Flashcards in Thyroid Physiology and Pathophys (5/19) Deck (84):
1
What is a goiter?
Enlarged thyroid gland...does not imply etiology
2
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
3
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
4
How do we define endemic goiter?
>10% of a population has it
5
How many iodines do T3 and T4 have?
3 and 4 respectively...
6
What is iodine specifically req for?
Coupling of 2 iodotyrosines, catalyzed by TPO, does not occur unless they are iodinated
7
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
8
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
9
Which has more neg feedback, T3 or T4?
T3
10
Describe the thyroid hormone axis
Hypothal-->THR-->ant pit-->TSH-->thyroid-->T3 and T4 production
11
How does T4 undergo deiodination?
Via extrathyroidal deiodinase enzymes in the liver and skeletal muscles
12
How much T3 is circulating vs in the thyroid?
80% circulating
20% in the thyroid
13
What decreases deiodinase activity?
Caloric restriction
MAjor systemic illness
Severe hepatic disease
Fetal life
Some drugs
Selenium deficiency (cofactor for enzyme)
14
How are T3 and T4 transported?
Binding proteins (mainly TBG)
15
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
16
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.
17
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
18
What dec TBG levels?
-Androgens
-Dec hepatic production (liv disease, illness, malnut)
-Inc renal loss (nephrotic syndrome)
-Congenital causes
19
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
20
What is the T4:T3 ratio sec by thyroid?
10:1
21
Where are type 2 deiodinases?
CNS, pituitary (outer ring) makes active T3 only
22
Where are type 3 deiodinases?
PLacenta (inner ring) -->makes reverse T3=inactive hormone
can also make inactive T2
23
What drugs can cause a dec in deiodinase activity?
PTU, propranolol, glucocorticoids, amiodarone
24
What family of receptors do thyroid receptors belong to?
Nuclear receptor family
25
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
26
In what tissues does T3 inc O2 consumptions?
All except spleen and testes
27
What does TH effect in the brain?
Mood
28
What does TH effect in the heart?
HR, contractility
29
What does TH effect in the liver?
Prot synthesis, lipid metab
30
What does TH effect in the GI
Inc gut motility
31
What does TH effect in the nerve?
Sympathetic tone, reflexes
32
What does TH effect in the bone?
inc bone turnover
33
What does TH effect in the bone marrow?
erythropoiesis
34
What does TH effect in the reproductive system?
menstrual fxn
35
What does TH effect in the kidney?
free water excretion
36
What is a low TSH and what does it show?
Hyperthyroid, <0.5mU/L
37
What is a high TSH and what does it show?
Hypothyroid, >5.0mU/L
38
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.
39
In hypothyroidism what are the TSH, T4 and T3 levels? (high/low)
High, low, low
40
In hyperthyroidism what are the TSH, T4 and T3 levels?(high/low)
Low, high, high
41
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)
42
What causes central hypothyroidism?
Pituitary or hypothalamic dysregulation (rare)
43
What causes transient hypothyroidism?
Hypothyroid phase of thyroiditis (autoimmune or subacute)
44
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
45
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
46
What inc your risk of hypothyroidism?
Being older and a woman (10 more common in W than M, inc risk among women >40y.o)
47
What are the CNS symptoms of hypothyroid?
Fatigue
Slower thinking/forgetfulness
Depression
Poor mental concentration and memory
Thinning hair/hair loss
Puffy eyes
48
What are they physical features of hypothyroidism?
-Periorbital edema
-Goiter
-Dry/patchy skin
-Brittle nails
49
What are the throat symptoms of hypothyroid?
Hoarseness/deeper voice
Dysphagia
50
What are the physical symp of hypothyroidism?
-Cold intolerance
-Parasthesia
-Wt gain
-Constipation
-Menstrual irreg
-delayed relaxation of deep tendon reflexes
51
What are the heart symp of hypothy
Diastolic hperT
bradycardia
pericardial effusion
52
What are the consequences of hyppthy?
Elevated cholesterol (w elevated ACTH...even in mild)
Fetal death
Atherosclerosis
53
What inc fetal death rate
High TSH associated with 4x inc in fetal death rate and is associated with inc complications
54
TSH >4 causes...
Inc MI and aortic atherosclerosis risk
55
What is myxedema coma?
-Severe, life-threatening hypothyroidism
-Very rare
-Elderly pts with pre-existing hypothy and acute illness like MI or sepsis
-Characterized by hypothermia, coma
-Mortality is 20-25%
56
How do we treat hypothyroidism?
Levothyroxine sodium (LT4)
-take 1x/d
-half life is 7 days, recheck every 6 wks (binding prot)
-target therapy to achieve normal serum TSH
57
What is the best initial screening test for eval thyroid fxn?
TSH
58
What is hyperthyroidism caused by?
Overproduction of thyroid h or leakage of thyroid hormone
59
What diseases cause overprod of thyroid hormone?
Graves
Toxic solitary or multinod goiter
60
What dis cause leakage of TH
Autoimmune thyroiditis
Subacute/viral thyroiditits
61
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
62
What causes thyroiditis?
-Autoimmune dis
-Viral infec
-Bac/fungal infec
-Toxic (amiodarone)
63
What are the clinical symptoms of hyperthyroidism?
Non-specific symptoms like heat intolerance, anxiety, heart palpitations etc
64
What are the clinical signs of hyperthyroidism?
-Goiter
-Hyperactivity
-Hyperreflexia
etc...non specific also
65
What is Graves' disease?
TSH stimulating autoimmune antibody, causes papillary hyperplasia of follicular cells
66
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)
67
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
68
What is onycholysis of thyrotoxicosis?
distal sep of nail plate from nail bed (hyperthy sympt)
69
What is thyroid acropachy
clibbing of fingers, painless, periosteal bone formation and proliferation. Tissue swelling that is soft pigmented and hyperkeratotic. (hyperthy sympt)
70
How do you dif between graves, toxic nodules and thyroiditis?
Radioiodine uptake
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
71
What are the therapeutic options of Graves'?
Antithyroid drugs (first line)
Radioiodine ablation
Survery
72
What antithyroid drugs are used in graves?
PTU and methimazole
73
What are complications of antithyroid drugs?
Can get rash, agranulocytosis, hepatitis (not with PTU tho)
PTU may interfere with I-131 radiation
74
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
75
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
76
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)
Multisystemic disorder
77
What is a thyroid nodule?
Palpable mass or nodule documented by imaging
78
What makes you more suceptible to thyroid nodules?
Older woman
79
What are the malignant thyroid nodules?
5-10% of nodules are malig
Papillary
Follicular
Medullary
Lymphoma
Anaplastic
Mets to thyroid
80
What are the benign thyroid nodules?
Colloid or adenomatous nodules
Follicular/Hurthle cell adenomas
Lymphocytic thyroiditis
81
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)
Male gender
82
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
83
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
84