Endocrine Flashcards
What is the purpose of the Endocrine System? How does it control this?
Maintain homeostasis using hormones
What are the lipid soluble hormones?
Steroids
What are the water soluble hormones?
Amines, Peptides, Proteins
What 3 factors determine circulation levels of hormones?
Synthesis, secretion, and transport
What do water soluble hormones need to get into the cell (usually)
Receptors
How is peptide hormone syntehsis controlled?
Modulating transcription
How is amine hormone synthesis controlled?
REgulation of enymes and substrate availability
Are precursor hormones active?
Usually not
How can Hormone Secretion be controlled?
Exocytosis via signaling
diffusion
pulsatile manner using gradients
How are hormones transported
In the Blood
What are the dependant factors of hormones reaching their target site in free-form?
Affinity of hormone for plasma protein carriers
hormone degradation
availabilty or receptors
receptor binding
hormone uptake
What functions do protein binding hormones have?
protect hormone from degradation or uptake
Allows for fine control of circulating levels
prevents hormone from binding to unintended sites
Allows transport of lipid soluble hormones
T or F, are plasma protein carriers regulated?
True
What influences the availability of receptors?
Up-regulation
Down-regulation
What is the difference in uptake of water soluble hormones and Lipid-soluble hormones?
Water soluble need an active uptake whereas lipid soluble use passive uptake
What do hormones regulate to maintain homeostasis
Extracellular fluid
Metabolism
Biological clock
Contraction of cardiac and smooth muscle
Glandular secretion
immune functions
growth and development
reprodcution
What can hormone binding cause a cell to do?
Synthesize a new molecule
Change permeability of the membrane
alter rate of reaction
what is a permissive hormone action?
bind to a target cellallowing different hormone to have its full effect
What is a synergistic hormone action?
2 hormones act together to achieve a greater effect
What is an antagonistic hormone action?
2 hormones produce an opposite effect
What is a negatve feedback loop?
High levels of hormone signal to reduce secretion/ production of itself
Low levels of hormone signl to increase secretion/ production
What is a positive feedback loop?
Action of the hormone causes more of the hormone to be released
Where is the pineal gland located?
Epithalamus
What is the function of the pineal gland?
Production of melatonin
What can stimulate/ inhibit melatonin?
Darkness/ Light
What can high levels of melatonin inhibit in children?
Puberty
What does the Pituitary gland do?
Control hormones sent from hypothalamus that cause secretion of various hormones
What are some hormones controled by the pituitary gland?
HGH
Thyroid stimulating hormone (TSH)
Folicle-stimulating and lutenizing hormone
Adrenocorticoiphic hormone
Melanocyte-stimulating hormone
Prolactin (inhbited by dopamine)
What does HGH do?
Promotes synthesis of a protein insulin-like growth factors. Increase cell growth and ATP use
How is HGH released?
Pulsatile secretion peaks in puberty, declines afterwards
Where does HGH normally bind?
Lier, Skeletal muscle, cartilage, and bone
How does Low blood sugar stimulate HGH?
LBS stimulates the release of growth hormone rleasing hormone; increases secretion of HGH from the pituitary gland
How does High blood sugar stimulate HGH?
HBS stimulates the release of growth hormone inhibiting hormone fro hypothalmus; reduces secretion of HGH
What is the consequence of excess HGH? How would it be treated?
Excess uncontorolled growth leading to extra stress on organs. Administration of somatostatin to lower HGH levels
How do you treat HGH defeciency?
Administration of an HGH analogue
What are the hypothalmus - Pituitary Gland interactions?
Growth hormone releasing hormone –> HGH
Thyrotropin releasing hormone –> thyroid stimulating hormone
Gonadotropin releasing hormone –> follicle stimulating and luteinizing hormone
Corticotropin releasing hormone –> adrenocorticotrophic hormone
Dopamine –> (inhib) prolactin
Somatostatin –> (inhib) HGH and thyroid stimulating hormone
What is the thyroid responsible for?
Synthesis, storage, and release of T3 and T4 thyroid hormones
What do T3 and T4 do?
Produce various physiological effects, crutial in homeostasis maintenance
Heart, adipose tissue, muscle, bone, nervouse system, gut, etc.
What is the colloid’s job?
Factory for T3 and T4 production; stores the building blocks as well as T3 and T4
What are the follicular cells function?
Responsible for producing thyroglobulin, pumping in iodine, and pumping out T3 and T4
What hormone controls the synthesis and secretion of T3 and T4?
Thyroid stimulating hormone (TSH) which is controlled bythyroglobulin releasing hormone
What are the building blocks for the creation of T3/T4?
Iodide, thyroglobulin, and tyrosine
How is T3/T4 created?
Iodine bindss with tyrosine that is attached to thyroglobulin (1I = MIT 2I - DIT). MIT+DIT = T3, DIT +DIT = T4
Which is more potent T3or T4? What is the split in production of each enzyme? (%)
T3 is much more potent, 10% T3 vs 90% T4. T4 resevoirs because it can be easily converted to T3
6 Steps to Thyroid hormone creation?
Thyroglobulin syntheisis
Iodide trapping
Oxidation of Iodide
Iodination of tyrosine
Coupling of MIT and DIT
Secretion of hormones
How is T3 and T4 secretion controlled?
Negative feedback loop
What can Excess iodide cause? Defeciency?
Excess causes intial decrease in production but, if excess is sustained the negative feedback loop can be ovecome.
DEfeciecny intially is a stimulant and mass produce T3 and T4 but with eventually be inhibitory as it will “run out”
T or F, Most T3 and T4 exist as free form molecules.
Flase, most exist in protein bound form
What does he parathyroid gland produce? what does it regulate?
Parathyroid hormone (PTH). REgulates calcium and phosphate
How does PTH increase calcium?
Stimulation of activity of osteoclasts
Increase calium and magnesium reabsorption from urine
Increase synthesis of calcitriol, which increases calcium and magnesium absoprtion
How does PTH decrease phosphate?
Increasing excretion from kidneys.
What hormone opposes PTH?
Calcitonin
What does the thymus do?
T-cell development, various hormones to stimulate T-cell development
What is the treatment for hyperthyrodisim?
Radioactive iodine or surgery,
No curative pharmacotherapy available.
What are the common causes of hyperthyroidism?
Toxic diffiuse goiter
Toxic multi-nodular goiter
Acute phase thyroiditis
Toxic adenoma
Which disorder is:
more common in younger females, most common cause of hyperthyroidism, autoimmune disorder, creation of anibiodies against TSH receptor, and can result in hyperplasia of thyroid gland; enlargment.
Toxic Diffuse Goiter (Graves disease)
Which disorder is: most common in older females (>50), second most common hyperthyroidism cause, iodide defeciecny most common trigger for growth, slowly develops over years.
Trigger causes receptors to mutate rather than be targeted.
Toxic multi-nodular goiter (Plummers disease)
Which disorder is: benign tumours growing on thyroid gland, become active and act just like thyroid cells secreting T3/T4 and do not respond to negative feedback.
Toxic adenoma
Which disorder is: causes inflammation and damage to thyroid gland, damage causes excess hormone release, eventually leads to hypothyroidism
Acute phase thyroiditis
What are symptoms of hyperthyroidism?
anxiety, hyperreflexia, atrial fibrilation, hyperactivity, papitations, hair loss, insomnia, etc. (excess stimulation symptoms)
What are clincial presentations/ symptoms of Toxic diffuse goiter disorder?
Exophthalmos (conective tissue around eye cosntantly stimualted)
Per-orbital edema
Diplopia (double vision)
Pretibial myxedema (waxy discoloration of skin usually on shins)
What are the specific Treatments of Hyperthyroidism?
- PHarmacotherapy: thioamides, beta-blockers
- radioactive iodine
- surgery
What are the thioamide drugs?
Propylthiouracil
Methimazole
What is the usage of thioamides?
Used to reduce severity of hyperthyroidism, prepare patient for curative therapy.
About 1-20% have effectiveness over 20-30 years.
What is the MOA of thioamides?
Inhibit T3 and T4 by preventing iodine from incorparating with tyrosine residue of thyroglobulin
Inbits coupling of MIT and DIT
This is done by inhibiton of thyroid peroxidase
What differs between Propylthiouracil and methimazole?
Propylthiouracil additionally inhibits the conversion of T4 to T3 through inhibition of 5` deiodinase
What are the thioamide treatment dosing for Mild? Moderate? Severe?
Methimazole:
Mild - Intial 10-15 mg OD, Maintanence 5-15mg OD
Moderate: Initial 20-30mg OD, Maintanence 5-15mg OD
Severe: intial 30-40mg OD, maintanence 5-15mg OD
Propylthiouracil:
Mild, Moderate, and Severe: Intial 300mg divided BID or TID, Maintanence 100-150mg BID -TID
How long in thioamide treatment does it take to maintain a new steady state
4-6 weeks
What are side effects of Thioamides?
GI upset
Rash
Arthralgia
What are some potentially serious side effects of THioamides?
Agranulocytosis (0.3-0.4%)
- occurs in first 90 days
- WBC falls < 0.5 x 10^9
- abrupt onset
- Fever, malaise, sore throat
Neutropenia:
- immunosupression
- can be life threatening with a fever or illness
Hepatotoxicity and cholestatic jaundice (0.1-0.2%)
Vasculitis
- most common
- auto-immune process
- can lead to acute renal dysfunction, arthritis, skin ulcers/rashes, and respiratory problems
Polyarthritis: (1-2%)
- involves many joints
What are the concerns with thioamides and pregnancy?
Propylthiouracil: low tetratogenacity but higher hepatotoxicity
Methimazole: some teratogenic cocnerns in 1st trimester but, less hepatotoxicity
How do beta-blockers treat hyperthyroidism?
No direct influence on thyroid hormones but reduce symptoms related to cardiac over-stimulation like
- palpations
-tachycardia
- tremors
- anxiety
- heat intolerance
What beta-blockers are not used in hyperthyroidism?
ISA beta blockers; acebutolol, pindolol
How does surgery “cure” hyperthyroidism?
Thyroidectomy removes the thyroid and leads to permanent hypothyroidism (Can be treated pharmacologically)
How does radioactive iodine “cure” hyperthyroidism?
Radioactive iodine taken up by thyroid causing ablation, causes temporary thyroiditis and worsening of hyperthyroidism followed by hypothroidism
What is Thyroid Storm?
rare life-threatening condition
Severe manifestation of hyperthyroidism
Causes liver damage, cardiovascular collapse and shock
How can thyroid storm occur?
Can occur in untreated hyperthyroidism
Often triggered by acute event such as:
- thyroid surgery or radioactive iodine
- trauma
- infection
- giving birth
How do you treat thyroid storm?
supportive care (oxygen, ventilator, IV fluids), correct electrolyte imbalance, treat cardiac arrhythmias, control hyperthermia, administer beta-blockers to reduce symptoms, adminsiter anti-thyroid meds, adminsiter iodine 1 hour after throid meds, steroids to block T4 to T3, treat underlying conditions
What is the most common cause of hypothyroidism?
Chronic autoimmune thyroiditis(Hashimoto’s disease)
antibodies form and bind to TSH receptors which directly destroy thyroid cells, other antibodies may form and interfere with production of T3 and T4
What are early clinical presentations of hypothyroidism?
Weight gain
fatigue
sluggishness
bradycardia
constipation
brittle hair/hairloss
dry flaky skin
Opposite of excess stimulation
What are advanced symptoms of hypothyroidism?
myxedema
hypothermia
confusion
stupor, coma
CO2 retention
hypoglycemia
hyponatremia
How is hypothyroidism treated?
Replacement therapy of thyroid hormone
- desicated thyroid
- liothyronine
- levothyroxine
- combined T3/T4
What are some characteristics of desicated thyroid?
Prepared from thyroid glands of animals
Contains both T3 and T4 and causes high T3 peaks
not well standardized from batch to batch
Normally 13:1 T4:T3 but with treatment ratio is 4:1
What is the discontinuation rate of desiccated thyroid?
20%
What are some characteristics of Liothyronine?
Contains T3 but no effect on T4
costly
fluctuations in serum levels
no routinely used but, is seen wehn T3 levels are still low while on levothyroxine
Why would T3 be less desirable than T4?
T4 can be converted to T3, T4 is the less potent but more stored hormone, rest hormone
What are some characteristics of levothyroxine?
Analogue of T4
standard first line therapy
half life of 7 days
conversion to T3 is regulated by body
What is the dosing for levothyroxine?
average dose is 1.6mcg/kg/d
starting dose range from 12.5mcg/kg/d to max wt based
average replacement dose is 100mcg OD
What facors can change levothyroxine dosing?
Age, weight, cardiac status, severity and duration of hypothyroidism, higher baseline TSH usually predicts higher T4 dose
When do you titrate up dosing? How so?
Any CVD, rhythm disturbances, >50, sever, long-standing hypothyroidism.
Start at 12.5-50mcg, titrate up 12.5-25mcg q4-6 weeks.
ADminister on empty stomach, 30 minutes before meals or 1 hur after
What are side effects of levothyroxine?
Minimal if dosed properly
hyperthyroidism symptoms
cardiac risk increase
aggrevate existing CVD
BMD reduction
What are drug interactions of levothyroxine?
Antacids, H2 blockers, PPIs, Iron, Calcium/mineral supplements, cholestyramine, raloxifene
Chelate as it is a large molecule reducing overally absorption
What monitoring parameters are taken for levothyroxine?
TSH levels
Free T3/T4 levels.
What would need to be done if TSH levels were high?
Increased dose, high levels TSH means low levels of T4/T3
What are some risks of subclincal hypothyroidism? Do patients need treatment?
increase risk of
atherosclerosis
heart failure
MI
depression
Low BMD
metabolic syndrome
Uncertain whether treatment is required; treat if pregnant, sever symptoms, heart failure, young.
