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66 Cards in this Set

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What are the 2 compartments of the Adrenal Cortex and what do they secrete?
1. Outer Zona Glomerulosa ➡ mineralcorticoid Aldosterone

2. Inner Zona Fasciculata ➡ Cortisol

3. Reticularis ➡ Adrenal Androgens
What regulates Aldosterone secretion from the Zona Granulosa?
1. extracellular K+ channels that sense Potassium levels
-Hyperkalemia = secretion

2. Angiotensin receptors
What regulates the secretion of Glucocorticoids?

What are the 2 enzymes that catalyze Glucocorticoid production?

17a-hydroxylase (P450c17)
11b-hydroxylase (P450c11)
What is the naturally-occuring Glucocorticoid?

What is it derived from?

What 2 things are the synthesis and secretion of Cortisol tightly regulated by?
CNS which is very sensitive to negative feedback by:
1. circulating Cortisol
2. Exogenous (synthetic) Glucocorticoids
__1__ mg of Cortisol is secreted daily following a Circadian rhythm regulated by __2__

3. What is the half-life of Cortisol?
1. 10-20


3. 60-90 min
What is 90% of circulating Cortisol bound to?

What about the other 5-10%?
Corticosteroid binding globulin (CBG) = synthesized by Liver

Free or loosely bound to Albumin
How is Cortisol inactivated?
Mostly in the Liver
1. ~ 20% is converted to Cortisone

2. only 1% is excreted in urine
Describe the Glucocorticoid receptors
Primarily Cytoplasmic, in the form of Oligomeric complexes with 2 molecules of Heat Shock Proteins (Hsp90)
List the 2 types of Glucocorticoid "orpha receptors"
Type 1 = mineralcorticoid receptor; expressed mainly in organs of excretion such as kidney, colon, salivary glands, sweat glands

Type 2 = Glucocorticoid receptor; broader tissue distribution
Describe the Steroid-Receptor Interaction for Cortisol
1. free steroid enter cell cytoplasm to release receptor from Hsp90
2. Steroid-receptor complex enters nucleus
3. S-R binds to the Glucocorticoid Response Element (GRE)
4. Regulates tsc by RNA polymerase and other factors
5. mRNA edited and exported to cytoplasm to form protein
What % of expressed genes do Glucocorticoids regulate in any given cell?
What are Glucocorticoid effects mainly due to?
Proteins synthesized from mRNA transcribed by their target genes
What are the 3 main effects Glucocorticoids produce?
1. Anti-growth

2. Anti-inflammatory

3. Immunosuppressive effects
Most of the effects of Corticosteroids (Cortisol) are __1__, while others are __2__
1. direct

2. "permissive" = effects that required glucocorticoid presence such that the fxn becomes deficient when glucocorticoid is absent
Glucocorticoids induce the synthesis of __1__, an inhibitor of __2__
1. Lipocortin

2. Phospholipase A2

**inhibits Prostaglandin and Leukotriene synthesis = Anti-inflammatory
Glucocorticoids inhibit the production of __1__, which inhibits the proliferation of __2__
1. IL-2

2. T lymphocytes

Glucocorticoids inhibit the release of these 2 things from Mast cells and Platelets
1. Histamine = decreases capillary permeability (usually causes permeability)

2. Serotonin = less platelet aggregation (usually causes aggregation)
How do Corticosteroids reduce the # of Lymphocytes, Monocytes, Eosinophils, and Basophils?
causes them to move from the Vascular bed to Lymphoid tissues
List the Metabolic effects Glucocorticoids (Corticosteroids) possess
1. Stimulate Gluconeogenesis and Glycogen synthesis

2. release Amino Acids during muscle catabolism = provide AA's to liver for Gluconeogenesis

3. Stimulate hormone-sensitive Lipase & Lipolysis = provides more glycerol to liver for gluconeogenesis

4. Elevate serum Glucose to stimulate Insulin release BUT inhibit glucose uptake by muscle cells = allows more delivery to brain
What is the ultimate purpose of the Metabolic effects of Cortisol?
Supply adequate glucose to the brain in the fasting state
Where do the Catabolic & Anabolic effects of Glucocorticoids occur?
1. Lymphoid tissue
2. Connective tissue
3. Muscle
4. Fat
5. Skin
What effects do supraphysiologic amounts of Corticosteroids have on muscle, skin, and bone?
Reduce muscle mass causing weakness

Skin thinning

Osteoporosis (in Cushing's syndrome)
Reduced growth in children on Corticosteroids can be partly prevented with what?
high doses of Growth Hormone
What effects do Glucocorticoids have on the CNS?
1. marked slowing of EEG alpha rhythm

2. behavioral disturbances initially as insomnia & euphoria followed by depression

3. large doses may increase Intracranial pressure

4. suppressed Pituitary release of ACTH, GH, TSH, LH
Describe how Cortisol maintains vascular responsiveness to catecholamines
cortisol up-regulates Alpha1-receptors on arterioles, increasing vasoconstrictor effect of Norepinephrine
How could Glucocorticoids contribute to Peptic Ulcers?
by suppressing local immune response to H. pylori
List 3 miscellaneous effects of Corticosteroids
1. promote fat redistribution to increase visceral, facial, nuchal and supraclavicular fat

2. antagonize Vitamin D effect on intestinal Calcium absorption

3. increase numbers of platelets and RBC's
What effect does Cortisol deficiency have on renal function?
Impairs renal function and augments (increase) Vasopressin (ADH) secretion resulting in an inability to excrete a water load normally

**Vasopressin (ADH) causes increased water reabsorption = decreased urination volume
When would Glucocorticoids be given to fetuses?
When they are premature = stimulate structural and functional development of fetal lungs including the production of Surfactant
List the names of commonly used Glucocorticoids (6)
1. Hydrocortisone
2. Prednisone
3. Triamcinolone
4. Betamethasone
5. Dexamethasone
6. Beclomethasone
How are the synthetic Corticosteroids traditionally grouped? What are their actions?
Glucocorticoids = affect glucose metabolism & inflammation

Mineralcorticoids = affect Na+ or Salt retention

**the 2 groups of effects are usually not closely related & reflect distinct actions at 2 distinct receptors
2 steroids classified as Glucocorticoids but also have some Mineralcorticoid activity

Steroid classified as a Mineralcorticoid but also affects Glucose metabolism (Glucocorticoid)
2 Steroids that have strong anti-inflammatory action but no salt-retaining activity


**are also long-lasting
Steroid that has Salt-retaining activity but no anti-inflammatory activity
What steroids should be used whenever Electrolyte Abnormalities are present?
Corticosteroids without Salt-retaining activity
What are the 2 Corticosteroids that have potent Salt-retention activity?

2 Corticosteroids that have high Anti-inflammatory activity but no Salt-retention activity


**both are long-acting
What is the treatment regimen for Adrenocortical Insufficiency (Addison's disease = adrenal atrophy)
Life-long combined glucocorticoid and mineralcorticoid; use HYDROCORTISONE + Mineralcorticoid (Fludro-cortisone)
What should you not use to treat Adrenocortical Insufficiency (Addison's disease)?
Glucocorticoids that have no salt-retaining activity
1. What is the cause of Bilateral Adrenal Hyperplasia (Cushing's disease)?

2. List the main characteristics

3. What is the treatment?
1. ACTH-secreting pituitary adenoma

2. moon facies, trunk obesity, muscle wasting, purple striae, skin bruising, osteoporosis

3. large dose Hydrocortisone following surgical removal of tumor
Condition referred to as "iatrogenic complication of long-term corticosteroid therapy"
Cushing's syndrome
What is used to treat Aldosteronism (aldosterone excess resulting from Adrenal Adenoma)
Describe the "Dexamethasone Suppression Test"
used to diagnose Cushing's disease
-high cortisol levels are reduced to 50% by Dexamethasone
Are glucocorticoids curative or not curative in Nonadrenal disorders?
Not curative, and whenever possible should be used only to supplement specific treatment for the disease
What are the most commonly used Glucocorticoids used to treat NONADRENAL disorders? (6)
1. Beta-methasone
2. Dexa-methasone
3. Hydrocortisone
4. Prednisolone
5. Methyl-prednisolone
6. Triam-cinolone
What 3 principles should be kept in mind when using Glucocorticoids to treat CHRONIC Nonadrenal disorders?
1. procede carefully with LOW DOSES

2. Intermittent administration (i.e. alternate days)

What can minimize systemic side-effects when giving Glucocorticoids?
Local administration
-hydrocortisone by enema for Ulcerative Colitis
-inhaled steroids for asthma
Toxicity of Synthetic Glucocorticoids:

When used for less than __1__ serious side-effects are infrequent, but these 3 things may occur: __2__
1. 2 weeks

2. Insomnia, Behavioral changes, Acute peptic ulcers
List the major side effects of Synthetic Glucocorticoids that may occur if given for long periods of time
1. Metabolic side-effects resulting from the hormonal actions = Iatrogenic Cushing's Syndrome
-moon facies, truncal obesity, punctate acne, muscle wasting, skin thinning, osteoporosis, diabetes

2. Peptic ulcer, myopathy, acute psychosis, depression, glaucoma, HTN, Fluid retention & edema

3. Adrenal suppression resulting in Anorexia, nausea or vomiting, weight loss, lethargy, headache
In what patients should caution be used when giving Synthetic Glucocorticoids? (8)
1. Peptic ulcer
2. Heart disease
3. HTN (up-regulate Alpha-1 receptors on arterioles)
4. Psychoses
5. Infections
6. Diabetes
7. Osteoporosis
8. Glaucoma
The most important mineralcorticoid in man that is synthesized in the Zona Glomerulosa
Where does Aldosterone bind?
receptors in:
1. Distal Convoluted tubule
2. Proximal Collecting tubules

Promotes Na+ reabsorption
What is the precursor of Aldosterone that is also normally synthesized and secreted?
Most commonly prescribed Mineralcorticoid; has potent Glucocorticoid and Mineralcorticoid activity
Mineralcorticoid that is used to treat Adrenocortical insufficiency associated with Mineralcorticoid deficiency
SELECTIVE INHIBITOR of STEROID SYNTHESIS commonly used for testing adrenal function
Nonselective inhibitor of Adrenal & Gonadal steroid synthesis used for treatment of Cushing's Disease
Glucocorticoid antagonist with strong Anti-progestin activity and has been used as an Abortifacient?
Aldosterone antagonist widely used to prevent Hypokalemia in treatment of HTN and Congestive Heart Failure