M5-ADRENAL FUNCTION Flashcards
1
Q
What regulates cortisol production via CRH and ACTH?
A
Hypothalamic-pituitary-adrenal axis (HPA axis)
2
Q
What detects low cortisol levels and initiates CRH release?
A
Hypothalamic glucocorticoid receptors
3
Q
What pituitary cells produce ACTH in response to CRH?
A
Corticotrophs
4
Q
What adrenal hormone suppresses CRH/ACTH via negative feedback?
A
Cortisol
5
Q
What are the adrenal gland’s two functional components?
A
Cortex (steroid production) and medulla (catecholamine release)
6
Q
What conditions result from adrenal hypofunction?
A
Addison’s disease
7
Q
What treatments replace deficient adrenal hormones?
A
Exogenous glucocorticoids (hydrocortisone) and mineralocorticoids (fludrocortisone)
8
Q
What embryological origins define adrenal cortex and medulla?
A
Cortex from mesoderm
9
Q
What arterial system supplies the adrenal glands?
A
Superior
10
Q
What neuropeptides are produced by the adrenal medulla?
A
ANP-like peptides (distinct from cardiac ANP)
11
Q
What clinical triad characterizes adrenal insufficiency?
A
Hypotension
12
Q
What distinguishes primary from secondary adrenal failure?
A
Primary: adrenal destruction; Secondary: ACTH deficiency
13
Q
What causes Cushing’s syndrome?
A
Excess cortisol from ACTH-secreting tumors or adrenal hyperplasia
14
Q
What system regulates aldosterone independently of ACTH?
A
Renin-angiotensin-aldosterone system (RAAS)
15
Q
What transports hypothalamic hormones to the anterior pituitary?
A
Hypophyseal portal system
16
Q
What neural tract connects hypothalamus to posterior pituitary?
A
Hypothalamohypophyseal tract
17
Q
What hormones are stored in the posterior pituitary?
A
Oxytocin and ADH (synthesized in hypothalamus)
18
Q
What mechanism detects plasma osmolality for ADH release?
A
Hypothalamic osmoreceptors
19
Q
What blood pressure drop triggers ADH secretion?
A
5-10% decrease detected by vascular baroreceptors
20
Q
What causes diabetes insipidus?
A
ADH deficiency (central) or renal resistance (nephrogenic)
21
Q
What structural similarity exists between oxytocin and ADH?
A
Both cyclic nonapeptides with disulfide bridges (differ by 2 amino acids)
22
Q
What postpartum condition causes pituitary necrosis?
A
Sheehan’s syndrome (hypovolemic shock during delivery)
23
Q
What autoimmune disorder involves pituitary lymphocyte infiltration?
A
Lymphocytic hypophysitis
24
Q
What genetic condition combines GnRH deficiency and anosmia?
A
Kallmann syndrome
25
What hormone deficiencies occur in panhypopituitarism?
ACTH
26
What replaces multiple hormones in panhypopituitarism?
Thyroxine
27
What imaging modality visualizes pituitary anatomy?
Sellar MRI with gadolinium contrast
28
What surgical approach treats pituitary stalk trauma?
Transsphenoidal repair if accessible
29
What lab findings suggest hypopituitarism?
Low T4/cortisol/sex hormones with inappropriately normal/low tropic hormones
30
What occurs in untreated Sheehan’s syndrome?
Lifelong panhypopituitarism requiring full hormone replacement
31
What stimulates oxytocin release during labor?
Cervical dilation and suckling reflex
32
What clotting factors does ADH enhance?
Factor VII and von Willebrand factor (vWF) via endothelial release
33
What are the three zones of the adrenal cortex?
Zona glomerulosa (outer)
34
What hormone does the zona glomerulosa primarily produce?
Aldosterone (mineralocorticoid)
35
What controls aldosterone secretion?
Renin-angiotensin system (RAS)
36
What enzyme deficiency causes 95% of congenital adrenal hyperplasia cases?
21-hydroxylase deficiency
37
What hormones does the zona fasciculata produce?
Cortisol (glucocorticoid) and small amounts of DHEA
38
What is the rate-limiting step in adrenal steroidogenesis?
Conversion of cholesterol to pregnenolone
39
What stimulates cholesterol transport into adrenal mitochondria?
ACTH from pituitary corticotrophs
40
What hormone does the zona reticularis convert to DHEAS?
Dehydroepiandrosterone (DHEA) via sulfation
41
What system regulates blood pressure through sodium retention?
Renin-angiotensin-aldosterone system (RAAS)
42
What factors stimulate renin production?
Volume depletion
43
What converts angiotensinogen to angiotensin I?
Renin from kidney juxtaglomerular cells
44
What enzyme converts angiotensin I to angiotensin II?
Angiotensin-converting enzyme (ACE)
45
What is angiotensin II's primary action?
Vasoconstriction and aldosterone stimulation
46
What inhibits aldosterone production?
Progesterone
47
What accumulates in 21-hydroxylase deficiency?
17-OH progesterone and androgens
48
What is the treatment for congenital adrenal hyperplasia?
Oral glucocorticoids (e.g.
49
What percentage of adrenal cortex volume does the zona fasciculata occupy?
70-80% (middle layer)
50
What adrenal zone is adjacent to the medulla?
Zona reticularis (innermost layer)
51
What adrenal steroids derive from cholesterol?
All corticosteroids (aldosterone
52
What stimulates aldosterone synthesis besides RAS?
ACTH and elevated serum potassium
53
What enzyme is unique to zona glomerulosa cells?
Aldosterone synthase (CYP11B2)
54
What maintains zona glomerulosa differentiation?
Angiotensin II
55
What happens to DHEA in the zona reticularis?
Sulfated to DHEAS (active storage form)
56
What causes isolated G-zone hypertrophy?
Chronic angiotensin II stimulation or low-salt diet
57
What is the functional consequence of aldosterone?
Sodium retention
58
What hormonal axis regulates cortisol production?
Hypothalamic-pituitary-adrenal (HPA) axis
59
What provides negative feedback on ACTH release?
Cortisol suppressing CRH and ACTH
60
What structural feature distinguishes zona fasciculata cells?
Lipid-rich cytoplasm with vacuoles (foamy appearance)
61
What distinguishes zona reticularis histology?
Reticular cell arrangement and lipofuscin granules
62
What clinical triad occurs in untreated congenital adrenal hyperplasia?
Salt wasting
63
What electrolyte imbalance occurs in aldosterone deficiency?
Hyperkalemia and hyponatremia
64
What enzyme converts pregnenolone to progesterone?
3β-hydroxysteroid dehydrogenase
65
What characterizes renal sodium wasting in hypoaldosteronism?
High urine sodium
66
What electrolyte imbalance occurs in hypoaldosteronism?
Hyponatremia and hyperkalemia
67
What causes isolated hypoaldosteronism?
Adrenal destruction
68
What is the treatment for isolated hypoaldosteronism?
Florinef (synthetic mineralocorticoid) and dietary sodium modification
69
What defines primary hyperaldosteronism?
Autonomous aldosterone overproduction with suppressed renin (Conn’s disease)
70
What distinguishes secondary hyperaldosteronism?
Elevated renin (RAS activation) due to extra-adrenal triggers (e.g.
71
What are pseudoaldosteronism syndromes?
Bartter’s (loop of Henle Cl- channel defect) and Gitelman’s (distal tubule Na-Cl transporter defect)
72
What metabolic imbalance occurs in hyperaldosteronism?
Metabolic alkalosis (H+/K+ secretion in exchange for Na+ reabsorption)
73
What adrenal pathology causes Conn’s disease?
Aldosterone-secreting adenoma or bilateral adrenal hyperplasia
74
What triggers secondary hyperaldosteronism?
RAS activation from hypovolemia
75
How does chronic heparin therapy affect aldosterone?
Inhibits aldosterone synthesis → hypoaldosteronism
76
What is Bartter’s syndrome’s key defect?
Mutated bumetanide-sensitive NKCC2 Cl- channel in the thick ascending limb
77
What defines Gitelman’s syndrome?
Thiazide-sensitive NCC transporter mutation in the distal convoluted tubule
78
Why does hyperaldosteronism cause hypokalemia?
Aldosterone-driven renal K+ excretion into urine
79
What clinical finding links to aldosterone’s sodium retention?
Hypertension (due to increased blood volume)
80
What distinguishes pseudoaldosteronism lab results?
Normal/low aldosterone with hypokalemia and metabolic alkalosis
81
What is the RAAS role in secondary hyperaldosteronism?
Renin-driven Ang II production → aldosterone hypersecretion
82
What is the transient cause of hypoaldosteronism?
Unilateral adrenalectomy (short-term aldosterone drop)
83
Why does hypoaldosteronism occur in renal insufficiency?
Impaired adrenal-kidney feedback loops in chronic disease
84
What genetic defect causes G-zone enzyme deficiency?
Mutations in aldosterone synthase (CYP11B2)
85
What are the three diagnostic criteria for primary aldosteronism?
Elevated aldosterone/renin ratio (>25)
86
What urinary potassium excretion level suggests hyperaldosteronism?
>30 mmol/day (indicates renal potassium wasting)
87
How is the upright PA/PRA ratio tested?
After overnight dehydration to stimulate renin; ratio >25 confirms primary aldosteronism
88
What defines a positive captopril suppression test?
Aldosterone remains elevated (PA/PRA >25) post-50mg captopril administration
89
What 18-hydroxycorticosterone level indicates aldosterone-producing adenoma?
>100 ng/dL (vs <100 ng/dL in idiopathic hyperplasia)
90
What imaging modalities localize adrenal tumors?
CT/MRI for adenoma detection (≥1 cm); limited for small tumors
91
What confirms unilateral vs bilateral aldosterone hypersecretion?
Adrenal vein sampling (lateralization ratio >4:1 = unilateral adenoma)
92
How does cortisol synthesis relate to glucose regulation?
Cortisol (8-15 mg/day) induces gluconeogenesis via muscle breakdown and lipolysis
93
What causes primary adrenal insufficiency (Addison’s)?
Autoimmune adrenalitis (70%)
94
What lab findings confirm primary adrenal insufficiency?
Low baseline cortisol (<3 mcg/dL) + ACTH >200 pg/mL
95
How does the cosyntropin test distinguish adrenal failure types?
Low cortisol post-stimulation = primary (adrenal dysfunction); low ACTH = secondary (pituitary origin)
96
What metyrapone test result indicates secondary adrenal insufficiency?
Elevated 11-deoxycortisol (>7 mcg/dL) with suppressed cortisol
97
What are key symptoms of adrenal insufficiency?
Weakness
98
What distinguishes Conn’s syndrome lab findings?
High aldosterone (>15 ng/dL) + suppressed renin (PRA <1 ng/mL/h)
99
What screening indications warrant primary aldosteronism testing?
Resistant HTN (>140/90 on ≥3 drugs)
100
How does saline infusion confirm primary aldosteronism?
Aldosterone remains >10 ng/dL post-infusion (autonomous secretion)
101
What fludrocortisone suppression test criteria diagnose PA?
Aldosterone >6 ng/dL + PRA <1 ng/mL/h post-fludrocortisone
102
What genetic factors contribute to primary aldosteronism?
Familial hyperaldosteronism (rare inherited forms)
103
What distinguishes idiopathic hyperplasia from adenoma?
Bilateral adrenal hypersecretion (AVS ratio <3:1) vs unilateral adenoma (AVS ratio >4:1)
104
What is the aldosterone escape phenomenon in PA?
Initial sodium retention → pressure natriuresis limits edema despite aldosterone excess
105
What drug interactions affect aldosterone testing?
Spironolactone/eplerenone require 4-6 week washout pre-testing
106
What histologic features distinguish zona fasciculata?
Lipid-rich vacuoles (foamy appearance) for cortisol synthesis
107
What is the role of 11β-hydroxylase in steroidogenesis?
Converts 11-deoxycortisol to cortisol; blocked by metyrapone
108
What CT finding suggests aldosterone-producing adenoma?
Unilateral hypodense adrenal nodule with rapid contrast washout
109
What distinguishes primary vs secondary adrenal insufficiency?
ACTH elevation (primary) vs ACTH deficiency (secondary)
110
What dietary modification treats hypoaldosteronism?
High-sodium diet + potassium restriction
111
What is the gold standard for PA subtype differentiation?
Adrenal vein sampling with lateralization index calculation
112
What are the primary synthetic steroids for adrenal insufficiency treatment?
Florinef (mineralocorticoid) and hydrocortisone/prednisone (glucocorticoid)12
113
What distinguishes primary vs secondary adrenal insufficiency treatment?
Primary requires mineralocorticoid + glucocorticoid; secondary needs only glucocorticoid12
114
What causes hypercortisolism?
CRH/ACTH overproduction
115
What is the most common cause of endogenous Cushing’s syndrome?
ACTH-secreting pituitary adenoma (Cushing’s disease - 68%)13
116
What tests distinguish ACTH-dependent vs ACTH-independent Cushing’s?
Plasma ACTH: <5 pg/mL (adrenal tumor) vs >15 pg/mL (ACTH-secreting tumor)13
117
What confirms pituitary vs ectopic ACTH secretion?
High-dose dexamethasone test (>50% cortisol suppression = pituitary origin)12
118
What is the gold standard test for ACTH-secreting pituitary adenomas?
Inferior petrosal sinus sampling (IPSS) with CRH stimulation (petrosal:peripheral ACTH ratio >2-3)14
119
What imaging localizes adrenal Cushing’s tumors?
Adrenal CT (tumor vs hyperplasia) + MRI T2-weighted for carcinoma detection14
120
What defines diagnostic urine free cortisol levels?
>300 μg/24h (830 nmol/day) confirms Cushing’s54
121
What characterizes late-night salivary cortisol in Cushing’s?
Loss of diurnal rhythm (>0.09 mcg/dL/7 nmol/L between 11PM-12AM)12
122
What CRH stimulation test result indicates pituitary Cushing’s?
ACTH rise >35% and cortisol rise >20% post-CRH26
123
What is the first-line screening test triad for Cushing’s?
24h urine free cortisol
124
What low-dose dexamethasone test result confirms Cushing’s?
Morning cortisol >1.8 μg/dL post-1mg dexamethasone26
125
What imaging detects ectopic ACTH sources?
Chest CT (most common: bronchial carcinoids)14
126
What treatment options exist for Cushing’s adenomas?
Transsphenoidal surgery (pituitary)
127
What medications suppress adrenal cortisol production?
Ketoconazole
128
What distinguishes Cushing’s disease from syndrome?
Disease: pituitary ACTH source; Syndrome: all hypercortisolism etiologies36
129
What ACTH-independent Cushing’s imaging finding is critical?
Unilateral adrenal mass on CT (adenoma) or bilateral hyperplasia14
130
What electrolyte pattern occurs in ectopic ACTH syndrome?
Hypokalemic metabolic alkalosis (severe cortisol/mineralocorticoid excess)13
131
What IPSS result confirms pituitary Cushing’s disease?
Central:peripheral ACTH ratio >3:1 baseline or >5:1 post-CRH46
132
What characterizes adrenal carcinoma imaging?
MRI T2 hyperintensity + heterogeneous contrast enhancement >4cm14
133
What test confirms autonomous cortisol secretion?
Midnight serum cortisol >7.5 μg/dL (loss of diurnal rhythm)74
134
What distinguishes pseudo-Cushing’s from true Cushing’s?
Normalization of cortisol with dexamethasone suppression in pseudo-Cushing’s26
135
What is the role of 24h urine cortisol in diagnosis?
Most specific test when >4x upper limit (>300 μg/day)54
136
What imaging modality visualizes pituitary microadenomas?
Sellar MRI with gadolinium (detects tumors >3mm)46
137
What test monitors Cushing’s treatment efficacy?
24h urine free cortisol + late-night salivary cortisol24
138
What are adrenal androgens primarily regulated by?
ACTH (adrenocorticotropic hormone) via cortisol synthesis pathways12
139
What enzymes are critical for adrenal androgen biosynthesis?
CYP17 (17α-hydroxylase/17
140
What suppresses adrenal androgen production?
HSD3B2 (3β-hydroxysteroid dehydrogenase type II) via Δ5 steroid conversion to cortisol precursors34
141
What are the primary adrenal androgens?
DHEA and DHEA-sulfate (DHEA-S) produced in the zona reticularis35
142
What causes adrenal hyperandrogenism symptoms in girls?
Ambiguous genitalia
143
How is adrenal hyperandrogenism diagnosed?
Elevated DHEA-S (>95% adrenal origin) and DHEA levels32
144
What distinguishes adrenal vs gonadal hyperandrogenism?
DHEA-S >500 μg/dL indicates adrenal origin (gonads contribute <10%)24
145
What treatments target adrenal hyperandrogenism?
Antiandrogens (spironolactone)
146
What regulates epinephrine synthesis in the adrenal medulla?
Phenylethanolamine N-methyltransferase (PNMT) converting NE to EPI74
147
What catecholamine metabolites are measured diagnostically?
Metanephrines (COMT product) and VMA (MAO/COMT product)74
148
Why prefer 24-hour urine over plasma catecholamines?
Longer half-life metabolites (VMA) and avoidance of transient spikes74
149
What is the NE:EPI ratio in adrenal medulla secretion?
9:1 (norepinephrine dominant)74
150
What genetic factors influence HSD3B2 expression?
NGFIB (NR4A1) and GATA transcription factors regulating cortisol/DHEA balance34
151
What characterizes ectopic ACTH-driven androgen excess?
Severe hypokalemia + mixed hypercortisolism/hyperandrogenism24
152
How does cytochrome b5 enhance adrenal androgen production?
Boosts CYP17 17
153
What imaging evaluates adrenal androgen-secreting tumors?
Adrenal CT/MRI for adenomas; chest CT for ectopic ACTH sources72
154
What enzyme deficiency causes androgen excess in CAH?
21-hydroxylase deficiency (95% of cases) with 17-OHP accumulation24
155
Why does HSD3B2 suppression increase DHEA?
Redirects Δ5 steroids (pregnenolone) away from cortisol to DHEA pathways34
156
What distinguishes adrenal vs ovarian testosterone sources?
Simultaneous DHEA-S elevation confirms adrenal origin62
157
What is adrenarche's hormonal signature?
Rising DHEA-S at age 6-8 due to zona reticularis maturation51
158
What are primary causes of sympathetic hyperactivity?
Autonomic dysfunction
159
What drugs exacerbate sympathetic activity?
Decongestants
160
Which foods trigger sympathetic surges via tyramine?
Imported beer
161
What defines pheochromocytoma's hormonal profile?
Catecholamine-secreting adrenal medulla tumor causing episodic hypertension/tachycardia13
162
What is the gold standard for pheochromocytoma diagnosis?
24h urinary fractionated metanephrines (normetanephrine >900 μg/24h or metanephrine >400 μg/24h)13
163
How does the clonidine suppression test confirm pheochromocytoma?
Failure to suppress plasma metanephrines post-clonidine indicates autonomous secretion13
164
What imaging localizes pheochromocytomas?
Adrenal CT/MRI (sensitivity >90% for tumors >1 cm)13
165
What is first-line pheochromocytoma treatment?
Surgical resection after α-blockade (phenoxybenzamine) + volume expansion13
166
What defines adrenal incidentalomas?
Asymptomatic adrenal masses >1 cm found incidentally on imaging14
167
When is surgery indicated for incidentalomas?
Size ≥4 cm
168
What distinguishes PSH from pheochromocytoma?
PSH follows brain injury (TBI/stroke) with paroxysmal sympathetic storms; pheochromocytoma has adrenal catecholamine excess56
169
What mechanisms underlie PSH?
Loss of cortical inhibition on diencephalic/brainstem sympathetic centers post-brain injury56
170
How is PSH diagnosed?
PSH-AM score combining clinical features (hypertension/tachycardia/dystonia) and likelihood assessment56
171
What medications manage PSH episodes?
Morphine
