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BMS 460 FINAL > Lecture 36 > Flashcards

Lecture 36 Flashcards

1
Q

Working in to out, what are the layers of the adrenal gland?

A
  • Medulla
  • Zona reticularis
  • Zona fasciculata
  • Zona glomerulosa
  • Capsule
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2
Q

What three zones make up the cortex of the adrenal gland?

A
  • Zona reticularis
  • Zona fasciculata
  • Zona glomerulosa
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3
Q

What hormone is produced in the medulla?

A

Epinephrine

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4
Q

What hormones are synthesized in the zona reticularis and zona fasciculata?

A
  • Glucocorticoids (ex. cortisol)
  • Androgens (DHEA and androstenedione)
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5
Q

What hormone is made in the zona gomerulosa?

A

mineralocorticoid (aldosterone)

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6
Q

Which way does blood flow in the adrenal gland?

A

Capsulary artery -> capsule -> medula -> medullary vein

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7
Q

Where does the preganglionic sympathetic terminal of the adrenal gland synapse?

A

The medulla

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8
Q

What are the four basic systems that control stress and disease process?

A
  • Central nervous system
  • Peripheral nervous system (specifically autonomic nervous system)
  • Endocrine system
  • Immune system
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9
Q

What is the process of glucocorticoid synthesis?

A
  • Stress received
  • Hypothalamus secretes Corticotropin Releasing Hormone (CRH) which signals the anterior pituitary
  • Anterior Pituitary secretes Corticotropin (ACTH, 39 aa) which signals the adrenal cortex (specifically zona fasciculata)
  • Adrenal cortex creates 15-30 mg/day of corisol
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10
Q

What kinds of stress can trigger the hypothalamo-pituitary-adrenal cortex axis

A
  • Physical via the Reticular Activating System
  • Emotional via the Limbic System
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11
Q

How is corticotropin (ACTH) released in the anterior pituitary?

A

Through pituitary secretion with a diurnal variation (varied throughout the day

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12
Q

What is the half life of corticotropin (ACTH)?

A

15 minutes

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13
Q

What is the process of mineralocorticoid (aldosterone) synthesis?

A
  • Renal hypoperfusion leads to increased renin production from juxtaglomerular cells (located in the afferent arterioles of the kidney).
  • Renin combines with angiotensinogen to create Angiotensin I
  • Angiotensin-Converting Enzyme (ACE) from pulmonary vasculature combines with Angiotensin I to create Angiotensin II
  • Angiotensin II reaches the zona glomerulosa where it stimulates aldosterone secretion, which increases renal reabsorption of sodium and potassium excretion
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14
Q

What are the other uses of Angiotensin II?

A
  • Kidneys: Decreased perfusion and filtration, increased sodium reabsorption and potassium excretion
  • Hypothalamus: Increased thirst
  • Vascular smooth muscle cells: Systemic vasoconstriction
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15
Q

What is the system called that creates aldosterone?

A

Renin-Angiotensin-Aldosterone system

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16
Q

Where is the aldosterone stimulating in the kidney?

A

Distal (convoluted) tubule

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17
Q

Where are the secondary sites of aldosterone stimulation?

A
  • Proximal portion of kidney
  • Intestinal mucosa
  • Salivary glands
  • Sweat glands
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18
Q

What is the order of flow for the nephron?

A

Brush border -> thin descending limb of loop of Henle -> Thick ascending limb of loop of Henle -> distal convoluted tubule -> intercalated cells -> principal cells -> Medullary collecting tubule

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19
Q

Increasing potassium excretion is the minor effect of ACTH

A

TRUE

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20
Q

How do glucocorticoid drugs and cortisol effect mineralocorticoid activity?

A

Increase in salt and water retention as it increases the mineralocorticoid activity

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21
Q

How does sodium flow through renal tubular cells when mineralocorticoid receptors are activated?

A

Flows in from the tubular fluid and is excreted through paired diffusion with potassium into the peritubular capillary

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22
Q

How does potassium flow through renal tubular cells when mineralocorticoid receptors are activated?

A

It enters the cell through the peritubular capillary via paired diffusion with sodium, where it then flows out of the cell to the tubular fluid, maintaining a voltage of -40mV in the tubular fluid

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23
Q

What is the process of synthesizing aldosterone-induced proteins?

A
  • Mineralocorticoid receptor is activated
  • mRNA is created due to receptor activation, which encode for AIPs
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24
Q

What are the effects of AIPS?

A
  • Regulate the flow of sodium and potassium through the cell.
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25
Q

What can inhibit mineralocorticoid receptor binding?

A

Spironolactone

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26
Q

How does cortisol’s anti-inflammatory effect work?

A
  • Cortisol combines with phospholipase A2 to convert membrane phospholipids into arachidonic acid.
  • However, cortisol inhibits cyclo-oxygenase meaning prostaglandins are not formed from the arachidonic acid
  • Only leukotrines are created via reacting arachidonic acid with lipoxygenase
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27
Q

Cortisol exerts mainly catabolic actions

A

TRUE - with the exception of the liver, where it exerts anabolic actions

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28
Q

What are the effects of cortisol on the liver?

A
  • Gluconeogenesis
  • Potentiates actions of epinepherine and glucagon
  • Glycogenesis
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29
Q

What are the effects of cortisol on skeletal muscle?

A
  • Inhibits glucose uptake
  • Glycogenesis
  • Protein catabolism
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30
Q

What are the effects of cortisol on adipose tissue?

A
  • Inhibits glucose uptake
  • Lipolysis
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31
Q

How doe cortisol increase blood pressure?

A
  • Facilitates activity of SNS by increasing expression of alpha and beta adrenergic receptors in multiple tissues
  • At increased levels cortisol exerts mineralocorticoid actions on kidneys, which stimulates renal sodium reabsorption and increases plasma volume.
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32
Q

How does cortisol weaken bones?

A

At supraphysiologic levels cortisol reduces intestinal calcium absorption which precipitates an increase in PTH and causes osteoclastic activity.

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33
Q

What are the genomic actions of glucocorticoids?

A

Slows changes in gene expression that alter cellular function

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34
Q

How do genomic actions of glucocorticoids occur?

A
  • Cytosolic glucocorticoid receptors (GR) change the gene express (increase/decrease)
  • Transactivation through interaction of GC-GR with positive GC Response Element (pGRE)
  • Transrepression through interaction of GC-GR with negative GC Response Element (nGRE)
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35
Q

What is the non-genomic action of glucocorticoids?

A

Rapid changes in cellular function that do not involve changes in gene expression

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36
Q

How do non-genomic actions of glucocorticoids occur?

A
  • Multiple mechanisms mediated by cystolic GR, plasma membrane-bound Gr, and non-specific effects caused by GC interactions with cell membranes resulting in transmembrane currents, phosphorelation events, and calcium level changes
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37
Q

What is the pathway of steroidogenesis that creates C-21 Mineralocorticoids?

A
  • Cholesterol degraded into pregnenolone
  • Pregnenolone is synthesized into Progesterone using 3B-hydroxysteroid dehydrogenase/isomerase
  • Progesterone is synthesized into 11-deoxycorticosterone using 21a-hydroxylase (CYP21)
  • 11-deoxycorticosterone is synthesized into corticosterone using 11B-hydroxylase (CYP11B2)
  • Corticosterone is synthesized into Aldosterone using 18-hydroxylase (CYP18B2/CYP11B2) and aldosterone synthase (which is activated via Angiotensin II)
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38
Q

What is the pathway of steroidogenesis that creates C-21 Glucocorticoids and Cortisone?

A
  • Cholesterol degraded into pregnenolone
  • Pregnenolone is synthesized into Progesterone using 3B-hydroxysteroid dehydrogenase/isomerase
  • Pregnenolone is synthesized into 17-Hydroxypregnenolone using 17a-hydroxylase (CYP17)
  • Progesterone is synthesized into 17-Hydroxyprogesterone using 17a-hydroxylase (CYP17)
  • 17-Hydroxyprenenolone is also synthesized into 17- Hydroxyprogesterone using 3B-HSD
  • 17-Hydroxyprogesterone is synthesized into 11-deoxycortisol using 21a-hydroxylase (CYP21)
  • 11-Deoxycortisol is synthesized into cortisol using 11B-hydroxylase (CYP11B1)
  • Cortisol is synthesized into inactive cortisone using 11B-HSD2
  • Cortisone is synthesized into cortisol using 11B-HSD1
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39
Q

What is the pathway of steroidogenesis that creates C-19 Androgens?

A
  • Cholesterol degraded into pregnenolone
  • Pregnenolone is synthesized into Progesterone using 3B-hydroxysteroid dehydrogenase/isomerase
  • Pregnenolone is synthesized into 17-Hydroxypregnenolone using 17a-hydroxylase (CYP17)
  • Progesterone is synthesized into 17-Hydroxyprogesterone using 17a-hydroxylase (CYP17)
  • 17-Hydroxyprenenolone is also synthesized into 17- Hydroxyprogesterone using 3B-HSD
  • 17-Hydroxypregnenolone is synthesized into Dehydroepiandrosterone using 17,20-lyase (CYP17)
  • 17-Hydroxyprogesterone is synthesized into Androstenedione using 17,20-lyase (CYP17)
  • Dehydroepiandrosterone is also synthesized into Androstenedione using 3B-HSD
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40
Q

What is the pathway of steroidogenesis that creates C-18 Estrogens?

A
  • Cholesterol degraded into pregnenolone
  • Pregnenolone is synthesized into Progesterone using 3B-hydroxysteroid dehydrogenase/isomerase
  • Pregnenolone is synthesized into 17-Hydroxypregnenolone using 17a-hydroxylase (CYP17)
  • Progesterone is synthesized into 17-Hydroxyprogesterone using 17a-hydroxylase (CYP17)
  • 17-Hydroxyprenenolone is also synthesized into 17- Hydroxyprogesterone using 3B-HSD
  • 17-Hydroxypregnenolone is synthesized into Dehydroepiandrosterone using 17,20-lyase (CYP17)
  • 17-Hydroxyprogesterone is synthesized into Androstenedione using 17,20-lyase (CYP17)
  • Dehydroepiandrosterone is also synthesized into Androstenedione using 3B-HSD
  • Androstenedione is synthesized into Estrone using FSH and aromatase
  • Androstenedione is synthesized into testosterone using 17B-hydroxysteroid dehydrogenase/Oxidoreductase
  • Dehydroepiandrosterone is also synthesized into androstenediol using 17B-hydroxysteroid dehydrogenase/oxidoreductase type 1
  • Androstenendiol is synthesized into testosterone using 3B-HSD
  • Testosterone is synthesized into Estradiol using aromatase
  • Estadiol and estrone spontaneously transform into each other
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41
Q

What is the pathway of steroidogenesis that creates Dihydrotestosterone?

A
  • Cholesterol degraded into pregnenolone
  • Pregnenolone is synthesized into Progesterone using 3B-hydroxysteroid dehydrogenase/isomerase
  • Pregnenolone is synthesized into 17-Hydroxypregnenolone using 17a-hydroxylase (CYP17)
  • Progesterone is synthesized into 17-Hydroxyprogesterone using 17a-hydroxylase (CYP17)
  • 17-Hydroxyprenenolone is also synthesized into 17- Hydroxyprogesterone using 3B-HSD
  • 17-Hydroxypregnenolone is synthesized into Dehydroepiandrosterone using 17,20-lyase (CYP17)
  • 17-Hydroxyprogesterone is synthesized into Androstenedione using 17,20-lyase (CYP17)
  • Dehydroepiandrosterone is also synthesized into Androstenedione using 3B-HSD
  • Androstenedione is synthesized into testosterone using 17B-hydroxysteroid dehydrogenase/Oxidoreductase
  • Dehydroepiandrosterone is also synthesized into androstenediol using 17B-hydroxysteroid dehydrogenase/oxidoreductase type 1
  • Androstenendiol is synthesized into testosterone using 3B-HSD
  • Testosterone is synthesized into dihydrotestosterone using 5a-reductase from peripheral tissues
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42
Q

What controls the rate-limiting step of cholesterol catalysis?

A

StAR (steroidogenic acute regulatory protein) which mediates transport of cholesterol from the outer to inner mitochondrial membrane where P450scc is located

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43
Q

What is the rate limiting step of cholesterol catalysis?

A

CYP11A (cholesterol desmolase/P450scc enzyme)

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44
Q

Where does the majority of the cholesterol for steroidogenesis come from?

A

About 80% of cholesterol comes from LDL-cholesterol. Alternatively, steroidogenic cells can synthesized cholesterol de novo from acetate

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45
Q

What major hormones are used during cholesterol catalysis?

A

ACTH (corticotropin) and LH (leutinizing hormone)

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46
Q

What are the C-21 Progestagens?

A

Pregnenolone, progesterone, 11-deoxycorticosterone

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47
Q

How many carbons in cholesterol?

A

27

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48
Q

What are the C-21 mineralocorticoids?

A

Corticosterone, aldosterone

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49
Q

What are the C-21 Glucocorticoids?

A

17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol

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50
Q

What are the C-19 Androgens?

A

Dehydroepiandrosterone, Androstendione

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51
Q

What are the 17-keto steroids?

A

Dehydroepiandrosterone, androstenedione

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52
Q

What are the 17-hydroxy corticoids?

A

11-deoxycortisol, cortisol

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53
Q

What are the C-18 Estrogens?

A

Estrone, Estradiol

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54
Q

What molecules are synthesized in the zona glomerulosa?

A

C-21 mineralocorticoids

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55
Q

What molecules are synthesized in the zona fasciculata?

A

C-21 Glucocorticoids

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56
Q

What molecules are synthesized in the zona reticularis?

A

C-19 Androgens

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57
Q

Where is 11B-HSD1 expressed?

A

It is expressed in glucocorticoid target tissues where it is reversible.

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58
Q

Where is 11B-HSD2 expressed?

A

It is expressed in the kidney where it irreversibly catalyzes cortisol into inactive cortisone, which allows aldosterone to regulate non-specific mineralocorticoid recetors without interference from cortisol

59
Q

C-19 Androgens are considered weak androgens

A

TRUE - they are used to produce strong androgens

60
Q

What is a disorder of the zona glomerulosa?

A

Hyperaldosteronism - usually due to enzyme mutation/hypefunction or tumors

61
Q

What is a disorder of the zona fasciculata?

A

Hypercortisolism (Cushing’s syndrome) - usually due to enzyme mutation/hypefunction or tumors

62
Q

What is a disorder of the zona reticularis?

A

Adrenogenital syndrome

63
Q

What is a disorder of the medulla of the adrenal gland?

A

Pheochromocytoma

64
Q

What results in Addison’s disease?

A

Hypofunction/insufficiencey of zona fasciculata and zona glomerulosa

65
Q

When is the human fetal hypothalamic-pituitary-adrenal axis fully functional?

A

When genitalia differentiate

66
Q

What is required for normal sexual differentiation?

A

Timing and balance of fetal cortisol and androgen secretion

67
Q

What does enzymatic mutations in adrenal steroidogenic pathways result in?

A

Secondary effects on sex steroid production and have lasting effects on sexual differentation

68
Q

What is congenital adrenal hyperplasia?

A

21- and/or 11-hydroxylase deficiency, which impairs the synthesis of cortisol and aldosterone

69
Q

What does the decrease in feedback inhibition due to 21- and/or 11- hydroxylase deficiency effect?

A

Increases secretion of ACTH, leading to incrased testosterone -> virilization and adrenogenital syndrome.

70
Q

What does a deficiency in 3B-Hydroxysteroid dehydronase affect?

A
  • No glucocorticoids, mineralocorticoids, androgens, and estrogens
  • Salt excretion in urine
  • Early death
71
Q

What does a deficiency in 21a-Hydroxylase affect?

A
  • Most common form of CAH
  • Usually a partial deficiency
  • ACTH elevated, causing an incresed shift to sex hormones and masculinization
72
Q

What does a deficiency in 11B-Hydroxylase affect?

A
  • Decresased cortisol, aldosterone, corticosterone
  • Increased deoxycorticosterone leading to fluid retention and hypertension
  • Masculinization
73
Q

Mutations affecting enzymes primarily responsible for the production of cortisol and mineralocorticoids can have secondary effects on sex steroid prodution.

A

TRUE - the steroids that can no longer create the cortisol/mineralocorticoids can still be used for the creation of sex steroids, which is now its primary pathway.

74
Q

Sequelae of 21-hydroxylse deficiency CAH

A
  1. Salt waster (75%) (salt loss leading to vomiting, weight loss, adrenal crisis and failure to thrive -> hyponatremic encephalopathy)
  2. Virilizers (25%) (Adrenogenital syndrome + dependent on sex)
  3. Non-classics (<1%)
75
Q

What is hyponatremic encephalopathy?

A

Sodium levels in blood become very low -> water to enter brain cells and cause them to swell -> increased pressure and potential herniation

76
Q

Symptoms of hyponatremic encephalopathy

A
  • Headache
  • Nausea
  • Vomiting
  • Confusion
  • Seizures
  • Brain stem compression and respiratory arrest
  • Non-cardiogenic accumulation of fluid in lungs
  • Fatal if not immediately treated
77
Q

What is Adrenogenital Syndrome?

A

Virilization continues after birth, resulting in rapid bone growth and maturation

78
Q

How does Adrenogenital Syndrome affect females?

A
  • Pseudohermaphrodites
  • Progressive masculinization, hirsutism (growth of hair in place men usually get hair but women don’t), epiphyseal closure
  • Secondary amenorrhea/oligomenorrhea
79
Q

How does Adrenogenital Syndrom affect males?

A
  • Appear normal at birth
  • Somatic and sexual precocity <2-3 years
  • “Little Hercules”
80
Q

What do laboratory studies show comes with a 21-hydroxylase deficiency?

A
  • Hyponatremia (low sodium) (due to hypoaldosteronism)
  • Hyperkalemia (high potassium (due to hypoaldosteronism)
  • Hypoglycemia (due to hypocortisolism)
  • Elevated 17a-OH P (17a-hydroxyprogesterone) > 240 nmol/L (may not occur in mild cases, but will rise during a corticotropin (ACTH) stimulation test)
81
Q

What is a normal value for an infant for 17a-OH P?

A

<3 nmol/L. Many neonatal screening programs have specific ranges because high levels may be seen in premies without CAH

82
Q

21-hydroxylase deficiency is the most common cause of CAH

A

TRUE - 90-95% cases are caused by 21-hydroxylase deficiency

83
Q

What is 17a-hydroxylase deficiency-induced hyperaldosteronism?

A

Deficiency shunts precursors into the aldosterone pathway only, as it is a bifunctional enzyme, and can lead to hypertension.

84
Q

What are the causes of primary adrenocortical insufficiency?

A
  • Hyposecretion of adrenal cortex
  • Autoimmune (ex. antibodies to several steroidogenic enzymes with destruction of steroidogenic cells)
  • Genetic (ex. adrenal insufficiency without neurologic disease in adrenoleukodystrophy)
  • Infections (ex. tuberculosis)
  • Injury (Addison Disease)
85
Q

What is adrenoleukodystrophy?

A

A rare genetic disorder that affects the nervous system and adrenal glands, causing adrenocortical insufficiency

86
Q

What are symptoms of Addison Disease?

A
  • Lethargy
  • Easy fatigability
  • Depression
  • Nausea, vomiing
  • Hyperpigmentation
  • Weight loss
  • Arrhythmia
  • Postural hypotension
  • Syncope
  • Amenorrhea
  • Abdominal pain
  • Diarrhea/constipation
  • Anorexia
  • Muscle weakness/atrophy
87
Q

What are the lab results of Addison Disease?

A
  • Decreased corticosteroids
  • Increased ACTH and potassium
  • Decreased sodium, chlorine, bicarbonate, and glucose
88
Q

Why do Addison Disease Symptoms occur?

A

Results from the deficiency of glucocorticoids and mineralocorticoids. Adrenal androgens also missing, but is less obvious clinically

89
Q

What are the causes of secondary adrenocortical insufficiency?

A
  • Inadequate secretion of ACTH (anterior pituitary)
  • Iatrogenic: prolonged exogenous corticosteroid therapy
90
Q

What are the causes of tertiary adrenocortical insufficiency?

A

Lack of CRH secretion (hypothalamus), injury, and disease

91
Q

Cause of generalized hyperpigmentation with vitiligo in Addison Disease?

A

When ACTH is cleaved from POMC (pro-opiomelanocortin), melanocyte-stimulatin hormone (MSH) is concurrently released. Both MSH and ACTH bind to Melanocortin 1 receptor on melanocytes and cause hyper-pigmentation of the skin.

92
Q

What is the cause of primary hypercortisolism?

A

Hyperfunction of adrenal cortex

93
Q

What is the causes of secondary hypercortisolism?

A
  • Hyperfunction of ACTH-secreting cells (corticotrophs in the anterior pituitary)
  • Cushing Disease aka Itsenko-Cushing Disease
94
Q

What is the cause of tertiary (hypothalamus) hypercortisolism?

A
  • CRH hypersecretion
95
Q

What is a mnemonic to remember important features of Cushing Syndrome?

A

ADIPOSE:
- Adiposity
- Diabetes
- Infertility
- Pychologic problems
- Osteoporosis and muscle wasting
- Skin changes
- Elevated blood pressure

96
Q

What is the process of Pituitary Cushing Syndrome?

A

Tumor in anterior pituitary -> hypersecretion of ACTH -> adrenal hyperplasia -> cortisol hypersecretion

97
Q

What is the process of Adrenal Cushing Syndrome?

A

Both nodular hyperplasia and tumors of the adrenal gland will cause hypersecretion of cortisol

98
Q

What is the process of Paraneoplastic Cushing Syndrome?

A

Lung or nonendocrine cancer -> hypersecretion of ACTH -> adrenal hyperplasia -> hypersecretion of cortisol

99
Q

What is the process of Iatrogenic Cushing Syndrome?

A

Patient takes steroids which leads to Cushing Syndrome and adrenal atrophy

100
Q

Are ACTH-secretin pituitary adenomas responsive to its feedback mechanism?

A

It is only partially responsive to the feedback suppression of CRH.

101
Q

Does paraneoplastic tumors respond to its feedback mechanism?

A

No, since they don’t have the corresponding receptors and ACTH is produced out side the hypothalamic-pituitary axis

102
Q

Why is it important ectopic tumors don’t respond to cortisol?

A

Because the high levels of cortisol that is created to control the ACTH secretion will completely shut off ACTH from pituitary glands

103
Q

Why does adrenal atrophy happen?

A

Because of low ACTH secretion (such as with chronic corticoid therapy)

104
Q

How to diagnose Cushing Syndrome?

A
  • Increased urinary free cortisol must be present
    -Failure of serum cortisol to be suppressed to <5 micrograms/dL in response to low-dose dexamethasone
105
Q

What laboratory tests are used in diagnosing Cushing syndrome?

A
  • Free cortisol in urine collected over 24 hours (best and first screening for Cushing from simple obesity)
  • Low dose (1-2 mg) dexamethasone suppression test (injected IV in a low dose at bed time and tested to see if suppresses normal morning rise of cortisol)
  • High-dose (8mg) dexamethasone suppression test (injected to test pituitary adenoma vs. ectopic tumor ACTH suppression)
106
Q

What are the laboratory value increases due to Cushing Syndrome?

A

Increased cortisol, insulin (leads to acanthosis nigricans), Glucose, Sodium and red blood cells

107
Q

What are the symptoms of Cushing syndrome?

A
  • Pituitary adenoma (70%)
  • Depression
  • Mood changes
  • Thinning of hair
  • Moon facies (round and puffy face due to swelling of fat deposits on sides of face)
  • Androgen based hirsutism
  • Buffalo hump (buildup of fat between shoulder blades)
  • Acanthosis nigricans (dark velvety patches due to insulin spill over)
  • Hypertension
  • Adrenal lesion (hyperplasia or tumor)
  • Cetral obesity
  • Abdominal striae and stretch marks
  • Amenorrhea
  • Muscle weakness and atrophy
  • Ecchymoses and thin skin (Large bruising that changes colors (red-> blue-green-> gold-brown))
  • Poor wound healing
108
Q

How does the body react after adrenal or pituitary tumor removal or treatment?

A

Body returns to physiological state

109
Q

What is Conn syndrome?

A

Primary hypo-reninemic hyperaldosteronism, often caused by a tumor.

110
Q

What is the pathway for secondary hyper-reninemic hyperaldosteronism?

A

Renin increased, which increases angiotensin II and increases aldosterone

111
Q

What is the result of hyperaldosteronism?

A

Sodium and water retention, potassium excretion

112
Q

What is the effect of aldosterone on kidneys?

A

Acts on distal renal tubule to promote sodium exchange for the potassium lost in urine

113
Q

What does higher sodium and water retention do?

A
  • Increased sodium in plasma
  • Increased extracellular fluid volume (hypervolemia) -> increased cardiac output
  • In Conn Syndrome, decreased Renin
  • Hypertension
114
Q

What does higher potassium excretion levels do?

A
  • Lowered potassium in plasma
  • Vasoconstriction -> increased cardiac output
  • Hypertension
115
Q

What is a pheochromocytoma?

A

In most instances, a functionally active tumor that secretes epinepthrine and norepinephrine, resulting in hypertention and related paroxysmal sympathetic effects

116
Q

What is a paroxysmal sympathetic effect?

A

A spasm of muscles that are innervated by the sympathetic nervous system.

117
Q

What pheochromocytomas are familial?

A
  • Mutations in VHL, RET, NF1 (Gene 17 Neurofibromatosis type 1),SDHB and SDHD
  • If it is a tumor of multiple endocrine neoplasia syndrome type IIA or Type IIB
  • Up to 25% of pheochromocytomas are familial
118
Q

When is a pheochromocytoma suspected?

A

Hypertension is diagnosed in a young person that does not respond to standard antihypertensive treatment and is episodic

119
Q

Can paroxysms of hypertension be triggered?

A

Yes, by exercise, anesthesia or even palpation of the abdomen

120
Q

How are pheochromocytomas treated?

A

Surgically with excellent prognosis (90% benign)

121
Q

What is the term for characteristic nests of cells with abundant cytoplasm?

A

Zellballen

122
Q

What are Autoimmune Polyendocrine Syndromes (APS)?

A

Forms of autoimmune adrenalitis, which is the most common cause of primary adrenal insufficiency in developed countries

123
Q

What are other names for APS1?

A
  • Autoimmune polyendocrinopathy
  • Canidiasis
  • Ectodermal dystrophy
  • Whitaker Syndrome
124
Q

What are the symptoms of APS 1?

A
  • Chronic mucocutaneous candidiasis
  • Abnormalities of skin
  • Abnormal dental enamel
  • Absnormal nails (ectodermal dystrophy)
  • Organ-specific autoimmune disorders
125
Q

What is chronic mucocutaneous candidiasis?

A

A rare, hereditary immune disorder that causes chronic infections with the Candida fungus (skin, nails, mucous membranes)

126
Q

What disorders is Whitaker Syndrome a combination of?

A
  • Autoimmune adrenalitis
  • Autoimmune hypoparathyroidim
  • Idiopathic hypogonadism
  • Pernicious anemia

All result in immune destruction of target organs

127
Q

What is the cause of APS1?

A

Mutations in the autoimmune regulator (AIRE) gene on chromosome 21q22

128
Q

When does APS 2 start?

A

Early adulthood

129
Q

What does APS2 present as?

A
  • Adrenal insufficiency
  • Autoimmune thyroiditis or type 1 diabetes
130
Q

What is the cause of APS2?

A

It is more heterogeneous, but has not been linked to one gene.

131
Q

APS 2 is the most common form of the polyglandular failure syndromes

A

TRUE

132
Q

What all is left after the destruction of the adrenal gland due to autoimmune adrenalitis?

A

Subcapsular rim of cortical cells and extensive mononuclear cell infiltrate.

133
Q

What is another name for APS2?

A

Schmidt Syndrome

134
Q

What are Multiple Endocrine Neoplasia syndromes?

A

A group of genetically inherited diseases resulting in proliferative lesions (hyperplasia, adenomas and carcinomas) of multiple endocrine organs

135
Q

What is MEN1?

A

Germline point mutations of the MEN1 tumor suppressor gene that normally enhances signalling through TGF-Beta to decrease cell proliferation and enhance p53 function

136
Q

What is involved in MEN1?

A
  • Parathyroid (in all cases)
  • Pancreas
  • Pituitary involved 3Ps
137
Q

What is MEN2?

A

Activating germ line mutations of RET protooncogene encoding tyrosine kinase receptor

138
Q

What is affected in MEN2A?

A
  • Thyroid (all cases)
  • Parathyroid
  • Adrenal medulla
139
Q

What is affected in MEN2B?

A
  • Thyroid (all cases)
  • Adrenal medulla
  • GI ganglia
140
Q

What are the distinct features of MEN syndrome tumors compared to sporadic tumors?

A
  • Occur at a younger age
  • Arise in multiple endocrine organs either synchronously or metachronously (different times)
  • Even in one organ the tumor is often multifocal
  • Tumors are usually preceded by an asymptomatic stage of endocrine hyperplasia
  • Tumors are usually more aggressive and recur in a higher proportion of cases
141
Q

How are MEN2 patients managed?

A

Prophylactic thyroidectomy because of near certainty of their developing medullary thyroid carcinoma, a potentialy deadly cancer of C-cells

142
Q

How does the spectrum of MEN1 extend beyond the 3Ps (parathyroid, pancreas, pituitary)?

A
  • Duodenum is the most common site of gastrinomas (far in excess of frequency of pancreatic gastrinomas)
  • Carcinoid tumors
  • Thyroid adenomas
  • Adrenocortical adenomas
143
Q

What happens in MEN1 with loss-of-function mutations of RET?

A
  • Intestinal anganglionosis
  • Hirschsprung disease
144
Q

What is Hirschsprung disease?

A

Nerve cells of the large intestine don’t develop properly before birth, leading to limited or absence of peristalsis.

BMS 460 FINAL (11 decks)

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