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Endocrine
Pharmacy
125
Pharmacology
Graduate
11/05/2011

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Term
Nuclei of the Hypothalamus
*Paraventricular
*Periventricular
*Preoptic
*Arcuate
Definition
*Paraventricular - CRH, TRH
*Periventricular - GHIH
*Preoptic - GnRH
*Arcuate - PIH(DA), GHRH
Term
The Pituitary
Location
Posterior Pituitary
Anterior Pituitary
Definition
Location - Within a recess of the Sphenoid bone called the Sella Turcica
Posterior Pituitary - Direct extension of the brain.
Anterior Pituitary - Communicates with hypothalamus through portal plexus capillaries.
Term
Hypothalamus -> Pituitary
(Peptide -> Resulting hormone)
CRH ->
TRH ->
GnRH ->
GHIH ->
PIH(DA) ->
GHRH ->
ADH ->
Oxytocin ->
Definition
CRH -> ACTH
TRH -> TSH, Prolactin
GnRH -> LH, FSH
GHIH -> Inhibits GH/TSH
PIH(DA) -> Inhibits Prolactin
GHRH -> GH
ADH -> Neuronal release from Anterior Pituitary
Oxytocin -> Neuronal release from Anterior Pituitary
Term
Cells types within Anterior Pituitary
*Somatotroph
*Lactotroph
*Corticotroph
*Thyrotroph
*Gonadotroph
Definition
*Somatotroph - Responds to GHRH to release GH
*Lactotroph - Responds to TRH to release Prolactin
*Corticotroph - Responds to CRH to release ACTH
*Thyrotroph - Responds to TRH to release TSH
*Gonadotroph - Responds to GnRH to release LH, FSH
Term
Which hormones are made up of Alpha/Beta subunits. What does that mean?
Definition
TSH, LH, FSH, HcG
The Alpha units are identical to each other. Because of this cross-interactions can occur.
Term
Function of hormones
*FSH
*LH
*ACTH
*TSH
*GH
*Prolactin
*ADH(Vasopressin)
*Oxytocin
Definition
*FSH - Growth and maturation of ovarian folicles. Sperm Production
*LH - Required for Ovulation. Required for testosterone secretion from Leydig cells
*ACTH - Stimulates Glucocorticoids, sex hormones, and aldosterone.
*TSH - Stimulates T3/T4 secretion from Thyroid
*GH - Role in METABOLISM and body growth
*Prolactin - Stimulates production and secretion of milk into alveolar sacs of mammaries.
*ADH - Increases H2O reabsorption in kidney
*Oxytocin - Stimulates milk "let down"
Term
Examples of hormone pathways:
CRH ->
TRH ->
Definition
Hypothalamus:CRH -> Pituitary:ACTH -> Adrenals:Cortisol -> End organ:Response
Hypothalamus:TRH -> Pituitary:TSH -> Thyroid:T3/T4 -> End organ:Response
Term
Hormone receptors
*Gs -
*Gq -
*Tyrosine Kinase -
*Intracellular -
Definition
Hormone receptors
*Gs - AC->cAMP ; LH, FSH, TSH, hCG, ACTH, ADH-2,
*Gq - PLC->IP3,DAG ; ADH-1
*Tyrosine Kinase - Phosphorylated->Activated Dimer ; GH, IGF-1, Prolactin, Insulin,
*Intracellular - Hormone->HRE(stim/inhib DNA) ; Steroids(Estrogen, Testosterone, Progestin, Glucocorticoids, Mineralcorticoids)
Term
Feedback Mechanisms
*Hormones
*Extermal Stimuli
*Cations
Definition
*Negative Feedback - The products will inhibit synthesis of precursors. (ACTH inhibits CRH secretion)
*Hormones - GHIH, PIH(DA)
*Extermal Stimuli - (Starvation/fear)
*Cations (Ca-negativefeedback->PTH)(NA/K->ADH, Renin, Aldosterone)
Term
Difficulties of testing hormone levels:
* e.g. ACTH
* e.g. GH
* e.g. cortisol
Definition
* e.g. ACTH - many hormones have very short half-lifes.
* e.g. GH - Secretion of hormones may be episodic/Diurnal
* e.g. cortisol - the physiologically important free(non-bound) portion of the hormone may not be easily measure.
Term
Endocrine Pathologies:
*Hypofunction
*Hyperfunction
Definition
*Hypofunction - Agenesis(Absence) or organ, Defect in biosynthetic pathway, Organ destruction(hashimoto's), Precursor deficiency
*Hyperfunction - Autoimmune stimulation (Grave's), decreased protein binding or metabolism, Ectopic hormone, Iatrogenic,
Term
Tests for hypo/hyper fuction.
*HYPOfunction:
*HYPERfunction:
*Imaging:
Definition
*HYPOfunction: Stimulation testing to see if precursor stimulates downstream response.
*HYPERfunction: Suppression testing to see if end hormone will feedback and inhibit precursor levels.
*Imaging: To look for size, shape, and functional abnormalities. e.g. RAIU
Term
*Order of testing:
Definition
*Order of testing:
First check for Signs/Symptoms.
Then hormone levels.
Then do dynamic testing (suppression/stimulation) or imaging.
Term
Etiology of HYPOpituitarism
*Children -
*Adults -
Definition
*Children - Structural defects, Hormone abnormalities, Usually CONGENITAL.
*Adults - Usually due to ADENOMAS. Other factors: Genetics, growths, cancer, vascular, immune, injury, trauma,
Term
What would you see in Panhypopituitarism (all hormones missing)?
Definition
Disregulation of Temperature, Disregulation of Water/food intake, somnolence/coma, Autonomic dysfunction(arrythmias, epilepsy, pulmonary edema), Psychic disorder (rage/hallucination), METABOLIC dysfunction.
Term
What other organ symptoms might be indirectly affected in pituitary/hypothalamus dysfunction?
Definition
Due to nearby location: ocular, nasal, and CNS may be affected due to compression by an adenoma.
Term
What levels would differentiate hypothalamic vs. Pituitary disease.
Definition
Levels of most hormones will be decreased overall in both. GH will be variable in both.
Pituitary Disease: Oxytocin and ADH are UNAFFECTED. Prolactin will be decreased like the others.
Hypothalamic Disease: Will have DECREASED Oxytocin and ADH. Prolactin will be INCREASED due to decreased PIH(DA) inhibition from hypothalamus.
Term
1. A patient has levels of decreased ACTH, LH, oxytocin, and increased prolactin, GH. Do they likely have pituitary or hypothalamic disease?
2. Decreased FSH, TSH, prolactin, and increased GH?
Definition
1. Hypothalamic Disease
2. Pituitary Disease.
*GH is useless info. It could be up or down in either.
Term
1. What is decreased in Hypocortisolism?
2. What are prominent symptoms?
Definition
1. Glucocorticoids(DANGER!), Estrogen/Testosterone(Until Puberty), Aldosterone(Renin/Angiotensin system will compensate in deficiency)
2. Weight loss, Anorexia, N/V, Abdominal Pain, HYPOglycemia, HYPOnatremia, Circulatory collapse.
Term
What are tests for Hypocortisolism?
*Stimulation Testing:
*Metyrapone Test:
*Insulin Tolerance Test(ITT):
Definition
*Stimulation Testing: CRH to test Pituitary (Should increase ACTH, cortisol). ACTH to test Adrenals (Should increase cortisol.) If levels DO increase like they should, that shows that the problem is at a different organ!
*Metyrapone Test: Should increase CRH(hypothalamus) and ACTH(pituitary). Works by blocking synthesis of cortisol therefore blocking negative feedback.
*Insulin Tolerance Test(ITT): Should increase ACTH/GH if hypothalamus and pituitary work (and also increase IGF-1 and cortisol) Works by decreasesing glucose to less than 40mg/dL
Term
Patient has low cortisol. Testing is done. What can you conclude from each step?
1. CRH: ACTH,cortisol increases
2. ACTH: cortisol increases
3. Metyrapone test: No increase in CRH or ACTH
Definition
1. Problem is not in Pituitary
2. Problem is not in adrenals (If it was it would be Addison's Disease)
3. Problem is likely in the Hypothalamus.
Term
Patient has low cortisol. Testing is done. What can you conclude from each step?
1. ITT: GH increases, ACTH does not.
2. Metyrapone test: CRH increases, ACTH does not.
Definition
1. There is a problem somewhere in hypothalamus/pituitary for ACTH, but GH is ok.
2. Problem is likely in the pituitary.
Term
1. What is decreased in hypothyroidism?
2. What are prominent symptoms?
Definition
1. T3/T4 will be low.
2. CNS problems, unusually dry, coarse hair, Goiter, Sensitivity to Cold
*Note: Hypothyroidism could result from increased GHIH
Term
What are tests for Hypothyroidism?
Stimulation Testing:
Definition
Stimulation Testing: TRH to test Pituitary (TSH, Prolactin should increase)
Term
A patient with low T3/T4 also has low TRH and High TSH. What would be your initial guess as to what's going on?
Definition
Since TSH is high, the pituitary is obviously producing it. So the hypothalamus and pituitary are likely working. TRH is probably low due to negative feedback from TSH. There is likely a problem with the thyroid itself because their is plenty of TSH to stimulate it and it is not responding.
Term
3 patients with symptoms of hypothyroidism iare tested with TRH stimulation.
1. TSH/Prolactin increases. Still low T3/T4
2. TSH/Prolactin increases. T3/T4 also increases
3. No change in levels of anything
Definition
1. Thyroid is likely the problem
2. Hypothalamus is likely the problem
3. Pituitary is likely the problem
Term
What occurs in Prolactin deficiency?
Definition
Poor or absent lactation
Term
1. What is decreased in hypogonadism?
2. What are prominent symptoms?
Definition
1. LH, FSH, and therefore testosterone and estrogen are also decreased.
*Note: End Organ ~Adults: Repro organs ~Children Adrenals
2. Decreased Development. Puberty would not occur. Before puberty there would be few problems. After puberty: Amenorrhea, Infertiility, Breast atropy, Loss of secondary sexual hair, decreased libido, small/soft testes. Testosterone: Decreased muscle mass and strength. Decreased erythropoiesis. Estrogen: Osteoporosis.
Term
What would you conclude if you saw decreased estrogen with increased FSH?
Definition
End organ failure. AKA: Menopause
Term
1. What is decreased in Growth Hormone Deficiency?
2. What are prominent symptoms?
Definition
1. Decreased GH and therefore IGF-1.
2. Decreased Growth, Increased BMI, Increased lipid and glucose levels.
*Note GH deficiency could result from increased GHIH or decreased GHRH.
Term
Test for Growth Hormone Deficiency
ITT Test:
Definition
*Insulin Tolerance Test(ITT): Should increase ACTH/GH if hypothalamus and pituitary work (and also increase IGF-1 and cortisol) Works by decreasesing glucose to less than 40mg/dL
Term
1. What is decreased in Diabetes Insipidus?
2. What are prominent symptoms?
Definition
1. It due to an ADH(vasopressin) deficiency
2. Inability to concentrate Urine. Increased Na concentration in plasma due to lack of water and decreased Na in urine.
Term
Differentiate CDI (Central Diabetes Insipidus) and NDI(Nephrogenic Diabetes Insipidus)
Definition
CDI: Due to hypothalamic/Pituitary Disease. Therefore serum ADH is decreased. Can be treated with DDAVP (synthetic ADH)
NDI: The kidney itself is insensitive to ADH. Therefore serum ADH is Increased. (Actual cause must be treated)
Term
What is the mechanism of ADH?
Definition
ADH increases the amount of aquaporins in the kidney. These allow H2O to return to the blood stream
Term
A patient is experiencing frequrent urination. You find that urine is dilute and that blood plasma has high osmolarity. Surprisingly, you find high levels of ADH in the blood. What do you conclude?
Definition
Nephrogenic Diabetes Insipidus. The Kidney has become insensitive to ADH.
Term
What is the precursor to corisol that will build up during a Metyrapone test?
Definition
11-Deoxycorticosterone.
*Be able to tell apart structure of 11-deoxycorticosterone and cortisol(which has had a second hydroxylation).
Term
Treatments for Hypopituitarism/Deficiencies
(Often the therapy is the end hormone, but there are exceptions)
*ACTH:
*TSH:
*Prolactin:
*LH/FSH:
*GH:
*ADH:
Definition
*ACTH: Glucocorticoids
*TSH: Thyroxine (T4)
*Prolactin: Not treated
*LH/FSH: Estrogen, Progesterone, Testosterone (Synthetic GnRH is also used)
*GH: hGH is used because there are too many end hormones!
*ADH: DDAVP
Term
Why aren't ACTH, TSH, Prolactin, or LH/FSH used for treatment of deficiencies?
Definition
Because they are peptides with FAR too short half-lives. Would need constant IV.
*And Prolactin deficiency isn't treated.
Term
What would be most important to replace in an 8 yo with Panhypopituitarianism?
What about in a 14 yo?
Definition
1.Glucocorticoids for ACTH most important 2.TSH is next-most important 3. GH
In a 14 yo it would also be very important to give Estrogen/Testosterone so that puberty can occur.
Term
Causes of Pituitary Hypersecretion
*Stress
*Menopause
*Hyperplasia
*Pituitary Adenoma
Definition
*Stress - ACTCH rises during stress. Occurs in non-disease patient
*Menopause - LH and FSH rise due to loss of feedback inhibition by sex hormones. Occurs in non-disease patients
*Hyperplasia of pituitary - Due to hypersecretion of releasing factors from tumors of the hypothalamus.
*Pituitary Adenoma - The MOST common cause.
Term
Pituitary Adenoma Random Facts:
% of intracranial Neoplasms:
Can be visualized by:
% of individuals with one at autopsy
Local growth can result in:
Benign or Malignant:
30-40% of somatotroph adenomas have what defect in the Gs coupled receptor?
Definition
*Adenomas are what % of intracranial *Neoplasms: 10%
*Can be visualized by: MRI
*% of individuals with one at autopsy: 27%
*Local growth can result in: compression of adjacent structures(hypopituitarism)
*Benign or Malignant: MOST are benign.
*30-40% of somatotroph adenomas have what defect in the Gs coupled receptor? The Gs protein is constitutively ON, increasing GH secretion.
Term
A pituitary adenoma could cause hyper or hypo pituitarism.
*Secreting Adenomas
*Non-secreting Adenomas
Definition
*Secreting Adenomas: If hormone is functional, then NORMAL or HYPER. If hormone is non-functional, then could cause HYPO by compression.
*Non-secreting Adenomas: Could cause HYPO by compression.
Term
What is the most common type of Pituitary Adenoma?
Definition
50% are Prolactinomas
34% are non-secreting/non-functional
Term
What are the causes of hyperprolactinemia?
Definition
Decreases in PIH(DA) or disconnection with hypothalamus, DA blockers, Decreased renal elimination, Increased TRH or VIP(vasoactive intestinal polypeptide), and obviously secreting pituitary adenomas,
Term
Symptoms of Hyperprolactinemia
Definition
*Galactorrhea(30-80% women; <10% men, Impotence, hypogonadism
*With Macroadenomas(so compression might occur: Visual field abnormalities, Extra-ocular muscle palsies, Headaches, nasal symptoms,
Term
1. Effects of hyperprolactinemia on hormone levels
2. Treatments of hyperprolactinemia
Definition
1. Decreased GnRH, Testosterone/Estrogen, Androgens
2. DA Agonists, Surgery
Term
What are the causes of hypersecretion of growth hormone?
Definition
1) Adenoma
2) Hyperplasia
3) Genetic
DA and somatostatins inhibit GH so any disruption in those will increase gGH
Term
What will be the effect of hypersecretion of Growth Hormone?
*In children vs. Adults
*In which structures?
Definition
*If before closure of the epiphyseal plates in children, then gigantism. In Adults, acromegaly will occur.
*Acral(long) Bones, Cartilage, and Joints. These will usually be considerably weaker bones than average. The facial bones such as mandible and the jaw will grow large, facial features will thicken and skin creases are very pronounced due to Na and H2O retention(facial swelling).
Term
Why is it difficult to measure levels of GH as compared to IGF-1?
Definition
GH has a very short half-life(20-25 min), and is pulsatile in nature, with pusles every 2-4 hrs). IGF-1 in contrast, has fairly constant levels in the blood.
Term
Mechanisms of GH and IGF-1
*GH
*IGF-1
Definition
*GH: Increasees Insulin resistance, Lipolysis, and IGF-1 Synthesis
*IGF-1: Stimulation of skeletal Growth, protein synth, immunomodulation,
Term
How can you test for hypersecretion of GH/acromegaly?
How can you treat it?
Definition
*(1)OGTT. In acromegaly, a glucose load will not be able to suppress GH secretion. (2)Measurement of IGF-1 levels, however this can be elevated in puberty or pregnancy and lowered in liver/renal disease.
*(1)Transsphenoidal Surgery. There is a higher success rate in removing Microadenomas(80%) vs Macroadenomas(50%) (2)Radiation (3)Drugs [A different flash card]
Term
What are the greatest dangers of Hypersecretion of growth hormone?
Definition
CV disease, Respiratory disease, and increased risk of cancer. These can result in mortality.
Term
What are the drugs used in the treatment of hypersecretion of GH?
Definition
*DA Agonists: Bromocriptine, Cabergoline, Pergolide.
*GHIH/Somatostatin analogues: Octreolide (SC TID), Octreolide-LAR (IM monthly), Lanreotide (SC monthly)
*GH antagonist: Pegvisomant (SC daily)
*Upcoming therapies: IGF antagonists
Term
Thyrotroph Adenomas
*Are they primarily macro or micro?
*What are the effects on the body?
*How are they treated?
Definition
*Macro Adenomas
*Increased TSH, Hyperthyroidism, Goiter,
*(1)Surgery (2) Radiation (3) Octreotide(minimal effect)
Term
*What are the causes of hypercortisolism?
Definition
(1)*Most commonly "Drug-induced" such as by GLUCOCORTICOIDS(2)Obesity (3) Pituitary Adenoma(Cushing's) and hypothalamic (4) Ectopic
Also caused by stress in normal individuals.
Term
What are symptoms of hypercortisolism?
Definition
*Pathognomic: Wide cutaneous, purple striae in Cushing's Disease!
*Lipid Tissue Redistribution (Central/Truncal), Facial Plethora(Moon face), Supracalicular Fullness(Buffalo hump),
*Osteopenia/Osteoporosis,
*"Steroid Mellitus" hyperglycemia,
*Increased aldosterone resulting in hypokalemia, water retention, and HTN.
*Peptic Ulcers
*Decreased immune function
*Mental disturbances, depression, and psychosis may be present {Differential Diagnosis!}
Term
*What are the treatments for Hypercortisolism?
Definition
(1)Surgery (2)Radiation (3)Drugs
-Metyrapone, Ketoconazole, Aminoglutethimide: Inhibit cortisol synthesis
-Mitotane: Destructive to the adrenal cortex. (will also decrease Aldosterone, though the RAS will compensate and also sex hormones before adolescence)
-Mifepristone: Glucocorticoid antagonist.
Term
Ketoconazole
Definition
Used as a treatment for hypercortisolism. Will inhibit Cholesterol -> Pregnenolone, therefore DECREASING Aldosterone, corticosteroids, and SEX HORMONES (bad in an 8 yo whose only source is from adrenals). As opposed to Metyrapone which results in an increase in Sex hormones.
Term
Metyrapone
Definition
Used as a treatment for hypercortisolism. Will inhibit 11-deoxycortisterone -> Cortisol (the enzyme is 11Beta-hydroxylase), therefore DECREASING Aldosterone, corticosteroids, and INCREASING sex hormones due to "back-up" of precursors. As opposed to Ketoconazole which results in a decrease in Sex hormones.
*Also used to test Hypo/Pituit function in hypocortisolism.
Term
Non-Secreting Pituitary Adenomas
*Most are what type of cell?
*Do you treat it?
*If so, with what?
Definition
*Most are gonadotrophs
*If they aren't a problem, don't treat it
*If they are, then (1) Surgery for large or malignant adenomas (2) Radiation (3)Drug treatments(Not very effective): Detreolide, DA Agonists, GnRH
Term
Syndrome of Inappropriate ADH secretion (SIADH)
*What is the effect on the body?
Definition
*ADH-> Aquaporins-> H2O reabsorption-> increased blood volume-> Increased BP. Also high urine concentration/osmolarity, low blood osmolarity(hyponatremia). Hyponatremia can lead to nausea, convulsions, vomiting, confusion, and coma.
Term
Syndrome of Inappropriate ADH secretion (SIADH)
*What are the causes of SIADH?
*What must be this be differentiated from?
Definition
Intracranial disease/surgery-> uncontrolled ADH release
Pulmonary infectious disease like TB
Ectopic ADH release
Severe N/V
Iatrogenic
*Lab levels may also be caused by renal, cardiac, liver, thyroid, or adrenal problems.
Term
Syndrome of Inappropriate ADH secretion (SIADH)
*What are the treatments for SIADH?
Definition
First: Remove or correct offending cause (eg. malignancy, medication)
Fluid Restriction, Oral salt or urea to promote solute diuresis, loope diurteics, Demeclocycline(tetracycline that blocks ADH receptors)
Term
Compare SIADH with Diabetes Insipidus
*Diabetes Insipidus(CDI):
*SIADH:
Definition
*Diabetes Insipidus(CDI): Dilute/high volume urine, concentrated(hypernatremia) blood,
*SIADH: Concentrated low volume urine, Dilute(hyponatremia)/high volume blood. May cause edema, and CNS effects
Term
Zona Glomerulosa of Adrenal Cortex
*Location
*Action
Definition
*The outer zone of the cortex
*Produces Aldosterone which increases reabsorption of Na+ at the renal nephron(While secreting K+) by acting on mineralcorticoid receptors. Therefore, indirectly increases H2O reabsorption which follows the Na+.
Term
How is Aldosterone regulated?
*ACTH
*Renin-Angiotensin System
Definition
*ACTH: Will somewhat increase Aldosterone secretion. Usually only effective under severe stress.
*RAS: Antiotensin II has a large effect on increasing Aldosterone secretion.
Term
*What is the Renin-angiotensin system(RAS)?
*How can the Renin-angiotensin system(RAS) be inhibited?
Definition
*Angiotensinogen is converted to angiotensin I by Renin(which is produced in the kidney in response to low BP) Angiotensin I is then converted to Angiotensin II by ACE. Angiotensin II then acts on to vasoconstrict and to stimulate Aldosterone release.
*Either by Renin Inhibitors, ACE inhibitors, or by ARBs(Angiotensin receptor blockers)
Term
Differentiate primary disease failure and secondary disease failure.
Definition
Primary means that the end organ is what fails (such as adrenal gland hyperplasia in hypersecretion of aldosterone)
Secondary is caused by some other organ.
Term
Differentiate the lab values of primary vs secondary hypersecretion of aldosterone.
Give examples of each
Definition
*Both will have increased BP, Na+, and decreased K+ in the blood.
*Primary will have increased Aldosterone, but DECREASED RENIN due to negative feedback. (Examples:Adrenal Adenoma/Conn's, Adrenal Hyperplasia)
*Secondary will have BOTH increased aldosterone and Renin(Because the kidney is cranking it out). (Examples:Pregnancy, CHF, Renin producing tumor, Renal Disease, and in rare cases Hypothalamic/Pituitary)
Term
Hyposecretion of Aldosterone
*Cause
*Symptoms
Definition
*Typically associated with Addison's disease(low ACTH).
*Decreased Na+ and therefore H2O reabsorption. Increased serum K+. The altered K+ could result in changes in membrane potentials and disrupt neural and muscular function.
Term
Zona Reticularis of the Adrenal Cortex
*Location
*Action
Definition
*Inner Zone of the Adrenal Cortex
*Pre-puberty source of sex hormones (Testosterone/Estrogen)
Term
Hypersecretion of the Zona Reticularis
*Cause
*Symptoms
Definition
*Cushing's(increased ACTH) due to Hypothalamic/Pituitary failure, CAH(Congenital Adrenal Hyperplasia) which is a hydroxylase deficiency(decreased Km and/or Vmax),
*Results in rapid masculinization in males and formation of male-like genitalia in females.
Term
Why will an 11B-hydroxylase or 21-Hydroxylase deficiency result in an increase in sex hormones from the Zona Reticularis?
Definition
Because those hydroxylase enzymes are used in the cortisol pathway of Cholesterol. If there is a deficiency, a "back-up" will occur in the precursors until they "spill-over" into the sex hormone pathway.
Term
Zona Fasciculata of the Adrenal Cortex
*Location
*Action
Hemodynamic
Metabolism
Immune
Distribution of total body water
Definition
*The middle zone of the Adrenal cortex
*Produces cortisol, a glucocorticoid.
Cortisol Regulates a number of functions:
Hemodynamic: Maintains Cardiac Output and helps maintain vascular tone.
Metabolism: Regulates glucose, amino acid, and fat metabolism (Stimulates glycogen synthesis and gluconeogensis)
Immune system: Anti-inflammatory and modulates immune response
Distribution of total body water: Regulates extra cellular water by retarding migration its migration into cells. Suppresses ADH and increases GFR.
Term
Addison's Disease (Adrenal insufficiency)
*A decrease in:
*An increase in:
Definition
*Decrease in cortisol, and sometimes, but not always Aldosterone.
*ACTH due to lack of negative feedback.
Term
Causes of primary Adrenal Insufficiency (Addison's)
*Autoimmune
*Infection
*Drugs
*Hemorrhage
*Cancer
*Genetic
Definition
Autoimmune: APS-1 against cholesterol P450-SSC side chain cleavage. APS-2 against 21-B hydroxylase.
*Infection: Usually multicellular organisms. TB is the most common cause. HIV progression can increase risk of infection.
*Drugs: Ketoconazole can block steroid synthesis
*Hemorrhage: Hemorrhage of the adrenals can occur when postoperative, or on anticoagulants.
*Cancer: Metastatic disease of the adrenals that destroys 90% of adrenals.
*Genetic: Familial Glucocorticoid deficiency. The adrenals are unresponsive to ACTH at the receptor (Gs->cAMP)
Term
Causes of secondary Adrenal Insufficiency
Definition
*Hypothalamic/Pituitary Disease
*GLUCOCORTICOID Drug Treatment may suppress the H/P Axis: Risk increases with increased potency, duration, and when system(oral)
*Also cancer, infection, inflammation, and immune failure.
Term
Risk Factors for Autoimmune Addison's Disease:
Definition
*Women have higher risk
*Onset is usually in young adulthood
*Other autoimmune disorders shows higher risk.
Term
Addison's Disease Pathologies
(Aside from Anorexia, fatigue, weight loss,)
Definition
(1) The decrease in cortisol synthesis will:
*Decrease Cardiac output and decreased vascular tone leading to hypovolemia. ADH will then increase in response. This will lead to increased plasma H2O and hyponatremia.
(2) The decrease in aldosterone will decrease plasma sodium and increase K+, also leading to hyponatremia. (Aldosterone will be normal in secondary deficiency because it is regulated by RAS, and not hypothalamic/pituitary)
In primary(Addison's) Hyperpigmentation will also occur due to the increased MSH(which is a component of ACTH precursor)
Term
Adrenal insufficiency/Addison's Disease pathologies (put another way)
Definition
*Fatigue, anorexia, and weight loss will always be present, whether primary or secondary.
*Hyperkalemia, Hyperpigmentation, and increased ACTH will only occur in primary disease
*Decreased ACTH will be likely in secondary. Aldosterone will not decrease in secondary disease
Term
A patient complains of weakness and a lack of hunger. You take lab values and find that she has low cortisol, hyponatremia, and hyperkalemia. What would you guess she has?
Definition
It is Addison's disease(primary) because hyperkalemia is not present in secondary.
This patient will likely develop darker skin if she has not already.
Term
How to test for Adrenal Insufficiency
*CRH:
*ACTH(cortrosyn):
*ITT
*Metyrapone
Definition
*CRH: If ACTH is low and secondary insufficiency is suspected, use this to test the pituitary. ACTH would increase if the pituitary works correctly.
*ACTH(cortrosyn): Cortisol should increase if the adrenals work
*ITT: If H/P is working fine, then ACTH and GH should increase.
*Metyrapone: If H/P is working, then CRH and ACTH should increase.
Term
How to treat Adrenal Insufficiency
*Treat the cause
*Drugs (for both primary and secondary)
Definition
*Fix secondary insufficiency by fixing the gland that is causing it.
*Drugs: Corticosteroid replacement therapy. Prednisone is usually used because it is average in potency and duration, thus a sufficient half-life, but decreased risk of glucocorticoid side effects.
Term
What do you do during corticosteroid replacement therapy if the patient becomes ill?
Definition
Increase the dose to mimic how the adrenals would respond under similar conditions.
Term
Differentiate Primary and secondary Hyperaldosteronism
Definition
Primary: Increased Aldosterone with DECREASED Renin due to negative feedback
Secondary: Increased Aldosterone is due to INCREASED Renin
Term
Etiology of primary Hyperaldosteronism
Definition
*UNILATERAL aldosterone producing Adenoma(65%). Treat with adrenalectomy.
*Idiopathic Hyperaldosteronism (30%) Treat medically
Term
Drugs used in primary Hyperaldosteronism
Definition
*Eplernone - Receptor Antagonist for Aldosterone
*Amiloride - Blocks Renal Na+ channels
*ACE inhibitors have been shown effective in IHA(Ideopathic Hyperaldosteronism)
*Nifedipine has also been shown to decrease aldosterone levels.
Term
Pheochromocytoma (MEN - Multiple endocrine neoplasia)
*Defined as:
*Results in hypersecretion of:
Definition
*Catecholamine producing tumor which arises from the chromafiin cells of the adrenal medulla.
*Epinephrine which is selective for Beta receptors over alpha.
Term
Pheochromocytoma
*What syndromes are associated with pheochromocytoma?
Definition
The following syndromes can lead to growths, sometimes malignant, and pheochromocytoma is a possibilty along with others listed:
*MEN2A - pheocrhomo., medullary thyroid carcinoma, and hyperparathyroidis
*MEN2B - pheochromo., medullary thyroid carcinoma, and mucosal neuromas
*Neurofibromatosis - pheochromo., and neurofibromas
*Von Hippel Lindau Syndrome - pheochromo., renal and pancreatic cysts, and renal cell carcinoma,
Term
*What is the clinical presentation of Pheochromocytoma?
Definition
The 5 "P's"
*Pressure - sudden and dramatic upon moving
*Pain - chest, abdominal, abrupt/throbbing headache,
*Perspiration
*Palpitations with tachycardia and feelings of panic or anxiety.
*Pallor due to skin vasoconstriction
Term
*How do you test for Pheochromocytoma?
Definition
*24 hour urine collection for catecholamines and metabolites (NE, E, metanephrines, and VMA)
*A MAOI could interfere with results.
*Another option would be to insert the needle for blood drawing, have the patient lay supine in a quiet environment for at least 30 minutes, and then take blood levels of E, NE.
*Finally, MRI imaging may be taken if labs lend toward pheochromocytoma.
Term
Treatments of Pheochromocytoma.
Definition
(1) Start with an Alpha-1 blockade like phenoxybenzamine to vasodilate.
(2) Volume expansion with liberal salt intake.
(3) Beta blockers will be started after adequate alpha-blockade. Too soon will result in unopposed alpha stimulation and will worsen HTN!
(4) Watch out for reflex hypotension or hyperglycemia in resopnse to treatment.
Term
Cushing's disease
*Defined as:
*Caused by:
Definition
*Symptoms and signs of cortisol excess
*(1) Primarily by exogenous glucocorticoids. (2) Next most common is pituitary hypersecretion of ACTH (3) Could also be due to Adrenal adenoma/hyperplasia. (4) An ectopic secreting tumor
Term
Differentiate Cushings' by ACTH dependent, and ACTH independent, and Iatrogenic
Definition
*ACTH dependent: Hi ACTH, Hi Cortisol. Due to H/P axis, or an ectopic(differentiate by imaging) tumor releasing CRH, ACTH.
*ACTH independent: Lo ACTH, Hi Cortisol. Due to adrenal adenoma/hyperplasia, or is drug induced. Negative Feedback is what lowers ACTH.
*Iatrogenic: Lo ACTH, LOW CORTISOL. May be due to use of Glucocorticoids.
Term
How to test for Cushing's Disease
Definition
Dexamethasone suppression testing: A normal dose will suppress cortisol in a normal individual. However a HI dose is necessary to suppress cortisol in an individual with Cushing's
Term
Treatment of
*Adrenal Carcinomas and Adrenal Cushing's
Definition
*Adrenal cortical carcinoma (often also wit elevated sex hormones) whether secreting or not is malignant and should be treated with surgery (You've got more than one!).
Term
Treatment of
*Indidental Adrenal Mall (Incidentalomas)
Definition
*This means that there is an abnormal mass that has no signs or symptoms.
No treatment is necessary at this point. Simply monitor for changes in size and functionality.
Term
Drug - DDAVP
Definition
Synthetic ADH(vasopressin) used for ADH replacement therapy. (Such as Central Diabetes Insipidus)
Term
Drug - Cortrosyn
Definition
Synthetic ACTH used for Stimulation testing to diagnose hypopituitarism/hypocortisolism
Term
Drug - Insulin Tolerance Test
Definition
Lowers glucose to below 40
*Measures for hypofunction of pituitary in deficiency of growth hormone and hypocortisolism (ACTH and GH should increase in normal H/P)
Term
Drug - Arginine Stimulation Test
Definition
Similar to ITT(Insulin Tolerance Test)
Term
Drug - GHRH Stimulation Test
Definition
Measures for hypo function of pituitary during deficiency of growth hormone. (GH should increase in normal pituitary)
Term
Drug - TRH Stimulation Test
Definition
Measures for hypo function pituitary during hypothyroidism (TSH and Prolactin should increase in normal pituitary) (This test is not very good for differentiating hypothalamus from pituitary failure)
Term
Drug - Glucocorticoids (hydrocortisone, prednisone, dexamethasone)
Definition
Used for ACTH replacement therapy. (Prednisone is usually preferred because it is intermediate giving fewer doses/day than the less potent and less side effects than the more potent)
Term
Drug - Thyroxine (T4)
Definition
Used for TSH replacement therapy
Term
Drug - Estradiol + Progesterone
Definition
Used for LH/FSH replacement therapy
Term
Drug - Testosterone
Definition
Used for LH/FSH replacement therapy
Term
Drug - hGH (Human recombinant growth hormone)
Definition
Used for GH replacement therapy. (The end hormones are not used in this case because there are too many!)
Term
Drug - Dopamine Agonists
Definition
*Used in treatment of hyperprolactinemia
*Used in treatment of hypersecretion of GH
*Used in treatment of non-secreting pituitary adenomas (not very effective)
Term
Drug - Ergot Alkaloids (Bromocriptine, Cabergoline, Pergolide)
Definition
Used in treatment of hypersecretion of Growth hormone such as in a somatotroph adenoma.
Term
Drug - Octreotide
Definition
Somatostatin analog for treatment
*Of hypersecretion of Growth hormone such as in a somatotroph adenoma.
*Of Thyrotroph(TSH) adenoma
(Can be [SC,TID] or [IM,monthly])
Term
Drug - Lanreotide
Definition
Somatostatin analog for treatment of hypersecretion of Growth hormone such as in a somatotroph adenoma.
(Can be [SC,Monthly])
Term
Drug - Pegvisomant
Definition
*Prevents dimerization of the GH's tyrosine kinase receptor, thereby preventing IGF-1 release.
*Used for treatment of hypersecretion of Growth hormone such as in a somatotroph adenoma
Term
Drug - DEXA/Dexamethasone suppression test
Definition
*Used for testing of hypercortisolism such as in a corticotroph adenoma.
(At low dose ACTH and CRH should decrease in a normal H/P. Hi dose needed to suppress in a secreting adenoma. No suppression would occur in Ectopic disease)
Term
Drug - Ketoconazole
Definition
Antifungal. Blocks Biosynthesis of corticosteroids and sex hormones. Can be used in hypercortisolism
Term
Drug - Metyrapone
Definition
Will decrease cortisol synthesis by inhibiting 11B-hydroxylase.
*Can be used in hypercortisolism
*Can be used to diagnose H/P hypofunction of CRH, ACTH.
(May also cause HTN, hypokalemia, and hirsutism. Will result in increased sex hormones.)
Term
Drug - Aminoglutethimide
Definition
Will decrease cortisol synthesis by inhibiting 11B-hydroxylase AND 18-hydroxylase. Can be used in hypercortisolism (May also cause hypothyroidism by interfereing with iodine incorportation)
Term
Drug - Mitotane
Definition
*Is destructive to the adrenal cortex; Used to treat hypercortisolism *Will reduce cortisol, sex hormones before/during adolescence, and Aldosterone
Term
Drug - Mifepristone
Definition
Glucocorticoids receptor antagonist. Can be used in hypercortisolism.
Term
Drug - Detreolide
Definition
Can be used to treat non-secreting pituitary adenomas. Not very effective
Term
Drug - Eplerenone
Definition
Receptor Antagonist for Aldosterone
*Used in Hyperaldosteronism
Term
Drug - Amiloride
Definition
Blocks Renal Na+ channels
*Used in Hyperaldosteronism
Term
Drug - Phenoxybenzamine
Definition
Irreversible Alpha-1 blocker.
*Used along with volume expansion of blood in pheochromocytoma before the non-selective beta blockade is begun.
Term
Drug - Prazosin
Definition
Alpha-1 blocker.
*Used along with volume expansion of blood in pheochromocytoma before the non-selective beta blockade is begun.
Term
Drug - Beta Blockers
Definition
*Used to treat Pheochromocytoma only AFTER alpha-1 blockade and blood volume expansion.
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