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CC 2 LAB > Glucocorticoids > Flashcards

Glucocorticoids Flashcards

1
Q

Glucocorticoids synthesized in

A

Zona fasciculata

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2
Q

_ most important glucocorticoid

A

Cortisol

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3
Q

maintain blood glucose by lipolysis, gluconeogenesis, and glycogenolysis

most tissues are the target cells

A

Glucocorticoids

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4
Q

Cortisol
- bound to CBG (transcortin) and albumin

  • free or unbound
A

90%

10%

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5
Q

Hypothalamopituitary adrenal (HPA) axis: Negative Feedback

  1. Hypothalamus:
    • The hypothalamus is a part of the brain that detects stress or low cortisol levels.
    • It releases_____ into the bloodstream.
  2. Pituitary Gland:
    • CRH travels to the anterior pituitary gland, which is just below the brain.
    • The pituitary responds by releasing______
  3. Adrenal Glands:
    • ACTH stimulates the adrenal glands (located on top of the kidneys) to produce and release______ into the bloodstream.
A

Corticotropin-Releasing Hormone (CRH)

Adrenocorticotropic Hormone (ACTH)

cortisol

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6
Q

Negative Feedback Mechanism

  1. When cortisol levels rise:
    • High cortisol levels signal the hypothalamus and pituitary gland to reduce _____ and _____secretion.
    • This reduces stimulation of the adrenal glands, slowing cortisol production.
  2. When cortisol levels drop:
    • Low cortisol levels stimulate the hypothalamus to release more____.
    • This increases_____ release from the pituitary, leading to more cortisol production.
A

CRH and ACTH

CRH; ACTH

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7
Q

Glucocorticoids- Anti inflammatory effect

Inhibit Prostaglandins and Leukotrienes

What are Prostaglandins and Leukotrienes?
• These are molecules that cause pain, redness, and swelling during inflammation.
• They are produced by the enzyme_______₂, which releases arachidonic acid (the starting material for these molecules).

• What Glucocorticoids Do:
• Glucocorticoids stimulate the production of a protein called lipocortin, which blocks______.
• This stops the production of prostaglandins and leukotrienes, effectively shutting down the inflammation process.

A

phospholipase A

phospholipase A₂

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8
Q

Glucocorticoids- Anti inflammatory effect

Decrease Capillary Permeability

What is Capillary Permeability?
• During inflammation, the walls of capillaries (tiny blood vessels) become “leaky.”
• This allows fluids and immune cells to move into tissues, causing swelling (edema).

What Glucocorticoids Do:
• They make capillary walls______, reducing the amount of fluid and immune cells entering tissues.
• This leads to less swelling and a reduction in visible redness.

A

less permeable

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9
Q

In inflammation,_______ suppress the effects of histamine, reducing symptoms like redness and itching.

A

glucocorticoids

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10
Q

Circadian Rhythm of Cortisol Secretion

Highest

Lowest

A

Highest: 6am-noon

Lowest: Midnight- 6am

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11
Q

Adrenal Insufficiency: Symptoms and Signs by Frequency

Most common symptoms (100%) include…

…(90%) is seen primarily in primary adrenal insufficiency due to high ACTH levels.

Less frequent symptoms include….. (50%), and…..(10%).

A

generalized weakness, loss of appetite, and weight loss.

Hyperpigmentation

nausea, diarrhea

pain with adrenal calcification

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12
Q

Glucocorticoids Laboratory Tests
Adrenal Insufficiency

A

• Cortisol Level
• ACTH Stimulation Assay
• Cosyntropin Administration

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13
Q

• Purpose: Measures cortisol levels in the blood to assess adrenal gland function.

A

Serum Cortisol Level

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14
Q

• Methods:
• ______
• Developed by Nelson and Samuels, based on earlier work by Porter and Silber.
• Measures cortisol fluorescence after chemical reaction.

A

Fluorometric Assay

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15
Q

Baseline cortisol (______am, supine):
• (83 nmol/L): Indicates adrenal insufficiency.

Random cortisol:
• : Suggests low cortisol production.

A

8:00-9:00

<3 µg/dL

<10 µg/dL

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16
Q

Plasma ACTH
ASSAYS??

A

Two site immunoradiometric assay
Immunochemiluminometric assay

17
Q

Plasma ACTH

Pre-chilled EDTA tube and kept in an ice bath

Normal range:

A

2 to 12 pmol/L (9 to 52 pg/mL)
between *7 am and 10 am¥

18
Q

Metyrapone is a drug that inhibits_______, an enzyme needed to convert 11-deoxycortisol into cortisol.

• When cortisol levels drop, the body should compensate by increasing ACTH secretion, which should result in higher 11-deoxycortisol levels.

A

11-β-hydroxylase

19
Q

Metyrapone

  1. At midnight (12:00 am):
    • The patient takes _____metyrapone orally.
  2. At_____ am the next day:
    • Blood samples are taken to measure: (2)
A

30 mg/kg

8:00 am

• 11-deoxycortisol.
• Cortisol.

20
Q

Metyrapone
• Normal: 11-deoxycortisol ______
• Abnormal:_______ of 11-deoxycortisol, accompanied by______ cortisol

A

> 7 ug/dL (200 nmol/L)

<7 ug/dL; <5 ug/dL

21
Q

CRH Test (Corticotropin-Releasing Hormone Test)

• ______ is injected to stimulate the pituitary gland to release ACTH.

• ACTH then stimulates the adrenal glands to produce______.

A

CRH (Corticotropin-Releasing Hormone)

cortisol

22
Q

• CRH (Corticotropin-Releasing Hormone TEST

Procedure

  1. Baseline ACTH and Cortisol:
    • Blood samples are collected before the test to measure existing levels.
  2. CRH Injection:
    • ______ of CRH is administered intravenously (IV).
  3. Follow-Up Blood Samples:
    • Blood is collected every____ minutes for _____minutes after injection.
A

100 µg

15mins

60-90 mins

23
Q

CRH TEST

Normal response:

Cortisol Peak:

A

Cortisol greater than 20 ug/dL

30-40 minutes post-injection

24
Q

Excess production of glucocorticoids, or glucocorticoids and androgens

A

Cushing’s Syndrome

25
Q

Is a group of clinical and metabolic disorders characterized by adrenocortical hyperfunction

A

Cushing’s Syndrome

26
Q

Hypercortisolism
• Cushing’s Syndrome: Signs

A

• Fat is deposited in the body trunk (central obesity)
• Buffalo hump
• Moon facies (subcutaneus fat in cheeks and submandibular)
• Purple striae
• Blood-glucose levels rises chronically, causing adrenal diabetes
• May cause beta cells to die

27
Q

Is a state of glucocorticoid excess resulting from an ACTH-secreting pituitary adenoma

Most commonly iatrogenic in origin

However, may be due to ectopic production of CRH or ACTH by a tumor or due to a primary adrenal malignancy

A

Cushing’s Disease

28
Q

• Purpose: Used as a sensitive indicator of endogenous cortisolism (excess cortisol production).

A

Urine Free Cortisol

29
Q

Urine Free Cortisol

When serum cortisol exceeds the capacity of carrier proteins (like CBG or albumin), free cortisol levels rise.

• This free cortisol gets filtered into the urine, making it measurable in urine tests.

• Hydration affects the result: A higher fluid intake (_______) can dilute the urine and affect the measurement.

A

Urine Free Cortisol

3-5 liters/day

30
Q

Urine free cortisol

Measurement Methods:

• : Separates cortisol from other substances for accurate measurement.

• : Provides precise and specific identification and quantification of cortisol.

A

High-Performance Liquid Chromatography (HPLC)

Gas Chromatography-Mass Spectrometry (GC-MS)

31
Q

• Purpose: More sensitive and specific for detecting excess cortisol over a full day.

A

24-Hour Urine Cortisol

32
Q

• Procedure:
• Urine is collected over 24 hours, including the night (10 pm - 8 am).

• Creatinine levels are also measured to correct for urine dilution (as hydration can affect results).

A

24-Hour urine cortisol

33
Q

24-hour urine cortisol

Measurement:
• Measured using______, which provides highly sensitive and accurate results.

A

Tandem Mass Spectrometry

34
Q

• Key Point:
• Not affected by volume changes (unlike free cortisol in urine), making it more

A

Urine 17-Hydroxycorticosteroid (17-OHCS)

35
Q

• Purpose: Helps differentiate between central Cushing’s syndrome (pituitary problem) and primary adrenal syndrome (adrenal problem).

A

CRH (Corticotropin-Releasing Hormone) Stimulation Test

36
Q

CRH stimulation test

How it Works:
• At____ am, blood is drawn to measure serum cortisol and ACTH levels.
• CRH is then injected, stimulating the pituitary to release ACTH and test the adrenal response.

A

8:00

37
Q

• Purpose: Used to diagnose Cushing’s syndrome and test how the body responds to cortisol.

A

Dexamethasone Suppression Test (DST)

38
Q

• How it Works:
• Dexamethasone (a synthetic glucocorticoid) is administered at 11 pm to suppress ACTH and cortisol production.

•	Overnight DST:
•	1 mg of dexamethasone is taken at 11 pm.
•	Cortisol levels are measured between 8-9 am the next morning.
A
39
Q

DST Suppression Test

Interpretation:
• If free cortisol is_____, the test is negative, meaning the pituitary and adrenal glands are responding normally to cortisol.
• If cortisol remains high, it suggests Cushing’s syndrome (abnormal cortisol regulation).

A

<1.8 µg/dL

CC 2 LAB (34 decks)

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