ketoconazole, heparin, ACE inhibitors, NSAIDs)
82
acts on ↑ BP by promoting vasodilation and Na2+ excretion
Atrial Natriuretic Peptide
83
T/F
ACTH only stimulate aldosterone by stimulation of cholesterol entry to G-zone; does NOT DIRECTLY stimulate aldosterone production (RAAS is still the main stimulant)
T
84
aka Primary Hyperaldosteronism
Primary Aldosteronism
Conn's disease
85
increased and decreased values in primary hyperaldosteronism
↑: plasma aldosterone
↓: plasma renin
86
causes of Primary Aldosteronism
1. Aldosterone-secreting adrenal adenoma
2. Unilateral/Bilateral adrenal hyperplasia
3. Familial hyperaldosteronism
4. Adrenocortical carcinomas
5. Ectopic aldosterone production
87
Autonomous aldosterone production
1. Aldosterone-secreting adrenal adenoma
2. Unilateral/Bilateral adrenal hyperplasia
88
genetics/hereditary primary Hyperaldosteronism
Familial hyperaldosteronism
89
Primary hyperaldosteronism caused by cancer that produces ACTH
Adrenocortical carcinomas
90
aldosterone production aside from adrenal cortex
Ectopic aldosterone production
91
condition with excess renin production
Secondary Hyperaldosteronism
92
aldosterone & renin lvl in secondary hyperaldosteronism
INCREASED
93
3 Pseudohyperaldosteronism
Liddle’s syndrome - ↓ aldosterone
Bartter’s Syndrome - ↑ aldosterone
Gitelman’s Syndrome - ↑ aldosterone
94
Variation in renin & aldosterone conc. but in most cases aldosterone is ↓
Pseudohyperaldosteronism
95
aka Bartter’s Syndrome
bumetanide-sensitive chloride channel mutation
96
aka Gitelman’s Syndrome
thiazide-sensitive transporter mutation
97
Due to adrenal gland destruction and glucocorticoid deficiency
Isolated Hypoaldosteronism
98
Associated with 21-hydroxylase deficiency
Isolated Hypoaldosteronism
99
associated with ↑ 17a-hydroxyprogesterone
Isolated Hypoaldosteronism
(increased in 17a-hydroxyprogesterone is due to 21-hydroxylase deficiency)
100
Diagnostic Tests for Aldosterone
Captopril Suppression Test
Urinary Potassium Excretion
Plasma Aldosterone Concentration (PAC)/Plasma Renin Activity (PRA) ratio
Oral Salt Loading
Saline Infusion Test
101
Aldosterone antagonists
Captopril
102
normal effect of captopril in aldosterone?
what is the abnormal effect?
normal: ↓ aldosterone
primary hyperaldosteronism (Aldosterone-producing adenoma [APA]): ↑ aldosterone (AUTONOMOUS PROD)
103
sample used in urinary potassium excretion and oral salt loading
24 hr urine
104
principle of Urinary Potassium Excretion
aldosterone promotes K+ excretion in urine
105
value suggestive of hyperaldosteronism in Urinary Potassium Excretion
>30 mEq/day
*↑ Aldosterone = ↑ K+ excretion
106
value suggestive of renal potassium retention in Urinary Potassium Excretion
<30 mEq/day
107
2 cause of ↓ urinary K+ excretion:
1. Diuretic use – ↑ Na2+ excretion, ↑ K+ reabsorption
2. GI loss
108
Most reliable method for screening primary aldosteronism
Plasma Aldosterone Concentration (PAC)/Plasma Renin Activity (PRA) ratio
109
Special Patient Consideration in PAC/PRA ratio
Ambulatory/walking: 2 hr prior blood collection
Seated for 5-15 mins: during blood collection
110
value suggestive of primary hyperaldosteronism in PAC/PRA ratio
>30
111
value diagnostic of primary hyperaldosteronism in PAC/PRA ratio
>50
112
administered in oral salt loading for diagnosing primary aldosteronism; what is the duration?; what is collected after?
5,000 mg/day for 3 days
24 hr urine is collected after 3 days
113
what is measured in oral salt loading
urine sodium
urine aldosterone
114
values suggestive of primary aldosteronism in oral salt loading
urine sodium: >200 mEq
urine aldosterone: >12 μg/day
115
administered in saline infusion test and its duration? what is measured?
IV infusion of 2L NaCl for 2 hr
plasma aldosterone
116
effect of saline infusion in aldosterone
↓ aldosterone (since there is already ↑ Na2+)
117
normal PAC for saline infusion test
<5 ng/dL
118
PAC for saline infusion test suggestive of primary hyperaldosteronism
>10 ng/dL
119
what is required to consider if it is primary adrenal insufficiency
90% of adrenal gland must be destroyed
120
Used for Androgen excess diagnosis
Plasma DHEA
Plasma DHEAS
121
aka CORTISOL
stress hormone
122
Principal glucocorticoid
CORTISOL
123
Only adrenal hormone that inhibits ACTH secretion
CORTISOL
124
Hormone regulated by ACTH
Cortisol
125
ACTH in circulation is bound to
Glycoproteins
Transcortin
126
effect of cortisol in glucose
INCREASE GLU
Hyperglycemic (stimulates gluconeogenesis & lipolysis)
127
Has an anti-inflammatory and immunosuppressive actions by inhibiting Ab production
cortisol
128
used as therapeutic agent for RA, SLE, MS
cortisol
129
Body’s natural alarm clock
cortisol
130
reason why there is increased cortisol at the end of sleep
↑ energy metabolism by the cells
131
hormone that exhibits diurnal rhythm
cortisol
132
↑ cortisol levels are seen during
8-10am
133
↓ cortisol levels are seen during
10pm-12mn
134
ref value of cortisol
5-25 ug/dL
135
specimen for cortisol
Blood - 8am collection (red top tube)
24 hr Urine
136
Sensitive indicators of adrenal hyperfunction
Urine Free Cortisol
137
All glucocorticoids degraded in the liver and excreted in urine in these forms (urinary metabolites):
17-hydroxycorticosteroids
17-ketogenic steroid
138
Method for 17-hydroxycorticosteroids determination
Porter Silber Method
139
Reagent for 17-hydroxycorticosteroids determination
Phenylhydrazine in sulfuric acid (H2SO4) + alcohol
(Porter Silber Method)
140
Endcolor for 17-hydroxycorticosteroids determination
Yellow
(Porter Silber Method)
141
Method for 17-ketogenic steroid determination
Zimmerman reaction
142
Reagent for 17-ketogenic steroid determination
Meta-dinitrobenzene
(Zimmerman reaction)
143
Endcolor for 17-ketogenic steroid determination
reddish-purple
(Zimmerman reaction)
144
aka HYPERCORTISOLISM
Cushing’s Syndrome
145
Excessive glucocorticoid production
Cushing’s Syndrome
146
Major common cause of Hypercortisolism
1) ACTH-secreting pituitary adenoma – CD
2) Autonomous Cortisol production (adrenal tumor) – CS
3) Excess ACTH or CRH production - CD
147
Features of Cushing’s Syndrome
Obesity with thin extremities
Buffalo hump
Hirsutism
Pendulum abdomen
Moonfaced
148
condition with ↑ cortisol, ↓/N ACTH
Cushing’s Syndrome / Primary hypercortisolism
149
condition with ↑ ACTH, ↑ cortisol
Cushing’s Disease / Secondary hypercortisolism
150
Cause of Cushing’s Disease / Secondary hypercortisolism
pituitary tumor (autonomously secretes ACTH)
151
Less serious, More common hypercortisolism
Cushing’s Syndrome
152
More serious, Less common hypercortisolism
Cushing’s Disease
153
Develops due to tumor growth, associated with hyperpigmentation
Cushing’s Disease
154
Develops most often from taking medications that increases cortisol
Cushing’s Syndrome
155
Screening Tests for HYPERCORTISOLISM
24-hour urine free cortisol
Overnight Dexamethasone Suppression Test
Midnight Salivary Cortisol Test / Late Night Salivary Cortisol Test
156
Confirmatory Tests for HYPERCORTISOLISM
Low-dose Dexamethasone Suppression Test
Midnight Plasma Cortisol
Corticotropin-Releasing Hormone Stimulation test
157
screening test that requires accurate collection and urine volume measurement
24-hour urine free cortisol
158
In 24-hour urine free cortisol, if cortisol is 3x above normal it indicates?
suggestive of cortisol excess
159
sources of false positive in 24-hour urine free cortisol
Increased fluid intake: >5L/day
Urine volume: >3L
160
administered in Overnight Dexamethasone Suppression Test and time of administration? type of specimen and time of collection?
1mg dexamethasone
11-12pm
blood at 8 am
161
Results of Overnight Dexamethasone Suppression Test
Normal = <1.8 ug/dL
Cortisol excess = >1.8 ug/dL
162
requirement for Midnight Salivary Cortisol Test / Late Night Salivary Cortisol Test
avoid smoking prior to collection
163
administered in Low-dose Dexamethasone Suppression Test and time of administration? type of specimen and time of collection?
0.5mg dexamethasone every 6 hr for 2 days
Blood collection every 15 mins after
164
Results of Low-dose Dexamethasone Suppression Test
Normal = ↓ cortisol
Hypercortisolism = ↑ cortisol
165
Special Requirement in Midnight Plasma Cortisol
Px admitted to the hospital before 10pm
Blood collection while asleep
166
Identifies if increased cortisol is ACTH-dependent or independent
Corticotropin-Releasing Hormone Stimulation test
167
Measure Cortisol & ACTH after CRH administration
Corticotropin-Releasing Hormone Stimulation test
168
Differentiate ACTH-dependent to ACTH-independent
ACTH-dependent ↑ cortisol ↑ ACTH
ACTH-independent ↑ cortisol ↓ ACTH
169
aka Addison’s Disease
Primary adrenal insufficiency (hypocortisolism)
170
Primary Adrenal Problems
o Autoimmune adrenalitis – Ab against adrenal gland
o Fungal disease
o HIV Infection
o Tuberculosis
o Bilateral Adrenal Hemorrhage
o Adrenoleukodystrophy
o Infiltrative processes
o Metastasis
171
Other causes of Addison's dse
o Secondary to ACTH deficiency – secondary adrenal insufficiency
o Glucocorticoid therapy
o Tumors
o Developmental abnormalities
o Malignancies
172
Secondary to ACTH deficiency
secondary adrenal insufficiency
173
most common cause of Addison's dse
Glucocorticoid therapy
cause hypocortisolism due to neg. feedback loop
↑ cortisol = ↓ CRH = ↓ ACTH = ↓ cortisol
174
Screening test for HYPOCORTISOLISM
ACTH Stimulation Test
Metyrapone Suppression Test (MTS)
175
Confirmatory test for HYPOCORTISOLISM
Insulin Tolerance Test
176
requirement in ACTH Stimulation Test
Px in fasting state
177
Procedure for ACTH Stimulation Test
* Obtain baseline in fasting state: measure ACTH & Cortisol
* Administer 200ug cosyntropin (synthetic ACTH)
* Collect blood after 30-60 mins
* Measure ACTH & Cortisol
178
what is administered in ACTH Stimulation Test
200ug cosyntropin (synthetic ACTH)
179
Result of ACTH Stimulation test
o Primary Hypocortisolism: low cortisol
o Secondary Hypocortisolism: low cortisol
*perform MTS to differentiate
180
used for confirmation of secondary hypocortisolism
Metyrapone Suppression Test (MTS)
181
Blocks certain enzymes in steroidogenesis
Metyrapone Suppression Test (MTS)
182
administered in Metyrapone Suppression Test (MTS)? time of administration? specimen type and time of collection?
30mg Metyropone = midnight
collect blood = 8 am
183
Result of Metyrapone Suppression Test (MTS)
↑ 11-deoxycorticosterone (blocks 11ß-hydroxylase, increasing its substrate): >7ug/dL
↓ Aldosterone = <5ug/dL
184
after MTS, Secondary hypocortisolism is indicated by?
decreased ACTH
185
NORMAL effect of Insulin Tolerance Test in cortisol and ACTH
↑ cortisol, ↑ ACTH
due to insulin administration causing hypoglycemia
186
ABNORMAL effect of Insulin Tolerance Test in cortisol and ACTH
Hypocortisolism – ↓ cortisol & ACTH, regardless of glucose concentration
187
Insulin Tolerance Test is not performed among px with
CV disease
Seizure disorder
188
Produced as by-products of cortisol synthesis regulated by ACTH
ANDROGENS
189
Precursors for the production of more potent androgens and estrogens in tissues
ANDROGENS
190
Stimulants of Androgen
ACTH
Prolactin
Pro-opiomelanocortin
T cells
191
DHEAS will serve as precursors to more active androgens such as:
Testosterone
5-dihydrotestosterone
Androstenedione
192
DHEAS can also serve as precursors to estrogens such as:
Estradiol
Estrone
193
Excess of this hormone results to virilization
Androgen
194
Normal Values of Androgen
Plasma DHEAS: 4mg/day
Plasma DHEA: 7-15mg/dL
*If values are greater than the normal values = Androgen excess
