Conditions Effecting the Endocrine System and PharmacotherapyPart Three: Hypothalamus & Pituitary Flashcards
Exam 3
Hypothalamus: Where is it located?
Located at the base of the brain
Hypothalamus: what is it connected to and how?
Connected to the pituitary gland by pituitary stalk
Connected to anterior pituitary through blood vessel network
Connected to posterior pit. via a nerve tract
Hypothalamus: What does it produce?
Produces releasing and inhibiting hormones that work on the anterior pituitary
Hypothalamus: What does it produce (having to do with water)?
It produces antidiuretic hormone (ADH), which is stored in the posterior pituitary until it is needed.
Regulation by Hypothalamus:
What type of hormones does it release?
Growth hormone–releasing hormone
Thyrotropin-releasing hormone
Gonadotropin-releasing hormone
Corticotropin-releasing hormone
Regulation by Hypothalamus:
Negative feedback loop having to do with hypothalamus?
Hypothalamus: Releasing factor X –> pituitary: hormone A –>
Target organ get stimulated, causing release of hormone B –> Produces biologic effect
Hormone B –> hypothalamus & pituitary to suppress further release of factor X & hormone A, suppressing further release of hormone B
Hypopituitarism
Insufficient amounts/absence of anterior pituitary hormones
Panhypopituitarism
Is a rare condition that involves a lack of all the hormones your pituitary gland makes.
Hypopituitarism:
What is the most common cause of this?
Pituitary infarction or space-occupying lesions (most common)
Hypopituitarism:
Causes are: Pituitary infarction or space-occupying lesions (most common) what are examples?
Pit tumors, adenomas, aneurysms, significant blood loss
Hypopituitarism:
Causes include:
Pit infarction or space-occupying lesions (most common)
Congenital defects
Cerebral or pituitary trauma
Autoimmune conditions
Infections of brain & supporting tissues
Traumatic brain injury
Hypopituitarism:
Caused by: Congenital defects like what?
Pituitary hypoplasia, or aplasia
Hypopituitarism:
Caused by: Cerebral or pituitary trauma
such as?
Surgery,
infections,
stroke,
radiation,
injury
Hypopituitarism:
Cause by: Autoimmune conditions like?
Hypophysitis (inflamed pituitary)
Hypopituitarism:
Patho: How is the pituitary?
Pituitary highly vascular
Hypopituitarism:
Patho: What does the pituitary heavily rely on?
Relies heavily on blood from the hypothalamus
Hypopituitarism:
Patho: What does this make you vulnerable to? What does that lead to?
Vulnerable to ischemia & infarction –> tissue necrosis, edema, fibrosis –> sx of hypopituitarism
Hypopituitarism:
Patho: What may compress pituitary cells? What does that lead to?
Adenomas & aneurysms may compress pit cells –> compromised hormonal output
Hypopituitarism: Clinical Presentation/Tx - What does it depend on?
Depends on which hormones affected
Hypopituitarism: Clinical Presentation/Tx
Depends on which hormones affected
What are examples?
E.g. ACTH, TSH, FSH, LH, Growth hormone deficiency
Hypopituitarism: Clinical Presentation/Tx
What is evaluation and treatment?
Levels of pituitary hormones
Imaging – MRI, CT
Replacement of target hormones
Hyperpituitarism: Patho
What is it?
Hypersecretion of ant pit hormones
Hyperpituitarism:
Patho
What is caused by?
Commonly caused by a benign, slow-growing pituitary adenoma
Hyperpituitarism:
Patho
What does it do to nerves? What does that lead to?
Impingement on nerves: Visual & cranial nerve disturbances
Hyperpituitarism:
Patho: Because it is an extension to hypothalamus, what else is effected?
Extension to hypothalamus disturbs controls of wakefulness, thirst, appetite, & temp
Hyperpituitarism: Patho- Can be caused by what else?
Hypersecretion from tumor
Hyperpituitarism: Patho-Hypersecretion from tumor
Why does this occur?
Adenomatous tissue secretes hormones of the cell type from which it arose
Hyperpituitarism: Patho
How may HYPOpituitarism occur from this?
Hypopituitarism may occur from pressure exerted by tumor
Hyperpituitarism: Clinical Manifestations
What occurs?
Increased section of growth hormone from tumor
Hyperpituitarism: Clinical Manifestations
If tumor exerts enough pressure on surrounding pituitary cells what occurs?
Hypothyroid
Adrenal hypofunction
Hyperpituitarism: Clinical Manifestations
If tumor exerts enough pressure on surrounding pituitary cells hypothyroid occurs-why?
Hypothyroid-Because of lack of TSH
Hyperpituitarism: Clinical Manifestations
If tumor exerts enough pressure on surrounding pituitary cells adrenal hypofunction occurs-why?
Adrenal hypofunction
Low ACTH –> hypocortisolism
Hyperpituitarism: Clinical Manifestations
What are they related to?
Related to tumor growth & hyper or hyposecretion
Hyperpituitarism: Clinical Manifestations
What manifestations occur?
Visual changes, impairment –> blindness
Increased tumor size
Cranial nerves –> neuromuscular function
Hyperpituitarism: Clinical Manifestations
Increased tumor size leads to?
Increased tumor size –> headache, fatigue, neck pain, seizures
Acromegaly- what is it?
Is an increase in growth hormone which leads to grow huge bones
Patho of acromegaly:
How does production of too much growth hormone occur?
Cells produce too much growth hormone that is released into the bloodstream
Patho of acromegaly:
Cells produce too much growth hormone that is released into the bloodstream- What does this do to the liver?
Caused the liver to release a hormone called insulin growth factor-1 (IGF-1)
Patho of acromegaly:
Cells produce too much growth hormone that is released into the bloodstream- What does this do to the bones and soft tissue?
Causes the bones and soft tissue to grow
Patho of acromegaly
When is it diagnosed?
Usually dx’d adults aged 40-59
Patho of acromegaly
What occurs in children?
Peds – gigantism
Patho of acromegaly
Peds – gigantism
How does it occur?
Children & adolescents
Growth plates have not yet closed
Excessive skeletal growth ≈ 8-9ft
Patho of acromegaly
What are results of this?
overgrowth of bones and soft tissue (especially in the face, hand, and feet),
joints become enlarged, thicker, wider and arthritic
Patho of acromegaly:
Results:
What kind of issues occur?
cardiac disease,
arthritis,
carpal tunnel syndrome,
cardiomegaly,
sleep apnea, diabetes,
and hypertension,
hyperglycemia
Patho of acromegaly:
What are signs and symptoms?
Thicker eyelids,
widened nose,
protruding mandible and brow,
thicker lips,
widening of space btwn teeth
Secondary diabetes mellitus
Patho of acromegaly:
Signs and symptoms: Why does Secondary diabetes mellitus occur?
GH antagonizes insulin
Acromegaly Management:
What diagnostic tests are done?
PMH
PE
Serum hormone levels
Brain CT
Pituitary MRI
Vision testing
X-rays
Acromegaly Management:
Diagnostic tests done: How do serum hormone levels appear for acromegaly?
Acromegaly - ↑’d IGF-1 & GH
Acromegaly Management:
Treatment strategies: How to treat?
Underlying etiology & hormone affected
Somatostatin analogues (Octreotide)
GH receptor antagonists
Acromegaly Management:
Treatment strategies: How to treat tumors?
Tumors, often reoccurring:
SX
Radiation
Chemo
Acromegaly Management: What do Somatostatin analogues (Octreotide) do?
Inhibit GH production
Antidiuretic Hormone:
What is it known as?
ADH (also known as vasopressin)
Antidiuretic Hormone:
What does it promote?
Promotes renal conservation of water
Antidiuretic Hormone: What does it work on?
Works on the collecting ducts of the kidney to increase their permeability to water
Antidiuretic Hormone: Where does the water come from?
H2O withdrawn from the tubular urine back into extracellular space
Antidiuretic Hormone:
What does water reabsorption lead to?
Reabsorption (conservation) of H2O leads to very concentrated urine by the time it leaves the body
Antidiuretic Hormone:
What factors promoting/stimulating ~
controlled via hypothalamus
Antidiuretic Hormone:
Factors promoting/stimulating ~ controlled via hypothalamus
High blood osmolality sensed by hypothalamus –> ADH gets released from posterior pituitary to reabsorb water to dilute body fluids
Hypotension
Decrease in plasma volume
Diabetes Insipidus- What is it?
Deficiency of ADH
Diabetes Insipidus- What is it?
Excessive fluid excretion
DI= “Dry Inside”
Diabetes Insipidus- What do the kidneys do?
Kidneys unable to conserve water
What is DI deficit in?
While both have excess urine output, DI is from a deficit of antidiuretic hormone.
Diabetes Insipidus: What is it?
Partial or complete deficiency of ADH
Diabetes Insipidus:
What is it a diagnosis of?
DX of inability to produce concentrated urine
Diabetes Insipidus:
What area is diseased?
Disease of posterior pituitary
Diabetes Insipidus:
Patho: What does insufficient ADH lead to?
Insufficient ADH –> Large volumes of dilute urine, increased plasma osmolality
Diabetes Insipidus: What are the two types?
Central (neurogenic) DI (hypothalamus/pituitary is the cause)
Nephrogenic DI (kidneys are at fault)
Diabetes Insipidus:
What are examples of Central (neurogenic) DI (hypothalamus/pituitary is the cause)?
Examples:
Brain tumor,
head injury,
brain surgery,
CNS infections,
TBI,
thrombosis,
infections
Diabetes Insipidus:
Central (neurogenic) DI (hypothalamus/pituitary is the cause): How does it?
Pressure to the posterior pituitary from inflammation in the brain or a growth
Diabetes Insipidus:
Central (neurogenic) DI (hypothalamus/pituitary is the cause): How is the onset?
Abrupt onset
Diabetes Insipidus:
Nephrogenic DI (kidneys are at fault):
What occurs?
Adequate amount of vasopressin secreted by the posterior pituitary, but kidneys fail to respond because of other abnormalities
Diabetes Insipidus:
Nephrogenic DI (kidneys are at fault):
Why does it occur?
Genetic mutation
Diabetes Insipidus:
Nephrogenic DI (kidneys are at fault):
How is onset?
Gradual onset
Diabetes Insipidus: Nephrogenic DI (kidneys are at fault)
What are examples?
Examples: renal damage,
meds (eg loop diuretics, colchicine, lithium),
pyelonephritis,
uropathy,
polycystic kidney disease
Diabetes Insipidus: How is ADH secretion in Central (neurogenic) DI?
Decreased antidiuretic hormone
Diabetes Insipidus: Central (neurogenic) DI leads to decreased ADH. What does that cause?
Decreased water reabsorption in renal tubules
Diabetes Insipidus: Nephrogenic DI -how does it effect ADH?
Adequate ADH released
Diabetes Insipidus: Nephrogenic DI -causes adequate ADH released what does that lead to?
Decreased response of collecting ducts to ADH
Diabetes Insipidus: What does Central (nephrogenic) DI and Nephrogenic DI both lead to?
Increases excessive urine loss (polyuria)
Diabetes Insipidus: Central (nephrogenic) DI and Nephrogenic DI both lead to Increases excessive urine loss (polyuria): What does this cause?
Decreases intravascular fluid volume
Clinical Manifestations of Diabetes Insipidus include:
Polyuria
Polydipsia
Nocturia
Clinical Manifestations of Diabetes Insipidus: Why does polyuria occur?
kidneys excrete excessive dilute urine
Clinical Manifestations of Diabetes Insipidus: How much urine is lost with polyuria?
Can lose up to 8 to 12L/day (normal output 1-2L/day)
Clinical Manifestations of Diabetes Insipidus: Polyuria- What is the quality of the urine?
Low urine osmolality
Clinical Manifestations of Diabetes Insipidus:
Polydipsia- Why is this common?
Excessive thirst common due to quickly excreted water causing dehydration
Clinical Manifestations of Diabetes Insipidus:
What is thirst a compensation for?
Thirst is a compensation reaction for the loss of hydration
Clinical Manifestations of Diabetes Insipidus:
Complications
Hypernatremia
Severe dehydration
Clinical Manifestations of Diabetes Insipidus:
Hypernatremia: Why does this occur?
Hypernatremia - ADH primarily affects water reabsorption, not electrolytes; thus, sodium is retained in the body
Clinical Manifestations of Diabetes Insipidus:
Why does severe dehydration occur?
Severe dehydration - Excessive fluid loss through urine leads to intravascular fluid loss
Diabetes Insipidus: What is the treatment?
Fluid replacement – oral or IV
Eliminate causes
ADH replacement
Diabetes Insipidus Treatment:
What does ADH replacement consist of?
Vasopressin
DesmopressinDDAVP
Diabetes Insipidus Treatment:
ADH replacement - Vasopressin:
What is Vasopressin identical to?
Identical to naturally occurring ADH
Diabetes Insipidus Treatment:
ADH replacement - Vasopressin:
What kind of actions does it have?
Has powerful vasoconstrictive actions
Diabetes Insipidus Treatment:
Vasopressin:
Has powerful vasoconstrictive actions: What does it cause?
Can cause CV events, ischemia
Diabetes Insipidus Treatment:
Desmopressin DDAVP : What is it?
Structural analogue
Diabetes Insipidus Treatment:
DesmopressinDDAVP: How fast is response?
Response is rapid
Diabetes Insipidus Treatment:
DesmopressinDDAVP: How is urine levels?
Urine volume quickly drops to normal
Diabetes Insipidus Treatment:
DesmopressinDDAVP: How long is treatment?
Tx may be lifelong
Diabetes Insipidus Treatment:
DesmopressinDDAVP: How is the medication administered?
Adm PO, Sq, IV or nasal spray
Diabetes Insipidus Treatment:
What are adverse effects?
Water Intoxication
Diabetes Insipidus Treatment:
How does water intoxication occur?
Occurs from excessive water retention
Diabetes Insipidus Treatment:
Adverse Effects:
How does water intoxication present?
Preceding drowsiness, listlessness, HA
Severe –> convulsions, terminal coma
Diabetes Insipidus Treatment:
Adverse Effects: Water intoxification
What is treatment?
Tx: diuretic tx/fluid restriction
Diabetes Insipidus Treatment:
Adverse Effects: Water intoxification
How to prevent water intoxication?
Prevent with reduction of fluid intake @ TX start
Diabetes Insipidus Treatment:
Adverse Effects: Water intoxication
What does water intoxication cause an increased risk for?
↑ risk with renal impairment
Syndrome of Inappropriate ADH (SIADH): In basic terms, what is it
Excessive ADH
Syndrome of Inappropriate ADH (SIADH): What happens to renal water retention?
Increased renal water retention Siadh = “Soaked Inside”
SIADH: How is ADH?
Too much ADH is secreted from the pituitary or kidney’s response to it is excessive
SIADH:
What does ADH cause the body to do in general (not related to disease)?
ADH causes the kidney to reabsorb H2O so urine production decrease
SIADH: When does excessive ADH occur?
Increases after spinal surgery, with traumatic brain injuries, and certain drugs
SIADH: Who is it common in?
More common in older adults and hospitalized patients
SIADH: How is urine concentration?
Urine inappropriately concentrated because H2O reabsorbed that normally would be excreted.
SIADH: Patho
What effect does SIADH have on salt levels of the body?
Patho:Dilutional hyponatremia (hypoosmolality)
SIADH: What are causes of this?
Meds
Cancers
Pulmonary disorders
GI fluid losses
Fluid loss replaced only with D5W
CNS disorders
Self-induced water intoxication
Adrenal insufficiency (lack of aldosterone)
Post op
SIADH: Causes of SIADH
What meds could cause SIADH?
Meds:
Thiazides diuretics,
Chemo,
antidepressants,
antipsychotics,
narcs,
anesthetics,
NSAIDs,
thiazides
SIADH: Causes of SIADH
How could cancers cause SIADH?
*Cancers: ectopic production of ADH by solid tumors
SIADH: Causes of SIADH
What pulmonary disorders can cause SIADH?
Pulmonary disorders:
pneumonia,
TB,
CF,
resp failure
SIADH: Causes of SIADH
What *CNS disorders can cause SIADH?
brain tumors,
head injury,
meningitis,
intracranial hemorrhages,
stroke
SIADH:
Why would SIADH occur post op?
Postop: ADH released in response to stress of surgery, anesthesia, pain, nausea
Patho of SIADH:
What are the steps to SIADH?
(4 steps)
- ADH is released despite normal or low plasma osmolarity
- Increases water reabsorption in renal tubules
- Decreases urine production (oliguria)
- Increases intravascular fluid volume
Clinical Manifestations of SIADH include:
Fluid Retention and Weight Gain
Oliguria, Hyponatremia, Muscle Cramping, Weakness, GI sx
Mental Confusion, Lethargy, Muscle twitches, Irritability, Seizures, Coma
Clinical Manifestations of SIADH:
Why does fluid retention occur?
Water is reabsorbed back into circulation due to an increase in permeability of the renal distal tubule and collecting ducts caused by increased ADH.
Clinical Manifestations of SIADH:
Why does weight gain occur?
Weight gain is from retained fluids, not excess fat
Clinical Manifestations of SIADH:
Why does weight gain occur but no edema present?
Since most fluids are located intravascularly, fluid is retained leading to weight gain but usually no edema is present (no peripheral edema).
Clinical Manifestations of SIADH:
Why does Hyponatremia occur?
The reabsorption of water increases intravascular fluid volume which dilutes sodium in the blood (dilutional hyponatremia).
Clinical Manifestations of SIADH:
Why does Oliguria occur?
Reabsorption of water also causes a decrease in urine output.
Clinical Manifestations of SIADH:
Why does Oliguria, Hyponatremia, Muscle Cramping, Weakness, GI sx
occur?
Hyponatremia affects normal functioning of nerve and muscle tissue causing cramping and weakness.
Clinical Manifestations of SIADH:
Why does Mental Confusion, Lethargy, Muscle twitches, Irritability, Seizures, Coma occur?
Cerebral edema due to declining plasma osmolality and serum sodium levels.
Clinical Manifestations of SIADH:
Why does swelling of brain cells occur?
Swelling of brain cells and neuron occurs due to hyponatremia from dilution of the excess fluid.
Clinical Manifestations of SIADH:
Why does Mental Confusion, Lethargy, Muscle twitches, Irritability, Seizures, Coma occur?
Hyponatremia affects normal nerve synapses in the brain causing confusion and irritability and even seizure and coma.
SIADH: How is it diagnosed?
Serum hypoosmolality
Hyponatremia
Urine hyperosmolarity
SIADH:
What is treatment?
Correct the cause
Fluid restriction because of hyponatremia
Monitor neuro status
For Na loss – replacement
Administration of vasopressin (ADH) receptor antagonists – the vaptans
SIADH:
What is treatment if Na loss is severe?
If severe: cautious administration of hypertonic saline to prevent damage to myelin sheath & injury & death to nerve cells in CNS
SIADH:
Treatment: Administration of vasopressin (ADH) receptor antagonists – the vaptans
What are the examples?
Conivaptan
SIADH:
Conivaptan Treatment: What does Conivaptan do?
Conivaptan – blocks vasopressin (V2) receptors in renal collecting ducts, thus promoting renal excretion of free water, leaving Na behind for reabsorption into blood which leads to increase in Na+ in blood
SIADH:
Conivaptan Treatment: What is this a treatment for specifically?
Tx of hyponatremia/hypervolemia
SIADH:
Conivaptan Treatment: What are Adverse Drug Reactions to this?
ADRs: hypokalemia,
headache,
fever,
constipation,
diarrhea,
vomiting,
thirst,
dry mouth,
polyuira
S/sx of DI & SIADH:
How are daily weights for DI?
Decreases
S/sx of DI & SIADH:
How are daily weights for SIADH?
Increases without edema
S/sx of DI & SIADH:
What are mental changes related to that occur with DI?
What happens to cells and neurons
Related to electrolyte imbalance and hypotension
Cells and neurons shrink
S/sx of DI & SIADH:
What are mental changes related to that occur with SIADH?
What happens to cells and neurons?
Related to degree of hyponatremia
Cells and neurons swell
Adrenal Glands: Where are they located?
Located on each kidney
Adrenal Glands:
What is the medulla? What does it produce?
Medulla: inner portion (of kidney), produces epinephrine and norepinephrine
Adrenal Glands:
Medulla: inner portion (of kidney), produces epinephrine and norepinephrine
What is this involved in?
fight-or-flight stress response
Adrenal Glands:
What is the cortex? What does it produce?
Cortex: outer portion that produces steroids, cortisol
Adrenal Glands:
What steroids and stuff does the cortex produce?
Mineralocorticoids
Glucocorticoids
Gonadocorticoids
Adrenal Glands:
Mineralocorticoids: What are they primarily?
Primarily aldosterone, which acts to conserve sodium and water
Adrenal Glands:
Mineralocorticoids: What electrolytes do they effect? How?
Sodium retention, potassium & hydrogen loss
Adrenal Glands:
What is the most potent mineralcorticoid?
Aldosterone is most potent naturally occurring MC & conserves Na
Adrenal Glands:
Glucocorticoids: What do they primarily control?
Primarily cortisol
Adrenal Glands:
Glucocorticoids: What is it needed for?
Needed to maintain life
Protect body from stress
Adrenal Glands:
Glucocorticoids: What do they have an influence over?
Influence carbohydrate metabolism
Adrenal Glands:
Gonadocorticoids are also called?
Gonadocorticoids, or sex hormones
Adrenal Glands:
Gonadocorticoids are involved in what?
Male & female sexual characteristics
Adrenal Glands:
Hypothalamus produces ______ to stimulate pituitary to release ______.
Hypothalamus produces CRH to stimulate pituitary to release ACTH
Adrenal Glands: What does ACTH alert the adrenals to do?
ACTH alerts adrenals to produce cortisol
What is the most important glucocorticoid?
Cortisol
Physiological Effects of Glucocorticoids include effects on:
Carbohydrate metabolism
Protein metabolism
Fat metabolism
Stress
CV system
Water & Electrolytes
Physiological Effects of Glucocorticoids:
Carbohydrate metabolism: What do glucocorticoids do for this?
Elevation of glucose & increase its availability to ensure brain has adequate supply
Physiological Effects of Glucocorticoids:
Carbohydrate metabolism: Elevation of glucose & increase its availability to ensure brain has adequate supply- How does it do this?
Stimulates gluconeogenesis
Reduction of peripheral glucose uptake by muscle & adipose tissue
Physiological Effects of Glucocorticoids:
Protein metabolism: What effect does glucocorticoids have on this?
Catabolism (breakdown) –> can cause muscle wasting & skin thinning @ high levels for prolonged time
Physiological Effects of Glucocorticoids:
Protein metabolism: What is glucocorticoids the opposite of?
Opposite of insulin
Physiological Effects of Glucocorticoids:
Fat metabolism: What do glucocorticoids have to do with fat metabolism?
Promote fat breakdown –> can cause fat redistribution
Physiological Effects of Glucocorticoids:
Fat metabolism: When glucocorticoids are used for a long time what can occur?
When present for long time – potbelly, moon face, buffalo hump
Physiological Effects of Glucocorticoids:
Stress: Effect of glucocorticoids on stress?
Adrenals secrete large amts of cortisol (during stress?)
Physiological Effects of Glucocorticoids:
Stress: Effect of glucocorticoids on stress (bp and blood glucose)
Maintain BP & blood glucose.
Physiological Effects of Glucocorticoids: What will happen with severe deficiency of cortisol?
In severe deficiency –> circulatory collapse & death
Physiological Effects of Glucocorticoids:
CV system: Effect of glucocorticoids on this?
Maintains vascular system integrity, BP, perfusion to muscles
Physiological Effects of Glucocorticoids:
CV system: Effect of decreased glucocorticoids on this?
Decreased GCs –> capillaries more permeable, vessels less able to constrict –> hypotension
Physiological Effects of Glucocorticoids:
CV system: effect of glucocorticoids on rbcs and hgb?
Increased RBC, Hgb
Physiological Effects of Glucocorticoids:
Water & Electrolytes: What does glucocorticoids work similar to?
Similar actions to aldosterone
Physiological Effects of Glucocorticoids:
Water & Electrolytes: What does glucocorticoids to with these?
Retention of sodium & water
Excretion of potassium
Pharmacologic Effects of Glucocorticoids:
What happens when there are high doses taken?
At high doses effects more intense
Pharmacologic Effects of Glucocorticoids:
At high doses, what are the intense effects that occur?
Glucose levels rise
Protein synthesis suppressed
Fat deposits mobilized
Inhibits intestinal absorption of calcium
Some pts experience mineralocorticoid activity
Anti-inflammatory/immunosuppressant effects
Pharmacologic Effects of Glucocorticoids:
Some pts experience mineralocorticoid activity: Like what?
Na+ retention, K+ loss
Pharmacologic Effects of Glucocorticoids:
Anti-inflammatory/immunosuppressant effects: What happens to chemical mediators?
Inhibit synthesis of chemical mediators (PGs, leukotrienes, histamine)
Pharmacologic Effects of Glucocorticoids:
Anti-inflammatory/immunosuppressant effects: What is it used for?
Reduce pain, swelling, warmth, redness, pain
Pharmacologic Effects of Glucocorticoids:
Anti-inflammatory/immunosuppressant effects : How does it do this?
Suppress infiltration of phagocytes & suppress lymphocytes, reducing the immune component of inflammation
Pharmacologic Effects of Glucocorticoids:
ADRs:
Adrenal insufficiency
Iatrogenic Cushing’s syndrome
Osteoporosis
Infection
Elevated WBC (leukocytosis)
Glucose intolerance
Myopathy (muscle injury)/weakness
Psychological agitation
PUD
Cataract/Glaucoma
Fluid & Electrolyte disturbance
Pharmacologic Effects of Glucocorticoids:
Fluid & Electrolyte disturbance lead to?
Na/H2O retention –> htn, edema
Pharmacologic Effects of Glucocorticoids:
Cataract/Glaucoma is caused by:
Ocular htn
Mineralocorticoids: What do they influence?
Influence renal processing of sodium, potassium, and hydrogen
Mineralocorticoids: What is an example?
Aldosterone
Mineralocorticoids:
Aldosterone- what does it promote?
Promotes sodium and potassium hemostasis
Mineralocorticoids:
Aldosterone- how does it promote sodium and potassium hemostasis?
Acts on collecting ducts of nephron to reabsorb Na+ & secrete K+ and H+
Mineralocorticoids:
Aldosterone- what does it maintain?
Maintains intravascular volume
Mineralocorticoids:
Aldosterone- what kind of effects does it have on high levels?
Has harmful cardiovascular effects at high levels
Mineralocorticoids:
Aldosterone-Has harmful cardiovascular effects at high levels- like what?
Myocardial remodeling impairing pumping cardiac activity,
myocardial/vascular stiffening,
SNS activation,
stimulation of cardiac activity
Mineralocorticoids:
Aldosterone-Has harmful cardiovascular effects at high levels-how is it regulated?
Regulated by renin-angiotensin-aldosterone system (RAAS)
Patho of Cushing’s: What is Cushing’s caused by?
Excessive cortisol
Patho of Cushing’s:
What is Cushing’s syndrome?
Cushing syndrome – clinical manifestations resulting from chronic exposure to excess cortisol in the body, regardless of cause
Patho of Cushing’s:
Cushing’s syndrome causes can include what?
Can include iatrogenic steroids tx, over-secretion of cortisol from adrenals, over-secretion of adrenal glands by ACTH-secreting tumor in pituitary, ectopic ACTH-secreting tumor
Patho of Cushing’s:
Cushing’s disease (specific case) –
excess endogenous secretion of ACTH caused by an ACTH-producing pituitary tumor
Cushing’s Syndrome/Disease:
What are predisposing factors?
Adrenal adenoma: Cushing’s syndrome
Pituitary adenoma/carcinoma: Cushing’s disease
An ectopic carcinoma
Iatrogenic (caused by medical treatment)
Cushing’s Syndrome/Disease:
Predisposing factors: Adrenal adenoma: Cushing’s syndrome- What is it?
Hypersecretion of corticosteroids (rare, benign)
Cushing’s Syndrome/Disease:
Predisposing factors: Adrenal adenoma: Cushing’s syndrome- Who is it common in?
More common in children
Cushing’s Syndrome/Disease:
Pituitary adenoma/carcinoma: Cushing’s disease
Hypersection ACTH from pituitary over-stimulates adrenals
Cushing’s Syndrome/Disease:
An ectopic carcinoma-
An ectopic carcinoma causing paraneoplastic syndrome from a substance produced by a tumor (eg small cell cancer of lung)
Cushing’s Syndrome/Disease:
Iatrogenic (caused by medical treatment) conditions:
Treatment with large amounts of exogenous glucocorticoids
Cushing-like syndrome
Cushing’s Syndrome/Disease:
Pituitary adenoma/carcinoma:
What does a pituitary tumor do? What does it lead to? (Having to do with ACTH)
Pituitary tumor causes overproduction of the hormones ACTH and cortisol.
Loss of feedback control of ACTH.
Cushing’s Syndrome/Disease:
Adrenal adenoma:
What does a adrenal cortex tumor cause? What does it lead to? (Having to do with ACTH)
Adrenal cortex tumor causes increased production of cortisol, which inhibits ACTH secretion due to negative feedback.
Cushing’s Syndrome/Disease:
What does paraneoplastic syndrome arise from? (Having to do with ACTH)
Paraneoplastic syndrome (cancer) arises from tumor secretion of hormones that increases ACTH, resulting in excessive cortisol production
Cushing’s Syndrome/Disease:
What do Iatrogenic conditions do (having to do with ACTH)
Iatrogenic conditions inhibit ACTH secretion and give a false elevated cortisol reading.
Administration of large amounts of oral steroids.
Steroid abuse is also a possibility.
Effects of Cushing’s Syndrome/Disease:
Excessive amounts of glucocorticoids (primarily cortisol) are released from hyperplastic, thickened adrenal cortex.
Cushing’s Clinical Manifestations cont’d:
What are symptoms of face and body?
Moon face (round and puffy)
Buffalo hump (fat pad back of neck)
Cushing’s Clinical Manifestations cont’d:
Why does moon face and buffalo hump occur?
Excess cortisol redistributes body fat
Cushing’s Clinical Manifestations cont’d:
How is stress response?
Poor stress response
Cushing’s Clinical Manifestations cont’d:
Why is there poor stress response?
Hyperfunctioning adrenals overwhelmed by additional stress
Cushing’s Clinical Manifestations cont’d:
How is hair and wound healing?
Thinning hair & delayed wound healing
Cushing’s Clinical Manifestations cont’d:
Why is there thinning hair and delayed wound healing?
Protein synthesis is decreased
Cushing’s Clinical Manifestations cont’d:
Why does weight gain occur?
Adipose tissue accumulates and fluid retention occurs
Cushing’s Clinical Manifestations cont’d:
What happens with weight?
Weight gain
Cushing’s Clinical Manifestations cont’d:
What happens to muscle and what else happens?
Wasting of muscle in the limbs with truncal obesity
Cushing’s Clinical Manifestations cont’d:
Why does Wasting of muscle in the limbs with truncal obesity occur?
Muscles atrophy from excess cortisol
Cushing’s Clinical Manifestations cont’d:
How is skin?
Thin, fragile skin with red or purple streaks, bruising
Cushing’s Clinical Manifestations cont’d:
How is hair GROWTH?
Hirsutism (excessive hair growth) on chin, chest
Cushing’s Clinical Manifestations cont’d:
Why is there Hirsutism?
Excess androgens (sex hormones) are secreted
Cushing’s Clinical Manifestations cont’d:
How is emotional state?
Emotional liability and euphoria (mood swings)
Cushing’s Clinical Manifestations cont’d:
Why is there Emotional liability and euphoria (mood swings)?
Altered metabolism of glucose, need it for brain
Cushing’s Clinical Manifestations cont’d:
How are bones?
Osteoporosis
Cushing’s Clinical Manifestations cont’d: Why is there osteoporosis?
Catabolic effects of bone matrix develops from excess cortisol
Cushing’s Clinical Manifestations cont’d: How is glucose?
Glucose intolerance, possibly resulting in secondary diabetes
Cushing’s Clinical Manifestations cont’d: Glucose intolerance, possibly resulting in secondary diabetes- why?
Gluconeogenesis and insulin resistance increase from cortisol excess
Cushing’s Clinical Manifestations cont’d:
How is bp and electrolytes?
Hypertension, edema, and hypokalemia (decreased serum potassium)
Cushing’s Clinical Manifestations cont’d:
Why is there Hypertension, edema, and hypokalemia (decreased serum potassium)?
Mineralocorticoid (aldosterone) effect is increased, retaining sodium and water, high cortisol can also act on mineralocorticoid receptors
Cushing’s Clinical Manifestations cont’d:
What are people prone to?
Prone to infections
Cushing’s Clinical Manifestations cont’d:
Why are they prone to infections?
Immune & inflammatory response suppressed
Cushing’s Clinical Manifestations:
What are labs?
Mineralocorticoid effects:
Hyperglycemia
Metabolic alkalosis
Serum & urine cortisol, ACTH levels
Cushing’s Clinical Manifestations:
Evaluation
Labs: What are Mineralocorticoid effects?
Mineralocorticoid effects:
Hypokalemia & Hypernatremia (Na & H2O retention)
Cushing’s Clinical Manifestations:
Evaluation- How is Cushing’s evaluated?
Dexamethasone Suppression Test (ACTH suppression test; Cortisol suppression test)
Read slide 45 when time
Treatment: For Adrenal adenoma/carcinoma – ?
surgical removal adrenal gland
Bilateral adrenalectomy –
Treatment: For Adrenal adenoma/carcinoma – What is needed for a Bilateral adrenalectomy?
– need replacement with GCs & mineralocorticoids
Treatment:If inoperable adrenal carcinoma – What is needed?
If inoperable adrenal carcinoma – Mitotane
Treatment: What is Mitotane? What does it do?
anticancer drug – destroys adrenocortical cells
Cushing’s Clinical Manifestations cont’d:
Treatment:
Pituitary adenoma: How to treat? If first treatment not successful, what should be done?
Partial removal of pituitary may be enough lower ACTH
If partial removal unsuccessful –> may need full removal
Cushing’s Clinical Manifestations cont’d
Treatment: What does Ketoconazole do?
Blocks GC synthesis & inhibits enzymes for cortisol synthesis
Cushing’s Clinical Manifestations cont’d
Treatment: How is Ketoconazole used?
Off-label
used as adjunct to radiation & surgery
Cushing’s Clinical Manifestations cont’d
Treatment: What is Ketoconazole considered?
Anti-androgenic
Cushing’s Clinical Manifestations cont’d
Treatment: Ketoconazole can effect what?
Can cause significant liver function
Addison Disease- What is it?
Adrenal Hormone Insufficiency
Adrenal Hormone Insufficiency: What is it hypofunction of?
Adrenocortical hypofunction (hypocortisolism)
Adrenal Hormone Insufficiency:
Adrenocortical hypofunction (hypocortisolism)- What is an example disease?
Addison disease (Primary adrenal insufficiency)
Adrenal Hormone Insufficiency:
Addison disease (Primary adrenal insufficiency): What is it a pathology of?
Pathology of one or both adrenal glands
Adrenal Hormone Insufficiency:
Addison disease (Primary adrenal insufficiency): How does it effect synthesis of steroids?
Inadequate corticosteroid & mineralcorticoid synthesis
Adrenal Hormone Insufficiency:
Adrenocortical hypofunction (hypocortisolism)= Addison disease (Primary adrenal insufficiency): What happens to ACTH levels?
Elevated ACTH (loss of neg feedback) – no cortisol to stop ACTH
Adrenal Hormone Insufficiency:
Adrenocortical hypofunction (hypocortisolism)= Addison disease (Primary adrenal insufficiency)- Who is it common in?
Most common in adults 30-60 years old, both genders affected
Adrenal Hormone Insufficiency:
Adrenocortical hypofunction (hypocortisolism)= Addison disease (Primary adrenal insufficiency)- What are causes?
Causes: Genetics, other autoimmune diseases, chronic infections
Adrenal Hormone Insufficiency:
Adrenocortical hypofunction (hypocortisolism)= Addison disease (Primary adrenal insufficiency)- How does T cells work?
AutoAbs & T cells attack the adrenal cortical cells
Adrenal Hormone Insufficiency:
Adrenocortical hypofunction (hypocortisolism): Addison disease (Primary adrenal insufficiency)-
What is Addisonian Crisis?
Addisonian crisis—hypotension leading to vascular collapse and shock
Adrenal Hormone Insufficiency:
Adrenocortical hypofunction (hypocortisolism)
Addison disease (Primary adrenal insufficiency): What two hormones are effected? Why?
Both cortisol & aldosterone affected because adrenal gland itself fails
Adrenal Hormone Insufficiency:
Secondary hypocortisolism: What is it?
Adrenal atrophy
Adrenal Hormone Insufficiency:
Secondary hypocortisolism: What does it result from?
Often results from prolonged exposure to exogenous glucocorticoids (steroids)
Adrenal Hormone Insufficiency
Secondary hypocortisolism: What is the role of GCs?
GCs suppress ACTH secretion –> adrenal atrophy –> inadequate corticoid steroid synthesis once exogenous GCs withdrawn – never withdraw steroids, taper!
Adrenal Hormone Insufficiency:
Secondary hypocortisolism: SLIDE NO MAKE SENSE TO MEEEE!
Pit infarction, pit tumors that compress ACTH-secreting cells or removal of pit gland (Decreased ACTH)
Low ACTH —> adrenal atrophy occurs & adrenal steroid synthesis depressed
Pathophysiology of Addison’s Disease: Why does this disease occur?
Adrenocortical insufficiency.
Pathophysiology of Addison’s Disease:
What happens to adrenal tissue?
Adrenal tissue is destroyed by autoantibodies against adrenal cortex.
Pathophysiology of Addison’s Disease:
What does adrenal gland atrophy lead to?
Adrenal gland atrophy decreases production of all the adrenocortical secretions: glucocorticoids (cortisol and cortisone), mineralocorticoids (aldosterone), and androgens (sex hormones).
Addison’s: Clinical Manifestations:
Symptoms occur based on what fact?
Sx of hypocortisolism & hypoaldosteronism
Addison’s: Clinical Manifestations:
What are symptoms?
Weakness & easily fatigued
Skin changes – hyperpigmentation
Anorexia, n/v
Salt craving, mood changes, depression
Hyperkalemia, Hyponatremia, Hypoglycemia
Addison’s: Clinical Manifestations:
How are electrolytes?
Hyperkalemia, Hyponatremia, Hypoglycemia
Addisons’s Clinical Manifestations:
What occurs with Adrenal crisis/Addisonian crisis? (bp, water levels)
Hypotension –> complete vascular collapse & shock
Dehydration, lethargy, GI sx
Addisons’s Clinical Manifestations:
When does Adrenal crisis/Addisonian crisis occur? (in who)
Developed in the undiagnosed & under physiologic stress
Addison’s Clinical Manifestations cont’d:
Why does Hypoglycemia, hyponatremia, hyperkalemia occur?
Impaired gluconeogenesis & decreased mineralocorticoid (aldosterone activity)
Addison’s Clinical Manifestations cont’d: How is body hair?
Decreased body hair
Addison’s Clinical Manifestations cont’d:
Why is there decreased body hair?
Decreased androgens
Addison’s Clinical Manifestations cont’d:
How is skin?
Hyperpigmentation (bronze color) in extremities, skin creases, buccal mucosa, and tongue
Addison’s Clinical Manifestations cont’d:
Why does hyperpigmentation occur?
Increased ACTH, resulting from low cortisol secretion, stimulates melanocytes (skin pigmentation cells)
Addison’s Clinical Manifestations cont’d:
What happens with blood volume?
Decreased blood volume
Addison’s Clinical Manifestations cont’d:
Why is there decreased blood volume?
Decreased mineralocorticoid (aldosterone) activity results in fluid loss through the urine
Addison’s Clinical Manifestations cont’d:
What happens to bp- and what does that lead to?
Hypotension, syncope
Addison’s Clinical Manifestations cont’d:
Why does hypotension and syncope occur?
Decreased effectiveness of epinephrine and norepinephrine to vasoconstrict vessels from lack of cortisol; secondary to decreased blood volume
Addison’s Clinical Manifestations cont’d:
How is weight?
Fatigue, weight loss
Addison’s Clinical Manifestations cont’d:
Why is there weight loss?
Hypoglycemia
Addison’s Clinical Manifestations cont’d:
Why are there personality changes?
Altered emotional stability from decreased glucocorticoids; brain needs glucose to function
Addison’s Clinical Manifestations cont’d:
Why is there poor stress response?
Overwhelmed and underfunctioning adrenals: Cannot produce enough hormones for the additional stress; can lead to an Addisonian crisis (all the symptoms happen quickly and severely), a life-threatening situation
Adrenal Crisis: What are symptoms of this?
Hypotension,
dehydration,
weakness,
lethargy,
GI sx
Adrenal Crisis: What happens if it is left untreated?
Left untreated –> shock, death
Adrenal Crisis:
Causes
Adrenal or pituitary failure
Undiagnosed disease
Failure to provide pts receiving replacement therapy with adequate GC doses
Adrenal crisis may also be triggered by abrupt withdrawal from chronic high-dose GC therapy
Adrenal Crisis: What is treatment?
Rapid replacement of fluid, salt, GCs, glucose for energy
Hydrocortisone 100mg IV bolus followed by 50mg every 8 hrs
NS with dextrose
Adrenal Crisis: Evaluation of Labs?
Hyponatremia & hyperkalemia
Depressed serum & urine levels of cortisol
Dehydration –> elevated BUN
Hypoglycemia
Adrenal Crisis: Evaluation of Labs?
What does increased ACTH indicate?
ACTH increased – primary adrenal insufficiency
Adrenal Crisis: Evaluation of Labs?
What does decreased ACTH indicate?
Decreased ACTH – pituitary infarction or tumor-compressing ACTH-secreting cells
Slide 53- Cosyntropin
Agents for Replacement Therapy in Adrenocortical Insufficiency:
What is required?
Replacement therapy with corticosteroids/Glucocorticoids required
Agents for Replacement Therapy in Adrenocortical Insufficiency:
In addition to Replacement therapy with corticosteroids/Glucocorticoids required, what else may some people need?
Some patients also require a mineralocorticoid (eg fludrocortisone)
Agents for Replacement Therapy in Adrenocortical Insufficiency:
What is the only mineralocorticoid available?
Fludrocortisone is the only mineralocorticoid available
Agents for Replacement Therapy in Adrenocortical Insufficiency:
What are the principal glucocorticoids used?
Principal glucocorticoids used are hydrocortisone, dexamethasone, and prednisone
Agents for Replacement Therapy in Adrenocortical Insufficiency:
What does chronic insufficiency require?
Chronic insufficiency requires LIFELONg tx (pt education a must!!!)
Agents for Replacement Therapy in Adrenocortical Insufficiency:
What must be done in times of stress?
At times of stress (infections, surgery, trauma) pts MUST increase GC dose. Failure to do so could be fatal.
Take 3x the usual dose for 3 days
Agents for Replacement Therapy in Adrenocortical Insufficiency: How is it given?
Oral for chronic replacement of glucocorticoids
Agents for Replacement Therapy in Adrenocortical Insufficiency: How is the oral for chronic replacement of glucocorticoids taken?
Take entire dose upon awakening since levels of GCs normally peak in the AM or take ⅔ in the morning and ⅓ in the afternoon
Agents for Replacement Therapy in Adrenocortical Insufficiency:
How are mineralcorticoids taken?
Mineralocorticoids taken daily
Hydrocortisone: What is it and what is it similar to?
Synthetic steroid with a structure identical to that of cortisol
Hydrocortisone: What is it used for?
Used for replacement therapy in adrenocortical insufficiency
Hydrocortisone : When is oral used?
Oral is used for chronic therapy
Hydrocortisone: What kind of action does it have?
Has both glucocorticoid & mineralocorticoid actions
Hydrocortisone: When would parental administration occur?
Parental administration for acute insufficiency & to supplement oral therapy in times of stress
Hydrocortisone: Adverse effects
Low dose, devoid of adverse effects
Large doses, chronic – highly toxic
Hydrocortisone:
What are large doses for?
Adrenal suppression and promotion Cushing’s syndrome
Nursing Implications of Hydrocortisone : Read slide 59
What is a potent mineralcorticoid?
Fludrocortisone
Fludrocortisone: What can it be used with?
In most cases, used in combination with hydrocortisone
Fludrocortisone:
ADRs
If dose too high: Na & H2O retained, K+ is lost
Expansion of blood volume, htn , edema, cardiac enlargement
Monitor for weight gain, swelling of lower exts, irregular heartbeat, hypertension, hypoK
If these changes occur, d/c med temporarily