115 Questions
What is the precursor of steroids of both gonadal and adrenal origin?
Cholesterol
Which hormone plays a role in the regulation of blood pressure by acting on the kidneys to increase sodium reabsorption?
Aldosterone
What process does cortisol from the zona fasciculata regulate throughout the body?
Metabolism, immune response, and response to stress
Which hormone causes water to be doubly absorbed along with sodium, thus increasing blood volume?
Aldosterone
What do adrenal androgens serve as precursors for?
Gonadal steroids formation
What stimulates the production of ACTH from the pituitary?
Corticotropin-releasing hormone (CRH)
When does cortisol peak in healthy individuals?
Early morning, around 4-6am
What influences the release of Corticotropin from the hypothalamus?
Stress, physical activity, and illness
What is essential for the maintenance of homeostasis and enables the organism to prepare to manage stress?
Cortisol
At what time does cortisol peak in healthy individuals?
4-6am
What does CRH stimulate the production of from the pituitary gland?
Cortisol
In addition to stress and physical activity, what influences the release of Corticotropin from the hypothalamus?
Blood glucose levels
What is the primary influence on the release of Corticotropin from the hypothalamus?
Blood levels of cortisol
What percentage of the circulating cortisol is typically bound to Corticosteroid-binding globulin (CBG) under normal circumstances?
90%
What happens to the concentration of free cortisol when cortisol levels exceed 20–30 mcg/dL?
Rises rapidly
From which precursor is cortisol synthesized?
Cholesterol
What regulates glucocorticoid (GC) synthesis and secretion, and is very sensitive to negative feedback by circulating cortisol?
Hypothalamic-Pituitary axis (H-P)
What happens to the half-life of cortisol when large amounts of the drug hydrocortisone are administered?
Increases
Which protein is largely responsible for binding synthetic corticosteroids such as dexamethasone?
Albumin
In which conditions might the half-life of cortisol be increased?
Liver disease
What is the role of the steroid-receptor complex after it has entered the nucleus?
Bind to a glucocorticoid response element (GRE) and regulate transcription
What is the main function of corticosteroid-binding globulin (CBG) in relation to cortisol?
To bind to cortisol in the blood
What happens to the steroid-receptor complex when it binds a molecule of cortisol?
An unstable complex is created and heat-shock proteins are released
What is the main function of FKBP5 in relation to the intracellular receptor complex?
Stabilize proteins including heat-shock protein 90 (hsp90)
What enables the steroid-receptor complex to regulate transcription after entering the nucleus?
Dimerization of the complex
What is the immediate effect of cortisol binding to the steroid-receptor complex?
Creation of an unstable complex and release of hsp90
What is the main physiological effect of glucocorticoids?
Stimulating gluconeogenesis and glycogen synthesis
What is the metabolic effect of glucocorticoids in the fasting state?
Releasing amino acids from muscle catabolism
What are the catabolic and anti-anabolic effects of supraphysiologic amounts of glucocorticoids?
Stimulating lipolysis and reducing growth in children
Which effect makes glucocorticoids dramatically reduce the manifestations of inflammation?
Influencing leukocyte function
What is the primary effect of glucocorticoids on tissue macrophages and other antigen-presenting cells?
Limiting their ability to phagocytose and kill microorganisms
What effect do supraphysiologic amounts of glucocorticoids have on muscle mass?
Decrease muscle mass and cause thinning of the skin
How do glucocorticoids maintain an adequate glucose supply to the brain in the fasting state?
By releasing amino acids from muscle catabolism
What effect do glucocorticoids have on the fetal lungs?
Stimulate the production of surfactant
How does cortisol deficiency affect renal function?
Diminishes ability to excrete a water load
What is the long-term predisposition associated with the use of glucocorticoids?
Depression, obesity, and metabolic syndrome
What is the main influence of alterations in the glucocorticoid molecule?
Stability of the side chain
What is the primary function of synthetic corticosteroids given by mouth?
Rapid and complete absorption
What effect do alterations in the glucocorticoid molecule have on its affinity for receptors?
Decreased affinity for glucocorticoid and mineralocorticoid receptors
Which characteristics of synthetic corticosteroids are pharmacologically and therapeutically important?
Protein-binding affinity
What is the primary effect of synthetic corticosteroids binding to specific intracellular receptor proteins?
Production of different effects with varied ratios of potency
Which glucocorticoid is approximately 25-30 times more potent than Hydrocortisone in terms of antiinflammatory effect?
Dexamethasone
What is the salt-retaining effect of Hydrocortisone and Prednisone?
They both have a salt-retaining effect
What is the equivalent oral dose of Prednisone for 20mg of Hydrocortisone?
5mg
Which glucocorticoids have a salt-retaining effect when Fludrocortisone is not available?
Hydrocortisone and Methylprednisolone
In what form are all the available glucocorticoids?
Some injectable and some used topically
What makes the mineralocorticoids different from Hydrocortisone and Methylprednisolone?
They have a higher salt-retaining effect
In what condition would increasing the dose of Hydrocortisone or Prednisone be necessary?
To manage salt retention when Fludrocortisone is not available
What are the characteristic symptoms of chronic adrenocortical insufficiency (Addison’s disease)?
Hypotension, weight loss, and hyperpigmentation
What is the replacement therapy for chronic adrenocortical insufficiency (Addison's disease) if fludrocortisone is not available?
Sodium tablets
What may produce acute adrenal insufficiency with circulatory shock and even death in patients with chronic adrenocortical insufficiency?
Minor noxious, traumatic, or infectious stimuli
What is the most common cause of adrenal gland failure due to bleeding into the adrenal glands?
Neisseria meningitides infection
What is the recommended immediate treatment for acute adrenocortical insufficiency?
High dose of parenteral hydrocortisone every 8 hrs
Which syndrome is commonly associated with adrenal gland failure due to bleeding into the adrenal glands?
Waterhouse–Friderichsen syndrome
Which form of congenital adrenal hyperplasia is the most common?
21-hydroxylase deficiency
What is the condition characterized by a defect in the synthesis of cortisol due to a mutation or deletion of genes?
Congenital adrenal hyperplasia
Which deficiency is NOT one of the six forms of congenital adrenal hyperplasia?
Corticosteroid-binding globulin deficiency
What is the primary characteristic of the genitalia in individuals with CAH due to 21-hydroxylase deficiency?
Ambiguous genitalia with clitoromegaly and empty labioscrotal folds
What is the purpose of adjusting the dosage of Hydrocortisone or Prednisone in the treatment of CAH due to 21-hydroxylase deficiency?
To allow normal growth, bone maturation, and prevent androgen excess
What is the most common treatment for CAH due to 21-hydroxylase deficiency?
Hydrocortisone and Fludrocortisone
What is a potential cause of secondary adrenal insufficiency?
Sellar/suprasellar tumors
Which treatment could lead to secondary adrenal insufficiency?
Radiation treatment of the pituitary gland
What is the recommended course of action for patients with adrenal insufficiency during times of illness or surgery?
Increase the steroid dose 2-4 times the maintenance level
Why do patients with adrenal insufficiency need to increase their steroid dose during times of stress?
Their body does not produce enough cortisol
What is the consequence of not increasing the steroid dose for patients with adrenal insufficiency during times of stress?
Risk of circulatory shock and even death
What differentiates the response to stress in normal individuals from those with adrenal insufficiency?
The ability to produce excess cortisol in times of stress
What is the purpose of reducing the corticosteroid dose slowly until reaching replacement levels?
To minimize the risk of acute adrenal insufficiency
What is the purpose of conducting a stimulation test during corticosteroid therapy withdrawal?
To assess the activity of the Hypothalamopituitary axis
What is the purpose of conducting a stimulation test during corticosteroid therapy withdrawal?
To assess the activity of the Hypothalamopituitary axis
What is the effect of ACTH suppression during acute corticosteroid treatment?
It inhibits the activity of the Hypothalamopituitary axis
Why is ACTH suppression a concern during acute corticosteroid treatment?
It may lead to adrenal insufficiency when the treatment is discontinued
What is a potential cause of Cushing’s syndrome?
Ectopic production of ACTH by other tumors
What is a treatment option for Cushing’s syndrome?
Surgical removal of tumor
What can result from bilateral adrenalectomy without glucocorticoid maintenance therapy?
Adrenal insufficiency
What physical manifestation is typically seen in individuals with Cushing syndrome?
Moon facie
What is a common symptom of Cushing syndrome resulting from protein loss?
Muscle wasting
Which of the following is a consequence of prolonged and marked increase in glucocorticoid secretion in Cushing syndrome?
Thinning or purple striae
What are the characteristic symptoms of primary aldosteronism?
Hypertension, weakness, and tetany
What can cause primary aldosteronism besides excessive production by an adrenal adenoma?
Abnormal secretion by hyperplastic glands
What is the recommended treatment for secondary aldosteronism?
Fludrocortisone
What is the purpose of the dexamethasone suppression test for the diagnosis of Cushing’s syndrome?
To measure the response of the adrenal glands to ACTH
What does a normal result indicate in the dexamethasone suppression test for the diagnosis of Cushing’s syndrome?
Decrease in cortisol levels in response to dexamethasone
What is the expected result of the dexamethasone suppression test in individuals with Cushing’s syndrome?
No change in cortisol levels in response to dexamethasone
How does the fetal secretion of cortisol regulate lung maturation in the fetus?
It reduces the risk of respiratory distress syndrome in premature infants
What is the impact of treating the mother with large doses of glucocorticoid on premature infants delivered before 34 weeks of gestation?
It reduces the risk of respiratory distress syndrome
Which synthetic glucocorticoids have been shown to reduce the incidence of respiratory distress syndrome in prematurely delivered infants?
Betamethasone, Dexamethasone
What undesirable side effects may be observed when steroids are given in a long term or high doses?
Insomnia and hypomania
When is adrenal suppression likely to occur after steroid use?
After 2 weeks of continuous use
What can be observed even after only a few days of steroid treatment?
Acute peptic ulcers
In patients with normal adrenals, what was ACTH used for in the past?
To induce the endogenous production of cortisol
Why has the use of ACTH as a therapeutic agent been abandoned, except when an increase in androgens is desirable?
Because it causes adrenal insufficiency
What was the historical purpose of using ACTH in patients with normal adrenals?
To stimulate cortisol production
What factors should be considered in determining the dosage regimen to be used?
The seriousness of the disease, the required drug amount, and the therapy duration
For some diseases, what is the relationship between the amount needed for maintenance of therapeutic effect and the initial dose?
The amount required for maintenance is less than the initial dose
What is recommended in determining the lowest possible dosage for the needed effect?
Gradually lowering the dose until a significant decrease in signs or symptoms is noted
Which dosage form is specifically recommended for joint disease?
Intra-articular injections
What is the primary role of mineralocorticoids?
Increase plasma volume and lead to hypokalemia
What are the effects of excessive levels of aldosterone?
Hypokalemia, metabolic alkalosis, increased plasma volume, and hypertension
Which steroid serves as a precursor of aldosterone?
Deoxycorticosterone (DOC)
Which steroid is the most widely used mineralocorticoid?
Fludrocortisone
Which enzyme required for steroid hormone synthesis is inhibited by ketoconazole?
P450c17
What is the primary function of aminoglutethimide in patients with breast carcinoma?
Reducing or eliminating estrogen production
At what level does etomidate inhibit adrenal steroidogenesis?
11β hydroxylase
In patients with Cushing’s syndrome due to adrenocortical cancer who do not respond to mitotane, aminoglutethimide is used in conjunction with which medication to reduce steroid secretion?
Metyrapone
What is the main use of etomidate at subhypnotic doses?
Treating Cushing’s syndrome
Which medication can be administered to pregnant women with Cushing’s syndrome?
Mifepristone
What is the primary effect of high doses of mifepristone in patients with Cushing's Syndrome due to ectopic ACTH production or adrenal carcinoma?
Antiglucocorticoid activity
What is the primary function of METYRAPONE?
Reducing cortisol production
What is the pharmacologic activity of MIFEPRISTONE (RU-486) at the steroid receptor?
Antiglucocorticoid activity
Which adverse effect is most likely to be associated with Spironolactone use?
Gynecomastia
In what condition might Spironolactone be used as a diagnostic test?
Hyperkalemia
Which medication is primarily used as an oral contraceptive?
Drospirenone
What is the primary use of Eplerenone?
Treatment of hypertension
How does MIFEPRISTONE (RU-486) differ from other adrenal-inhibiting medications with respect to pregnancy?
It is recommended for inoperable patients with ectopic ACTH secretion or adrenal carcinoma
What is the main benefit of Spironolactone in heart failure?
Diuretic benefits
Test your knowledge on the synthesis of hormones from cholesterol and their role in the regulation of blood pressure. Understand the sequential action of enzymes in converting cholesterol into hormones and the functions of aldosterone in maintaining blood pressure.
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