Glucocorticoids Flashcards
Glucocorticoids synthesized in
Zona fasciculata
_ most important glucocorticoid
Cortisol
maintain blood glucose by lipolysis, gluconeogenesis, and glycogenolysis
most tissues are the target cells
Glucocorticoids
Cortisol
- bound to CBG (transcortin) and albumin
- free or unbound
90%
10%
Hypothalamopituitary adrenal (HPA) axis: Negative Feedback
- Hypothalamus:
• The hypothalamus is a part of the brain that detects stress or low cortisol levels.
• It releases_____ into the bloodstream. - Pituitary Gland:
• CRH travels to the anterior pituitary gland, which is just below the brain.
• The pituitary responds by releasing______ - Adrenal Glands:
• ACTH stimulates the adrenal glands (located on top of the kidneys) to produce and release______ into the bloodstream.
Corticotropin-Releasing Hormone (CRH)
Adrenocorticotropic Hormone (ACTH)
cortisol
Negative Feedback Mechanism
- 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. - When cortisol levels drop:
• Low cortisol levels stimulate the hypothalamus to release more____.
• This increases_____ release from the pituitary, leading to more cortisol production.
CRH and ACTH
CRH; ACTH
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.
phospholipase A
phospholipase A₂
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.
less permeable
In inflammation,_______ suppress the effects of histamine, reducing symptoms like redness and itching.
glucocorticoids
Circadian Rhythm of Cortisol Secretion
Highest
Lowest
Highest: 6am-noon
Lowest: Midnight- 6am
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%).
generalized weakness, loss of appetite, and weight loss.
Hyperpigmentation
nausea, diarrhea
pain with adrenal calcification
Glucocorticoids Laboratory Tests
Adrenal Insufficiency
• Cortisol Level
• ACTH Stimulation Assay
• Cosyntropin Administration
• Purpose: Measures cortisol levels in the blood to assess adrenal gland function.
Serum Cortisol Level
• Methods:
• ______
• Developed by Nelson and Samuels, based on earlier work by Porter and Silber.
• Measures cortisol fluorescence after chemical reaction.
Fluorometric Assay
Baseline cortisol (______am, supine):
• (83 nmol/L): Indicates adrenal insufficiency.
Random cortisol:
• : Suggests low cortisol production.
8:00-9:00
<3 µg/dL
<10 µg/dL
Plasma ACTH
ASSAYS??
Two site immunoradiometric assay
Immunochemiluminometric assay
Plasma ACTH
Pre-chilled EDTA tube and kept in an ice bath
Normal range:
2 to 12 pmol/L (9 to 52 pg/mL)
between *7 am and 10 am¥
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.
11-β-hydroxylase
Metyrapone
- At midnight (12:00 am):
• The patient takes _____metyrapone orally. - At_____ am the next day:
• Blood samples are taken to measure: (2)
30 mg/kg
8:00 am
• 11-deoxycortisol.
• Cortisol.
Metyrapone
• Normal: 11-deoxycortisol ______
• Abnormal:_______ of 11-deoxycortisol, accompanied by______ cortisol
> 7 ug/dL (200 nmol/L)
<7 ug/dL; <5 ug/dL
CRH Test (Corticotropin-Releasing Hormone Test)
• ______ is injected to stimulate the pituitary gland to release ACTH.
• ACTH then stimulates the adrenal glands to produce______.
CRH (Corticotropin-Releasing Hormone)
cortisol
• CRH (Corticotropin-Releasing Hormone TEST
Procedure
- Baseline ACTH and Cortisol:
• Blood samples are collected before the test to measure existing levels. - CRH Injection:
• ______ of CRH is administered intravenously (IV). - Follow-Up Blood Samples:
• Blood is collected every____ minutes for _____minutes after injection.
100 µg
15mins
60-90 mins
CRH TEST
Normal response:
Cortisol Peak:
Cortisol greater than 20 ug/dL
30-40 minutes post-injection
Excess production of glucocorticoids, or glucocorticoids and androgens
Cushing’s Syndrome
Is a group of clinical and metabolic disorders characterized by adrenocortical hyperfunction
Cushing’s Syndrome
Hypercortisolism
• Cushing’s Syndrome: Signs
• 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
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
Cushing’s Disease
• Purpose: Used as a sensitive indicator of endogenous cortisolism (excess cortisol production).
Urine Free Cortisol
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.
Urine Free Cortisol
3-5 liters/day
Urine free cortisol
Measurement Methods:
• : Separates cortisol from other substances for accurate measurement.
• : Provides precise and specific identification and quantification of cortisol.
High-Performance Liquid Chromatography (HPLC)
Gas Chromatography-Mass Spectrometry (GC-MS)
• Purpose: More sensitive and specific for detecting excess cortisol over a full day.
24-Hour Urine Cortisol
• 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).
24-Hour urine cortisol
24-hour urine cortisol
Measurement:
• Measured using______, which provides highly sensitive and accurate results.
Tandem Mass Spectrometry
• Key Point:
• Not affected by volume changes (unlike free cortisol in urine), making it more
Urine 17-Hydroxycorticosteroid (17-OHCS)
• Purpose: Helps differentiate between central Cushing’s syndrome (pituitary problem) and primary adrenal syndrome (adrenal problem).
CRH (Corticotropin-Releasing Hormone) Stimulation Test
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.
8:00
• Purpose: Used to diagnose Cushing’s syndrome and test how the body responds to cortisol.
Dexamethasone Suppression Test (DST)
• 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.
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).
<1.8 µg/dL
