M5.1-ADRENAL TRANS Flashcards
(206 cards)
1
Q
Which hormones are produced by the adrenal gland and are essential for life?
A
Steroid hormones and neuropeptides
2
Q
What are examples of steroid hormones produced by the adrenal gland?
A
Cortisol+Aldosterone+DHEA-S
3
Q
What is an example of a neuropeptide produced by the adrenal gland?
A
ANP
4
Q
Which major functions are most adrenal pathologies linked to?
A
Blood pressure and electrolyte balance
5
Q
What is the treatment for adrenal hypofunction?
A
Hormone replacement
6
Q
What is the treatment for adrenal hyperfunction?
A
Pharmacologic suppression and/or surgery
7
Q
What is another name for the adrenal gland?
A
Suprarenal gland
8
Q
Where are the adrenal glands located?
A
On top of the kidneys
9
Q
What is the shape and color of the outer adrenal cortex?
A
Yellow and pyramid-shaped
10
Q
What is the color of the inner adrenal medulla?
A
Dark mahogany
11
Q
Which part of the adrenal gland is derived from the embryonic mesoderm?
A
Adrenal cortex
12
Q
Which part of the adrenal gland is derived from neural crest cells?
A
Adrenal medulla
13
Q
Which direction do axons reach the adrenal medulla?
A
Through the cortex
14
Q
What is the outermost layer of the adrenal cortex?
A
Zona glomerulosa
15
Q
What percentage of the adrenal cortex does the zona glomerulosa comprise?
A
0.1
16
Q
What hormone is synthesized in the zona glomerulosa?
A
Aldosterone
17
Q
What is the main function of aldosterone?
A
Sodium retention+potassium excretion+acid–base homeostasis+regulation of blood pressure
18
Q
What regulates aldosterone release?
A
RAAS (Renin-Angiotensin-Aldosterone System)
19
Q
What is the middle layer of the adrenal cortex?
A
Zona fasciculata
20
Q
What percentage of the adrenal cortex does the zona fasciculata comprise?
A
0.75
21
Q
Which hormones are synthesized in the zona fasciculata?
A
Glucocorticoids (cortisol+cortisone+corticosterone)
22
Q
What is the main function of glucocorticoids?
A
Blood glucose homeostasis and blood pressure regulation
23
Q
What is the innermost layer of the adrenal cortex?
A
Zona reticularis
24
Q
What percentage of the adrenal cortex does the zona reticularis comprise?
A
0.15
25
Which hormones are synthesized in the zona reticularis?
Adrenal androgens (DHEA-S+androstenedione+testosterone) and estrogens
26
What is the role of adrenal androgens and estrogens?
Sexual development
27
Where can DHEA produced by the F-zone be converted to DHEA-S?
Zona reticularis
28
What is a distinguishing feature of zona reticularis cells?
Lipid-deficient cords of irregular dense cells with lipofuscin deposits
29
What is the rate-limiting step in adrenal steroid synthesis?
Conversion of cholesterol to pregnenolone
30
Which protein facilitates cholesterol transport into mitochondria?
StAR (steroidogenic acute regulatory protein)
31
What is the common precursor for all adrenal steroids?
Cholesterol
32
Which enzyme converts cholesterol to pregnenolone?
CYP11A1 (P450scc) cholesterol side chain cleavage enzyme
33
Which enzyme is unique to the zona glomerulosa?
CYP11B2 (aldosterone synthase)
34
What regulates aldosterone synthesis?
RAAS (renin-angiotensin system)+ potassium levels+ and ACTH
35
What are the three enzymatic steps catalyzed by aldosterone synthase
11β-hydroxylation → 18-hydroxylation → 18-oxidation
36
What is the final product of the G-zone pathway?
Aldosterone
37
Which enzyme directs synthesis toward glucocorticoids?
CYP17A1 (17α-hydroxylase)
38
What is the primary glucocorticoid produced?
Cortisol
39
Which enzyme converts 11-deoxycortisol to cortisol?
CYP11B1 (11β-hydroxylase)
40
How does cortisol regulate its own production?
Negative feedback on ACTH
41
Which cofactor enhances androgen synthesis?
Cytochrome b5 (CYB5)
42
What is the primary adrenal androgen?
DHEA/DHEA-S
43
Which enzyme sulfates DHEA?
SULT2A1
44
Why does the R-zone produce minimal estrogens?
Lacks aromatase
45
What is the most common enzyme defect in CAH?
21-hydroxylase deficiency (CYP21A2)
46
Which hormone accumulates in 21-hydroxylase deficiency?
17-hydroxyprogesterone
47
What clinical features occur in female infants with CAH?
Virilization (ambiguous genitalia)
48
How is CAH managed?
Glucocorticoid ± mineralocorticoid replacement
49
What stimulates aldosterone secretion?
Angiotensin II+ hyperkalemia+ ACTH
50
What inhibits aldosterone?
ANP+ dopamine+ calcium
51
What electrolyte disturbances occur in hyperaldosteronism?
Hypokalemia + metabolic alkalosis
52
Which drug suppresses aldosterone?
Heparin
53
Which enzyme converts pregnenolone → progesterone?
3-beta-hydroxysteroid dehydrogenase (3β-HSD) enzyme,
54
Which enzyme converts progesterone → 11-deoxycorticosterone?
21-hydroxylase
55
What distinguishes CYP11B1 from CYP11B2?
CYP11B1 produces cortisol+ CYP11B2 produces aldosterone
56
Where does 18-hydroxylation occur?
Exclusively in zona glomerulosa via CYP11B2
57
Why does 17OHP rise in 21-hydroxylase deficiency?
Blocked conversion to 11-deoxycortisol
58
What causes hypertension in CAH?
Accumulated DOC (11-deoxycorticosterone)
59
What is the treatment for adrenal crisis?
IV hydrocortisone + fluid resuscitation
60
Which lab test confirms hyperaldosteronism?
Elevated aldosterone-to-renin ratio
61
What characterizes zona reticularis cells histologically?
Lipid-deficient cords with lipofuscin deposits
62
Which zone has foamy cytoplasm?
Zona fasciculata
63
Why is the G-zone susceptible to hypertrophy?
Chronic angiotensin II stimulation
64
What happens to G-zone size in low-sodium diets?
Hypertrophy
65
How does aldosterone increase blood pressure?
Sodium retention → water retention
66
What is cortisol’s primary metabolic effect?
Gluconeogenesis stimulation
67
Why are adrenal androgens clinically significant?
Precursors for peripheral sex hormone synthesis
68
Which hormone counteracts aldosterone?
ANP (atrial natriuretic peptide)
69
What indicates 11β-hydroxylase deficiency?
Hypertension + virilization
70
Which hormone deficiency causes salt-wasting in CAH?
Aldosterone
71
What confirms adrenal insufficiency?
Low cortisol + high ACTH
72
What lab finding suggests CAH in newborns?
Elevated 17OHP on screening
73
Why does ketoconazole inhibit steroidogenesis?
Blocks CYP enzymes
74
What causes metabolic alkalosis in hyperaldosteronism?
Hydrogen ion excretion
75
Which steroid is absent in 17α-hydroxylase deficiency?
Cortisol
76
What triggers StAR protein activation?
ACTH signaling
77
What are the causes of isolated hypoaldosteronism?
Adrenal gland destruction+chronic heparin therapy+following unilateral adrenalectomy (transient)+G-zone enzyme deficiencies (most cases occur in patients with mild renal insufficiency)
78
What are the treatments for isolated hypoaldosteronism?
Dietary changes+fludrocortisone or Florinef (enhances salt retention and secretion of both potassium and hydrogen)
79
What is the primary cause of primary aldosteronism (Conn's disease)?
Aldosterone-secreting adrenal adenoma
80
What are the laboratory findings in primary aldosteronism?
Elevated plasma aldosterone+low plasma renin
81
What is the cause of secondary aldosteronism?
Excessive production of renin
82
What are the laboratory findings in secondary aldosteronism?
Elevated plasma levels of aldosterone and renin
83
What is pseudoaldosteronism?
Renal tubular diseases causing urinary potassium loss by aldosterone-independent mechanism
84
What are examples of pseudoaldosteronism?
Bartter's syndrome (bumetanide-sensitive chloride channel mutation)+Gitelman's syndrome (thiazide-sensitive transporter mutation)
85
What is the clinical entity where excessive secretion of aldosterone cannot be suppressed with salt or volume replacement?
Primary aldosteronism (PA)
86
What are the Endocrine Society guidelines for screening for primary aldosteronism?
Systolic BP > 160+diastolic BP > 100+drug-resistant HTN+hypokalemia associated with HPN+presence of adrenal mass+family history of early HTN and stroke+first-degree relatives of patients with PA
87
What are the causes of primary aldosteronism?
Aldosterone-producing adenoma+unilateral or bilateral adrenal hyperplasia+familial hyperaldosteronism+adrenal carcinomas that secrete aldosterone+ectopic aldosterone secretion
88
What are the three diagnostic criteria for primary aldosteronism?
Plasma Aldo (PA)/plasma renin activity (PRA) > 25+low plasma renin that fails to increase with volume depletion+high Aldo that fails to decrease with saline/angiotensin inhibition
89
What are the screening tests for primary aldosteronism?
Plasma aldosterone concentration (PAC) > 15 ng/dL+PAC/PRA ratio of 30 or greater
90
What are the confirmatory tests for primary aldosteronism?
Aldosterone measurement after oral salt loading or IV saline infusion+adrenal imaging+adrenal venous sampling
91
What is the threshold for urinary potassium excretion in hyperaldosteronism?
> 30 mEq/L (hyperaldosteronism); < 30 mEq/L (renal potassium retention)
92
What is the significance of the upright PA/PRA ratio in diagnosing primary aldosteronism?
> 25 ratio
93
What is the captopril suppression test result in primary aldosteronism?
PA remains high (PA/PRA is > 25 ng/dL before and after test)
94
What 18-hydroxycorticosterone level suggests aldosterone-producing adenoma or idiopathic hyperaldosteronism?
> 100 ng/dL
95
What imaging is used in the diagnosis of primary aldosteronism?
Adrenal CT or MRI
96
What is the purpose of adrenal vein sampling?
To distinguish between unilateral adenoma and bilateral hyperplasia
97
What is the treatment for aldosterone-producing adenoma?
Surgery
98
What is the treatment for adrenal hyperplasia causing hyperaldosteronism?
Mineralocorticoid antagonists (spironolactone or eplerenone)
99
What is the treatment for familial hyperaldosteronism?
Prednisone
100
What is adrenal insufficiency?
Inadequate hormone secretion from the adrenal cortex
101
How is adrenal insufficiency classified by affected gland?
Primary (adrenal)+Secondary (pituitary)+Tertiary (hypothalamus)
102
What are the symptoms of adrenal insufficiency?
Fatigue+decreased appetite+weight loss+nausea+low BP+low blood sugar+low serum sodium+high potassium
103
What is the reference range for peak morning serum cortisol?
7-25 μg/dL (6-8 AM)
104
What is the reference range for midnight serum cortisol?
2-14 μg/dL
105
What lab findings suggest primary adrenal insufficiency?
Low 8:00 AM serum cortisol+elevated ACTH
106
What morning cortisol level is highly suggestive of adrenal insufficiency?
< 3 μg/dL
107
What is the ACTH stimulation test used for?
Diagnosis of adrenal insufficiency
108
What is a normal response to the ACTH stimulation test?
Cortisol of 18 μg/dL or greater at 30 or 60 minutes post-ACTH
109
What test is used for suspected secondary adrenal insufficiency?
Metyrapone suppression test
110
What is a metyrapone suppression test result for secondary adrenal insufficiency?
Low cortisol (< 5 μg/dL)+high 11-deoxycortisol (> 7 μg/dL)
111
What is the insulin tolerance test used for?
To stimulate the HPA axis and assess cortisol response
112
What is the treatment for primary adrenal insufficiency?
Glucocorticoid (prednisone and hydrocortisone) replacement+mineralocorticoid (fludrocortisone) replacement
113
What is the treatment for secondary adrenal insufficiency?
Glucocorticoid replacement only
114
What are the lab findings in primary adrenal insufficiency?
Low serum cortisol+high ACTH
115
What are the lab findings in secondary adrenal insufficiency?
Low serum cortisol+low ACTH
116
What is hypercortisolism (Cushing’s syndrome)?
Excess cortisol production
117
What are clinical manifestations of Cushing’s syndrome?
Hypertension+progressive central obesity+dorsocervical fat pad (“buffalo hump”)+moon face+skin atrophy+easy bruising+purple striae+hyperpigmentation+menstrual irregularity+androgen excess+muscle weakness
118
What are causes of Cushing’s syndrome?
Adrenal tumors+pituitary tumors+ectopic sources
119
What is the specific term for Cushing’s syndrome due to pituitary ACTH excess?
Cushing’s disease
120
What is the reference range for 24-hour urine free cortisol (UFC)?
3.5-45 μg/24 hour
121
How much above normal should UFC be to suggest cortisol excess?
Three times above normal
122
What factors can cause false positives in UFC testing?
Fluid intake > 5 L/day+urine volume > 3 L+depression+alcohol intake
123
What is the significance of late-night salivary cortisol (LNSC) in Cushing's syndrome?
Loss of diurnal variability+increased LNSC levels
124
What does an increased late-night salivary cortisol indicate?
True endogenous cortisol excess
125
How is the dexamethasone suppression test (DST) performed?
1 mg dexamethasone at 11 PM-midnight+8 AM serum cortisol measurement
126
What is an abnormal DST result?
Failure to suppress 8 AM serum cortisol to < 1.8 μg/dL
127
What conditions can show abnormal DST results?
Cushing’s syndrome+pseudo-Cushing’s+some normal patients
128
What is the daily rate of cortisol synthesis?
15-20 mg/day
129
What is the primary role of glucocorticoids in metabolism?
Maintain blood glucose by inducing lipolysis and amino acid release for gluconeogenesis and glycogen storage
130
What are the causes of adrenal insufficiency?
Primary adrenal problem or ACTH deficiency (hypothalamic-pituitary abnormality)
131
What is the most common cause of primary adrenal insufficiency?
Autoimmune adrenalitis
132
What is the most common cause of secondary adrenal insufficiency?
Glucocorticoid therapy
133
What are the symptoms of adrenal insufficiency?
Weakness+fatigue+anorexia+nausea+diarrhea+abdominal pain+weight loss
134
What are the diagnostic findings in primary adrenal insufficiency?
Low baseline cortisol+elevated ACTH (>200 pg/mL)
135
Why is ACTH elevated in primary adrenal insufficiency?
Adrenal cortex problem leads to low cortisol
136
What is cosyntropin used for?
Synthetic stimulator of cortisol and aldosterone secretion
137
What does low serum cortisol and ACTH after cosyntropin indicate?
Secondary adrenal failure (pituitary problem)
138
What is metyrapone used for?
Alternate diagnostic/confirmatory test for secondary adrenal insufficiency
139
What is the expected metyrapone test result in secondary adrenal insufficiency?
Low cortisol+ACTH+11-deoxycortisol
140
What is the treatment for primary adrenal insufficiency?
Synthetic steroids (aldosterone+Florinef+cortisol+hydrocortisone or prednisone)
141
What is the treatment for secondary adrenal insufficiency?
Cortisol replacement only (G-zone intact)
142
What is hypercortisolism caused by?
Overproduction of CRH+ACTH+adrenal glucocorticoid secretion+exogenous intake
143
What is Cushing’s syndrome caused by?
Excess glucocorticoid production or prolonged exogenous steroid use
144
What are the causes of Cushing’s syndrome?
ACTH-secreting pituitary adenoma (68%)+autonomous cortisol production from adrenal tumor (17%)+ectopic ACTH/CRH production (15%)
145
How is ACTH-dependent vs. ACTH-independent hypercortisolism determined?
Electrochemiluminescence assay for ACTH
146
What ACTH level indicates ACTH-dependent hypercortisolism?
ACTH > 15 µg/dL at 8 AM
147
What ACTH level indicates ACTH-independent hypercortisolism?
ACTH < 5 µg/dL
148
What imaging is used for ACTH-independent Cushing’s syndrome?
CT or MRI of adrenal glands
149
What causes ACTH-independent hypercortisolism?
Adrenal adenoma/carcinoma+adrenal hyperplasia+exogenous glucocorticoids
150
What assay determines ACTH-dependency in hypercortisolism?
2-site IRMA (immunoradiometric assay)
151
How does the IRMA assay work?
Radiolabeled antibodies bind to ACTH antigens for detection
152
What test distinguishes pituitary vs. ectopic ACTH secretion?
High-dose dexamethasone suppression test
153
What is the procedure for the high-dose dexamethasone suppression test?
8 mg dexamethasone at 11 PM→8 AM cortisol measurement
154
What result indicates pituitary ACTH secretion in the high-dose test?
Cortisol suppressed by ≥50% from baseline
155
What result indicates ectopic ACTH secretion in the high-dose test?
Cortisol remains unsuppressed
156
What is the gold standard for locating ACTH production?
Inferior petrosal sinus sampling (IPSS)
157
How is IPSS performed?
Simultaneous blood sampling from petrosal sinus and peripheral vein pre/post-CRH stimulation
158
What IPSS ratio confirms pituitary ACTH hypersecretion?
Petrosal:peripheral ACTH ratio ≥2:1 (baseline) or ≥3:1 (post-CRH)
159
What imaging localizes pituitary or ectopic ACTH-secreting tumors?
CT or MRI
160
What is the most sensitive and specific test to document cortisol excess in Cushing’s syndrome?
Urine free cortisol (24-hour urine
161
Why are baseline a.m. cortisol concentrations measured?
Because cortisol secretion is diurnal
162
What indicates loss of diurnal rhythm in Cushing’s syndrome?
Late-night plasma or salivary cortisol values remain high
163
When is plasma cortisol highest during the day?
Between 6-8 am
164
How much lower is plasma cortisol between 10 pm and 12 am compared to morning?
50%-80% lower
165
What test determines loss of normal cortisol suppression?
Dexamethasone suppression test
166
What is the expected dexamethasone suppression test result in Cushing’s syndrome?
Cortisol is not suppressed
167
What test is used to determine ACTH dependency in Cushing’s syndrome?
CRH stimulation test
168
What are the findings in ACTH-independent Cushing’s syndrome after CRH stimulation?
Serum cortisol is high (>25 μg/dL) and ACTH is low
169
What are the findings in ACTH-dependent Cushing’s syndrome after CRH stimulation?
Both serum cortisol (>25 μg/dL) and ACTH (>10 pg/mL) are high
170
What imaging is used for adrenal Cushing’s syndrome?
Adrenal CT or adrenal MRI (T2-weighted)
171
What imaging is used for pituitary Cushing’s syndrome?
Pituitary MRI
172
What imaging is used for ectopic Cushing’s syndrome?
Chest CT
173
What are the main treatment options for Cushing’s syndrome?
Surgery+radiation+medications to suppress adrenal cortisol production
174
What is the preferred treatment for Cushing’s disease (pituitary tumor)?
Transsphenoidal resection of pituitary tumor
175
What is the treatment for adrenal or ectopic Cushing’s syndrome?
Surgical resection+medical therapy if hypercortisolism persists
176
What medications can be used to suppress adrenal cortisol production?
Adrenal enzyme inhibitors (ketoconazole)+adrenolytic agents (mitotane)+pituitary ACTH secretion suppressors (pasireotide and cabergoline)+glucocorticoid receptor blockers
177
What is a surgical option for refractory Cushing’s syndrome?
Bilateral adrenalectomy
178
What does high DHEA and DHEA-S indicate?
Adrenal hyperandrogenism
179
What does high testosterone indicate?
Adrenal or gonadal hyperandrogenism
180
What are the treatments for hyperandrogenism?
Surgical removal of tumors+antiandrogenic drugs (minoxidil+spironolactone+birth control pills)+exogenous DHEA as nutritional supplement
181
What is the main function of the adrenal medulla?
Secretes catecholamines (norepinephrine/epinephrine) directly into circulation
182
What are the primary catecholamines secreted by the adrenal medulla?
Epinephrine (adrenaline)+norepinephrine (noradrenaline)+small amount of dopamine
183
What is the physiological effect of adrenal medulla catecholamine secretion?
Promotes fight-or-flight response+increases cardiac output and blood pressure
184
From which embryonic origin are chromaffin cells derived?
Neural crest cells
185
What is the main biosynthetic pathway for catecholamines in the adrenal medulla?
Phenylalanine → tyrosine → DOPA → dopamine → norepinephrine → epinephrine
186
Which enzyme converts norepinephrine to epinephrine in chromaffin cells?
Phenylethanolamine N-methyltransferase (PNMT)
187
What stimulates epinephrine production in the adrenal medulla?
Cortisol (increased during stress)
188
What is the typical serum ratio of norepinephrine to epinephrine?
0.37569444444444455
189
What are the three main methods of catecholamine elimination?
Reuptake into secretory vesicles+uptake in non-neuronal cells (liver)+degradation by COMT and MAO
190
What are the main metabolites of catecholamine degradation?
Metanephrines+VMA (vanillylmandelic acid)
191
How are catecholamines and their metabolites excreted?
Filtered into urine as free NE (5%)+conjugated NE (85%)+metanephrines (20%)+VMA (30%)
192
What is the preferred specimen for accurate catecholamine measurement?
24-hour urine catecholamine levels
193
What is the main regulatory stimulus for catecholamine release from the adrenal medulla?
Cholinergic stimulation (acetylcholine from preganglionic sympathetic neurons)
194
What are common causes of sympathetic hyperactivity?
Autonomic dysfunction+panic attack (emotions)+stress responses (hypoglycemia+injury+infection+psychosis+seizures)+drugs (decongestants+appetite suppressors+stimulants+bronchodilators+MAO inhibitors+thyroid hormone+cortisol)+foods containing tyramine (imported beer+red wine+soy sauce+overripe/fermented foods+smoked or aged meats)+pheochromocytoma (catecholamine-producing tumor)
195
What rare tumor is a classic cause of sympathetic hyperactivity?
Pheochromocytoma (catecholamine-secreting tumor from chromaffin cells)
196
What are the classic symptoms of pheochromocytoma?
Palpitations+diaphoresis (sweating)+headaches (classic triad)+pallor+hand tremors+shortness of breath+weakness+panic attacks
197
What is the best diagnostic test for pheochromocytoma?
Fractionated metanephrines and catecholamines in a 24-hour urine collection
198
What are the diagnostic thresholds for catecholamines in pheochromocytoma?
NE > 170 μg/24h+EPI > 35 μg/24h+dopamine > 700 μg/24h+normetanephrine > 900 μg/24h+metanephrine > 400 μg/24h
199
What plasma catecholamine level is highly suggestive of pheochromocytoma?
Plasma catecholamines > 2000 pg/mL
200
What is the most sensitive and specific screening test for pheochromocytoma?
Plasma metanephrines (measured by HPLC or RIA)
201
What additional laboratory marker is increased in pheochromocytoma?
Serum chromogranin
202
What is the purpose of the clonidine suppression test?
To determine if excess catecholamine production is suppressed (not suppressed in pheochromocytoma)
203
What imaging studies are used to localize pheochromocytoma?
CT or MRI of the abdomen and adrenal glands
204
What is the primary treatment for pheochromocytoma?
Surgery after appropriate medical preparation
205
What is an adrenal incidentaloma?
Adrenal mass >1 cm found incidentally on imaging
206
What features of an adrenal incidentaloma warrant surgery?
Cancerous lesion+autonomous secretion of cortisol/aldosterone/catecholamines+size ≥ 4 cm+growth on follow-up
