(M) Lec 4: Adrenal Glands (Intro & Cortisol)

Question 1

The adrenal glands are:
1. ____ in shape
2. Located ____ each kidney
3. Composed of distinct but conjoined glands, the outer adrenal ____ and the inner adrenal ____

Answer 1

1. Pyramidal
2. Above
3. Cortex; Medulla

Question 2

Structure and Synthesis of Cortical Hormones

The cortical hormones are composed of a basic structure known as a ____ ring, a 17C skeleton derived from cholesterol

Answer 2

Cyclopentanoperhydrophenanthrene (CP) Ring

Question 3

Structure and Synthesis of Cortical Hormones

What is the parent cell of all steroid hormones?

Answer 3

Cholesterol

Question 4

Structure and Synthesis of Cortical Hormones

G cells are able to convert cholesterol to ____ which is the precursor substance for androgens, cortisol, and aldosterone

Answer 4

Pregnenolone

Question 5

Structure and Synthesis of Cortical Hormones

Cholesterol is converted to pregnenolone by what enzyme?

Answer 5

Cholesterol Desmolase

Question 6

Structure and Synthesis of Cortical Hormones

1. The cortical hormones are synthesized from what type of cholesterol?
2. The cortical hormones will be delivered to the adrenals where it will be taken up by what receptors?

Answer 6

1. LDL
2. LDL Receptors

Question 7

Structure and Synthesis of Cortical Hormones

The secretion of adrenal glucocorticoids (cortisol) and androgens (sex hormones) is regulated by the ____ hormone which is under the control of another hormone called, ____

Answer 7

1. Adrenocorticotrophic hormone (ACTH)
2. Corticotropin-Releasing Hormone (CRH); from the hypothalamus

Question 8

Structure and Synthesis of Cortical Hormones

The mineralocorticoid secretion is controlled by the ____ system

Answer 8

Renin-Angiotensin-Aldosterone System (RAAS)

Question 9

Cortisol has a hyper-____ effect but glucose is still elevated because it is a ____ agent

Answer 9

1. Hyperinsulin
2. Hyperglycemic

Question 10

Structure and Synthesis of Cortical Hormones

Regulated by the ACTH, CRH, RAAS, or Neither?
1. Mineralocorticoids (aldosterone)
2. Glucocorticoids (cortisol)
3. Androgens (sex hormones)
4. Secretion of an adrenal hormone from the pituitary gland
5. Epinephrine and Norepinephrine

Answer 10

1. RAAS
2. ACTH
3. ACTH
4. CRH
5. Neither (adrenal medulla)

Question 11

What are the 2 stimulants of CRH?

Answer 11

1. Low cortisol levels (positive feedback)
2. Stress

Question 12

The Adrenal Cortex

This zone makes up 10% of the adrenal cortex and is able to produce mineralocorticoids (aldosterone/salts)

Answer 12

Zona Glomerulosa (G-zone)

Question 13

The Adrenal Cortex

This zone makes up 75% of the adrenal cortex and is able to produce glucocorticoids (cortisol/glucose)

Answer 13

Zona Fasciculata (F-zone)

Question 14

The Adrenal Cortex

This zone makes up 15% of the adrenal cortex and is able to produce weak androgens (sex hormones)

Answer 14

Zona Reticularis (R-zone)

Question 15

• The principal and most important glucocorticoid produced by the adrenal cortex
• Its synthesis is regulated by ACTH from the pituitary gland

Answer 15

Cortisol

Question 16

Cortisol circulates as predominantly bound to this corticosteroid binding globulin

Answer 16

Transcortin

Question 17

1. If cortisol promotes lipolysis and gluconeogenesis, it (increases/decreases) blood glucose levels during stress
2. Cortisol functions in a (positive/negative) feedback loop as the only adrenal hormone that inhibits ACTH secretion

Answer 17

1. Increases
2. Negative

Question 18

1. Cortisol is a valuable therapeutic agent for ____ conditions such as RA, SLE, and MS
2. Cortisol exhibits a diurnal secretion pattern with the highest levels observed in the ____ while the lowest levels are observed in the ____

Answer 18

1. Inflammatory
2. Early morning (6-7AM); Night (11PM-12MN)

Question 19

Urinary Metabolites of Cortisol

• Measured by the PORTER SILBER method
• Phenylhydrazine in H2SO4 produces a ____ end color

Answer 19

17-Hydroxycorticosteroid (Yellow)

Question 20

Urinary Metabolites of Cortisol

• Measured by the ZIMMERMAN reaction
• Meta-dinitrobenzene undergoes the Norymberski oxidation procedure to produce a ____ end color

Answer 20

17-Ketogenic Steroids (Reddish Purple)

Question 21

Cortisol as a Sample

1. If collecting serum, use a ____ top tube
2. If collecting plasma, use an ____ tube
3. Aside from blood, what are the 2 other sample types?

Answer 21

1. Red
2. EDTA
3. 24H urine and Saliva

Question 22

Cortisol as a Sample

This type of cortisol is a sensitive indicator of adrenal hyperfunction

Answer 22

Urine Free Cortisol

Question 23

Cortisol as a Sample

Blood samples should be drawn at this time as it is when the cortisol level reaches its equilibrium level or value in the blood (consider the diurnal pattern of cortisol)

Answer 23

8 to 10AM

Question 24

Cortisol as a Sample

Match the Specimen to the Testing Method:
1. Serum and Saliva Cortisol
2. Urine Free Cortisol
3. Alternative to the routine method
4. Reference method

A. HPLC-MS/MS
B. Immunoassay
C. LC-MS/MS
D. GC-MS/MS

Answer 24

1. (B) - Immunoassay
2. (D) - GC-MS/MS
3. (C) - LC-MS/MS
4. (A) - HPLC-MS/MS

Question 25

# Clinical Disorders of Cortisol - A form of hypercortisolism primarily caused by the excessive production of cortisol and ACTH (although it is ACTH independent) - Also caused by the overuse of corticosteroidal drugs - Manifestations include: truncal obesity, hirsutism, a "buffalo hump," and others

Answer 25

Cushing's Syndrome

Question 26

# Clinical Disorders of Cortisol A type of Cushing's Syndrome caused by depression and excessive alcohol intake

Answer 26

Pseudo-Cushing’s

Question 27

# Tests for Cushing's Syndrome Screening or Confirmatory? - 24H urinary free cortisol - Overnight dexamethasone suppression test - Midnight salivary test

Answer 27

Screening

Question 28

# Tests for Cushing's Syndrome Screening or Confirmatory? - Low dose dexamethasone suppression test - Midnight plasma cortisol - CRH stimulation test

Answer 28

Confirmatory

Question 29

# Tests for Cushing's Syndrome - The most specific and sensitive screening test for adrenal hyperfunction - A positive result is a urine free cortisol level of more than (>) 120 µg/day

Answer 29

24-hour urinary free cortisol

Question 30

# Tests for Cushing's Syndrome What causes a false positive (+) in the 24-hour urinary free cortisol?

Answer 30

Urine cortisol level of greater than (>) 3L

Question 31

# Tests for Cushing's Syndrome - 1mg of dexamethasone (which suppresses ACTH) is orally given between 11pm to 12 midnight - Blood is collected the following day between 8am to 9am (urine may also be tested for 17-OHCS) - Negative result: cortisol is less than (<) 1.8µg/dL - Positive result: cortisol levels are not suppressed

Answer 31

Overnight/Rapid Dexamethasone Suppression Test

Question 32

# Tests for Cushing's Syndrome - There is a cotton roll or sponge roll that the patient needs to lightly chew so that saliva will accumulate in the cotton - Must be collected between 11pm to 12mn

Answer 32

Midnight Salivary Test

Question 33

# Tests for Cushing's Syndrome - 0.5mg of dexamethasone (which suppresses ACTH) is orally given every 6 hours for 48 hours - 24-hour urine and serum samples are collected - Negative result: cortisol is less than (<) 1.8µg/dL and urine free cortisol is less than (<) 10µg/24 hours on the second day of the dose - Positive result: serum and urine cortisol levels are not suppressed

Answer 33

Low-Dose Dexamethasone Suppression Test

Question 34

# Tests for Cushing's Syndrome - Day 1: 8mg of dexamethasone (which suppresses ACTH) is given between 11pm to 12mn - Plasma is collected at 8am - Day 2: 2mg is administered every 6 hours for 48 hours - 24 hour urine free cortisol is measured

Answer 34

High-Dose Dexamethasone Suppression Test

Question 35

# Tests for Cushing's Syndrome This test differentiates ACTH-dependent hypercortisolism from ACTH-independent (ectopic) hypercortisolism

Answer 35

High-Dose Dexamethasone Suppression Test

Question 36

# Tests for Cushing's Syndrome What is the source of the hypercortisolism if serum cortisol is less than (<) 5µg/dL or if it is suppressed by more than (>) 50% from the baseline?

Answer 36

Pituitary Gland (ACTH-dependent)

Question 37

# Tests for Cushing's Syndrome - The gold standard for determining the source of ACTH production - IPS ACTH and blood ACTH are measured

Answer 37

Inferior Petrosal Sinus Sampling (IPSS)

Question 38

# Tests for Cushing's Syndrome What is the source of ACTH production if: - IPS ACTH and blood ACTH ratio is > 2:1 - IPS ACTH and blood ACTH ratio is > 3:1 (after CRH stimulation)

Answer 38

Pituitary Gland

Question 39

# Tests for Cushing's Syndrome - This directly measures the amount of midnight (lowest) plasma cortisol - Positive result: cortisol level is greater than (>) 5.0 ug/dL

Answer 39

Midnight Plasma Cortisol

Question 40

# Types of Adrenal Insufficiency - There is a destruction of over 90% of the adrenal cortex leading to decreased cortisol production - Leads to aldosterone deficiency as well - There is excess ACTH release due to the negative feedback mechanism

Answer 40

Primary Hypocortisolism

Question 41

# Diseases of Primary Hypocortisolism - Presents with hypotension, hyponatremia, hyperkalemia, weight loss, and hyperpigmentation - Due to autoimmune adrenalitis, TB, and HIV/AIDS - The hyponatremia and hyperkalemia are caused by low aldosterone levels which is responsible for sodium retention

Answer 41

Addison's Disease | Note: ACTH communicates with the MSH to produce pigmentation

Question 42

# Diseases of Primary Hypocortisolism What is the pathognomonic feature of Addison's Disease?

Answer 42

Presence of F21-hydroxylase autoantibodies (21-OH-AA)

Question 43

# Diseases of Primary Hypocortisolism What is the screening test for Addison's Disease and what are the interpreptations for a positive result?

Answer 43

- Screening test: ACTH Stimulation - Positive result: Increased ACTH with decreased cortisol and aldosterone (no changes)

Question 44

# Types of Adrenal Insufficiency - Due to hypothalamic-pituitary insufficiency with a loss of ACTH - There is no problem with the mineralocorticoid (aldosterone) secretion - Presents with absence of hyperpigmentation - Caused by pituitary tumors/surgeries, Sheehan's syndrome, and bacterial infections

Answer 44

Secondary Hypocortisolism

Question 45

# Diseases of Secondary Hypocortisolism What is the screening test for Secondary Hypocortisolism and what are the interpreptations for a positive result?

Answer 45

- Screening test: ACTH Stimulation - Positive result: Delayed response to stimulation (decreased ACTH and cortisol)

Question 46

# Types of Adrenal Insufficiency - Related to defective hypothalamic release of corticotropin-releasing hormone (CRH) with decreased production of ACTH - Mostly drug-induced or caused by the overuse of synthetic glucocorticoids - Can be caused by hypothalamic tumors or surgeries, bacterial infections, or can be drug-induced

Answer 46

Tertiary Hypocortisolism

Question 47

# Diseases of Tertiary Hypocortisolism What are the levels of cortisol, ACTH, and CRH in tertiary hypocortisolism?

Answer 47

All decreased

Question 48

# Diagnostic Tests for Hypoadrenalism/Adrenal Insufficiency - This determines the capacity of the adrenal gland to increase hormone production in response to stimulation - Requires the administration of 250ug of Cosyntropin (IV or IM) - Negative result: cortisol levels greater than (>) 18-20µg/dL at any time of the day - Positive result: cortisol levels less than 18µg/dL

Answer 48

ACTH/Cosyntropin (synthetic ACTH) Stimulation Test

Question 49

# Diagnostic Tests for Hypoadrenalism/Adrenal Insufficiency - This measures the ability of the pituitary gland to respond to declining levels of circulating cortisol - Is performed when ACTH stimulation test results are normal

Answer 49

Metyrapone Test

Question 50

# Diagnostic Tests for Hypoadrenalism/Adrenal Insufficiency The Metyrapone Test blocks the ____ enzyme which does the ff.: - Increases ____ by greater than 7µg/dL - Decreases ____ by less than 5µg/dL

Answer 50

1. 11B-hydroxylase 2. 11-deoxycortisol 3. Cortisol

Question 51

# Diagnostic Tests for Hypoadrenalism/Adrenal Insufficiency - The confirmatory test for hypoadrenalism - The gold standard for differentiating secondary from tertiary hypoadrenalism - Used to confirm a borderline response to the ACTH stimulation test

Answer 51

Insulin Tolerance Test

Question 52

# Diagnostic Tests for Hypoadrenalism/Adrenal Insufficiency - Hypoglycemia is induced by administering 0.05 U/kg of insulin (a natural stessor for the body) - Negative result: cortisol levels are greater than 18-20µg/dL at anytime of the day - Positive result: cortisol levels are still decreased

Answer 52

Insulin Tolerance Test

Question 53

# Diseases of the Adrenal Gland - Results from deficiency of 21-hydroxylase, 11B-hydroxylase, and 3B hydroxysteroid dehydrogenase isomerase - 24-hour urinary free cortisol is not a consistent sample as this disease affects newborns - Manifestations include: atypical sexual development, hirsutism, infertility, and salt wasting

Answer 53

Congenital Adrenal Hyperplasia (CAH)

Question 54

# Diseases of the Adrenal Gland What are the 2 definitive tests for Congenital Adrenal Hyperplasia?

Answer 54

1. 17-OHP (17-hydroxyprogesterone) measurement in amniotic fluid 2. Genotyping of cells from chorionic villous sampling

Question 55

# Types of Congenital Adrenal Hyperplasia - Most common form - Elevated levels of 17alpha-hydroxyprogesterone (17-OHP) and urinary excretion of pregnanetriol are indicative of this disorder - Symptoms caused by excess androgen levels are: virilization, infertility, amenorrhea, and hirsutism

Answer 55

21-Hydroxylase Deficiency

Question 56

# Types of Congenital Adrenal Hyperplasia What gene is defective in 21-Hydroxylase Deficiency?

Answer 56

CYP21

Question 57

# Types of Congenital Adrenal Hyperplasia What 2 tests are used for 21-Hydroxylase Deficiency?

Answer 57

1. ACTH Stimulation Test 2. 17A-Hydroxyprogesterone Test

Question 58

# Types of Congenital Adrenal Hyperplasia - Second most common form - Increased levels of 11-deoxycortisol are indicative of this disorder - Associated with virilization and hypertension

Answer 58

11B-Hydroxylase Deficiency

Question 59

# Types of Congenital Adrenal Hyperplasia This deficiency results in: - An elevated ratio of 17 alpha-hydroxylpregnenolone - An increased ratio of DHEA to androstenedione - Characterized by pseudohermaphroditism in females and incomplete masculinization in males

Answer 59

3B Hydroxysteroid Dehydrogenase Isomerase Deficiency

Question 60

# Types of Congenital Adrenal Hyperplasia Characterized by the inability to convert: - 17 alpha-hydroxypregnenolone to DHEA - 17 alpha-hydroxyprogesterone to androstenedione - In females, there is absence of menstruation and defective ovarian maturation - In males, there is pseudohermaphroditism

Answer 60

C-17,20-Lyase/17 Alpha-Hydroxylase Deficiency