Lectures 3 and 4 Flashcards
True or False: Familial Hyperaldosteronism (Type 1) is caused by overexpression of Cyp11B2 and, therefore, leads to overproduction of hormones
True
Polyclonal and Monoclonal Expansions arise due to proliferation (increase in number of hormone producing cells) - lead to ___ production of hormones
over
Graves Disease is proliferation due to: abnormal stimulus and it is associated with:
A. Polyclonal Expansion
B. Monoclonal Expansion
A. Polyclonal Expansion
Monoclonal expansions are due to proliferation of somatic mutation. What are two types of tumors that may result as a consequence?
1) Pituitary tumor
2) Parathyroid tumor
True or False: Deletion of GH gene can result in abnormal hormone synthesis while mutations in calcium receptor can result in hypoparathyroidism
True
In ____ Syndrome, there is abnormal development of hormone producing cells, which leads to: hypogonadism
Kallman Syndrome
True or False: Auto-immunity (T1DM), genetics, and surgery can result in hormone underproduction
True
True or False: Endocrine gland tumors usually lead to excess of hormone production
True
True or False: Lack of endocrine hormones due to endocrine tumor can result in: thyroid cancer, non-functioning pituitary tumor, or metastasis
True
Iodothyronine Deiodinase Type 3 (D3) expressing tumor deactivates T3 and T4 leading to a condition known as _____ ____
Consumptive Hypothyroidism
What are the three major portions of the adrenal gland cortex? What molecule are they associated with?
Zona Glomerulosa
- Aldosterone
Zona Fasiculata
- Cortisol
Zona Reticularis
- Androgens
True or False: All coricosteroids have cholesterol backbone
True
___ are made on demand and have a slow response to stimulus
Steroid hormones
The zona glomerulosa is the only region that expresses CYP_____.
However, it does not express CYP____
- expresses: CYP11B2
- does not express: CYP17A1 (17a-hydroxylase)
High levels of cytochrome b5 confers 17,20-lyase activity on CYP17A1 located in the ___
A. Zona Glomerulosa
B. Zona Reticularis
C. Zona Fasiculata
B. Zona Reticularis
There is no 17-hydroxylase co-factor in the Zona ____
Zona Fasciculata
ACTH regulates the synthesis of cortisol and testosterone (via their respective zones) – but does NOT regulate it in the Zona ___
glomerulosa
ACTH is not involves in the synthesis of:
A. Aldosterone
B. Testosterone
C. Cortisol
A. Aldosterone
Mineralcorticoids regulate extracellular volume and control homeostasis of __
A. Na
B. Cl
C. K
D. Ca
C. K
Which of the following actions does not belong to the mineralcorticoids?
A. Upregulate and activate basolateral Na/K pumps and ENaC/s
B. Secrete Na/H20 into the blood
C. Reabsorb Na/H2O into blood
D. Secrete K ions into urine
B. Secrete Na/H20 into the blood
How does Aldostersone affect:
- Na reabsorption
- Blood volume
- Renal perfusion pressure
- Renin release
Aldosterone increases all except renin release (decrease)
What effect does Ang II have on blood pressure and renin release?
Ang II causes vasoconstriction, thereby increasing blood pressure and decreasing renin release
____ is a condition associated with excess mineralcorticoids
___ is a syndrome or disease associated with excess cortisol
Hyperaldosteronism
Cushing Syndrome or Disease
What is the main symptom see in primary hyperaldosteronism?
A. Chest pain
B. Bruising
C. Striae
D. Hypertension
D. Hypertension
- Na retention
- Most common cause of secondary HTN
Is hypokalemia a good predictor of primary aldosteronism?
No
To diagnose primary aldosteronism, plasma ___ concentration must be ELEVATED while plasma ___ activity or concentration must be LOW
elevated = plasma aldosterone concentration
low = PRA (plasma renin activity) or PRC (plasma renin concentration)
True or False: Familial hyperaldosteronism type 1 (inappropriate ACTH-dependent activity of CYP11B2) can lead to primary aldosteronism
True
What is the cause of a majority (60%) of primary aldosteronism?
A. Familial Hyperaldosteronism Type 1
B. Conn Syndrome (Adrenocortical Neoplasm)
C. Bilateral Idiopathic Hyperaldosteronism
C. Bilateral Idiopathic Hyperaldosteronism
What is the most common cause of Conn Syndrome (Adrenocortical Neoplasm)?
APA (aldosterone producing adenoma)
- rare: adrenocortical carcinoma
A sodium restricted diet and which two MC receptor antagonists can be used to treat Bilateral Idiopathic Hyperaldosteronism (form of primary hyperaldosteronism)?
Eplerenone
Spironolactone
True or False: A unilateral adrenalectomy can treat ____ ___and ____ ___
adrenal adenomas and unilateral hyperplasias
____ is secreted in a pulsatile fashion with a circadian rhythm
ACTH
When is one’s ACTH at its highest?
Upon waking
(lowest in evening)
How does cortisol affect the skeletal muscle?
1) decreases glucose uptake - [also case in adipocytes]
2) net protein catabolism
3) suppress synthesis of amino acid transporters
True or False: Cortisol decreases epinephrine synthesis in adrenal medulla and decreases glucose release in the liver
False - cortisol increase epi and glucose release
Cortisol is permissive for the actions of which five molecules?
NE
Epi
ADH (vasopressin)
GH
Glucagon
Striae, obesity/weight gain, round face, dorsal fat pad, and ecchymoses is most suggestive of ______
A. excess aldosterone
B. excess androgens
C. excess cortisol
C. excess cortisol (hypercortisolemia)
A patient with hypercortisolemia has an adrenocortical tumor and has been taking prednisone for a long-term infection. Is her excess cortisol level likely ACTH independent or ACTH dependent?
ACTH-independent
Pituitary hypersecretion of ACTH can lead to ___ Disease (ACTH dependent). The majority of ACTH-secreting masses are ___ or ___
Cushing’s Disease; adenomas/microadenomas
Four common causes of Cushing’s Syndrome?
1) Taking ‘roids
2) Adrenocortical tumor
3) Ectopic secretin of CRH
4) Ectopic secretion of ACTH by non-pit tumor
B/l adrenocortical hyperplasia with widening of ZF and ZR is associated with:
A. Adrenocortical Tumors
B. Cushing’s Disease
C. Cushing’s Syndrome
B. Cushing’s Disease
True or False: Both ACTH and Cortisol follow a circadian rhythm, meaning levels are highest in AM and low in the PM
True
True or False: There is resistance to normal GC feedback inhibition in Cushing’s Syndrome
False - this is the case in Cushing’s Disease
How are ACTH pulse frequency, pulse amplitude, and circadian rhythmic secretion affected by Cushing’s Disease?
Frequency and pulse amplitude is increased
Circadian rhythmic secretion is lost
Transphenoidal hypophysectomy is used to treat ___ _____
Cushing’s Disease
What is the most common cause of pathogenesis in Cushing’s Syndrome?
Iatrogenic Cushing’s Syndrome
What is the most common endogenous cause of Cushing’s Syndrome?
1) Primary adrenal neoplasm (carcinoma or adenoma)
2) Secretion of ectopic ACTH (non-pit) tumor
- small cell carcinoma of lung
In Cushing’s Syndrome, non-pituitary tumors that secrete ACTH are frequently small cell _____ of the lung
carcinoma
note: rapid decline in pt health is to be expected
In Cushing’s Syndrome, a patient with a primary adrenal neoplasm (e.g adenoma or carcinoma) have ACTH-___ secretion of cortisol (elevated cortisol and low ACTH)
ACTH-independent
How are adrenal adenomas treated?
Unilateral adrenalectomy
What are the effects of abruptly decreasing serum free cortisol?
Suppress endogenous ACTH secretion
Lower plasma ACTH
Atrophy of adrenal cortex
Limited endogenous cortisol synthesis
**hard time maintaining blood pressure and elevating glucose during stress
What two medications can be used to inhibit steroidogenic enzymes to treat Cushing’s Syndrome?
Metyrapone and Ketoconazole
True or False: Ketoconazole is more selective for cortisol and does not affect the synthesis of other steroid hormones
False - Metyrapone more closely targets cortisol and is more selective for cortisol
Ketoconazole does affect synthesis of other steroid hormones - less specific for cortisol
Which of the following is a glucocorticoid receptor antagonists used for treating patients with Cushing’s Syndrome and accompany hyperglycermia?
A. Mitotane
B. Mifepristone
C. Metyrapone
D. Octreotide
B. Mifepristone
Which of the following drugs treats Cushing’s Syndrome by suppressing ACTH secretion?
A. Mitotane
B. Mifepristone
C. Metyrapone
D. Octreotide
D. Octreotide
Which of the following is a chemotherapeutic drug that is primarily used to treat adrenal carcinomas (Cushing’s Syndrome)?
A. Mitotane
B. Mifepristone
C. Metyrapone
D. Octreotide
A. Mitotane
A patient has decreasing height percentile and increasing weight, as well as osteoporosis and HTN. What should be ruled out in their case?
Cushing’s Syndrome
Unexplained osteoporosis, striae, muscle weakness, and easy bruising are the most discriminating signs of ____ ____
Cushing’s Syndrome
Which of the following methods for measuring cortisol is an integrated measure of serum free cortisol that can be normal in 8-15% of Cushing’s Syndrome patients?
A. Longer Low Dose Dex (2mg) Suppression
B. Low Dose Dex (1 mg) Suppression
C. Late Night Salivary Cortisol
D. Urinary Free Cortisol Excretion (24 hrs)
D. Urinary Free Cortisol Excretion (24 hrs)
True or False: In Urinary Free Cortisol Excretion, as cortisol secretion increases, binding capacity of cortisol-binding globulin is exceeded and results in a disproportionate rise in urinary free cortisol
True
Where is cortisol oxidized, reduced (conjugated) or hydroxylated?
A. Liver
B. Kidney
C. Urine
A. Liver
Where is cortisol reduced, thereby preventing cortisol activation of aldosterone-R?
A. Liver
B. Kidney
C. Urine
B. Kidney
______ is measured to identify the cortisol level in urine
17-hydroxycorticosteroids
Which of the following molecules is elevated in hypercortisolemia?
A. Tetrohydrocortisols
B. Cortols
C. 6 beta-hydroxycortisol
C. 6 beta-hydroxycortisol
Hypercortisolemia results in elevated urinary ____ and its metabolites
free cortisol
Which of the following more closely reflects serum free cortisol and is 96% specific for dx of Cushing’s Syndrome?
A. Longer Low Dose Dex (2mg) Suppression
B. Low Dose Dex (1 mg) Suppression
C. Late Night Salivary Cortisol
D. Urinary Free Cortisol Excretion (24 hrs)
C. Late Night Salivary Cortisol
- two measurements between 23-2400
How does a supraphysiologic dose of dexamethasone affect ACTH and cortisol secretion in normal person vs. Cushing’s Syndrome patient?
Normal: suppression of ACTH and cortisol secretion
Cushing’s Syndrome: failure to suppress
What could cause false positive in the longer, low-dose dexamethasone suppression test (2 mg/day for 48 hrs)?
Certain drugs may increased clearance of dexamethasone
A patient has Cushing’s Syndrome. Which is most likely the dx?
A. ACTH dependent Cushing’s Syndrome
B. ACTH independent Cushing’s Syndrome
A. ACTH dependent Cushing’s Syndrome
If morning plasma ACTH (8-10 AM) is below normal, what does that suggest?
A. Ectopic ACTH
B. Adrenal tumor
C. Cushing’s Disease
B. Adrenal tumor
- ACTH independent hypercortisolemia
Measuring ______ can aid in differentiating between ACTH -dependent and ACTH-independent causes of Cushing’s Syndrome
morning plasma ACTH
Normal ACTH levels at 9 AM, with MODESTLY elevated in the remainder suggests:
A. Ectopic ACTH
B. Adrenal tumor
C. Cushing’s Disease
C. Cushing’s Disease
Extremely high ACTH levels indicate:
A. Ectopic ACTH
B. Adrenal tumor
C. Cushing’s Disease
A. Ectopic ACTH
True or False: In Cushing’s Disease, the negative feedback control of ACTH is reset to a higher level than normal
True
True or False: In Cushing’s Disease, cortisol levels may not suppressed with low level dexa, but do with high doses
True
In the high dose dexa test, ___ mg of dex is given Q6hrs for 48hrs (16 mg total) and plasma/urinary free cortisol is measured at 0 and 48 hrs.
It is a positive test in 90% of patients with _____
2 mg; Cushing’s Disease
A CRH test is done on a patient and there is no response. What is the dx?
A. Normal
B. Cushing’s disease
C. Ectopic ACTH syndrome
C. Ectopic ACTH syndrome
A CRH test is done on a patient and there is a more than 50% increased in ACTH and more than 20% increase in cortisol. What is the dx?
A. Normal
B. Cushing’s disease
C. Ectopic ACTH syndrome
B. Cushing’s disease
A CRH test is done on a patient and there is a 15-20% increased in ACTH and cortisol. What is the dx?
A. Normal
B. Cushing’s disease
C. Ectopic ACTH syndrome
A. Normal
What is the method of choice for examining the pituitary?
MRI
If a patient has hypokalemic alkalosis, they most likely have:
A. Cushing’s Disease
B. Ectopic ACTH syndrome
B. Ectopic ACTH syndrome
What is the mechanism by which hypokalemic alkalosis develops in patient’s with ectopic ACTH syndrome?
- Cortisol saturates HSD11B2, result in: cortisol-induced MC HTN
- Also have high levels of DOC (deoxycorticosterone) – which is an ACTH dependent MC
High definition CT/MRI scan of thorax, abdomen, and pelvis can be used to detect ______
ectopic ACTH syndrome
Adrenal disease is an example of ___ adrenocortical insufficiency
ACTH deficiency is an example of ___ adrenocortical insufficiency
Primary
Secondary
True or False: Low glucocorticoids and low androgens is found in both ACTH deficiency (secondary adrenocortical insufficiency) and adrenal disease (primary AD insufficiency)
True
Although GC are low in adrenal disease, how is ACTH affected?
ACTH is elevated
Hyperpigementation of skin, progressive weakness and fatigue, as well as GI disturbances suggests which primary adrenocortical insufficiency?
Addison’s Disease
In anterior pituitary corticotrophs, pre-opiomelanocortin (POMC) can be cleaved into which four molecules?
N-terminal protein
Joining protein
ACTH
and B-lipotropin
In melanocytes and hypothalamus, __ is produced, allow for appetite regulation and melanin production
a-MSH
True or False: a-MSH regulates weightloss via acting in the hypothalamus
True
What does it mean if a patient with Addison’s Disease has low cortisol secretion and low ACTH?
A. Secondary adrenocortical insufficiency
B. Primary adrenocortical insufficiency
A. Secondary adrenocortical insufficiency
If a patient has low cortisol secretion and high ACTH. Upon measuring Aldosterone levels, they are low. What is the dx?
A. Secondary adrenocortical insufficiency
B. Primary adrenocortical insufficiency
B. Primary adrenocortical insufficiency
What is responsible for 70% of all cases of Addison’s Disease in the West?
What is responsible for Addison’s disease worldwide?
Autoimmune adrenalitis
Infectious disease
In autoimmune adrenalitis, there are autoimmune antibodies to which two key steroidogenic enzymes?
21-hydroxylase (CYP21A2)
17-hydroxylase (CYP17)
In autoimmune adrenalitis, there are autoantibodies to CYP21A2 , which is found in the Zona __ and Zona ___
In autoimmune adrenalitis, there are autoantibodies to CYP17, which is found in the Zona ___ and Zona ___
- CYP21A2: Zone glomerulosa and Zona fasciculata
- CYP17: Zona fasciculata and Zona reticularis
How can long-term replacement therapy be used to treat Addison’s Disease?
Hydrocortisone/Pred to mimic normal cortisol secretion
- Large dose upon waking
- Small dose at night
___ is a mineralcorticoid replacement and liberal salt intake can be used to treat Addison’s Disease long-term
Fludrocortisone
___ is an androgen replacement in women that can treat Addison’s Disease
DHEA
Three causes of secondary adrenocorticoid insufficiency (pituitary hypofunction)?
1) Pituitary surgery
2) Hypothalamic impaired CRH secretion
3) Pituitary adenoma that comprises normal function - low or absent ACTH
A patient has severe Cushing’s Disease. Surgery cannot be scheduled for several months, so the physician plans to treat patient in interim with a drug she describes as a “potent inhibitor of corticosteroid synthesis.” Which drug best fits that description?
A. Dexamethasone
B. Hydrocortisone
C. Ketoconazole
D. Prednisone
E. Spironolactone
C. Ketoconazole
