Week 4 - Thyroid A/P Flashcards
What is the anatomical location of the thyroid gland?
Straddling the trachea at the level of C5-T1, just below the laryngeal prominence
Thyroid first becomes functional in _____ _____ _____
Early fetal life
The thyroid gland is comprised of numerous _________
Follicles
What do follicular cells secrete?
Thyroid hormones
Follicular cells have transporters for which mineral? What is this transporter and what does it do?
Iodine
Na/I symporter
Traps iodine from the plasma and concentrates it within the thyroid follicle (iodine in follicle 30-40x more concentrated than in plasma
What do parafollicular cells (C-cells) secrete? What does this do?
Secretes calcitonin: inhibits bone resorption.
T/F: Calcitonin is clinically important as a tumor marker produced by medullary thyroid cancer
True
What is mostly composed of thyroglobulin: an iodine-protein secreted by the follicular cells into the lumen of the follicle?
Colloid
Thyroid follicular cells arise from _______ _______ _________
Midline thyroid diverticulum
Parafollicular cells arise from _________ _____ ______
Neural crest cells
Follicular cells descend via the ____________ duct to the anterior trachea and bifurcates forming 2 lobes.
Thyroglossal duct
Thyroglossal duct may give rise to what pathology? What are possible consequences?
Midline cysts lined by squamous epithelium.
May become infected or give rise to thyroid tumors
Which nerve courses behind the thyroid?
Recurrent laryngeal nerve
Which glands lie behind the upper and middle portions of the thyroid lobes? How many pairs are there?
Parathyroid glands; 2 pair
Which structure does the thyroid wrap around?
Trachea
What is the cause of bruits or thrills in the thyroid?
Rich blood supply increased in hyperthyroidism
What are the 5 iodine-containing hormones? From which amino acid are they all derived?
- Thyroxine (LT4)
- Triiodothyronine
- T2 (DIT)
- T1 (MIT)
- rT3 (Reverse T3)
Derived from tyrosine
Which thyroid hormone is known pharmaceutically as Synthroid?
Thyroxine (LT4)
Which thyroid hormone contains 4 iodine atoms, levels reach significant amount at 18-20 weeks gestation and plasma half-life is 7 days?
Thyroxine (LT4)
Which thyroid hormone is pharmaceutically known as “Liothyronine” - Cytomel?
Triiodothyronine (T3)
Which thyroid hormone contains 3 iodine atoms, about 15% of the total body’s release of this hormone comes from the thyroid gland, and levels remain low until 30 weeks gestation?
Triiodothyronine (T3)
Where is T4 converted to T3?
Peripheral tissues
Which enzyme converts T4 to T3?
Deiodinases
Which thyroid hormone binds and activates thyroid hormone receptors?
T3
Which thyroid hormone is considered inactive and may stimulate mitochondria?
T2 (DIT)
Which 3 thyroid hormones are considered inactive?
T2, T1, and rT3
Which hormone is released by the parafollicular cells in the thyroid?
Calcitonin
Calcitonin opposes effects of which other hormone?
Parathyroid hormone
Calcitonin serves as a marker for which type of cancer?
Medullary thyroid cancer
What is the process where an iodine ion (I-) is brought into follicular cells (co-transported with Na+)?
Iodination
What is the enzyme that oxides iodine ion to iodide (I2)?
Thyroperoxidase (TPO)
What is the term for TSH from the anterior pituitary binding to TSH-receptors on the surfaces of follicular cells and stimulating the endocytosis of the colloid?
TSH binding
TSH increases the production of thyroglobulin and the number of follicular cells: high TSH levels may lead to which issues with they thyroid?
Excessive synthesis of thyroglobulin and follicular cell hypertrophy, causing an enlarged thyroid (goiter)
The release of T4 occurs with endocytosed vesicles fusing with ________ of the follicular cell? Lysosomal enzymes cleave the T4 from the ________ _____________
lysosomes
iodinated thyroglobulin
Iodine is found as iodide (I-) or iodate (IO3-) in food/water. It is converted to iodide in which organ?
stomach
World Health Organization (WHO) daily dietary iodine intake:
____ mcg for adults (1100 mcg/max = 1.1 mg)
____ mcg for pregnant/lactating women
___-____ mcg for children
150 mcg for adults
200 mcg for pregnant/lactating women
50-250 mcg for children
Intake < ____ mcg/day: gland can’t maintain normal hormone production & enlarges (goiter, hypothyroidism)
50 mcg/day
Thyroid stores ___-___mg of iodine (thyroid hormones & iodinated tyrosines)
8-10 mg of iodine
What are the main sources of iodine?
- Seafood: fish, shellfish, kelp, etc.
- Dairy products: milk, cheese, eggs
- Plants grown on iodine-rich soils
- Iodized salt: fortified with iodine
- Excess may induce hyperthyroidism: Jod-Basedown phenomena
- Supersaturated potassium iodide (SSKI)
Iodine may be displaced from body tissues by which other halogens?
- Bromine: found in baked goods, plastics, soft drinks, medications, pesticides
- Fluorine: fluoridated drinking water
- Perchlorate (rocket fuel) contamination in food
Which 2 conditions can be associated with iodine deficiency?
- Fibrocystic breasts/Breast cancer
2. Stomach cancer
What is a radioactive isotope of iodine
that is a component of nuclear fallout: that becomes concentrated in the thyroid? What is the treatment?
Iodine-131
High dose non-radioactive iodine given as treatment: 130 mg/24 hours (supplies 100 mg of iodine)
Secretion of TSH is primarily regulated by what?
Levels of T4 & T3
Thyroid-releasing hormone (TRH) from the
hypothalamus stimulates the release of _____.
TSH
TRH also found in which 7 other areas of the body?
- pancreatic islet cells
- GI tract
- placenta
- heart
- prostate
- testes
- ovaries (role is unknown in these tissues)
Which 3 factors increase TSH release?
- Cold
- Alpha-adrenergic agonists
- Hypothyroidism
Which 4 factors decrease TSH release?
- Hyperthyroidism
- Somatostatin
- Dopamine, dopamine agonists (bromocriptine)
- Glucocorticoids/cortisol
What are 6 effects of TSH on the thyroid cell?
- Upregulates sodium-iodide symporter
- Stimulates iodination of thyroglobulin
- Stimulates conjugation of iodinated tyrosine residues
- Increases endocytosis of iodinated thyroglobulin
- Stimulates proteolysis of iodinated thyroglobulin to form
T4 & T3 - Secretion of T4 & T3 into blood
TSH has which 3 trophic effects?
- Causes hypertrophy & hyperplasia of follicular cells
- Increases vascularity of thyroid gland
- Excess TSH may lead to goiter
TSH Circadian Rhythm - TRH-stimulated TSH secretion is pulsatile: mean TSH pulse amplitude of _____ mU/L every ___ hours.
Normal individuals have a circadian rhythm in TSH release: peak between _____ and ____.
0.6 mU/L every 2 hours;
midnight and 4am
T/F: Thyroid hormones are lipid-like and poorly soluble in water, requiring transport proteins
True
_____% of T4 & T3 are non-covalently bound to carrier proteins. The remainder of free thyroid hormone can move into tissues (fT4, fT3)
~99.9%
Binding globulins are synthesized in the ______.
liver
What are the 3 carrier proteins in the transport of thyroid hormones in plasma?
- Thyroxine-binding globulin (TBG) (70%)
Increased in: pregnancy, high estrogen states (OCP use), liver disease - Transthyretin (Thyroxine-binding prealbumin) (10-15%)
- Albumin (15-20%)
The plasma half-life of T4 is _____ days.
7
What % of T4 is metabolized by deiodination? Some is converted to T3 & rT3, and the remainder is removed via which 2 processes?
80%
liver glucuronidation & sulfation
Plasma half-life of T3 is ____ day(s). Half-life of rT3 is _____ day(s).
1 day; 0.2 days
Deiodinase enzymes either:
Activate thyroid hormone (T4 —> T3), which means…
-or-
Inactivate thyroid hormone (T4 —> reverse T3 (rT3)), which means…
Outer ring of T4 is 5’ deiodinated to produce T3
Inner ring of T4 is deiodinated to produce rT3. T3 can also be converted to T2.
Deiodinases are which type of proteins (uses which mineral as a cofactor)?
Selenoprotiens - uses selenium as a co-factor
Once inside the cell, T4 —> T3 via the action of ___ or ___. T3 then enters the nucleus, where it binds to a ____
DI or DII; Thyroid hormone receptor
Thyroid hormone receptors regulate gene expression by binding to ______ _____ ______ in DNA (several types exist,
but the most common are retinoid X receptors (RXR)) —->
once bound the TR/RXR initiates gene
transcription/protein synthesis.
hormone response elements (HREs)
T3 is [more/less] actively bound to TR than T4?
MORE
What are 3 isoforms of the thyroid hormone receptor?
- alpha-1
- beta-1
- beta-2
How and where are the following expressed? TR-alpha1: TR-alpha2: TR-beta1: TR-beta2:
TR-alpha1: widely expressed, especially in cardiac & skeletal muscle
TR-alpha2: widely expressed, but unable to bind hormone
TR-beta1: mostly expressed in brain, liver, kidney
TR-beta2: mostly expressed in pituitary & hypothalamus
Thyroid hormone (TH) receptors are located in the _____ of most of the body’s cells
nuclei
By ___-___ weeks of development, fetus is largely dependent on it’s own production of thyroid hormones
15-18
What is the absence of thyroid hormone during fetal life resulting in a poorly developed nervous system and a form of mental retardation?
Cretinism
What is the most common cause of cretinism worldwide?
iodine deficiency
T/F: The nervous system may develop normally if iodine is given to the child starting at birth, although mental function may not be totally restored.
True
What is the primary action of T3? What is the result?
Stimulation of Na/K-ATPases throughout the body and increases O2 consumption.
Results in a net increase in metabolic rate with an increase in the amount of body heat produced.
T/F: The calorigenic action of thyroid hormone accounts for a large portion of the total heat produced by a person each day
True
Thyroid hormone stimulates carbohydrate absorption from the SI resulting in increases in hepatic ______ and _______.
Gluconeogenesis and glycogenolysis
T/F: Thyroid hormones decrease fatty acid release from adipocytes
FALSE! TH increases fatty acid release
TH up-regulates which receptors in tissues like the heart and nervous system
Beta-adrenergic
Unlike the sympathetic nervous system, how do thyroid hormones impact gut motility and blood pressure?
Increase GI motility
Induce vasodilation
Lower blood pressure
What are 5 cardiovascular effects of TH?
- Stimulates transcription of sarcoplasmic reticulum Ca2+ ATPase: increases rate of myocardial diastolic relaxation
- Increases expression of myosin: enhances systolic function
- Increases expression of alpha-adrenergic receptors
- Increases rates of depolarization & repolarization of the SA node (increases heart rate)
- Decreases peripheral vascular resistance, diastolic function & ventricular filling
T3 [decreases/increases] production of erythropoietin: [decreases/increases] erythropoiesis.
Increases; increases
What are the musculoskeletal responses to Hyperthyroidism:
Hypothyroidism:
Hyperthyroidism: increased bone loss, muscle turnover, hyperreflexia, fine distal hand tremor
Hypothyroidism: hyporeflexia (delayed deep tendon reflex relaxation)
Which endocrine hormones are stimulated to be released by TH?
- Growth hormone
- Hypothyroidism: hyperprolactinemia
- Response of HPA axis to stress is blunted in hypothyroidism
