Term
| What enzymatic deficiencies can cause congenital adrenal hyperplasia? |
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Definition
21B-hydroxylase or 11B-hydroxylase deficiency result in congenital adrenal hyperplasia. (virulization of young girls)
The pathway to cortisol is blocked, and the cholesterol is pushed into the androgen synthesis pathway. There is no cortisol for feedback inhibition, so angrogens continue to be made, and made, and made, leading to the virulization.
Tx=cortisol (hydrocortisone, cortisone)
This enzyme deficiency will also result in precocious puberty in boys. |
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Term
| is mineralocorticoid function blocked in 11 or 21B hydroxylase deficiency? |
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Definition
In both deficiencies, cortisol synthesis is blocked, but in 11B-hydroxylase deficiency, there is a buildup of the substrate 11-deoxycorticosterone, which has mineralocorticoid function. This can lead to Na+ and water retention, causing increased blood pressure.
prrogesterone - 21B-hydroxylase -> 11deoxycorticosterone - 11B-hydroxylase -> coricosterone -> aldosterone |
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Term
| What is the preferred glucocorticoid to be administered to the mother to help fetal lung development? |
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Definition
| Betamethasone, because it is less bound by plasma proteins, allowing it to cross the placenta more readily. |
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Term
| Why are glucocorticoids administered alongside albuterol in asthma attacks? |
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Definition
| glucocorticoids have permissive actions as well as direct actions. One example of their permissive actions is in the bronchial smooth muscle. Administering glucocorticoids increases the response of bronchial smooth muscle to beta-2 agonists! |
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Term
| Why can glucocorticoids promote peptic ulcers? |
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Definition
Glucocorticoids stimulate lipocortin synthesis. Lipocortin inhibits phospholipase A2, thereby blocking both prostaglandin and leukotriene synthesis. Recall that prostaglandins (PGE1, 2) have a protective effect on the stomach by causing mucous production and acid inhibition. Therefore, glucocorticoids decrease this protective effect.
Glucocorticoids also inhibit the immune system response (leukocyte migration etc), thereby decreasing the body's ability to fight off H. pylori, which is strongly associated with peptic ulcers! |
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Term
Describe the adverse effects of glucocorticoids:
hyperglycemia
Striae
Decreased muscle mass
osteoporosis
Hypertension |
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Definition
Glucocorticoids are diabetogenic because they promote gluconeogenesis and inhibit glucose uptake by cells
Glucocorticoids stimulate catabolism of proteins. This results in muscle loss, as well as catabolism of connective tissue in the skin, leading to striae. K+ wasting also results in muscle weakness.
Glucocorticoids stimulate bone resorption and inhibit osteoblasts, which promotes osteoporosis!
Most glucocorticoids have mineralocorticoid function, so they can promote salt and water retention, leading to elevated blood pressure! |
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Term
| What drug is administered in the case of Conn's Syndrome (hyperaldosteronism)? |
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Definition
| Give the aldosterone antagonist Spironolactone! |
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Term
| You suspect Cushing's Syndrome... what drug would you use to confirm your diagnosis? |
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Definition
Perform a dexamethasone suppression test! Administer dexamethasone, which will provide a negative feedback to the pituitary release of corticotropin (ACTH)... this should decrease cortisol levels. If the cortisol levels are not decreased, the patient has an ectopic source of cortisol or ACTH!
If the patient has Cushings and the cortisol levels drop, it is likely Cushing's Disease, in which there is a pituitary adenoma producing excessive ACTH. These adenomas still have a negative feedback mechanism, so the cortisol levels will drop with a suppression test... |
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Term
| How do you treat Addison's Disease? What about an Addison Crisis? |
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Definition
Addison's disease is also called "chronic adrenal insufficiency"... you must replace both the glucocorticoids and mineralocorticoids. So give prednisone and fludrocortisone.
Addison's crises must be treated with the short acting glucocorticoid Hydrocortisone administered by IV. This is the active form of the drug, as there is not enough time to convert cortisone in this emergency situation.
MUST INCREASE THE GLUCOCORTICOID DOSE DURING STRESS! |
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Term
| How do you treat congenital adrenal hyperplasia? |
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Definition
Treat it with cortisone! this will provide a negative feedback to the Hypothalamic-Pituitary axis, thereby decreasing the androgen production and inhibiting the virulizing effects of the disease.
Also supply the mineralocorticoid Fludrocortisone.
Recall, 95% of CAH cases are due to a deficiency in 21beta-hydroxylase |
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Term
| A patient presents with weakness, weight loss, hypotension, hyperpigmentation. What disease of the adrenals could this be? |
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Definition
| This is likely Addison's Disease, a primary deficiency of the adrenals that produces a deficiency in all adrenal hormones! Recall that there is no negative feedback to ACTH release. ACTH is made from POMC, which is cleaved to a number of proteins including MSH (melanocyte stimulating hormone)... increased MSH levels cause an increased pigmentation of the skin! |
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Term
| Describe the changes of the HPA axis and adrenals with long-term steroid therapy. |
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Definition
| Corticosteroids cause a negative feedback on the HPA axis, which results in decreased ACTH release. Without ACTH, the adrenals undergo atrophy over time. For this reason, you cannot abruptly stop corticosteroid therapy because the adrenals will still be atrophied and no endogenous cortisol will be produced! You must taper the dose to allow for the recovery of the adrenals. |
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Term
| What drugs inhibit glucocorticoid synthesis by blocking the conversion of cholesterol to pregnenolone? |
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Definition
Aminoglutathimide and ketoconazole.
They are used in the treatment of cushing's syndrome and adrenocortical tumors.
Recall that ketoconazole has the adverse effect of gynecomastia in men because it also blocks androgen synthesis. |
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Term
| What glucocorticoid synthesis inhibitors act by inhibiting 11beta-hydroxylase? |
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Definition
| Metyrapone and ketoconazole inhibit 11beta-hydroxylase and are used in the treatment of cushing's syndrome. Because blocking this enzyme shifts the pathway toward androgens, metyrapone can cause hiruitism in female patients. |
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Term
| What is a glucocorticoid and progesterone antagonist that is also used to induce labor/abortion? |
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Definition
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Term
| Describe the biological vs. plasma half life of glucocorticoids |
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Definition
| The glucocorticoids have a short plasma half-life. However, they produce changes in gene transcription, so their effect/duration of action (their biological half life) is much, much longer! |
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