Clinical Chemistry: Adrenal Function

autoimmune

70% of Addison's Disease are __________.

renin, angiotensinogen, AGI (angiotensin-I), AGII (angiotensin-II),

A decrease in renal blood flow, pressure, and/or dehydration stimulates the kidney to increase __a__ production. __a__ is an enzyme that converts a precursor molecule _____b______ (precursor: biologically inactive) to _c_. _c_ has very little biologic activity; when its released in the blood it comes into contact with epithelial cells that express angiotensin-converting enzyme (AGC) which converts _c_ to __d__, which is one of the most biologically active compounds in vertebrate biology. __d__ is a powerful stimulator of aldosterone synthesis and release.

cortisol, ACTH

A diagnosis of Addison's Disease requires low baseline AM & PM ________ levels and increased ____ (>200 pg/mL). Treatment: Synthetic steroids from G & R zones are replaced.

DHEA-S, DHEA, testosterone, tumors

A diagnosis of androgen excess requires high levels of _____, __x__, ad ____________. Treatment involves surgical removal of ______; exogenous __x__

F (zona fasciculata)

ACTH is converted to cortisol in the _ zone.

G (zona glomerulosa)

High potassium angiotensin II (AGII) is converted to aldosterone in the _ zone

aldosterone

Hormone that stimulates the kidney to retain sodium ions and water and increase blood pressure. Decreased Renal Blood Flow (RBQ) decreased blood pressure will stimulate the kidney to cause stimulation of the adrenal cortex and cause an increase in _____x_____. _____x_____ then directs the kidney to increase sodium reabsorption, (wherever sodium goes water goes) resulting in high water reabsorption. Increase in water comes back to the body and renal blood flow and blood pressure come back to normal.

Tyrosine, DOPA, Dopamine, Norepinephrine, Epinephrine

Biosynthetic pathway for major catecholamines: ________ → ____ → ________ → ______________ → ___________

tyrosine

Catecholamines derived from ________ include: 1. Dopamine 2. Norepinephrine 3. Epinephrine

Isolated hypoaldosteronism

Caused by adrenal gland destruction, chronic heparin therapy, unilateral adrenalectomy, and G-layer enzyme

autonomic, panic, stress, drugs, tyramine, pheochromocytoma

Causes of Sympathetic Hyperactivity: 1. _________ dysfunction. 2. _____ attack. 3. ______ responses: hypoglycemia, injury, infection, psychosis, seizures. 4. _____: decongestants, appetite suppressors, stimulants, bronchodilators, MAO inhibitors, thyroid hormone, cortisol, etc. 5. Foods containing ________: imported beer, red wine, soy sauce, overripe/fermented foods, smoked or aged meats 6. ________________: catecholamine-producing tumor

stress

Chronic ___x___ will cause the adrenal cortex to overproduce and release more cortisol. Because cortisol opposed the action of insulin, chronic ___x___ is also a predisposition to diabetes

ACTH, tumor, anterior pituitary, hypothalamus

Cushing's Syndrome can be an ____-secreting _____ on the __________ _________ in secondary or on the _____________ in tertiary.

hyperfunction

Cushing's Syndrome caused by _____________ is the result of glucocorticoid oversecretion.

metabolic alkalosis

In hyperaldosteronism, as sodium is reabsorbed and potassium excreted, aldosterone is going to stimulate the kidney to reabsorb more bicarbonate (HCO3-).

hypertension

In hyperaldosteronism, if the adrenal cortex's zona glomerulosa is producing too much aldosterone, that's going to cause an excessive reabsorption of water and overload the cardiovascular system with fluid.

urine, plasma, morning, night, ACTH, dirunal

In order to diagnose Cushing's Syndrome, cortisol excess must be documented.: 1._____ free cortisol. 2. Random ______ cortisol levels. 3. Baseline _______ vs. _____ cortisol concentration. 4. Measure ____ blood concentration. 5. Determine if the _______ rhythm is lost.

decreased, decreased, increased

In primary (I0) Cushing's Syndrome, due to adrenal defect, CRF is [increased/decreased], ACTH is [increased/decreased], and cortisol is [increased/decreased].

increased, increased, decreased, decreased

In primary (I0) adrenal insufficiency, due to adrenal defect, CRF is [increased/decreased], ACTH is [increased/decreased], cortisol is [increased/decreased], and aldosterone is [increased/decreased].

decreased, increased, increased

In secondary (I0) Cushing's Syndrome, due to pituitary defect, CRF is [increased/decreased], ACTH is [increased/decreased], and cortisol is [increased/decreased].

increased, decreased, decreased

In secondary (I0) adrenal insufficiency, due to pituitary defect, CRF is [increased/decreased], ACTH is [increased/decreased], and cortisol is [increased/decreased].

increased, increased, increased

In tertiary (I0) Cushing's Syndrome, due to hypothalamus defect, CRF is [increased/decreased], ACTH is [increased/decreased], and cortisol is [increased/decreased].

decreased, decreased, decreased

In tertiary (I0) adrenal insufficiency, due to hypothalamus defect, CRF is [increased/decreased], ACTH is [increased/decreased], and cortisol is [increased/decreased].

vanillylmandelic (VMA), homovanillic (HVA)

Major metabolites of catecholamine include: 1. ________________ acid 2. ____________ acid Measured in the urine.

inflammatory

Many people who have chronic ____________ disease are on maintenance doses of cortisol, but when they have an acute flare up, the doctor will increase that dosage. If this elevated dose is prolonged, the adrenal gland will begin to shut down.

metanephrines, catecholamine metabolites, plasma catecholamines, urine metanephrines, plasma metanephrines, urine metanephrines, radiologic

Diagnosis of Pheochromocytoma: Fractionated _____________ & _____________ ___________ (VMA in a 24-hour collection): best test for diagnosis - rare and difficult. Total ______ ______________ & _____ _____________: most sensitive screening profile. ______ _____________ (measured by HPLC or RIA): touted as most specific & sensitive diagnostic test. _____ _____________: possibly most sensitive urine test. __________ localization: CT, MRI, PET scanning.

iatrogenic

Most common cause of Cushing's syndrome; results from an overdosage of glucocorticoids, usually in patients with chronic inflammatory diseases.

VMA (vanillylmandelic acid)

Most common test for elevated catecholines is ___ in urine.

Adrenal Incidentaloma

Non-functioning adrenal mass, typically >1 cm in diameter, found by chance in CT, MRI, & ultrasound imaging of abdomen. Most are benign. 6% frequency, increases with age. All lesions should be assessed for malignancy or hypersecretion. Surgery should be considered if adrenal mass is cancerous; autonomously secreting cortisol, Aldo, or catecholamines; ≥4 cm in diameter; or growing.

dineral rhythm

Obliteration of the _______ ______ because the cortisol is always high or low is indicative of hyper-or-hypocortisolism (cushing's vs. addison's)

RAS (renin-angiotensin system)

Regulates aldosterone secretion, which in turn regulates blood pressure and water balance. Low blood volume → secretion of renin.

plasma renin, aldosterone

Screening test for adrenocarcinoma: ______ _____:___________ ratio.

Serum Potassium, K+

Screening test for primary aldosteronism: _____ __________. If low, urine __ exretion.

pregnenolone

Steroids are produced by the conversion of cholesterol to ____________.

catecholamines

The adrenal medulla secretes ______________, which have been produced by sympathetic nervous cells, directly into circulation in lieu of transmitting messages via efferent axons. Acts as first responder to stress to promote fight-or-flight response.

DHEA (dehydroepiandrosterone)

The zona reticularis produces ____, a hormone involved in muscle growth, bone density, and the functioning of the cardiovascular system.

aldosterone, renin

Three Criteria of Conn's Syndrome: 1. Elevated plasma _____x_____ and plasma __y__ activity >25. 2. Low plasma __y__ that fails to increase with volume depletion. 3. High _____x_____ that fails to decrease with saline/angiotensin inhibition - captopril suppression

secretory vesicles, non-neuronal, degradation

Three Methods of Catecholamine Elimination: 1. Reuptake into _________ ________. 2. Uptake in ____________ cells (mostly liver). 3. ___________.

surgery, perioperative alpha, familial.

Treatment of pheochromocytoma includes _______, a high-risk procedure. Catecholamines fall to normal within 1 week of resection. _____________ _____ blockade is widely recommended. Patients with ________ pheochromocytomas are more likely to have recurrence. Long-term monitoring is indicated in all patients.

COMT (catechol-o-methyl transferase), MAO (monoamine oxidase)

Two enzymes, ____ and ____ produce metabolites from free catecholamines. Metabolites and free catecholamines are filtered into urine and excreted.

Liquid Chromatography

Urine catecholamines are assayed using ______ ______________, fluorometrics, LC/MS/MS; 24-hour levels are more accurate

hypokalemia

Wherever sodium goes, potassium flees (both cations/repel) - In hyperaldosteronism, as aldosterone increases sodium reabsorption, potassium reabsorption will decrease (increase excretion).

17OH-Preg, 17OH-Prog, Glucocorticoids (cortisol)

Zona Fasciculata: Cholesterol → Pregnenolone → ____-____ → ____-____ →→ _______________.

pregnenolone, progesterone, mineralocorticoids (aldosterone)

Zona Glomerulosa: Cholesterol → ____________ → ____________ →→ ___________________.

DHEA, Androstenedione, androgens, estrogens (testosterone/estradiol)

Zona Reticularis: Cholesterol → Pregnenolone → 17-OH → ____ → ______________ →→ _________ and _________.

high

[Low/High] levels of ACTH cause Secondary & Tertiary Cushing's - these are ACTH dependent, can result from pituitary disease or ectopic ACTH/CRF, and can result in hyperpigmentation due to overabundant ACTH being prescribes to ⍺-MSH

low

[Low/High] levels of ACTH result from Primary Cushing's - this is ACTH independent, can be caused by an adrenal adenoma or carcinoma, nodular adrenal hyperplasia, nodular adrenal hyperplasia, or endogenous glucocorticoids.

norepinephrine, epinephrine

______________ and ___________ are synthesized in the adrenal medulla by conversion of phenylalanine substrates in a tightly regulated manner in a response to stress to stimulate the flight-or-fight response.

Aldosterone

_____x_____ exchanges Na+ reabsorption with H+ excretion. _____x_____ stimulates Na+ (and H2O) reabsorption with HCO3- regeneration in exchange for K+, H+ and NH4+ excretion.

Conn's syndrome (primary hyperaldosteronism)

a disorder of the adrenal glands due to excessive production of aldosterone

Dexamethasone

a synthetic steroidal hormone and acts as a cortisol analogue. If the pituitary is functioning in Cushing's syndrome, the ACTH will decrease in response.

Addison's disease

adrenal insufficiency, caused by primary adrenal problem or secondary ACTH deficiency. Symptoms: weakness, fatigue, anorexia, nausea, diarrhea, abdominal pain, weight loss.

cholesterol

all adrenal steroids are derived by conversion of a common substrate: _____x_____. Only free _____x_____ can enter steroidogenic pathways in response to ACTH. Conversion of _____x_____ to pregnenolone is a rate-limiting step in steroid biosynthesize. Decreased activity of any enzymes required for biosynthesis can occur as an acquired or inherited trait. ¢Evaluation of adrenal function requires measuring relevant adrenal hormones, metabolites etc.

AGII

causes vasoconstriction, increased blood pressure, and increased aldosterone, which stimulates K+ excretion

Androgen excess

characterized by altered secondary sex characteristics: virilization (manifestation of male secondary sex characteristics) in women and children and gonadal dysfunction and infertility in men and women.

hypoaldosteronism

characterized by hyperkalemia and renal salt wasting

hypercortisolism

characterized by hypertension, hyperglycemia, central obesity, and weakness. May also be accompanied with hyperaldosterone.

hyperaldosteronism

characterized by hypertension, hypokalemia, and metabolic alkalosis

Adrenal insufficiency

characterized by hypotension, hypoglycemia, weight loss, and weakness

Cushing's syndrome

condition characterized by hypercortisolism

cushing's syndrome

due to excess cortisol from anterior pituitary, adrenal, or other sources (exogenous glucocorticoids, ectopic ACTH, etc.)

MAO (monoamine oxidase)

enzyme that converts excess catecholamines and dopamine into synaptically inactive forms

cushing's disease

hypercortisolism due to excess pituitary secretion of ACTH

zona reticularis

inner 10% of the adrenal cortex; cells convert DHEA (dehydroepiandrosterone), the substrate for estrogens and testosterone, into androstenedione, which is the main adrenal androgen.

zimmerman reaction

metabolites of cortisol in urine measurement method: 17-KS

silber method

metabolites of cortisol in urine measurement method: 17-OHCS

zona fasciculata

middle 75% of the adrenal cortex; cells are organized into bundles - synthesize cortisol [glucocorticoids].

zona glomerulosa

outer 10% of the adrenal cortex; cells synthesize aldosterone [mineralocorticoids] critical for sodium and water reabsorption.

adrenal gland

produces mineralocorticoids, steroid hormones, and androgens essential for life. Conditions affect blood pressure and electrolyte balance.

Captopril

prototype ACE inhibitor for the treatment of hypertension. Inhibition of the ACE enzyme with _________ followed by measurement of aldosterone should produce a decrease in aldosterone. A tumor in the zona glomerulosa that is producing too much aldosterone will be resistant to ACE suppression.

cortisol

stress hormone released by the adrenal cortex; circadian (diurnal) secretion (peaks in morning, valleys at night), controlled by ACTH. For specimen, blood should be collected at 8 am and 8 pm - 8 pm blood levels should be half of that taken at 8 am. (Can measure metabolites and free in the urine).

renin, AGII,

Conn's Syndrome (primary hyperaldosteronism) is majorly resultant of renal hypertension: the kidneys produce excessive __x__, which results in excessive __y__, and subsequently excessive aldosterone, which, in a healthy individual, should feedback and decrease __x__.

immunosuppressant, diabetogenic, osteoporosis

Cortisol is an ________________, a ____________, and promotes the likelihood of ____________.

adenoma (tumor- can be benign or malignant)

Primary Cushing's Syndrome is characterized by cortisol-secreting adrenal ________.