Adrenal
adrenal glands
multifunctional organs that produce steroid hormones and neuropeptides; paired organs that sit on top of the kidneys
blood pressure, electrolyte balance, and androgen excess
three functions of the adrenal glands
hormone replacement therapy
hypofunction treatment
pharmacologic suppression and/or surgery
hyperfunction treatment
hyperaldosteronism
causes hypertension, hypokalemia, and metabolic alkalosis
pheochromocytoma
causes hypertension, anxiety, palpitations, dizziness, diaphoresis
Cushing's syndrome
causes hypertension, unexplained weight gain, red/purple stretch marks, proximal muscle weakness
congenital adrenal hyperplasia
causes inappropriate hirsutism/virilization and inability to conceive
primary adrenal insufficiency
causes loss of appetite, unintentional weight loss, pigmented skin
adrenal cortex and adrenal medulla
adrenal gland regions
zona reticularis, zona fasciculata, and zona glomerulosa
adrenal cortex zones
mineralcorticoids
hormones released from zona glomerulosa
glucocorticoids
hormones released from zona fasciculata
androgens
hormones released from zona reticularis
stress hormones
hormones released from adrenal medulla
mineralcorticoids
regulate mineral balance
glucocorticoids
regulate glucose metabolism
androgens
stimulate masculinization
stress hormones
stimulate sympathetic ANS
aldosterone
1 type of mineralcorticoids
cortisol, corticosterone, and cortisone
3 types of glucocorticoids
dehydroepiandrosterone
1 type of androgen hormone
epinephrine and norepinephrine
two types of stress hormones
adrenocorticotropic hormone
a cortex steroidogenesis stored in pituitary gland
cortex steroidogenesis
controls substrate availability, enzyme activity, inhibitory feedback specific to zone
pregnenolone
rate limiting step of steroidogenesis
cholesterol
common substrate of adrenal gland for cortex steroidogenesis; stored in parenchymal cells; additional synthesis possible via Acetyl-CoA; free enters pathway; ACTH stimulates free availability while LDL inhibits free availability
Hypothalamus releases corticotropin releasing hormone -> anterior pituitary releases ACTH -> adrenal cortex releases cortisol
cortex steroidgenesis
figures 21.1 and 21.3
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pregnenolone by cytochrome P450
rate limiting step cholesterol
returned to cortex for zonal reactions
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increased glucocorticoids
what suppresses CRH and ACTH
cortisol
primary regulator of ACTH
increased ACTH and CRH to stimulate cortisol
results of decreased enzymatic activity
leads to adrenal hyperplasia and possible overproduction of androgens
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congenital adrenal hyperplasia
group of conditions due to absent or diminished enzymes involved in steroidgenesis
mineralcorticoid, glucocorticoid, androgen production
pathways affected by congenital adrenal hyperplasia due to substrate build-up
21-hydroxylase
commonly affected enzyme of congenital adrenal hyperplasia
figure 21.4
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decreased glucocorticoid and increased 17-hydroxyprogesterone
hormonal result of congenial adrenal hyperplasia
failure to thrive and low blood pressure
classic form of congenital adrenal hyperplasia in infants
hirsutism, menstrual irregularities, and infertility
nonclassic form of congenial adrenal hyperplasia in women
aldosterone
60% transported bound to albumin or corticosteroid-binding globulin; 40% transported free
morning
diurnal variation of aldosterone where concentration is highest
upright position
postural changes that increase aldosterone levels
regulates extracellular fluid volume and potassium metabolism
aldosterone functions
renin-angiotensin system, potassium, and ACTH
three things that control aldosterone release
hyperkalemia, decreased blood pressure, and decreased Na+ concentration
three factors that stimulate aldosterone
primary aldosteronism
excessive secretion of aldosterone that cannot be suppressed by salt or volume replacement; symptoms include hypertension, metabolic alkalosis, vascular disease risk
aldosterone-producing adrenal adenoma and unilateral or bilateral hyperplasia
two of the most common primary aldosteronism
increased plasma aldosterone and increased plasma renin
lab tests seen in primary aldosteronism
isolate hypoaldosteronism
insufficient aldosterone secretion due to adrenal gland destruction; caused by chronic heparin therapy, adrenalectomy, G-zone enzyme deficiency, and mild renal insufficiency
adrenal insufficiency
inadequate hormone secretion from adrenal cortex
primary adrenal insufficiency
adequate stimulation but not release of hormones of adrenal cortex; inadequate release of glucocorticoids, mineralcorticoids, or adrenal androgens
secondary adrenal insufficiency
insufficient stimulus for adrenal gland hormone release such as pituitary gland insufficient release of ACTH
autoimmune destruction of the adrenal gland (Addison's disease)
most common cause of adrenal insufficiency
decreased blood pressure, glucose, and sodium, and increased potassium
nonspecific adrenal insufficiency diagnostics along with fatigue, weight loss, decreased appetite, and nausea
decreased cortisol and increased ACTH
adrenal insufficiency diagnostic labs
ACTH stimulation test
used to diagnose primary adrenal insufficiency; measures baseline ACTH and cortisol in the morning, give synthetic ACTH IV or IM, and remeasure cortisol at 30 and 60 minutes
rise in cortisol
normal ACTH stimulation test result
secondary adrenal insufficiency
ACTH stimulation test may be normal or abnormal depending on the issue; other stimulation tests optional
replacement of glucocorticoids or mineralcorticoids
treatment for adrenal insufficiency
maintains normal blood pressure, hematological effects, increased during stress, and regulation of metabolism
four functions of cortisol
stimulates GFR and decreases water reabsorption by kidneys
two ways cortisol maintains normal blood pressure
stimulates erythropoiesis, causes leukocytosis and lymphocytopenia, and suppresses inflammatory and immune reponse
three ways cortisol effects hematologically
carbohydrates, proteins and lipids, and anabolic effect on liver metabolism
three ways cortisol regulates metabolism
increase plasma glucose levels and antagonistic to effects on insulin
two ways cortisol regulates carbohydrate metabolism
catabolic effect
the way cortisol regulates protein and lipid metabolism
high levels of free cortisol in urine
indicates adrenal hyperfunction
cortisol
96% bound to Cortisol binding globulin, 6% to albumin; 4% free in plasma
high in morning, low in late afternoon to evening
normal diurnal variation of cortisol
CRH
synthesized and released by hypothalamus and acts on pituitary to release ACTH
ACTH
acts on adrenal cortex
stimulates CRH and cortisol
hypoglycemia effects on cortisol
CRH, ACTH, stress, and hypoglycemia
four ways cortisol is controlled and regulated
Cushing's Syndrome
excess cortisol production; manifestations are not unique to the condition but include hypertension, glucose intolerance, depression, obesity, skin changes; characteristic moon face and buffalo hump
adrenal tumors which produce excess cortisol causing ACTH to be low
primary cause of hypercortisolism
pituitary/non-pituitary tumor produces excess cortisol due to increased ACTH
secondary cause of hypercortisolism
ACTH dependent Cushing's disease
elevation of ACTH due to pituitary gland
ACTH independent Cushing's syndrome
increased cortisol no due to elevated ACTH
dexamethasone suppression test
synthetic cortisol (30x more potent) given in evening and blood cortisol drawn in AM; normal <140 mmol/L, Cushing's response >280 mmol/L
immunoradiometric test IRMA
used to determine the reason for hypercorticolism, the degree of ACTH elevation, and identify if it is ACTH dependent or independent
resection of pituitary tumor
Cushing's disease treatment
tumor resection or medical therapy to suppress ACTH
Cushing's syndrome treatment
DHEA and DHEA-S
precursors of adrenal androgens
androstenedione, testosterone, 5-dihydrotestosterone, and estrogen, some testosterone
5 active androgens
androgen edxcess
ambiguous genitalia in female infants and precocious puberty in children; simulates organ development and linear growth; physical affects in both girls and boys; short stature; infertility in men and women; additional physical effects in men and women
measure DHEA, DHEA-S, urinary 17-ketosteroid, and testosterone
4 diagnostic markers for adrenal androgens
adrenal medulla
responsible for synthesis of catecholamines from tyrosine; first responders to regulate body's response to stress
fight or flight response by adrenal medulla
increases cardiac output and blood pressure moving blood to muscle and brain tissue
epinephrine, norepinephrine, dopamine, and serotonin
four naturally occurring catecholamines
epinephrine
catecholamine produced in adrenal medulla
norepinephrine
catecholamine neurotransmitter produced in central nervous system and postganglionic sympathetic nerves
dopamine
highest concentration in brain and some peripheral organs
serotonin
signal transmitter in CNS and peripheral organs
phenylalanine
sequentially converted to epinephrines
increase cortisol and increase epinephrine production
product of norepinephrine to epinephrine by phenylethanolamine-N-methyltransferase (PNMT)
neurosecretory vesicles
location of NE and EPI storage
epinephrine
the main catecholamine
dopamine
sympathetic neuron vesicles in norepinephrine; hypothalamus synthesis
catecholamines (dopamine and epinephrine)
important transmitters of nerve signals that influence the vascular system
vanillylmandelic acid
principle end product of epinephrine and norepinephrine
fall in blood pressure or blood volume, thyroid hormone deficiency, congestive heart failure, arrhythmias, and stress
5 causes of excess levels of catecholamines
idiopathic postural hypotension
cause of decreased levels of catecholamines
pheochromocytoma
hypersecretion of catecholamines producing tumors; symptoms include weight loss, sustained or paroxysmal hypertension, headache, palpitations, and anxiety
urine metanephrine and VMA and plasma catecholamines
used to diagnose adrenal medulla disorders
neuroblastoma
one of the most common malignant tumors in children; 80% in children less than 5 years old; increased dopamine excretion is diagnostic; also increased norepinephrine, VMA, and HVA
fluorometric, spectrophotometric, chromatographic (HPLC), and imaging studies
analytic methods for measurement