(M) Lec 2: Thyroid Gland Flashcards
The thyroid gland’s location is on the ____ of the neck:
A. Lower posterior
B. Lower anterior
C. Upper posterior
D. Upper anterior
B. Lower anterior
The thyroid is a butterfly-shaped gland with a functional unit known as a what?
Thyroid Follicle
A thyroid follicle is surrounded with ____ cells with a central pink area known as the ____
Follicular; colloid
These cells produce T3 and T4
Follicular Cells
These cells are responsible for the production of calcitonin
Parafollicular Cells or C-cells
This substance is important to reduce blood calcium levels
Calcitonin
Thyroid Hormone Biosynthesis
Give the other names for T3 and T4
- T3: Triiodothyronine
- T4: Tetraiodothyronine/Thyroxine
Thyroid Hormone Biosynthesis
Step 1 is where iodide enters the follicular cells which is mediated by the sodium-iodide symporter, what is this step called?
Iodide Trapping
Thyroid Hormone Biosynthesis
Step 2 revolves around the passage of iodide from the follicular cells to the colloid, what is this step called?
Diffusion
Thyroid Hormone Biosynthesis
Step 3 is where the iodide in the colloid will be oxidized in the presence of thyroid peroxidase (TPO)
Oxidation of Inorganic Iodide to Iodine
Thyroid Hormone Biosynthesis
Step 4 is when iodine can now bind to tyrosine in the presence of iodinase, what 2 products can be produced in this process?
Note: Iodine and Tyrosine are the precursor cells of T3 and T4
- Monoiodothyronine (MIT)
- Diiodothyronine (DIT)
Note: Can be thyronine or tyrosine
Thyroid Hormone Biosynthesis
T3 or T4:
1. DIT + DIT (2 + 2)
2. MIT + DIT (2 + 1)
- T4
- T3
Thyroid Hormone Biosynthesis
Step 5 is where MIT and DIT can be stored in the form of what?
Thyroglobulin
Thyroid Hormone Biosynthesis
Step 5 is where thyroglobulin goes to the follicular cells via endocytosis and undergoes ____ with the help of lysosomes to release the T3 and T4 outside the follicle
Proteolysis
Thyroid Hormone Biosynthesis
Step 6 is where T3 and T4 are excreted out from the follicle, this step is called as?
Release of T3 and T4 into the circulation
Thyroid Hormones
- The most active/potent thyroid hormone
- 80% comes from the deiodination of the other hormone while 20% comes from the combination of MIT and DIT
- A good indicator of recovery and recurrence of hyperthyroidism
Triiodothyronine (T3)
Thyroid Hormones
- The most abundant thyroid hormone
- Has a longer effect than the other hormone
- A principal secretory product
- A prohormone of the other thyroid hormone
- A good indicator of the thyroid secretory rate
Tetraiodothyronine/Thyroxine (T4)
Thyroid Hormones
Approximately 80% of T4 is metabolized into either ____ or ____
T3 [35%] or Reverse T3 (rT3) [45%]
Note: T3 is the active form while rT3 is the inactive form
Thyroid Hormones
80% of T3 comes from the deiodination of the T4 through the help of what enzyme?
Deiodinase (reduces one DIT from T4 to form MIT + DIT)
Thyroid Hormone Binding Proteins
- This transports the majority of T3 hormones (affinity for T3 is lower than T4)
- It transports 70-75% of total T4
Thyroxine-Binding Globulin
Note: It don’t make sense to me but let go and let god
Thyroid Hormone Binding Proteins
- Transports 15-20% of total T4
- Has no affinity for T3
Thyroxine Binding Prealbumin (Transthyretin)
Thyroid Hormone Binding Proteins
- It transports T3 and the remaining 10% of T4
Thyroxine Binding Albumin
Hormone Releasing Process
- The hypothalamus releases ____
- This stimulates the anterior pituitary to produce ____
- This then stimulates the thyroid gland to produce ____ and ____
- Adequate/excess levels of thyroid hormones triggers a ____ feedback loop
- The feedback loop works on both the ____ gland and ____
- Thyrotropin-releasing hormone (TRH)
- Thyroid-stimulating hormone (TSH) or Thyrotropin
- T3 and T4
- Negative
- Pituitary and Hypothalamus
Hormone Releasing Process
What are the 2 stimuli for the release of Thyrotropin-releasing hormone (TRH)?
Cold Temperatures and Stressful Conditions (e.g. physical, mental, and emotional)
Actions of the Thyroid Hormones
(Increases/Decreases) the activity of intracellular metabolic enzymes
Increases
Actions of the Thyroid Hormones (Physiologic Actions)
- Stimulates and promotes ____ and ____ growth
- (Increased/Decreased) nerve myelination leading to increased synaptic transmission
- (Increased/Decreased) heart rate leads to (increased/decreased) myocardial contractility, cardiac output, and systolic pressure
- (Increased/Decreased) heat production leading to vasodilation causes (increased/decreased) diastolic pressure
- Physical and Mental
- Increased
- Increased; increased
- Increased; decreased
Actions of the Thyroid Hormones (Physiologic Actions)
- (Increased/Decreased) appetite leads to (increased/decreased) motility, secretion, and absorption
- (Increased/Decreased) oxygen consumption leading to (increased/decreased) pO2
- When there is hypoxia, ____ will be stimulated to produce more RBCs
- An increased pCO2 causes (acidosis/alkalosis)
- Increased; increased
- Increased; decreased
- Erythropoiesis
- Acidosis
Actions of the Thyroid Hormones (Physiologic Actions)
- (Increased/Decreased) metabolism and clearance of various hormones
- Stimulates the secretion of ____ and ____ (neuroreceptors)
- (Increased/Decreased) bone formation and resorption
- (Increased/Decreased) protein synthesis leads to (increased/decreased) muscle strength
- Increased
- Epinephrine and Norepinephrine
- Increased
- Increased; increased
Actions of the Thyroid Hormones (Physiologic Actions)
- There is increased heat (tolerance/intolerance) due to intracellular activities
- (Increased/Decreased) glucose absorption leads to (increased/decreased) cellular utilization of glucose
- It promotes ____ and protein synthesis
- It stimulates the conversion of carotene to ____
- Intolerance
- Increased; increased
- Lipolysis
- Vitamin A
Actions of the Thyroid Hormones (Physiologic Actions)
TOF: Patients with hyperthyroidism suffer from heat intolerance while those with hypothyroidism suffer from cold intolerance
True
Actions of the Thyroid Hormones (Physiologic Actions)
Since T3 and T4 decrease glucose and induce lipolysis:
1. Patients with hyperthyroidism have expected glucose and fat levels that are ____
2. Patients with hypothyroidism have expected glucose and fat levels that are ____
- Decreased
- Increased
Actions of the Thyroid Hormones (Physiologic Actions)
TOF: Increased thyroid hormones promote the increase of carotene
False (decreased hormones = increased carotenes)
Thyroid Disorders
- Refers to the enlargement of the thyroid
- It is usually misunderstood that it is due to hyperthyroidism, but it actually can be caused by either hyper-, hypo-, or euthyroidism
Note: Goiters caused by hyperthyroidism are known as Toxic Goiters
Thyromegaly
Thyroid Disorders
Refers to the enlargement of the thyroid even though hormone levels are normal
Euthyroid
Note: AKA “Non-Toxic Goiter”
Thyroid Disorders
Refers to decreased T3 and T4 which can present with Myxedema and Cretinism
Hypothyroidism
Thyroid Disorders
- A manifestation of hypothyroidism that occurs after birth
- Characterized by carotenemia, low IQ, and increased glucose and lipids
Myxedema
Thyroid Disorders
- A manifestation of hypothyroidism that occurs before or during birth
- Characterized with small statures, mental retardation, macroglossia (relatively enlarged tongue), and pot-belly
Cretinism
Thyroid Disorders
Cretinism or Dwarfism?
1. Decreased T3 and T4 leading to decreased development of the bones, brain, and muscles
2. Decreased growth hormone which affects physical characteristics but with normal brain development
- Cretinism
- Dwarfism
Thyroid Disorders
Familiarize yourself with the causes of hypothyroidism
- Iodine deficiency
- Intake of goitrogens
- Late stage thyroiditis and thyroid cancer
- TSH deficiency
- Post-thyroidectomy
- Post radiation therapy
- Drugs: Propylthiouracil, amiodarone, excess iodine, lithium, and dopamine
Note: Excess iodine causes a negative feedback loop
Thyroid Disorders
Primary vs. Secondary Hypothyroidism (Pituitary or Hypothalamus):
1. TRH ↑, TSH ↑, T3 ↓, and T4 ↓
2. TRH ↑, TSH ↓, T3 ↓, and T4 ↓
3. TRH ↓, TSH ↓, T3 ↓, and T4 ↓
- Primary
- Secondary (Pituitary)
- Secondary (Hypothalamus)
Thyroid Disorders
Characterized with a skinny figure due to increased metabolism
Hyperthyroidism
Thyroid Disorders
What are the 2 causes of hyperthyroidism (thyrotoxicosis)?
- Thyroidal
- Extrathyroidal
Thyroid Disorders
In Thyroidal Hyperthyroidism, this disease is characterized by the presence of thyroid-stimulating immunoglobulins leading to autoimmunity
Grave’s Disease
Thyroid Disorders
Familiarize with the 4 thyroidal causes of hyperthyroidism
- Grave’s Disease
- Solitary Toxic Adenoma
- Plummer’s Disease/Toxic Multi-Nodular Goiter (MNG)
- Early stages of thyroiditis
Thyroid Disorders
Familiarize with the 3 extrathyroidal causes of hyperthyroidism
- Secondary Hyperthyroidism (e.g. pituitary adenomas)
- Factitious/Iatrogenic Hyperthyroidism
- Ectopic Thyroid Tissue
Thyroid Disorders
In patients with this extrathyroidal form of hyperthyroidism, upon the administration of thyroxine to counter the initial effects of hypothyroidism, hyperthyroidism occurs when improper doses are given causing false positive results
Factitious/Iatrogenic Hyperthyroidism
Thyroid Disorders (Autoimmune Disease)
- Associated to HLA-DR4 and HLA-DR5
- The production of antibodies against the thyroid gland
Hashimoto’s Thyroiditis
Thyroid Disorders
Familiarize yourself with the antibodies against the thyroid gland in Hashimoto’s Thyroiditis
- Anti-thyroglobulin
- Anti-thyroid microsome (Microsomal Antibodies)
- Anti-second colloid antigen
- Anti-thyroid membrane receptors
- Anti-thyroxine (T4) and triiodothyronine (T3)
Thyroid Disorders
What is the initial and long term effect of Hashimoto’s Thyroiditis?
- Initial - Hyperthyroidism (↑ T3 and T4)
- Long term - Hypothyroidism (↓ T3 and T4)
Thyroid Disorders (Autoimmune Disease)
- The antibodies are able to stimulate the thyroid gland
- Consists of the Anti-thyroid Peroxidase (Anti-TPO) and TSH receptor antibodies (TRAb)
Note: TRAb differentiates Grave’s Disease from Toxic Nodular Goiter
Grave’s Disease
Thyroid Disorders
Primary vs. Secondary Hyperthyroidism (Pituitary or Hypothalamus):
1. TRH ↓, TSH ↓, T3 ↑, and T4 ↑
2. TRH ↓, TSH ↑, T3 ↑, and T4 ↑
3. TRH ↑, TSH ↑, T3 ↑, and T4 ↑
- Primary
- Secondary (Pituitary)
- Secondary (Hypothalamus)
Lab Determination and Methods of Measurement
Thyroid-Stimulating Hormone (TSH)/Thyrotropin:
1. First generation technique?
2. Second generation technique?
3. Third generation technique?
- Radioimmunoassay
- Immunometric Method
- Chemiluminometric Assay (commonly used in the lab)
Lab Determination and Methods of Measurement
Thyroid-Stimulating Hormone (TSH)/Thyrotropin:
Familiarize yourself with the different generational detection limits
- First generation (RIA): N/A
- Second generation (IM): 0.1 µU/L
- Third generation (CLIA): 0.005 µU/L
- Fourth generation: 0.0004 µU/L
Lab Determination and Methods of Measurement
What is the recommended detection limit (sensitivity) for TSH measurement?
0.01-0.02 µU/L with CV < 20%
Lab Determination and Methods of Measurement
What 3 immunoassays can be used for T3 and T4?
RIA, Immunometric, and CLIA
Lab Determination and Methods of Measurement
For T3 and T4:
- > 99% of the thyroid hormones are protein-bound
- The measurements of Free T4 (FT4) and Free T3 (FT3) are developed
Total vs. Free Forms
Note: Free forms are better measured than total forms
Lab Determination and Methods of Measurement
What is the reference method for Free T4 (FT4) measurement?
Equilibrium Dialysis
Lab Determination and Methods of Measurement
- This is the main serum carrier for both T3 and T4
- It is measured through immunoassays (very seldom)
- Reference value: 13-39 g/dL (150-360 nmol/L)
Thyroid Binding Globulin (TBG)
Lab Determination and Methods of Measurement
This is normally used as a post-operative marker for thyroid cancer
Thyroglobulin
Lab Determination and Methods of Measurement
What are the 2 anaytical methods for Thyroglobulin?
- Double antibody RIA, ELISA, and IRMA
- Immunochemiluminescent assays (ICMA)
Note: ICMA is the reference method
Lab Determination and Methods of Measurement
Other Thyroid Function Tests
- This measures the inactive form, a metabolite of T4
- This is eventually converted to the active thyroid hormone T3
- In some instances, T4 may be transformed into this form rather than T3, leading to decreased thyroid function
- Measured using LC-MS/MS
Reverse T3 (rT3)
Lab Determination and Methods of Measurement
Other Thyroid Function Tests
- Determines alterations in binding proteins
- Relies on the availability of binding sites (uses radiolabeled T3 and resin)
Note: Excess radiolabelled T3 is absorbed by the resin
Resin T3 Uptake
Lab Determination and Methods of Measurement
Resin T3 Uptake is usually done to determine this parameter
Free Thyroxine Index (FTI)
Note: Formula is (patient’s T3 uptake)/(reference pop.’s T3 uptake)
Lab Determination and Methods of Measurement
Familiarize yourself with the reference ranges shown at the end of the video (focus on the conversion factors)
Thanks boo.
