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Adrenal Function Testing




ADRENAL GLAND REVIEW
--cortex has three layers: glomerulosa, fasciculata, reticularis, each makes different hormone
--zona glomerulosa --> aldosterone (gAL)
--zona fasciculata --> cortisol (fasC)
--zona reticularis --> androgens, estrogen (rANE)
--medulla --> catecholamines, norepinephrine, epinephrine, metanephrine (catch no epi men)
--CRH = corticotropin-releasing hormone, made in hypothalamas, stims ACTH prod
--ACTH from ant pit, stims adrenal cortex to make cortisol



CORTISOL ACTIONS
--affects metabolism of carbs, prots, fats
--increases blood glucose by stimulating glycogenolysis and gluconeogenesis
--increases protein breakdown, results in negative nitrogen balance
--causes selective lipolysis: loss of fat in extremities and accumulation on trunk and lower face (buffalo hump, moon facies)
--suppresses inflammation, reduces synthesis of prostacyclins, suppresses eosinophils
--suppresses pituitary hormones: ACTH, LH, FSH, TSH, GH



CORTISOL
--the "stress hormone"
--a glucocorticoid produced by the adrenal cortex (in the zonas fasciculata and reticularis)
--controlled by CRH
--increases blood pressure and blood sugar, reduces immune responses
--major diurnal variation
--normal high: 8am or so
--1/3-2/3 of high level at 4pm
--lowest at midnight
--long term night workers may have opposite pattern
--NORMAL serum LEVELS: adult/elder 8am: 6-28, 4pm: 2-12, child 8am: 3-21, 4pm: 3-10
--Interfering factors: preg increases, stress (phys or emot) increases, drugs
--serum INCREASE ETIO: Cushing's dz or syndrome, ectopic ACTH tumor, stress, hyperthyroid, obesity, exogenous therapy
--serum DECREASE ETIO: Addisons's dz, adrenal hyperplasia, hypopituiarism, hypothyroidism
--URINE screen for Cushing's & Addisons: more reliable than blood levels for dx
--urine levels not affected by body weight
--urine levels best expressed as per gram creatinine, varies by <10% daily
--low in Addison's dz and w/ hypopituitary
--high in Cushing's syndrome and dz



CORTISOL/ACTH levels in adrenal dysfx
--Cushing's syndrome: high cort, low ACTH
--Cushing's dz: high cort, high ACTH
--Addison's dz: low cort, high ACTH
--hypopituatarism: low cort, low ACTH

CUSHING'S SYNDROME
--excess cortisol from any cause
--95% show elevation in urine cortisol
--hyperglycemia-->stimulates gluconeogenesis and glycogenolysis
--negative nitrogen balance-->osteoporosis, muscle wasting, reduced fibrogenesis, thin skin, easy bruising
--salt and water retention-->tendency to CHF with hypokalemia
--reduced immune response-->more infx
--abnormal fat metabolism-->central deposition, loss in extremities
--suppression of ACTH
--NEUTROPHILIA
--mental effects: depression, confusion, occ frank psychosis
--one common etio: exogenous glucocorticoids

CORTISOL DEFICIENCY
--incl Addison's dz
--tends toward HYPOGLYCEMIA, increased sensitivity to insulin
--reduced mobilization of peripheral protein and fat
--reduced gluconeogenesis
--loss of salt and water: low Na, high K
--LOW NEUTS, high eos
--non-specific malaise, fatigue, GI upsets

ADRENOCORTICOTROPIC HORMONE = ACTH
--test this to eval anterior pituitary function
--affords greatest insight into cause of Cushing's or Addison's
--normal levels show diurnal variation
--am: 15-100 pg/ml
--pm: < 50 pg/ml
--low in Cushing's syndrome and w/ hypopituitary
--high in Cushing's dz and Addison's dz
--INCREASE ETIO: Addisons = primary adrenal insufficiency, adrenogenital syndrome = congential adrenal hypoplasia (CAH);, Cushing's DZ (pituitary dependent adrenal hyperplasia, ectopic ACTH syndrome (tumor in lung, pancreas, thymus or ovary), stress
--DECREASE ETIO: Cushing's syndrome (exogenous cortisol intake, overproduction, any hypercortisolemia), adrenal adenoma or carcinoma, exogenous steroid administration, hypotituitarism-->secondary adrenal insufficiency

DEXAMETHASONE SUPPRESSION TEST
--used to evaluate pts presenting with glucocorticosteroid excess
--many other medical uses: anti-inflammatory (for RA), immunosuppressant in autoimmune dz, multiple myeloma tx, in preg to promote fetal pulmonary maturation, for high altitude cerebral edema, for side effects of chemo, in cases of CA compression of spinal cord, and lots more
--20-30 times more potent than hydrocortisone and 4-5 times prednisone
--a synthetic steroid
--suppresses ACTH secretion in normal people
--normally results in reduced stimulation to adrenal glands
--plasma cortisol levels should drop 50% (or >)
--this feedback system does not function properly in pts with Cushing's syndrome (cortisol production is not suppressed)
--pts with Cushing's dz relatively resistant to suppression: high dose will suppress
--imp in dx of adrenal hyperfx: Cushing's
--helps distinguish cause of hyperfunction: pituitary or ectopic ACTH?
--DS test based on pituitary ACTH secretion, dependence on plasma cortisol feedback mechanism
--increased plasma cortisol level suppress ACTH secretion
--decreased cortisol levels stimulate ACTH secretion
--HIGH DOSE DEX results in cases of Cushing's syndrome:
----if dt bilateral adrenal hyperplasia-->50% reduction in plasma cort.
----dt adrenal adenoma or CA, ectopic ACTH producing tumor or exogenous glucocorticoids-->no change in cortisol
----Cushing's dz + high dose dex --> 50% decrease in plasma cort or urinary free cortisol




FINAL EXAM STUDY QUESTIONS ON THIS MATERIAL:

9. Know cortisol & ACTH patterns for Cushing’s Syndrome vs. Cushing’s Dz & Addison’s Dz.
--Cushings syndrome: high cortisol, low ACTH
--Cushings dz: high cortisol, high ACTH
--Addisons dz: low cort, high ACTH

What test is useful to screen for Cushing’s Syndrome?
--24 hr urinary free cortisol (also useful for Addison’s dz)

10. How might Cushing’s Syndrome & Addison’s Dz influence test results on a Basic Metabolic Profile?

???
--Cushings: incr: Cl-, Glu, Na+, decr: K+, Ca++
--Addisons: decr: Cl-, Glu, Na+, incr: K+, Ca++
Cl- Glu K+ Na+ Ca++
Cushing’s > > < > <
Addison’s < < > < >

Be able to predict the effect of excess cortisol on thyroid gland function.
--From http://www.virginiahopkinstestkits.com/cortisolzava.html: “Too much cortisol, again caused by the adrenal glands’ response to excessive stressors, causes the tissues to no longer respond to the thyroid hormone signal. It creates a condition of thyroid resistance, meaning that thyroid hormone levels can be normal, but tissues fail to respond as efficiently to the thyroid signal. This resistance to the thyroid hormone signal caused by high cortisol is not just restricted to thyroid hormone but applies to all other hormones such as insulin, progesterone, estrogens, testosterone, and even cortisol itself. When cortisol gets too high, you start getting resistance from the hormone receptors, and it requires more hormones to create the same effect. That’s why chronic stress, which elevates cortisol levels, makes you feel so rotten—none of the hormones are allowed to work at optimal levels.”
--excess cortisol→thyroid hormone resistance
--low cortisol→decreased thyroid function

11. What is the Dexamethasone Suppression test used to dx?
--adrenal hyperfunction, Cushing’s
--distinguish cause of hyperfunction (pituitary-dependent Cushing’s or ectopic ACTH)
--increased plasma cortisol suppresses ACTH secretion, decreased stimulates

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