L11 - Thyroid Diseases

Question 1

Thyroid Gland?

Answer 1

Single layer of follicular cells surrounding lumen filled with colloid
Composed of two cell types
• Follicular Cells
• Parafollicular Cells

Question 2

Thyroid Hormone
Synthesis

Answer 2

1. Iodide Trapping through the Na I symporter
2. TSH stimulates Follicular cells to synthesize thyroglobulin ( Tg ), extruded into the follicular lumen
3. Oxidation of Iodine by Thyroid Peroxidase (TPO)
4. 1 Iodination of Tyrosine by TPO
5. 2 Couple DIT, MIT to create T4, T3
6. Endocytosis of Thyroglobulin - T4, T3
7. Lysosomal digestion to release T4, T3
8. Exocytosis of T4, T3 into blood circulation

**Check slide 4-9/39

Question 3

T3 vs. T4?

Answer 3

T3 has greater biologic activity vs T4

1. T4 is bound more tightly to plasma proteins than T3
2. Peripheral target cells convert T4 to T3
3. Nuclear receptors have greater affinity for T3 than T4, so that T3 is more potent on a molar basis

Question 4

Free and Bound forms of Thyroid Hormones?

Answer 4

**Check slide 11/39

Question 5

Changes of TBG Affect Thyroid Function Tests?

Answer 5

**Check slide 12/39

Question 6

Thyroid Hormones Actions?

Answer 6

C₆H₁₂O₆ + 6O₂ -> 6CO₂ + 6H₂O + 36ATP + heat
**Check slide 13-14/39

Question 7

Thyroid Disease: HYPOthyroidism?

Answer 7

Thyroid gland does not produce enough thyroid hormones
Slows down metabolism

Question 8

Thyroid Disease: HYPERthyroidism?

Answer 8

Excess production of thyroid hormones
Speeds up metabolism

Question 9

Hypothyroidism: Signs and Symptoms

Answer 9

Question 10

Hyperthyroidism: Signs and Symptoms

Answer 10

Question 11

Congenital Hypothyroidism

Answer 11

• Occurs with a frequency of 1:3,000 live births (ON)
• Etiology
- Thyroid gland dysgenesis
- Hereditary condition interrupting thyroid synthesis
- Iodine deficiency: endemic cretinism
• Ontario newborn screening program
• Screening test: TSH

Question 12

Hypothyroidism: Treatment

Answer 12

Replacement therapy:
• Synthetic thyroid hormone (oral medication):
Levothroid , Synthroid , others

Monitoring:
• Pituitary Lag = 4-8 week from serum TSH values to reach a new steady state after the therapy or dosing changes
• TSH level every 2-3 months

Question 13

Hashimoto’s Thyroiditis

Answer 13

Chronic inflammation of the thyroid, or thyroiditis, may be a result of infection or autoimmune disease
• Autoimmune Disease “Hashimoto’s thyroiditis”

Produce inflammation and destruction of thyroid tissue

Diagnosis:
TSH high
FT4, FT3 low
Anti-TPO+ (thyroperoxidase)
Anti-Tg+ve (thyroglobulin)

Question 14

Complications of Hypothyroidism

Answer 14

Pregnancy
• Irreversible fetal malformation, growth retardation and neurological deficits

Infancy and early childhood
• Decreased linear growth, inadequate brain maturation, low psychomotor development, severe
congenital hypothyroidism Cretinism

Adult
• Severe condition death from Myxedema Coma
• a loss of brain function as a result of severe,
longstanding low level of thyroid hormone

Question 15

Hyperthyroidism: “Thyrotoxicosis”?

Answer 15

Primary hyperthyroidism
• Grave’s disease
- Thyroid receptor antibody (TSHR Ab)
• Thyroid tumor
• Toxic Multinodular Goiter

Secondary hyperthyroidism
• Pituitary gland tumor producing too much TSH (rare)

Question 16

Hyperthyroidism: Grave’s Disease?

Answer 16

• Most common cause of hyperthyroidism
• Female: Male ~10:1, 4th decade
• Opthalmopathy (Exophthalmos)
• Autoimmune disease
- Autoantibodies to TSH receptor

Diagnosis:
• TSH low
• FT4, FT3 high
• Anti -TSH receptor antibodies (anti TSHR) + ve
• ¹²³I uptake and scan

Question 17

Thyroid Cancer?

Answer 17

Is fairly common malignancy occurring in younger people, particularly women

Risk factors:
• Female sex
• Exposure to high levels of radiation
• Certain inherited genetic syndromes

Treatments:
• Surgery
• Thyroid hormone therapy: levothyroxine ( Levoxyl, Synthroid, others)

Monitor:
• Plasma thyroglobulin ( Tg ) concentrations

Question 18

Types of treatment for Thyroid Cancer?

Answer 18

Immediate treatment:
• Beta blockers (to control or to reduce a rapid
heart rate, and prevent palpitation)
• Anti thyroid medications:
- propylthiouracil (PTU)
- methimazole

Long term treatment
• Radioactive iodine ablation
• Thyroidectomy

Question 19

Laboratory Investigation: Thyroid Disorders

Question 20

Provocative Test: TRH Stimulation Test?

Answer 20

Diagnostic Value:
• This test was formerly mainly used in the assessment of patients in whom other tests of thyroid function gave equivocal results.

Procedure:
• Draw baseline TSH
• Inject 200 500 ug synthetic TRH
• Draw TSH at 15, 30 and 60 min post injection

Question 21

Thyroid Function Test Interpretation?

Answer 21

**Check slide 29-31/39