Endocrine Module Flashcards
1
Q
What is the endocrine system responsible for?
A
Maintaining homeostasis
2
Q
What type of cues modulate the signals sent to the endocrine system? What are some examples of these cues
A
Homeostatic
Cytokines (cell signaling), Stress (cortisol), Hunger
3
Q
What are hormones comprised of?
A
Steroids, amines, peptides, proteins
4
Q
What controls hormone release?
A
The nervous system –> hypothalamus and pituitary hormones
5
Q
What are steroids? Provide examples.
A
They are lipid soluble
Can’t move thru the plasma membrane and require a transport protein
Once inside cell, they can diffuse thru the cell membrane
Ex) Glucocorticoids, androgens (both are made from cholesterol)
6
Q
Discuss amines
A
They are water soluble
ex) epinephrine, norepinephrine (both tyrosine derivatives), T3, T4
7
Q
Are peptide and proteins water or lipid soluble? Provide examples. What differentiates each?
A
They are water soluble. Proteins are much larger than peptides, but basically the same otherwise.
Ex) Thyroid hormone, PTH, etc.
8
Q
What are the three factors that determine the circulating levels of hormones?
A
Synthesis, secretion, and transport
9
Q
How is peptide hormone synthesis controlled?
A
By modulating transcription. Hormones require a signal to produce more hormone
10
Q
How is amine and steroid hormone synthesis controlled?
A
By regulating enzyme and substrate availability. Hormones require building blocks (such as iodide and tyrosine). If the need more, then they produce more
11
Q
True or False: Precursors to hormones are typically active.
A
False, they are typically inactive and cannot bind to targets
12
Q
How are hormones created and what needs to occur for them to be active?
A
They are synthesized as a large polypeptide. They need to be converted into their active form via enzyme cleavage
13
Q
What process controls hormone secretion?
A
Exocytosis
14
Q
What triggers exocytosis?
A
The cell receives a specific signal and the gland contracts to release the hormone
15
Q
How are other hormones secreted?
A
Via diffusion
16
Q
How can the rate of hormone diffusion be changed?
A
By modification of enzymes or proteins involved in its production ex) thyroid condition –> TSH dictates disease state
17
Q
What is another way that hormones can be secreted?
A
They can be secreted in a pulsative manner. Large conc of hormones may have different effects that constant low levels
ex) Insulin or puberty hormones
18
Q
Why are disorders involving a pulsative hormone difficult to treat?
A
Because we need to mimic the body’s pulsatile manner
19
Q
What must occur for a hormone to have its effect?
A
Must reach target site in its free-form
20
Q
What does hormone transport depend on?
A
Affinity of hormone for plasma protein carriers
Hormone degradation
Availability of receptors
Receptor binding
Hormone uptake
21
Q
What is accomplished when a hormone binds to a protein?
A
The hormone is protected from degradation or uptake
22
Q
What is accomplished when a hormone binds to a plasma protein?
A
The hormone is protected from degradation or uptake
Allows for a fine control over circulating levels –> there can be a large reservoir of hormones created
Prevents hormone from binding to unintended sites
Allows transport of lipid soluble hormones
*Plasma proteins carriers are regulated
23
Q
Explain hormone degradation
A
All hormones have a half-life and they will eventually degrade
24
Q
Explain availability of receptors
A
Influenced by up and down-regulation. If too many receptors, then down regulated and vice versa. Each cell has 2,000 to 200,000 receptors.
25
Explain receptor binding
The hormone must bind to the cell's receptor
Complications occur when the drug binds to the hormone OR when the drug binds to the receptor
26
Explain hormone uptake
Lipid hormones diffuse passively; whereas water-soluble hormones need to bind to something else before they can enter the cell
27
What can occur to a cell when a hormone binds to the cell surface or the cell nuclei. Provide examples
Synthesize new molecules, change permeability of the membrane, alter rate of reactions
Ex) Insulin binding to liver cells causes glycogen synthase and decreased blood sugar
Ex) Thyroid hormone binding to cardiac cells causes:
-Increased Na/K pump permeability and increased heart contractility
- Bind to adipose tissue and increased Na/K pump activity, more ATP/Energy
28
What are the types of hormone-hormone interactions?
1) Permissive - binding to a target cell allows a different hormone to have its full effect.
ex) thyroid to cardiac tissue - upregulation of epi + norepi receptors. Therefore, have a greater effect
2) Synergistic - Two hormones act tougher to achieve a greater effect
ex) lactation - 4 hormones work together to cause lactation
3) Antagonistic - Two hormones produce an opposite effect
ex) Insulin vs. Glucagon - Blood glucose control
ex) Parathyroid vs. Calcitonin
29
What controls hormone levels in the body?
Feedback loops
30
What controls feedback loops?
The nervous system, chemical changes in the blood, other hormones
31
What is negative feedback?
This occurs for most hormones. If hormone levels are too high, then a signal reduces secretion and vice versa
32
What is positive feedback? Provide an example.
Action of the hormone causes more of the hormone to be released.
Ex) Oxytocin
+ve feedback requires an external break such as delivering the baby to stop
If no external break, then it can be dangerous
33
Where is the pineal gland located?
In the epithalamus - center of the brain hemispheres, but not technically a part of the brain
34
What hormone the pineal gland produce? Explain the hormone
melatonin
- binds to melatonin receptors causing anti-excitatory effects
- Levels peak at 1-2 years of age, remain stable until puberty, and then declines.
- high levels during childhood inhibit puberty
- regulates sleep patterns (circadian and seasonal)
Stimulated by darkness; inhibited by light
35
Do melatonin supplements help with sleep, and do they work?
No, but good for delayed sleep disorder (melatonin works when the body doesn't respond to light)
It reduces the time to sleep by 10minutes; increases sleep time by 20 minutes
36
Explain the hypothalamus
major integrating link between the nervous and endocrine system
receives input from the cortex, thalamus, limbic system and other organs.
37
What are the hormones form the pituitary gland to control homeostasis?
Growth hormone-releasing (+) and inhibiting hormone (-) - 90% inhibiting
Somatostatin (-) - inhibits GH release, but only 10% of GH inhibition
Dopamine (-) inhibits prolactin
Corticotropin-releasing hormone (+) increases cortisol
Thyrotropin-releasing hormone (+)
Gonadotropin-releasing hormone (+)
Oxytocin (+)
Vasopressin (+)
38
What are the hormones that are secreted by the anterior pituitary gland?
HGH
TSH
FSH/LH
Adrenocorticotrophic hormone
melanocyte-stimulating hormone
Prolactin --> *Only controlled by inhibition (using dopamine)
Secretion is inhibited by production of target hormones
In hyperproteinemia, we give patients dopamine.
39
Explain HGH
The most plentiful anterior pituitary hormone
Promotes synthesis of a protein insulin-like growth factor (IGFs)
Pulsatile secretion peaks during puberty and declines after
40
Explain IGFs
Various stimuli promote and inhibit hGH production
binds mostly to the liver (energy and glucose use), skeletal muscle, cartilage and bone (growth)
Increases cell growth and ATP use
41
What does high and low blood sugar do to hGH?
Low: stimulates the release to growth hormone releasing hormone --> increases secretion of hGH from pituitary, increases glycogen breakdown
High: stimulates release of growth hormone inhibiting hormone form the hypothalamus --> reduces secretion of hGH from pituitary, decreases glycogen breakdown
42
What are the consequences of XS hGH?
Disorder.
Caused by a tumour on the pituitary gland, the gland continues to secrete hormones and there is uncontrolled growth of muscle and bone tissues.
There are large hands, feet, and face which causes extra stress on the organs + organ failure occurs.
43
How to treat XS hGH
Remove the tumour. use somatostatin to reduce hGH
44
How to treat hGH deficiency?
Looks like slow growth, delayed puberty
Due to brain injury
Treat by giving hGH such as somatotropin
45
Pituitary gland interaction summary
Growth hormone-releasing hormone -> hGH
Thyrotropin-releasing hormone -> TSH
Gonadotropin-releasing hormone -> FSH and LH
Corticotropin-releasing hormone -> Adrenocorticotropic hormone
Dopamine -> prolactin (inhibits)
Somatostatin -> hGH and TSH (inhibits)
46
What is the thyroid gland and where is it located?
Butterfly shaped endocrine gland in the front of the neck
Responsible for synthesis, storage and release of the two thyroid hormones T3 and T4
47
What is T3 and T4
T3 = triiodo tyrosine
T4 = Thyroxin
48
What are the three components of the thyroid gland and what do they do?
1. Colloid -large - like a factory/warehouse for building bocks (contain T3 and T4, thyroxin glob)
2. Follicular cells - synthesize thyroxin glob, introduce iodine into thyroid gland
3. Parafollicular cells - no function with thyroid hormone, functions to secrete calcitonin instead.
49
What controls synthesis and secretion of T3 and T4?
TSH, which is controlled by thyrotropin-releasing hormone
50
What are the building blocks of T3 and T4?
iodide, thyroglobulin, and tyrosine
51
Compare T3 and T4 based on the body's synthesis of each
T3 is much more portent due to its smaller size, it has a much higher receptor affinity, and it is more easily made
More T4 is still made in the body.
* The liver and kidneys convert T4 to T3
52
What are the steps for T3 and T4 synthesis?
1) iodide binds with tyrosine attached to thyroglobulin and mono or di-iodotyrosine is created (MIT or DIT)
2) MIT + DIT = T3 or DIT + DIT = T4
3) Then, secreted into circulation
53
What does T3 and T4 synthesis involve?
Thyroglobulin synth
Iodide trapping
Ox of iodide
Iodination of tyrosine
Coupling of MIT and DIT
Secretion of hormones
54
What are the actions of T3 and T4?
Heart - chronotropic and inotropic
Adipose tissue - catabolic
Muscle - catabolic
Bone - developmental
Nervous system - developmental
Gut - metabolic
Other tissues - calorigenic
55
Explain the control of T3 and T4 secretion
It is a negative feedback loop
Low blood levels stimulate the hypothalamus, which then stimulates the pituitary gland
Lithium and iodide levels also influence
Most T3 and T4 exists in protein-bound form
*See the photo in slides
56
Where is the parathyroid gland located and what does it do?
Posterior surfaces of the lateral lobes of thyroid
Produces parathyroid hormone (PTH) to regulate calcium and phosphate
- Increases blood calcium by:
stimulating number and activity of osteoclasts
increasing the number of calcium and magnesium reabsorption form urine
increasing the synthesis of calcitriol, which increases calcium and magnesium absorption from GI
- Decreases blood phosphate by
increasing excretion from kidneys
57
What opposes PTH? And what does it do?
Calcitonin
Secreted by follicular cells in thyroid
Inhibits osteoclast activity
Decrease reabsorption of calcium from urine
Circulating calcium levels act on PT gland to reduce PTH secretion
58
What is the thymus and where is it located?
Front of the heart and behind the sternum
Critical part of the immune system (T-cell development)
59
What are the thymus hormones that stimulate T-cell development?
Thymosin alpha 1
Thymulin
Thymopoietin
*Prolactin, T3, T4, and LH may also stimulate production
60
What is in cortex of the adrenal gland?
Zona glomerulosa: secretes mineralocorticoids
Zona fasciculata: secretes glucocorticoids
Zona reticularis: secretes sex hormones
61
What is the function of the medulla of the adrenal gland in terms of hormone secretion?
To secrete EPI and NE
62
What do mineralocorticoids do and provide an example
They help regulate bp and electrolytes (Na/K)
They send signals to the kidneys to promote sodium reabsorption and potassium excretion in the urine
ex) Aldosterone
63
What do glucocorticoids do and provide an example
Widespread effects on the body
Regulate body stress response, fat, protein, carb metabolism
Regulated the inflammatory response and the immune system
Ex) cortisol
Corticosteroid --> prednisone
64
What do androgens do and provide an example
They promote protein anabolism and growth
Main source of androgens in females
Weak sex hormone, 20% less potent as testosterone
ex) dehydro-epi-androsterone (DHEA) and DHEAS-S
65
What do epinephrine do?
Increases blood flow to muscles and brain
Increases conversion of glycogen to glucose
Stimulation of metabolic rate
66
What does norepinephrine do?
Similar, but less potent than epi
Vasoconstriction to increase blood pressure
Together, they control bp, hr, and sweating (sympathetic activities)
67
How is the adrenal cortex regulated?
ACTH stimulates cortex to release its hormones
Secreted hormones exhibit negative feedback to hypothalamus and the pituitary gland
Atrophy occurs if no ACTH or AP stimulation
(aldosterone secretion is also independently controlled by other factors)
68
How is the adrenal medulla regulated?
Release stimulated by fight or flight response of sympathetic nervous system
69
Explain low mineralocorticoid activity and low glucocorticoid activity
1. low aldosterone, less sodium (can manifest as HTN)
2. low bp, blood glucose, and cortisol
70
What is the HPA-axis
The feedback interaction of the hypothalamus, the pituitary gland, and the adrenal gland
71
What does HPA-axis regulate?
The body processes:
Stress response
Digestions
Immune system
Mood and emotions
Energy storage and expenditure
72
Explain normal cortisol secretion in humans
Normal secretions of 10-20 mg/d of cortisol
Secretion is the highest during the AM and decreases during the day
Secretion increases in times of stress
Secretions maintain appropriate amounts of glucocorticoids
73
Explain the HPA axis diagram
Hypothalamus -----CRH------> Pituitary -------ACTH-------> Adrenal makes Glucocorticoids and catecholamines
Glucocorticoids have negative feedback on the Hypothalamus and the pituitary
74
What does endogenous and exogenous cortisol do to the HPA-axis?
It suppresses it
Body won't feel the need to produce as much or any cortisol
75
How to test the HPA-axis?
Physicians can order lab tests to test the HPA-axis
76
What is the trend for the potency of corticosteroids?
The greater the glucocorticoid potency, the greater the HPA axis suppression
77
What is the shortest acting GC? Longest?
Cortisone (short acting, less potent)
Betamethasone (long acting, more potent)
78
What factors can predict the HPA-axis suppression?
1. The type of corticosteroid used
2. The dosage form
3. The overall amount (dose and duration)
79
What causes likely HPA suppression for corticosteroid use?
Maintenance dosing of more than 15mg of prednisone daily
Start consideration when using for more than 2 weeks
80
What is unlikely to cause HPA suppression from corticosteroid use?
Any dose that is less than 2 weeks (except if receiving short-bursts)
Alternate day dosing of less than 10kmg of prednisone per day
may take weeks to a year for HPA to recover after d/c
81
True or false: corticosteroids should be abruptly stopped
False, a taper is much better
- can decrease by set amounts every few days/weeks OR
- can decrease by set percentages every few days/weeks
- can also look into alternate-day regimen (Reduce to an amount every other day every week until you can stop using the corticosteroid every other day)
82
What is Cushing's syndrome?
Condition characterized by hypercortisolemia (too much cortisol)
Due to:
ACTH-producing pituitary tumour
ACTH-secretion by non-pituitary tumour
Cortisol secretion by adrenal adenoma (better prognosis) or carcinoma
XS glucocorticoid use
83
What is the clinical presentation of Cushing's disease?
Moon face, Obesity, Fat deposits on the shoulders, etc.
84
What is the treatment for Cushing's disease?
Surgery
85
Is pharmacologic therapy for Cushing's disease effective?
Less effective therapy option
Ketoconazole - inhibits cortisol biosynthesis at the first step
Metyrapone - inhibits cortisol biosynthesis at the final step
Mitotane - inhibits cortisol biosynthesis at various steps
Pasireotide - binds to somatostatin and inhibits ACTH secretion
86
When cortisol decreases to low levels, why must it be replaced with exogenous corticosteroids?
The tumour is removed and the body is not used to such low levels of cortisol
87
What is Addison's disease?
Primary adrenal insufficiency due to the destruction of the the adrenal glands
all 3 zones of the cortex
In N. America - autoimmune
Rest of world - Tuberculosis
88
What are some symptoms of gluco and mineralo deficiencies?
Gluco- fatigue, weight loss, loss of appetite, muscle and joint pain
Mineralo - Dehydration, hypotension
Other - Salt craving
These are very vague symptoms
89
What is the treatment for chronic and acute adrenal insufficiency/Addison's disease?
Chronic
- glucocorticoid and mineralocorticoid replacement
- may require stress dosing (doses for stress situations)
- Perhaps DHEA for women - may need androgen replacement
Acute
- Emergencies: IV corticosteroids and IV fluids
90
What do Islet cells do?
Regulate blood sugar
Alpha cells 30% --> glucagon increases blood sugar
Beta cells 60% --> Insulin decreases blood sugar
Delta 10% --> Somatostatin
91
What are the effects of fasting and eating a meal for insulin and glucagon?
Sugars from food stimulate insulin
Fasting releases glucagon
92
What stimulates the release of insulin?
Glucose
Fatty acids
Amino acids
Glucagon
Ketone bodies
GLP-1 (releases insulin when stimulated)
93
What inhibits insulin release?
Somatostatin
Stimulation of Alpha2 adrenergic receptors
94
What stimulates the release of glucagon?
Cortisol
Exercise
infections
Stressors
Gastrin
Insulin
95
What inhibits glucagon release?
Glucose
Somatostatin
96
Explain glucose homeostasis
When we eat blood glucose goes up
The pancreas releases insulin, and glucose uptake occurs at the fat and muscle cells (glycogenesis increases; gluconeogenesis decreases)
Blood glucose decreases when we sleep
Glycogenolysis and gluconeogenesis increases and glucagon is released
Back to normal blood glucose levels
97
Explain the ovaries
produces and secretes E, P, and T
LH and FSH from pituitary stimulate secretion
Release is inhibited by estrogen during the follicular and luteal phase
Release is inhibited by progesterone during the luteal phase
98
Explain the testes
Produces and secretes androgens, primarily testosterone
Release is stimulated by LH and FSH from the pituitary gland
Release is inhibited by testosterone and inhibin
99
What is hyperthyroidism? Explain
Disease caused by XS synthesis and secretion of thyroid hormone
Mild symptoms to life-threatening
No pharmacotherapy available --> just buy more time
Tx is radioactive iodine or surgery
100
What are the 4 causes of hyperthyroidism?
Toxic diffuse goiter (graves disease)
toxic multi-nodular goiter (plummers disease)
acute phase of thyroiditis
toxic adenoma
101
What is a goiter?
an enlargement of the thyroid gland
102
Explain toxic goiter disease.
More common in younger, female patients (20-50)
Most common cause of hyperthyroidism
Autoimmune disorder
Immune system secretes antibodies against the TSH receptor
- no -ve feedback and continuous T3/T4
Hyperplasia of the thyroid gland
103
Explain toxic multi-nodular goiter
Triggers cause this one. The TSH mutates and constantly active
More common in the older generation 50+
Second common cause of hyperthyroidism
Slow development over years
Iodine deficient is the most common trigger
Low iodine -> less T4 -> thyroid cells grow larger (TMDG), TSH receptos mutate -> constantly active
104
Explain toxic adenoma
benign tumours on the thyroid gland (no spreading)
Thyroid cells secrete T3 and T4, but no response to -ve feedback
105
Acute phase of thyroiditis
Causes inflammation + damage to the thyroid gland
Damage causes XS hormone to be release, which damages cells
Eventually leads to hypothyroidism when the T3 and T4 leaks all out
High risk during post-partum; after labour
106
What are some non-specific hyperthyroidism symptoms?
Tremor, anxiety, diarrhea, heat intolerance, atrial fibrillation, unintentional wight loss, weakness, tachycardia, hypertension, etc.
107
What are some symptoms specific to Toxic diffuse goiter?
exophthalmos (XS T3/4 causes eye tissue stimulation, looks like the eye is buldging, eye irritation to vision loss
Peri-orbital edema
diplopia
diffuse goiter
pre-tibial myxedema (waxy shin skin)
108
What are the thioamides for hyperthyroidism tx?
Propylathiouracil (PTU) and methimazole (MMI)
Not typically used life long due to drugs not working after a few years
Drug use is to reduce severity of hyperthyroidism to prepare pt for curative therapy
109
What is the MOA of thioamides?
Inhibits thyroid peroxidase, which inhibits iodine and tyrosine/thyroglobulin combination
Inhibits the coupling of MIT and DIT
PTU also inhibits conversion from T4 to T3 via inhibition of 5'-deiodinase enzyme
110
What is the dosing and administration of thioamides?
Begin with a high initial dose and then lowered maintenance doses
Titrate every 4-6 weeks
Decrease dose when the target is reached (watch out for TSH,T3/4 values, but TSH is the best value to monitor)
PTU is dosed much higher as there are no side effects with this medication
111
What are some common side effects of thioamides?
GI upset, Rash, arthralgia
112
True or False: Thioamides have serious side effects
True.
There are 5 main serious s/e
113
What is agranulocytosis?
A decrease in WBC and granulocytes
0.3% - 0.4% of patients (higher with PTU)
Usually occurs within the first 90 days
WBC falls below 5 x 10^9
Fever, malaise, sore throat are common symptoms
abrupt onset
Can't constantly monitor WBC because costly
114
What is neutropenia?
Can be from drug or from agranulocytosis
Neutrophil counts decline
Prevents the immune system from responding
Life-threatning fevers or illness
115
What is neutropenia?
Can be from drug or from agranulocytosis
Neutrophil counts decline
Prevents the immune system from responding
Life-threatening fevers or illness
116
Explain hepatotoxicity and cholestatic jaundice
0.1%-0.2% incidence (higher with PTU)
MMI -obstructive jaundice
PTU - allergic type hepatocellular damage
Resolves once the drug is d/c, but this can cause death
Drugs can increase AST/ALT, concern if three times above the upper limit, or if they are alcoholic
117
Explain vasculitis
More common with PTU
Auto-immune
Damages the vascular tissues causing inflammation and destruction of blood vessels
Leads to acute renal dysfxn, arthritis, skin ulcers/rashs, respiratory problems
118
Explain polyarthritis
1%-2% incidence
Involves many joints
high degree of pain and swelling
Need to d/c drug!
119
How does one approach thioamide treatment for pregnant women?
PTU has low teratogenicity concern, but high er hepatotoxicity
MMI has some teratogenic concern in the 1st trimester, but lower hepatotoxicity
Need to balance the risk of both of the above
1st trimester = use PTU
2nd or 3rd = switch to MMI
Safe to use during breastfeeding if the dose is low enough
120
Explain the clinical significance of beta-blockers for hyperthyroidism
They do not directly influence thyroid hormones
They reduce the HTY cardiac over-stim symptoms
(such as palpitations. tachycardia, tremors, anxiety, heat intolerance
** avoid the onces with intrinsic sympathomimetic activity
-> those with ISA, which decrease HR and increase CO (acebutolol and pindolol)
121
What are the non -pharm treatments for hyperthyroidism?
Surgery - Thyroidectomy
curative option
leads to permanent hypothyroidism
Radioactive iodine
curative option
taken up by the thyroid causing ablation
temporary thyroiditis and worsening of hyperthyroidism, then
hypothyroidism
122
What is thyroid storm?
Rare, but life-threatening
Characterized by severe manifestations of hyperthyroidism
Can occur in pt with untreated hyperthyroidism
Trigger by an event: Thyroid surgery or Rad. Iodine
Trauma, infxn, giving birth
123
What is hypothyroidism?
Basically a thyroid hormone deficiency due to a defect anywhere on the hypothalamus-pituitary-thyroid axis
124
What is the most common cause for hypothyroidism (Hashimoto's disease)?
Chronic autoimmune disorder
125
Explain Hashimoto's disease
Most common cause of hypothyroidism
Autoimmune disorder where antibodies dorm
Antibodies bind to TSH receptors which directly destroy thyroid cells
Other antibodies may form that interfere with production of T3/T4
126
What is the clinical presentation of hypothyroidism?
Weigh gain, fatigue, sluggishness, cold intolerance, bradycardia, constipation, heavy menses, confusion
-> opposites of hyperthyroidism
127
What is the treatment for hypothyroidism?
Replacement of thyroid hormone.
4 options:
desiccated thyroid
liothyronine levothyroxine
combined T3/4
128
Explain what desiccated thyroid is
First original agent
Prepared from the thyroid glands of pigs
Contains T3 and T4
Causes high peak of T3
Not well standardized between batches - variability
129
What is the physiological ratio of T3 and T4? What does desiccated thyroid give?
13:1 (for normal human)
1:4 (for desiccated thyroid)
desiccated thyroid gives xs stimulation and hyperthyroid risk increased
130
Why do patients prefer dessicated thyroid?
Because it is seen as more "natural"
T3 is also like a shot of caffeine or cocaine, so they feel better
This is not great for the long term because of cardiovascular considerations
131
What is liothyronine?
Contains T3, but no effect of T4 (same issues as d. thyroid)
Causes wide fluctuations in serum levels
Costly
Not routinely recommended
- used for ppl who can't convert T4 to T3 (rare)
132
What is levothyroxine?
Analogue of T4 (body sees it the exact same as T4)
Standard 1st line therapy
Half-life is 7 days
Conversion of T3 regulated by the body
133
What is the dosing of levothyroxine?
Avg dose of 1.6mcg/kg/day
Starting dose ranges from 12.5mcg/day to mat wt based
Often give 100mcg empirically (check 4-6 weeks then adjust)
depends on a lot of factors such as age, weight, cardiac status, severity, duration of hypo
Higher TSH or severe hypothyroidism usually predicts higher T4 dose
Always start low and titrate up if patient is 50+, CVD, rhythm disturbances, long-standing hypothyroidism
Start at 12.5-50 mcg and go up by 12.5-25 mcg every 4-6 weeks
Needs to be administered on an empty stomach due to poor bioavailability, 30m before or 1 hour after meals
134
What are some side effects of levothyroxine?
If dosed correctly, then minimal side effects
If target overshot, then hyperthyroidism symptoms, increase cardiac risk, aggravated existing CVD, BMD reduction
135
What are some drug interactions with levothyroxine?
Drug is large and likes to chelate
Antacids/H2 blockers/ PPIs
Iron
Calcium
Less common: Cholestyramine, raloxifene
Manage interactions by taking 2 hours before or 4 hours after meds
136
What is the relationship between TSH and T3/T4?
inverse relationship
If TSH high then T3/T4 must be low
-ve feedback loop always
Always check the free levels of T3/T4 because these are the active versions
137
What is considered to be subclinical hypothyroidism?
TSH of 4.5-10 mlU/L, normal T3 and T4, and "asymptomatic"
This is still clinically relevant as there is an increased risk of HF, MI, depression, low BMD, metabolic syndrome, and atherosclerosis.
