Hormone Releasing Process 1. The hypothalamus releases ____ 2. This stimulates the anterior pituitary to produce ____ 3. This then stimulates the thyroid gland to produce ____ and ____ 4. Adequate/excess levels of thyroid hormones triggers a ____ feedback loop 5. The feedback loop works on both the ____ gland and ____

1. Thyrotropin-releasing hormone (TRH) 2. Thyroid-stimulating hormone (TSH) or Thyrotropin 3. T3 and T4 4. Negative 5. Pituitary and Hypothalamus

(M) Lec 2: Thyroid Gland Flashcards by Kchianna Lauren Coronel

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

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The thyroid is a butterfly-shaped gland with a functional unit known as a what?

Thyroid Follicle

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A thyroid follicle is surrounded with ____ cells with a central pink area known as the ____

Follicular; colloid

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These cells produce T3 and T4

Follicular Cells

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These cells are responsible for the production of calcitonin

Parafollicular Cells or C-cells

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This substance is important to reduce blood calcium levels

Calcitonin

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Thyroid Hormone Biosynthesis

Give the other names for T3 and T4

T3: Triiodothyronine
T4: Tetraiodothyronine/Thyroxine

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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

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Thyroid Hormone Biosynthesis

Step 2 revolves around the passage of iodide from the follicular cells to the colloid, what is this step called?

Diffusion

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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

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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

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Thyroid Hormone Biosynthesis

T3 or T4:
1. DIT + DIT (2 + 2)
2. MIT + DIT (2 + 1)

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Thyroid Hormone Biosynthesis

Step 5 is where MIT and DIT can be stored in the form of what?

Thyroglobulin

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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

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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

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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)

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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)

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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

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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)

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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

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Thyroid Hormone Binding Proteins

Transports 15-20% of total T4
Has no affinity for T3

Thyroxine Binding Prealbumin (Transthyretin)

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Thyroid Hormone Binding Proteins

It transports T3 and the remaining 10% of T4

Thyroxine Binding Albumin

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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

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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)

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# Actions of the Thyroid Hormones (Increases/Decreases) the activity of intracellular metabolic enzymes

Increases

# Actions of the Thyroid Hormones (Physiologic Actions) 1. Stimulates and promotes ____ and ____ growth 2. (Increased/Decreased) nerve myelination leading to increased synaptic transmission 3. (Increased/Decreased) heart rate leads to (increased/decreased) myocardial contractility, cardiac output, and systolic pressure 4. (Increased/Decreased) heat production leading to vasodilation causes (increased/decreased) diastolic pressure

1. Physical and Mental 2. Increased 3. Increased; increased 4. Increased; decreased

# Actions of the Thyroid Hormones (Physiologic Actions) 1. (Increased/Decreased) appetite leads to (increased/decreased) motility, secretion, and absorption 2. (Increased/Decreased) oxygen consumption leading to (increased/decreased) pO2 3. When there is hypoxia, ____ will be stimulated to produce more RBCs 4. An increased pCO2 causes (acidosis/alkalosis)

1. Increased; increased 2. Increased; decreased 3. Erythropoiesis 4. Acidosis

# Actions of the Thyroid Hormones (Physiologic Actions) 1. (Increased/Decreased) metabolism and clearance of various hormones 2. Stimulates the secretion of ____ and ____ (neuroreceptors) 3. (Increased/Decreased) bone formation and resorption 4. (Increased/Decreased) protein synthesis leads to (increased/decreased) muscle strength

1. Increased 2. Epinephrine and Norepinephrine 3. Increased 4. Increased; increased

# Actions of the Thyroid Hormones (Physiologic Actions) 1. There is increased heat (tolerance/intolerance) due to intracellular activities 2. (Increased/Decreased) glucose absorption leads to (increased/decreased) cellular utilization of glucose 3. It promotes ____ and protein synthesis 4. It stimulates the conversion of carotene to ____

1. Intolerance 2. Increased; increased 3. Lipolysis 4. 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 ____

1. Decreased 2. 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

1. Cretinism 2. Dwarfism

# Thyroid Disorders Familiarize yourself with the causes of hypothyroidism

1. Iodine deficiency 2. Intake of goitrogens 3. Late stage thyroiditis and thyroid cancer 4. TSH deficiency 5. Post-thyroidectomy 6. Post radiation therapy 7. 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 ↓

1. Primary 2. Secondary (Pituitary) 3. Secondary (Hypothalamus)

# Thyroid Disorders Characterized with a skinny figure due to increased metabolism

Hyperthyroidism

# Thyroid Disorders What are the 2 causes of hyperthyroidism (thyrotoxicosis)?

1. Thyroidal 2. 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

1. Grave's Disease 2. Solitary Toxic Adenoma 3. Plummer's Disease/Toxic Multi-Nodular Goiter (MNG) 4. Early stages of thyroiditis

# Thyroid Disorders Familiarize with the 3 extrathyroidal causes of hyperthyroidism

1. Secondary Hyperthyroidism (e.g. pituitary adenomas) 2. Factitious/Iatrogenic Hyperthyroidism 3. 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

1. Anti-thyroglobulin 2. Anti-thyroid microsome (Microsomal Antibodies) 3. Anti-second colloid antigen 4. Anti-thyroid membrane receptors 5. Anti-thyroxine (T4) and triiodothyronine (T3)

# Thyroid Disorders What is the initial and long term effect of Hashimoto's Thyroiditis?

1. Initial - Hyperthyroidism (↑ T3 and T4) 2. 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 ↑

1. Primary 2. Secondary (Pituitary) 3. 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?

1. Radioimmunoassay 2. Immunometric Method 3. 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

1. First generation (RIA): N/A 2. Second generation (IM): 0.1 µU/L 3. Third generation (CLIA): 0.005 µU/L 4. 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?

1. Double antibody RIA, ELISA, and IRMA 2. 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.