Flashcards in Thyroid Physiology and Pathophys (5/19) Deck (84)
What is a goiter?
Enlarged thyroid gland...does not imply etiology
How do we describe goiter?
1. Prevalence: endemic or non-endemic
2. Structure: diffuse or nodular, solitary or multinodular
3. Fxn (TH production): toxic or non-toxic
What is the most common cause of goiter world-wide?
Iodine def. Without iodine, can't produce T3/T4, loss of neg feedback causes inc TSH, build up thyroglobulun and the gland hypertrophies
How do we define endemic goiter?
>10% of a population has it
How many iodines do T3 and T4 have?
3 and 4 respectively...
What is iodine specifically req for?
Coupling of 2 iodotyrosines, catalyzed by TPO, does not occur unless they are iodinated
Describe TH synthesis
1. I- is trapped via active transport across basement membrane of follicular cell (RLS)
2. Oxidation and iodination of tyrosine residues on thyroglobulin (precursor for TH)
3. Thyroglobulin's tyrosine residues are iodinated to form MIT/DIT/thyroglobulin complex
4. Coupling of iodotyrosine on thyroglobulin forms T3 and T4 via peroxidase transaminase
5. Proteolysis of thyroglobulin allows for release of T3 and T4 and iodotyrosines (MIT/DIT=monoiodotyrosine and diiodotyrosine)
6. Iodotyrosines are deiodinated in the follicular cell
Where is the hormone in the follicle stored?
Extracellular thyroid colloid in which the major material is thyroglobulin. This is entirely surrounded by thyroid follicular cells, which are responsible for the synth of thyroid hormones
Which has more neg feedback, T3 or T4?
Describe the thyroid hormone axis
Hypothal-->THR-->ant pit-->TSH-->thyroid-->T3 and T4 production
How does T4 undergo deiodination?
Via extrathyroidal deiodinase enzymes in the liver and skeletal muscles
How much T3 is circulating vs in the thyroid?
20% in the thyroid
What decreases deiodinase activity?
MAjor systemic illness
Severe hepatic disease
Selenium deficiency (cofactor for enzyme)
How are T3 and T4 transported?
Binding proteins (mainly TBG)
Why are THs carried by binding proteins?
Provides a large buffer pool of thyroid hormones in circ and prolongs the half life of T3 and T4
How are T3 and T4 levels affected by changes in TBG?
Inc TBG will cause dec in amt of free T3 and T4 initially, but there needs to be a set amt of free hormone so it will form a new steady state to replenish the free hormone levels.
What increases TBG levels?
-EStrogen (OCPs, HRT, pregnancy
-Inc hepatic release (hepatitis)
-note these raise TBG, but keep free thyroid hormone levels in a narrow range
What dec TBG levels?
-Dec hepatic production (liv disease, illness, malnut)
-Inc renal loss (nephrotic syndrome)
Where are type 1 deiodinases?
liver, kidney, thyroid (outer and inner ring)
ie can make reverse T3=inactive hormone and active T3
can also make inactive T2
What is the T4:T3 ratio sec by thyroid?
Where are type 2 deiodinases?
CNS, pituitary (outer ring) makes active T3 only
Where are type 3 deiodinases?
PLacenta (inner ring) -->makes reverse T3=inactive hormone
can also make inactive T2
What drugs can cause a dec in deiodinase activity?
PTU, propranolol, glucocorticoids, amiodarone
What family of receptors do thyroid receptors belong to?
Nuclear receptor family
What is the fxn of TR?
Gene expression by interacting through specific regions of DNA. TR acts as a transcriptional activator or repressor dep pn target gene and presence or absence of TH
In what tissues does T3 inc O2 consumptions?
All except spleen and testes
What does TH effect in the brain?
What does TH effect in the heart?
What does TH effect in the liver?
Prot synthesis, lipid metab
What does TH effect in the GI
Inc gut motility
What does TH effect in the nerve?
Sympathetic tone, reflexes
What does TH effect in the bone?
inc bone turnover
What does TH effect in the bone marrow?
What does TH effect in the reproductive system?
What does TH effect in the kidney?
free water excretion
What is a low TSH and what does it show?
What is a high TSH and what does it show?
What is the relationship between log TSH and T4
Linear inverse (less TSH=more T4)-->neg feedback. There is a TSH:T4 setpt for each individual though.
In hypothyroidism what are the TSH, T4 and T3 levels? (high/low)
High, low, low
In hyperthyroidism what are the TSH, T4 and T3 levels?(high/low)
Low, high, high
What causes primary hypothyroidism?
-Autoimmune destruction (hashimoto=most common cause of hypothyroidism in US)
-I-131 therapy for Graves' (radioactive iodine)
-Dysgenesis/agenesis of thyroid glands (congential)
-Defects in biosynth (congenital)
What causes central hypothyroidism?
Pituitary or hypothalamic dysregulation (rare)
What causes transient hypothyroidism?
Hypothyroid phase of thyroiditis (autoimmune or subacute)
Describe the progression of thyroid failure
Slow process. Start normal-->mild thyroid failure in which TSH rises first-->overt thyroid failure in which T4 levels continue to dec and then T3 levels dec last
What constitutes subclinical hypothyroidism/mild thyroid failure?
-Elevated serum TSH >5mU/L (normal is <2)
-Normal serum thyroid hormone levels
-Few or no clinical symptoms/signs
What inc your risk of hypothyroidism?
Being older and a woman (10 more common in W than M, inc risk among women >40y.o)
What are the CNS symptoms of hypothyroid?
Poor mental concentration and memory
Thinning hair/hair loss
What are they physical features of hypothyroidism?
What are the throat symptoms of hypothyroid?
What are the physical symp of hypothyroidism?
-delayed relaxation of deep tendon reflexes
What are the heart symp of hypothy
What are the consequences of hyppthy?
Elevated cholesterol (w elevated ACTH...even in mild)
What inc fetal death rate
High TSH associated with 4x inc in fetal death rate and is associated with inc complications
TSH >4 causes...
Inc MI and aortic atherosclerosis risk
What is myxedema coma?
-Severe, life-threatening hypothyroidism
-Elderly pts with pre-existing hypothy and acute illness like MI or sepsis
-Characterized by hypothermia, coma
-Mortality is 20-25%
How do we treat hypothyroidism?
Levothyroxine sodium (LT4)
-half life is 7 days, recheck every 6 wks (binding prot)
-target therapy to achieve normal serum TSH
What is the best initial screening test for eval thyroid fxn?
What is hyperthyroidism caused by?
Overproduction of thyroid h or leakage of thyroid hormone
What diseases cause overprod of thyroid hormone?
Toxic solitary or multinod goiter
What dis cause leakage of TH
What is thyroiditis?
Damage to thyroid gland causing leakage of stored TH leading to hyperthyroidism. Then the follicles become depleted and either go to a normal level/recover or swing to transient hypothyroidism
What causes thyroiditis?
What are the clinical symptoms of hyperthyroidism?
Non-specific symptoms like heat intolerance, anxiety, heart palpitations etc
What are the clinical signs of hyperthyroidism?
etc...non specific also
What is Graves' disease?
TSH stimulating autoimmune antibody, causes papillary hyperplasia of follicular cells
What does hyperthyroidism eye dis look like?
Lid lag, lid retraction, stare due to inc adrenergic tone stim levator palpebral muscles
In graves: proptosis (eye bulges), diplopia (double vision), inflammatory changes (conjunctival injection, perioribital edema, chemosis=conjunctival swelling)
What else can graves antibodies stim besides TSH?
CT in extraocular muscles and dermis of the lower extremities to synth mucopolysaccharides leading to thickening of muscle and dermis. Leads to diplopia and forward protrusion in eyes
What is onycholysis of thyrotoxicosis?
distal sep of nail plate from nail bed (hyperthy sympt)
What is thyroid acropachy
clibbing of fingers, painless, periosteal bone formation and proliferation. Tissue swelling that is soft pigmented and hyperkeratotic. (hyperthy sympt)
How do you dif between graves, toxic nodules and thyroiditis?
Non-diseased parts will not take up since TSH is low, it will not stimulate normal cells to uptake the iodine
G: bilateral uptake
Nodule: uptake only at nodule
Multinodular: uptake only at nodule sites
Subacute thyroiditis: no uptake, thyroid cells are destroyed
What are the therapeutic options of Graves'?
Antithyroid drugs (first line)
What antithyroid drugs are used in graves?
PTU and methimazole
What are complications of antithyroid drugs?
Can get rash, agranulocytosis, hepatitis (not with PTU tho)
PTU may interfere with I-131 radiation
What is radioiodine ablation?
Oral therapy to destroy thyroid
Cannot be pregnant
Doesnt cause secondary malig
Most become hypothyroid (goal because if any remains, ab will attack
Worsens pre-eixsting ophthalmopathy
Who gets surgery?
Pts with large toxic nodular goiters and compressive symptoms
Preg women who req large antithryoid drug doses
Pts who have had severe drug events
Pts will obviously become hypothyroid
What is a thyroid storm?
Very rare, life-threatening hyperthyroidism characterized by high fever, tachycardia, sweating and *altered mental status
Manifestation of thyrotoxicosis (too much T3/T4)
What is a thyroid nodule?
Palpable mass or nodule documented by imaging
What makes you more suceptible to thyroid nodules?
What are the malignant thyroid nodules?
5-10% of nodules are malig
Mets to thyroid
What are the benign thyroid nodules?
Colloid or adenomatous nodules
Follicular/Hurthle cell adenomas
What inc chances of having malignant nodules?
Hx childhood neck irradiation (no inc in risk if exposed after 16-18 yrs..incidence is dep on age exposed )
Fam hx of thyroid cancer
Age of pts (60)
What do you do to detect, examine and test a nodule?
Detect: feel or ultrasound
Examine: fixation to adj struc, adenopathy, firm nodule consistency
Test: TSH to determine if biopsy is needed (low, toxic nodule, do a scan and see how much radioactive iodine is taken up. High or normal do FNA to assess cytology)
-->always ultrasound before biopsy
Cytology helps det if need surgery or not
Describe hot and cold nodules on scans
Hot nodules are usually benign, they take up iodine
Cold nodules need to be aspirated, they are hypofunctioning