M&n Week 4: Pathology Of The Adrenal Cortex

Front 1

The adrenal cortex is derived from what tissue?

Back 1

Urogenital ridge

Front 2

What causes the adrenal cortex to be yellow-brown?

Back 2

1. Lipochrome pigment
2. Lipid precursors of steroid hormones

Front 3

Describe the opposite effects that acute stress and prolonged stress have on the adrenal cortex.

Back 3

Acute stress --> decreased weight

Prolonged stress --> increased weight (2 x normal)

Front 4

List the 3 layers that compose the adrenal cortex.

Back 4

1. Zona glomerulosa
2. Zona fasciculata
3. Zona reticularis

Front 5

Which layer of the adrenal cortex is the most abundant?

Back 5

Zona fasciculata
(75% of total cortex)

Front 6

What group of hormones are produced within the zona glomerulosa?

Back 6

Mineralcorticoids

Front 7

What is the function of aldosterone?

Back 7

Promotes:
1. Na+ reabsorption (water follows)
2. K+ excretion

Front 8

How is mineralcorticoid secretion primarily regulated?

Back 8

1. Serum K+ levels
2. Renin-angiotensin-system

Front 9

Under normal conditions, what is the effect of ACTH on mineralcorticoid secretion?

Back 9

No significant effect

Front 10

What types of hormones are produced within the zona fasciculata?

Back 10

1. **Glucocortiods
2. Androgens

Front 11

What hormone regulates the secretion of cortisol and sex steroids?

Back 11

ACTH

Front 12

What stimulates pituitary corticotrophs to release ACTH?

Back 12

Hypothalamic CRH

Front 13

What is the effect of cortisol on the hypothalamus and pituitary gland?

Back 13

Negative feedback
(inhibits CRH and ACTH)

Front 14

List 3 very general causes of adrenocortical hyperfunction.

Back 14

1. Cortical hyperplasia
2. Cortical adenoma
3. Cortical carcinoma

Front 15

Cortical hyperplasia is usually caused by...?

Back 15

Hypersecretion of ACTH

Front 16

Is cortical hyperplasia typically unilateral or bilateral?

Back 16

Bilateral
(usually caused by increased secretion of ACTH-- so adrenal glands are secondarily affected).

Front 17

Are cortical adenomas usually functional or non-functional?

Back 17

Most commonly non-functional

Front 18

Are cortical carcinomas usually functional or non-functional?

Back 18

Functional

*HIGHLY MALIGNANT

Front 19

Excess glucocorticoids can result in what syndrome?

Back 19

Cushing syndrome
(hypercortisolism)

Front 20

List the 4 forms of Cushing syndrome

Back 20

1. Pituitary
2. Adrenal
3. Paraneoplastic (usually lung cancer)
4. Iatrogenic

Front 21

Describe the two causes of adrenal Cushing syndrome.

Back 21

1. Neoplasm
2. Bilateral nodular hyperplasia

Front 22

What is the result of a cortical neoplasm on the size of the adrenal glands?

Back 22

While one adrenal gland is enlarged due to the tumor, the contralateral adrenal gland becomes atrophic

Front 23

Describe the serum level of ACTH in primary hypercortisolism.

Back 23

Low serum ACTH
(negative feedback inhibition of excess cortisol)

Front 24

What type of Cushing syndrome is ACTH-independent?

Back 24

Primary (neoplastic).

Front 25

If cortisol levels do not decrease with dexamethasone, what type of syndrome is suspected?

Back 25

Primary hypertcortisolism-- Cushing syndrome

Front 26

The majority of cases of endogenous hypercortisolism are caused by...?

Back 26

ACTH-producing pituitary adenomas (Secondary hypercortisolism)
(70% endogenous cases)

Front 27

Pituitary Cushing syndrome will have what effect on the serum levels of ACTH?

Back 27

HIGH serum ACTH

Front 28

Does Pituitary Cushing syndrome have unilateral or bilateral effects on the adrenal glands?

Back 28

Bilateral hyperplasia

Front 29

If cortisol levels decrease with administration of dexamethasone, what type of syndrome is suspected?

Back 29

Pituitary Cushing syndrome
(dexamethosone suppresses pituitary ACTH)

Front 30

Will serum ACTH levels be high or low in primary hypercortisolism?

Back 30

Low

Front 31

Does paraneoplastic Cushing syndrome result in unilateral or bilateral cortical hyperplasia?

Back 31

Bilateral

Front 32

In the case of Paraneoplastic Cushing syndrome, will cortisol levels decrease upon administration of dexamethasone?

Back 32

NO

Front 33

Are serum levels of ACTH high or low in Paraneoplastic Cushing syndrome?

Back 33

High

Front 34

What is the most common cause of Cushing syndrome?

Back 34

Iatrogenic
(administration of exogenous glucocorticoids)

Front 35

Which form of Cushing syndrome results in bilateral adrenal cortical atrophy?

Back 35

Iatrogenic Cushing syndrom
(due to suppression of pituitary ACTH by administered glucocorticoids)

Front 36

What is the effect of iatrogenic hypercortisolism on serum levels of ACTH?

Back 36

LOW

Front 37

What hormone regulates adrenal androgen formation?

Back 37

ACTH

Front 38

Group of inherited metabolic errors caused by a deficiency of a particular enzyme in the biosynthesis of cortical steroids.

Back 38

Congenital adrenal hyperplasia

Front 39

What are the common results of the metabolic errors seen in all forms of congenital adrenal hyperplasias?

Back 39

1. Block or partial block in the production of cortisol, resulting in a shunt steroid pathway toward androgen production
2. Decreased feedback inhibition on pituitary (CRH and ACTH not inhibited)
3. Increased serum ACTH
4. Bilateral cortical hyperplasia
5. Increased synthesis of testosterone

Front 40

What is the most common cause of Congenital Adrenal Hyperplasia?

Back 40

21-hydroxylase deficiency
(90% cases)

Front 41

What is the result of a 21-hydroxylase deficiency in females?

Back 41

Virilization of external genitalia in infants
(ambiguous genitalia)

*High levels of testosterone

Front 42

What is the result of a 21-hydroxylase deficiency in males?

Back 42

1. Precocious puberty
2. exaggerated secondary sex characteristics

(high levels of testosterone)

Front 43

Which enzyme deficiency results in virilization and salt-loss?

Back 43

Total 21-hydroxylase deficiency

*Deficient cortisol AND aldosterone production

Front 44

Is a 21-hydroxylase deficiency easier to diagnose in females or males? Why?

Back 44

Females-- recognized soon after birth due to virilization of external genitalia

(Male infants come to clinical attention because of salt-losing crises-- hyponatremia, hyperkalemia)

Front 45

What is the effect of a 21-hydroxylase deficiency on blood pressure?

Back 45

Hypotension
(deficient aldosterone)

Front 46

What is the effect of 11-hydroxylase deficiency on blood pressure?

Back 46

Hypertension

Front 47

Which steroidogenic enzyme deficiency results in virilization and hypertension?

Back 47

11-hydroxylase

Front 48

Which enzyme deficiency results in hypernatremia, hypokalemia, and hypertension?

Back 48

11-hydroxylase

Front 49

Are the consequences of androgen-producing tumors more obvious in males or females?

Back 49

Typically more obvious in females
(virilizing and defiminaizing symptoms)

Front 50

What is the effect of excess aldosterone on serum sodium and potassium levels?

Back 50

1. Sodium retention --> hypernatremia, hypertension
2. Potassium excretion --> hypokalemia, hypokalemic alkalosis, increased urine K+

Front 51

Secondary hyperaldosteronemia is caused by ..?

Back 51

Activation of renin-angiotensin system

Front 52

Is plasma renin activity increased or decreased with primary hyperaldosteronemia?

Back 52

Decreased
(autonomous overproduction of aldosterone results in suppression of renin-angiotensin system)

Front 53

What are some symptoms associated with hypokalemia?

Back 53

1. Chronic fatigue
2. Neuromuscular symptoms (weakness, paralysis)
3. Cardiac arrhythmias

Front 54

What syndrome is caused by excess aldosterone?

Back 54

Conn Syndrome
(primary hyperaldosteronemia)

Front 55

Conn syndrome is most frequently seen in which individuals?

Back 55

Middle-aged females
(excess aldosterone)

Front 56

What type of tumor is usually (2/3 cases) seen in Conn syndrome?

The remainder of cases are associated with what condition?

Back 56

Solitary aldosterone-secreting adenoma
< 2 cm in size

Minority cases --> bilateral cortical hyperplasia

Front 57

How do the cortical adenomas associated with Conn syndrome differ from those seen in Cushing syndrome?

How does this difference affect the sizes of the adrenal glands?

Back 57

Conn syndrome = aldosterone-secreting tumors do not usually surpress ACTH secretion
Contralateral adrenal gland NOT atrophic

Primary Cushing Syndrome = cortisol-producing tumors result in ACTH supression
Contralateral adrenal gland ATROPHIC

Front 58

What is the effect of secondary hyperaldosteronemia on plasma renin levels?

Back 58

Increased plasma renin
(due to activation of renin-angiotensin system)

Front 59

List 3 conditions that can cause secondary hyperaldosteronemia.

Back 59

1. Renal hypoperfusion (ischemia)
2. Arterial hypovolemia
3. Renin producing tumors

Front 60

Hypernatremia, hypokalemia, and high serum renin would indicate which condition?

Back 60

Secondary hyperaldosteronemia

Front 61

List 2 general causes of adrenal insufficiency.

Back 61

1. Primary adrenal disease
2. Deficiency of ACTH

Front 62

Primary chronic adrenocortical insufficiency is known as what disease?

Back 62

Addison disease

Front 63

What percentage of the adrenal cortex must be destroyed for symptoms of Addison's disease to arise?

Back 63

90%

Front 64

What sort of symptoms are associated with Addison disease?

Back 64

(adrenocortical insufficiency)

1. Progressive weakness and fatigue
2. GI problems (anorexia, weight loss, nausea/vomiting, diarrhea)
3. Hypotension
4. Hyperpigmentation

Front 65

What causes hyperpigmentation seen in Addison disease?

Back 65

Increased levels of ACTH precursor (pro-opiomelanocortin produced in the pituitary)

Front 66

What sort of clinical manifestations are seen in Addison disease?

Back 66

1. Decreased mineralcorticoid levels --> hyponatremia, hyperkalemia, volume depletion, hypotension

2.Decreased glucocorticoid levels --> hypoglycemia

Front 67

How is the diagnosis of Addison disease made?

Back 67

1. Decreased serum and urine cortisol
2. Lack of adrenal response to ACTH stimulation

Front 68

List 4 possible causes of Addison disease.

Which is the most common?

Back 68

1. Autoimmune adrenalitis <-- MOST COMMON
2. TB
3. AIDS
4. Metastatic cancers

Front 69

What two syndromes may Addison's disease be associated with?

Back 69

1. Autoimmune Polyendocrine Syndrome type 1 (APS1)
2. Autoimmune Polyendocrine Syndrome type 2 (ASPS2)

Front 70

Autoimmune polyendocrine syndrome Type 2 is also known as..?

Back 70

Schmidt's syndrome

Front 71

Which autoimmune polyendocrine syndrome is associated with polymorphisms in HLA loci?

Back 71

Type 2

Front 72

Which autoimmune polyendocrine syndrome is associated with a defect in T suppressor cell function?

Back 72

Type 1

Front 73

Which autoimmune polyendocrine syndrome is associated with insulin-dependent diabetes?

Back 73

Type 2

Front 74

Which autoimmune polyendocrine syndrome is associated with mucocutaneous Candidiasis and abnormalities of the skin, dental enamel, and nails?

Back 74

Type 1

Front 75

In general, what 3 types of diseases can cause Addison disease?

Back 75

1. Infectious
2. Infiltrative
3. Metastatic

Front 76

Describe the the appearance of the adrenal glands seen in Addison disease?

Back 76

Glands are grossly enlarged, but microscopically show extensive cortical destruction

Front 77

Which portion of the adrenal cortex is not affected by secondary hypoadrenalism?

Back 77

Zona glomerulosa

Front 78

Why is hyperpigmentation not seen in secondary hypoadrenalism?

Back 78

Because levels of ACTH precursor (pro-opiomelanocortin) are not elevated

Front 79

How can secondary hypoadrenalism be diagnosed?

Back 79

1. Low serum ACTH
2. Exogenous administration of ACTH leads to rise in serum cortisol

Front 80

A primary acute adrenocortical insuffiency is known as..?

Back 80

Addisonian crisis

Front 81

List 3 possible causes of an Addisonian crisis.

Back 81

1. Induced by stress in a patient with chronic adrenocortical insufficiency
2. Rapid withdrawal of exogenous corticosteroids
3. Massive adrenal hemorrhage

Front 82

Bacteremia-induced acute adrenal hemorrhage results in what syndrome?

Back 82

Waterhouse-Friderichsen syndrome

Front 83

Which bacterial infection is often responsible for Waterhouse-Friderichsen syndrome?

Back 83

Neisseria meningitidis

Front 84

Waterhouse-Friderichsen syndrome is most common in which individuals?

Back 84

Children