Adrenal Disorders Pharamcology Flashcards
Anatomic parts of adrenal gland with hormones it produces
Outer cortex
- cortisol
- vasopressin
- aldosterone
- DHEA
Inner medulla
- catecholamines (NE and epinephrine)
Cortisol and aldosterone effects
Cortisol
- Raises plasma glucose levels and stimulates gluconeogenesis
- inhibits glucose uptake except in the brain
- Promotes protein catabolism
- Promotes lipolysis and fat redistribution in the body
- enhances catecholamine effects on blood vessels (HTN)
- decreases osteogenesis and promotes osteoporosis
- immunosupression and anti-inflammation
Aldosterone
- alters sodium and water in the renal collecting duct
- synthesis and secretion regulated by angiotensin 2 at AT1 receptors on zona glomerulosa cells
Cushing syndrome
Excess glucocorticoids
(especially cortisol)
Symptoms:
- obesity
- hyperglycemia and HTN
- osteoporosis
- muscle weakness
- hirsutism
- buffalo hump and strain on abdomen
- poor wound healing
- moon-like facies
Treatment:
- surgical adrenal tumor with HRT therapy (hydrocortisone and cortisone)
- can also use: metyrapoine, aminoglutethimide, ketoconazole
3 drugs used to treat Cushing syndrome
On top of hydrocortisone or cortisone treatment
1) metyrapone:
- 11-B hydroxylase enzyme inhibitor
2) aminoglutethimide
- inhibits conversion of cholesterol -> pregneolone (chemical adrenalectomy)
3) ketoconazole
- inhibits synthesis of all hormones in testes and adrenal cortex
Primary hyperaldosteronism
Excess aldosterone secretion caused by adrenal tumors
Symptoms:
- edema
- fluid/electrolyte disturbances
- HTN
Treatment:
- surgical adrenal resection with fludrocortisone HRT
- Also can use spironolactone (antagonizes aldosterone)
Addison’s disease
Adrenal hormone deficiency
Caused by multiple causes but all result in insufficiency of cortisol and aldosterone levels
Symptoms:
- weakness
- emanciation
- hypoglycemia
- hyperpigmentation of skin
- hyperkalemia
- hyponatremia
- hypotension
Treatment: HRT with hydrocortisone/cortisone and fludrocortisone
What is the diurnal rhythm of cortisol release
Highest levels are in the morning/waking up
Lowest levels found at night
very closely related to sleep-wake cycle
How does stress regulate cortisol release
The Stress descending central pathways increases CRH release from the hypothalamus.
How does angiotensin 2 affect aldosterone secretion
Angiotensin 2 binds to AT1 receptors on zona glomerulosa cells
1) Regulates conversion of cholesterol -> pregneolone Via desmolase enzyme activity
2) Regulates conversion of corticosterone -> aldosterone via aldosterone synthase
Aldosterone effects are increase sodium reabsorption and potassium excretion via Na/K exchanger
DHEA
Produced by the zona reticularis in the adrenal cortex
In males = produces testosterone and is primary androgen throughout life
In females = induces puberty effects but under normal conditions is clinically insignificant after puberty
Glucocorticoid receptors (GRs)
Nuclear receptor family of transcription factors
- reside in the cytoplasm in an inactive form until steroid binding occurs (then it translocates to the nucleus to up-regulate transcriptions of glucocorticoid responsive elements (GREs). This upregulates glucocorticoid production while also inhibiting cycloxygenase 2, nitric oxide and inflammatory cytokine production
Mineralcorticoid receptors (MRs)
Ligand-activated transcription factors and bind to very similar hormone responsive elements
- are expressed in epithelial tissues involved in electrolyte transport (kidney,colon, salivary glands, etc) and in the heart, vasculature and adipose tissue
What is the purpose of the dexamethasone test
Diagnosing Cushing syndrome
Inject a patient with dexamethasone (contains potent glucocorticoid action but little Mineralcorticoid action)
- administer in the evening before bed and then measure in the morning
Normal functional HPA axis = ACTH release and cortisol levels are suppressed
Cushing syndrome = ACTRH levels are suppressed but cortisol levels will remain elevated
Corticosteroid toxicity
Occurs with cessation of chronic steroid use of acute high dose use
If abruptly stopped, results in acute Addison’s disease
- because of this tapered dose is required instead of going cold turkey (requires several weeks to months to taper off and minor ACTH and cortisol levels)
Withdrawal syndrome symptoms:
- fever
- myalgia
- arthralgia
- malaise
- *Continued use of high dose corticosteroids in high doses
- fluid electrolytes
- HTN
- hyperglycemia
- increased susceptibility to infections
- peptic ulcers, osteoporosis
- myopathy
- cataracts and growth arrest
What are the three most common characteristics of physical signs associated with excess glucocorticoid use
Fat redistribution (buffalo hump)
Striae (collagen rearrangement)
Ecchymoses (poor wound healing)