Thyroid Gland Flashcards
1
Q
_ is the prohormone of the thyroid gland
_ is the active hormone produced by the thyroid gland
The newly synthesized thyroid hormones are bound to _ and located in the _ of the thyroid gland
_ cells are also present in addition to follicular cells and are responsible for the productions of _
A
- T4
- T3
- Thyroglobulun, Colloid
- C cells, calcitonin
2
Q
The secretory products of the thyroid glands are _
Thyroid hormones contain large amounts of _
Part of synthesis is _ and some is extracellular
_ is the major secretory product
A
- Iodothyronines
- Iodine
- Intracellular
- T4
3
Q
- Iodide is added to peroxide to produce _
- Adding iodine to tyrosine produces what two products?
- Are these products biologically active?
A
- Iodine
- MIT and DIT
- Not biologically active, but used to synthesize T3 and T4
4
Q
- Two molecules of _ are used to make T4
- One molecule of _ and one molecule of _ are used to make T3
- T4 synthesis is 10x _ than T3 synthesis
A
- DIT
MIT, DIT - Greater (T4 is made much faster)
5
Q
- The enzyme _ is responsible for the peripheral conversion of T4 to T3 (80-90%)
- 10% of T3 comes from _
A
- Iodinase (different types of iodinase enzymes depending on where you are in the body)
- Type I-skeletal muscle
- Type II-provides feedback to anterior pituitary
- Direct secretion of T3 from thyroid
6
Q
- What are some clinical conditions where the conversion from T4 to T3 is reduced?
A
Fasting
Medical and surgical stress
Catabolic disease
7
Q
- How is thyroid hormone synthesized?
A
- Thyroglobulin is transported from Golgi/ReR into apical/luminal membrane of the follicular cell
- “Iodide trap”-iodide enters cell on basolateral surface using 2Na+/I- transporter
- I- is transported out of apical membrane via Peroxidase/TPO
- Peroxidase catalyzes addition of I- to thyroglobulin to make MIT and DIT (still bound to TG)
- Peroxidase reaction occurs again to make TG with bound MIT, DIT, T3 and T4 (stored as colloid)
- Endocytosis into cell from TSH stimulation
- Proteases in lysosomes cleave T3 and T4 off of TG and send them into circulation; MIT and DIT are recycled
- MIT and DIT are converted to tyrosine and TG via deiodinase
8
Q
- When the availability of iodide is restriction, the formation of _ is favored
- Deficiency of _ mimics dietart I- deficiency
- _ is an effective treatment for hyperthyroidism by inhibiting Na+/I- cotransporter on basolateral surface of follicular cell in thyroid
- High levels of _ inhibit organification and synthesis of thyroid hormone (WOLFF-CHAIKOFF EFFECT)
A
- T3
- deiodinase
- PTU
- I-
9
Q
- Enough hormone is stored as _ in the follicular colloid to last the body 2-3 months
A
- Iodinated TG
10
Q
- The activity of the thyroid gland can be assessed by _
- Identify the following
A
- Radioactive iodine uptake
- 1) Hyperthyroidism
- 2) Normal
- 3) Hypothyroidism
11
Q
- What are the main binding proteins that carry thyroid hormones in the blood?
- There is an _ between bound and free circulating T3 and T4 in the bloodstream
- What percentage of thyroid hormones are bound to proteins?
A
-
TBG (Thyroxine binding globulin)
- HIGHER AFFINITY FOR T4
- Made in liver
- TTR (Transthyretin)
- Albumin
Equilibrium
99%
12
Q
- TBG has a higher affinity for _, making the half life of this hormone longer
A
- T4 (half life is 6 days v. 1 day half life for T3)
13
Q
- Circulating levels of TGG can be measured with what test?
- How does this test work?
A
- T3 resin uptake test
- STEPS
- TGB with bound T4 is taken from serum
- Unbound and labeled T3 is added
- If there are binding sites available on TGB, T3 will bind
- Whatever is left over or unable to bind TGB will bind T3 resin and precipitate
- TGB with bound T3/4 is in solution
14
Q
- How are blood levels of TGB and free thyroid hormones affected in hyperthyroidism?
A
- TGB should not change
- Increase in T4 (thyroid is making excess)
- Increase in resin uptake of T3 (T4 taking up binding sites on TGB and T3 is also being made in excess)
15
Q
- How are blood levels of TGB and free thyroid hormones affected in a patient with hypothyroidism?
A
- TGB unchanged
- Decrease in T4 (thyroid isnt making as much)
- Decrease in T3 resin uptake (less T4 means more open binding sites on TGB for T3)
16
Q
- How are blood levels of TGB and free thyroid hormones affected in patients with High TGB?
A
- TGB elevated (obvi)
- Increase in T4 *
- Decrease in T3 resin uptake (more TGB-more binding sites for T3)
17
Q
- How are blood levels of TGB and free thyroid hormones affected in patients with Low TGB?
A
- TGB is low
- Decrease in bound T4
- Increase in T3 resin uptake (Less TGB for T3 to bind)
18
Q
- How are TGB and thyroid hormone concentrations altered in the blood during hepatic failure?
A
- Hepatic failure-decreases TGB (its made there)
- Increase in level of FREE T3 and T4
- Followed by inhibition of synthesis of T3 and T4 (via negative feedback on anterior pituitary)
19
Q
- How does pregnancy affect TGB and thyroid hormone levels in the blood?
A
- Pregnancy-increase in TGB levels
- Increase in bound T3 and T4
- Decrease in free T3 and T4
- Decrease in free T3 and T4 causes an increase in synthesis of T3 and T4
- Levels of free, physiologically active hormones increased, total thyroid hormones normal (clinically euthyroid)
20
Q
- HPT axis :
- TRH _ anterior pituitary to release _ which stimulates the thyroid gland to release thyroid hormones
- TSH is regulated by _ and _ (which one stimulates and which one inhibits?)
- _ secretion occurs at a steady rate, unlike GH
A
- TRH stimulates TSH release from anterior pituitary
- TSH is regulated by TRH (stimulatory) and Free T3 (Inhibitory)
- TSH secretion occurs at a steady rate
21
Q
_ enzyme has an indirect inhibitory effect on the hypothalamus and a direct inhibitory effect on the anterior pituitary
A
- Deiodinase
22
Q
_ is the second messenger for TSH
What are the two actions of TSH on the thyroid gland?
A
- cAMP
- Trophic effects on thyroid gland
- Thyroid hormone secretion
23
Q
- Stimulatory factors of thyroid hormone secretion
- Inhibitory factors of thyroid hormone secretion
A
-
Stimulatory factors:
- TSH
- Increased TBG (ex: pregnancy)
- Thyroid Stimulating IGs
-
Inhibitory factors:
- I- deficiency
- Diodenase deficiency
- Excessive I- intake (inhibits TPO activity)
- Drugs inhibiting Na+/I- cotransport (Perchlorate, thiocyanite)
- Drugs inhibiting peroxidase enzyme (PTU)
- Decreased TGB levels (Liver Disease)
24
Q
- Thyroid hormone is responsible for the synthesis of new _
- In the liver and adipose tissue, TH helps with synthesis of _
A
- Proteins
- Beta 1 adrenergic receptors
- Na+/K+ ATPase
- Transport proteins
- Lysosomal/Proteolytic enzymes
- Structural proteins
- Cariac proteins (myosin, beta adrenergic receptor, Ca2+ ATPase)
- Metabolic enzymes
25
* The receptor for thyroid hormone is located in the _ and has _ and _ domains
It is more sensitive to which thyroid hormone?
* Nucleus
* Retinoid X and Thyroid hormone receptor domains
* T3
26
* Systemic actions of thyroid hormone
27
* How does TH increase BMR?
* Hypothyroid patients will have a _ BMR
* Hyperthyroid patients will have a _ BMR
* Increases activity of Na+/K+
* Increase in O2 consumption and heat generation
* Single dose of T4 can last 6 hours in increasing BMR
* Low
* High
28
* ***How does thyroid hormone affect metabolism?***
* Lipids:
* Stimulates fat mobilization (increase FFAs in plasma)
* Stim beta oxidation
* **Plasma concentration of cholesterol and triglycerides are inversely correlated to thyroid hormones (High triglycerides and cholesterol in HYPOthyroidism)**
* Helps with conversion of Carotine to Vit A
* Carbs:
* Increased glycogenolysis and gluconeogenesis
* Increased insulin-dependent entry of glucose into cells
29
* ***Cardiovascular effects of thyroid hormones***
30
* How does thyroid hormone affect growth and the CNS?
* Thyroid hormone acts synergistically w/ GH and somatomedins-helps with bone formation
* CNS:
* Important for CNS maturation (dendritic branching, myelination)
31
* ***Thyroid Pathophysiology Summary***
32
* Hyperthyroidism
* Primary
* Secondary
* How are TSH levels affected?
* Primary (**Grave's)-problem with the thyroid gland itself**
* ****Low TSH levels-T3 being produced is inhibiting TSH secretion from the anterior pituitary
* Secondary (TSH secreting pituitary)
* High TSH
33
***Grave's disease***
* **Exopthalmos-**abnormal protrusion of the eyeballs and periobital edema
* Dx:
* Elevated serum free and total T3 or T4
* **Presence of circulating TSI (thyroid stumulating immunoglobulins)-helps distinguish grave's disease from adenoma of pituitary thyrotrophs (secondary hyperthyroidism)**
34
* Causes of hypothyroidism
* Primary
* Other causes
* Primary
* Agenesis
* **Gland destruction (Hashimoto's thyroditis-AID)**
* Inhibition of TH synthesis and release (iodine def, enzyme defects, drugs)
* Transient
* Other:
* Hypothalamic disease (tertiary)
* Pituitary disease (Sheehans's Syndrome-2ndary)
* Resistance to thyroid hormones
35
* Treatment for hypothyroidism
* T4 (longer 1/2 life than T3 because it binds TGB with more affinity and can just be converted to T3)
* Be careful w/ postmenopausal women -osteoporosis
36
* ***Hashimoto's Thyroiditis***
* How are TH levels affected?
* How is TSH affected?
* Thyroglobulin or TPO Abs attack thyroid gland
* T3 and T4 levels are low, so TSH levels are high
37
* ***Cretinism***
* ******Causes
* Symptoms
* Causes:
* Iodide def
* Maternal intake of anti-thyroid meds
* Impaired development of thyroid gland
* Inherent defects in the synthesis of thyroid hormones
* Symptoms:
* Feeding problems
* Resp difficulty
* Protruding tongue
* Curse facial features
* Growth retardation
* Mental retardation
* Jaundice
* Dry Skin
* Hypotonia
38
* ***Hypothyroidism d/t iodine deficiency***
* **How can this lead to goiter formation?**
* Goiter:
* Gland maintains normal levels of thyroid hormones, patient is euthyroid and asymptomatic
* If gland cannot maintain normal BGLs of thyroid hormones, patient will be hypothyroid
39
Goiter can be caused by _ and \_
* Hyperthyroidism
* Graves disease
* TSH producing tumor
* Primary hypothyroidism
* Lack of adequate iodine in the diet
* Sporadic hypothyroidism of unknown etiology
* Chronic thyroiditis
40
* _ test is used for the diagnosis of thyroid disorders?
