38 Questions
What is the primary function of the zona glomerulosa in the adrenal gland?
To produce mineralocorticoids
What is the normal daily secretion of cortisol in adults?
10-20 mg
What is the peak time of cortisol secretion in a normal adult?
8 AM
What is the primary regulator of adrenal steroid hormone synthesis?
Hypothalamic-Pituitary-Adrenal axis
What is the hormone released by the hypothalamus that stimulates the synthesis and release of ACTH?
Corticotropin-releasing hormone (CRH)
What is the precursor molecule for the synthesis of cortisol and aldosterone?
Cholesterol
What is the enzyme responsible for the conversion of 11-desoxycorticosterone to corticosterone?
11,β-hydroxylase
What is the normal plasma concentration of aldosterone in adults?
0.01 mcg/dl
What is the primary function of aldosterone in the human body?
To maintain water and electrolyte balance
In which disease is dexamethasone commonly used to promote lung maturation?
Respiratory distress syndrome in premature infants
What is a common side effect of glucocorticoids on the musculoskeletal system?
Myopathy and muscle wasting
Which of the following is an absolute contraindication for glucocorticoid therapy?
Cushing's disease
What is the mechanism by which glucocorticoids prevent graft rejection in organ transplants?
By inhibiting the host immune system
Which of the following is a common behavioral change associated with glucocorticoid therapy?
Hypomania or acute psychosis
What is the purpose of using glucocorticoids in the treatment of nephrotic syndrome?
To treat the underlying inflammatory condition
What is a common side effect of glucocorticoids on the eye?
All of the above
What is the primary effect of ACTH binding to its receptor on the adrenal cortex?
Induction of genes involved in adrenal steroid hormone synthesis
What is the effect of cortisol on glucose metabolism in the periphery?
Decreased peripheral glucose utilization
What is the result of cortisol's effect on lipid metabolism?
Increased lipolysis and glycerol production
What is the physiological response to increased cortisol levels during stress?
Increased glucose supply to glucose-dependent tissues
What is the negative feedback mechanism of cortisol on the HPA axis?
Inhibition of CRH and ACTH production
What is the characteristic distribution of fat in response to cortisol?
Redistribution of fat to the truncal region and upper chest
What is the primary protein that glucocorticoids bind to in plasma?
Corticosteroid binding globulin (CBG)
What is the half-life of corticosteroids in a healthy individual?
60-90 minutes
Why is prednisone preferred in pregnancy?
It minimizes steroid effects on the fetus
What is the primary use of fludrocortisone in replacement therapy for adrenocortical insufficiency?
To supplement mineralocorticoid deficiency
What is the effect of dexamethasone on cortisol release in normal individuals?
It suppresses cortisol release
What is the reason for dividing the daily dose of hydrocortisone in replacement therapy for primary adrenocortical insufficiency?
To mimic the natural circadian rhythm
What is the effect of hepatic dysfunction on the half-life of corticosteroids?
It increases the half-life
What is the primary reason for using glucocorticoids in the treatment of rheumatoid disorders?
To suppress the immune response
Which of the following factors has a moderate stimulating effect on aldosterone secretion, but only lasts for a few days?
ACTH
What is the half-life of desoxycorticosterone?
70 minutes
What is the primary use of fludrocortisone?
Treatment of adrenocortical insufficiency
Which of the following inhibitors of adrenocorticoid biosynthesis is used to treat patients with Cushing syndrome?
Ketoconazole
What is the primary mechanism of action of spironolactone?
Competing for the mineralocorticoid receptor
What is the daily dose of fludrocortisone used in replacement therapy?
50-200 μg/day
What is the amount of aldosterone excreted free or glucoronoid per day?
5-15 μg/24 hours
What is the daily secretion of desoxycorticosterone?
200 μg/day
Study Notes
Adrenal Gland Structure
- The adrenal gland consists of two parts: Cortex and Medulla
- Cortex is responsible for producing Adrenal Steroids or Corticosteroids
- Medulla produces Catecholamines
Corticosteroids Synthesis
- Both cortisol and aldosterone are synthesized from cholesterol
- Normal adults secrete 10-20 mg of cortisol daily and 0.125 mg of aldosterone daily
- The rate of secretion of cortisol is controlled by a circadian rhythm that peaks at 8 AM
Cortisol Plasma Concentration
- Cortisol plasma concentration is 16 mcg/dl at 8 AM and 4 mcg/dl at 4 PM
- Aldosterone plasma concentrations are constant at 0.01 mcg/dl
Hypothalamic-Pituitary-Adrenal (HPA) Axis
- The HPA axis regulates the synthesis of adrenal steroid hormones
- Corticotropin-releasing hormone (CRH) is released by the hypothalamus in response to circadian rhythms and stress inducers
- CRH acts on the cells of the corticotropes of the Anterior Pituitary to induce the synthesis and release of adrenocorticotrophic hormone (ACTH)
Physiological Effects of Glucocorticoids
Carbohydrate and Protein Metabolism
- Liver: ↑gluconeogenesis and ↑glycogen storage
- Periphery: ↑protein catabolism = ↑ substrate for gluconeogenesis
- ↓ peripheral glucose utilization
- ↑ blood glucose
Lipid Metabolism
- ↑ lipolysis by facilitating action of GH/B-adrenergic agents
- ↑ glycerol = ↑ substrate for liver gluconeogenesis
- ↑ FFA contributes to ↑ insulin resistance
- Redistribution of fat: ↑ truncal obesity, ↑ back of neck (buffalo hump)/upper chest, ↑ moon facies, ↓ extremities
Response to Stress
- Cortisol levels increase in times of stress
- The corresponding increase in blood glucose acts to protect glucose-dependent tissues
Pharmacological Uses
Endocrine Uses of Glucocorticoids
- Replacement therapy for primary adrenocortical insufficiency (Addison disease)
- Replacement therapy for secondary or tertiary adrenocortical insufficiency
- Diagnosis of Cushing syndrome
- Replacement therapy for congenital adrenal hyperplasia
Non-Endocrine Uses of Glucocorticoids
- Rheumatoid disorders (e.g., RA, SLE, vasculitis)
- Treatment of allergies
- Organ transplants (prevents graft rejection by inhibiting host immune system)
- Kidney (treats nephrotic syndrome)
- Treatment of inflammatory conditions (e.g., skin, inflammatory eye diseases, GI tract, inflammatory bowel disease, and ulcerative colitis)
- Cancer (treatment of acute lymphocytic leukemias and lymphomas)
Toxicity
- Immune response: increased susceptibility to infections
- Risk of peptic ulcers
- Myopathy & muscle wasting
- Osteoporosis
- Hyperglycemia
- Behavioral changes: hypomania or acute psychosis
- Cataracts (posterior subcapsular), glaucoma
- Fluid & electrolyte balance: Na retention, HT, hypokalemia
- HPA Axis suppression
- Others: acne, thinning of skin, purple striae, hirsutism, menstrual abnormalities, weight gain, pancreatitis
Mineralocorticoids
- Aldosterone
- Desoxycorticosterone
- Fludrocortisone (synthetic corticosteroid, the most commonly used salt-retaining hormone)
Inhibitors of Adrenocorticoid Biosynthesis or Function
- Ketoconazole (an antifungal agent that strongly inhibits all gonadal and adrenal steroid hormone synthesis)
- Spironolactone (antihypertensive drug that competes for the mineralocorticoid receptor and inhibits sodium reabsorption in the kidney)
Quiz about the adrenal gland, its structure, and the synthesis of corticosteroids, including cortisol and aldosterone.
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