16 - Adrenal Hormones Flashcards
Where are steroid hormones synthesized?
- Adrenal cortex (adrenocorticoids)
- Ovaries, testes (sex steroids)
Steroid secretion is controlled by _____ secreted from the _____
- Peptides
- Hypothalamus and pituitary
What are the general effects of glucocorticoids?
- Modulation of carbohydrate metabolism
- Increase levels of glycogen in liver and circulating glucose
- Early effects stimulate immune system
- Prolonged secretion leads to immune suppression and cell death
When does secretion of glucocorticoids increase?
During periods of stress
What are the general effects of adrenocorticoids?
- Modulation of water balance (control of water reabsorption)
- Promotes Na+ uptake in tubular epithelial cells
- Modulation of K+ ion transport
When are adrenocorticoids secreted?
During periods of stress
Secretion of ___ during stress is essential for life
Cortisol
Can glucocorticoids interact w/ mineralocorticoid receptors and vice versa?
Yes
Describe the humoral pathway response to stress
- Visceral brain activates limbic system
- Limbic system causes anterior pituitary to stimulate adrenal cortex to release cortisol
- Cortisol is converted into glycogen or interacts w/ GR receptor to produce anti-inflammatory effects and cell death
Describe the RAS pathway response to stress
- Visceral brain releases norepinephrine, which stimulates renin release
- Renin -> angiotensin 1 and 2 -> adrenal cortex -> aldosterone
- Aldosterone effects sodium uptake, which causes increased BP
Which factors increase cortisol levels?
- Stress
- Hypothyroidism
- Liver disease
What happens to circulating cortisol?
- 90% is bound to corticosteroid-binding globulin
- Remainder is free or loosely bound to albumin, allowing it exert its effect on target cells
What does increased transcription of glucocorticoids cause?
Production of anti-inflammatory or inhibitory cytokines (IL-10, IL-12, IL-1 receptor antagonists)
What does decreased transcription of glucocorticoids cause?
Production of inflammatory cytokines (IL-2, 3, 4, 5, 6, 13, and 15) and inflammatory enzymes (iNOS, COX-2)
What does increased serum glucose levels cause?
- Increased insulin release
- Decrease glucose uptake by muscle cells
What does increased insulin secretion cause?
- Increased lipogenesis
- Decreased lipolysis (to a lesser degree)
What is the effect of glucocorticoids in lymphoid and connective tissue, muscle, peripheral fat, and skin?
- Decreased muscle mass
- Weakness and thinning of skin
What is the effect of glucocorticoids on bone?
- Causes osteoporosis in Cushing’s syndrome and imposes a major limitation in the long-term therapeutic use of glucocorticoids
- Reduce growth in children
What are the GENERAL effects of glucocorticoids?
- Catabolic
- Anti-anabolic
- Anti-inflammatory
- Immunosuppressive
How are glucocorticoids anti-inflammatory?
- Effect concentration, distribution, and function of peripheral leukocytes
- Suppress inflammatory cytokines, chemokines, and other mediators of inflammation (increase neutrophils and decrease lymphocytes, monocytes, eosinophils, and basophils)
How are glucocorticoids immunosuppressive?
- Down regulate T-lymphocyte proliferation
- Inhibit T-lymphocyte activation
- Down regulate plasma cells
- Inhibit inflammatory cell migration
- Inhibit antigen phagocytosis by macrophages
- Suppress antibody production
Do glucocorticoids inhibit or activate phospholipase A2? How do they do this?
- Inhibit
- Decrease synthesis of arachidonic acid
- Decrease prostaglandins, leukotrienes, and platelet-activating factor
Do glucocorticoids increase or decrease expression of COX-2? How?
Decrease by decreasing prostaglandins
What is the effect of glucocorticoids on mast cell and basophil secretion?
Cause vasoconstriction and decrease capillary permeability, so depress mast cell and basophil secretion
What are some other effects of glucocorticoids?
- Associated w/ depression
- Behavioural disturbances (insomnia, euphoria, depression)
- Peptic ulcers
What effect do glucocorticoids have on the pituitary?
Decrease release of ACTH, growth hormone, thyroid-stimulating hormone, and luteinizing hormone
What effect do glucocorticoids have on fat?
Increase fat redistribution in the body (increase visceral, facial, and supraclavicular fat)
What are the haematopoietic effects of glucocorticoids?
Increase platelets and red blood cells
How is the appropriate dose of glucocorticoids determined? What is the minimum dose?
- Determined through trial and error
- Minimum is 10 mg b/c that is the normal amount in the body
Is a single dose of glucocorticoids harmful?
No
What is a problem w/ long-term corticosteroid use?
Increases incidence of disabling or life threatening effects
Why shouldn’t high dose corticosteroids be stopped abruptly?
May induce adrenal insufficiency that can be life threatening
What are the uses of exogenous glucocorticoids?
- Shock (ex: septic shock)
- Cerebral edema
- Increased intracranial pressure
- Allergies (hay fever, urticaria, bee stings, contact dermatitis)
- Arthritis
- Asthma
- Ulcerative colitis, Crohn’s disease
- Organ transplants
- Fetal lung maturation (before 34 weeks gestation)
What are 2 topical corticosteriods?
Betamethasone and hydrocortisone
What are some adverse effects of glucocorticoids?
- Decrease resistance to infections
- CNS effects
- Hyperglycemia/glycosuria
- Electrolyte imbalance
- Peptic ulcer
What can Cushing’s syndrome cause?
- Decrease resistance to infections
- Alterations in appearance
- CNS effects
- Hyperglycemia/glycosuria
- Muscle weakness and atrophy
- Poor wound healing
- Hirsutism, skin thinning
What is mifeprestone?
- Glucocorticoid antagonist, blocks cortisol binding
- Reduces excess cortisol effects in Cushing’s
What is Addison’s disease?
Decrease secretion of glucocorticoids and sometimes aldosterone
What are sx of Addison’s disease?
- Fatigue
- Syncope
- GI upset
- CNS effects
- Joint/muscle pain
- Hyperpigmentation
What can severe adrenal insufficiency cause?
- Hyponatremia
- Hyperkalemia
- Hypercalcemia
- Convulsions
- Fever
- Death
