1. Sarah Chaudhry and Eugenia Gisin
Thyroid disorders
Sarah Chaudhry and Eugenia Gisin
10/21/13

2. Lecture Overview Review of normal thyroid function Thyroid disorders
Hyperthyroidism
Causes, effects, treatment
Graves’ Disease
Hypothyroidism
Hashimoto’s Disease

3. Anatomy
Gland is located below larynx, and consists of two lobes – one on each side of trachea
Lobes connected by isthmus
Two types of cells:
Follicular cells
Majority
Secrete iodine-containing hormones: triiodothyronine (T3) and tetraiodothyronine or thyroxine (T4)
Parafollicular cells
Secrete calcitonin

4. Production of t4 and t3 Thyroglobulin is made/secreted
Iodination occurs on tyrosine residue of thyroglobulin
Proteolysis occurs resulting in T4 and T3 being cleaved off of thyroglobulin

5. Functions Calcitonin: calcium regulation
T3 and T4: increase the basal metabolic rate
↑ body temperature
↑ pulse
↑ attention and reflexes
In children:
Promotion of brain maturation
Promotion of growth
Cells are working harder = need more energy!
Food is utilized more quickly
↑ breakdown of energy resources

6. Regulation Hypothalamus releases thyroid releasing hormone (TRH) ↓
Pituitary gland releases thyroid stimulating hormone (TSH)
Thyroid gland releases T4/T3
Target tissues
Negative feedback to hypothalamus and pituitary
TSH = thyrotropin

7. Disorders: hyperthyroidism
Abnormal increase in thyroid hormone production
Speeds up metabolism and can cause:
Hot flushes, sweating
Trembling
Racing heart
Weight loss
Nervousness, hyperactivity
Irritableness
Insomnia and restlessness

8. Graves’ disease
Autoimmune disease that causes thyroid to swell and become overactive
Leading cause of hyperthyroidism
More common in women
Named after Sir Robert Graves who characterized it in the 19th century
Highly manageable

9. Autoimmune disorders Normal immune response
Antigens: foreign substances that stimulate an immune response
Response = production of antibodies that recognize and bind to that antigen
Autoimmune disorder
Immune system mistakes healthy tissue for being harmful
Illicits an immune response (antibodies) in response to normal tissue

10. Graves’ disease: cause
Immune system releases abnormal antibodies that mimic TSH (a.k.a. thyrotropin) and bind to its receptors
Antibodies: thyrotropin receptor antibodies – TRAb
“Antigen”: thyrotropin receptor
Unsure about why these antibodies are produced
Genetics?
Environmental?
Likely both
Normal
Graves’ Disease

11. Graves’ disease: Effect
Normal
Graves’ Disease
TRAb
HYPERTHYROIDISM!

12. Graves’ disease: effect
Generalized symptoms resulting from hyperthyroidism
Increased basal metabolic rate
Increased body temperature
Increased heart rate
Tremors, restlessness, irritability, insomnia
Graves’ ophthalmopathy
Thought to be caused by TRAb causing inflammation in retro-occipital tissue
Goiter
Can be caused by lack of iodine
Hyperthyroidism
Hypothyroidism

14. Graves’ disease: treatment
Treatment with radioactive iodine
Most common treatment in United States
Capsule/liquid
Destroys cells in thyroid gland and halts excess hormone production
Periodic check-ups to monitor hormone levels
Second dose can be given after three months if necessary
Many people become develop hypothyroidism as a result

15. Graves disease: Treatment
Antithyroid drugs: thioamides
Interferes with T3/T4 production
Blocks enzyme (thyroperoxidase) that adds iodine to thyroglobulin
May take several months to be effective
Relapse is common
Ex: methimazole
Surgery: thyroidectomy
For young or pregnant patients
Are usually prescribed meds to prevent hypothyroidism
Ex: levothyroxine
 (thyroperoxidase)

16. Disorders: hypothyroidism
Under production of T3 and T4
What Can Cause It?
Congenital thyroid abnormalities (ex. Thyroid Deficiency at birth)
Autoimmune disorders (ex. Hashimoto’s)
Iodine deficiency
Thyroid removal (ex. Cancer or excessive hyperthyroidism)
Secondary Pituitary dysfunction
Tertiary hypothalamic dysfunction

17. Disorders: hypothyroidism
Symptoms:
Abnormal weight gain
Tiredness
Baldness
Cold Intolerance
Slow movement and speech
Constipation
Bradycardia (low heart rate)
Thyroid grows (due to increased TSH and lack of negative feedback loop)
Cognitive impairment

18. Hashimoto’s Disease: Background
First described in a pathology report by Dr. Hashimoto in 1912
Individuals had large goiters (enlarger thyroid) and their thyroid cells showed high infiltration of lymphocytes
Autoimmune disorder (1st one recognized)
Autoimmune-mediated destruction of the thyroid gland involving apoptosis of thyroid epithelial cells
Most common cause of hypothyroidism
More common in women: 5 to 1
Gradual loss of thyroid function

19. Hashimoto’s: Causes
Self-reactive CD4+ T(helper T) lymphocytes recruit B cells and CD8+ T (killer T) cells into the thyroid.
Both autoantibodies (from B cells) and thyroid-specific cytotoxic T lymphocytes (CTLs) have been proposed to be responsible for autoimmune thyrocyte depletion.
Disease progression leads to the death of thyroid cells and hypothyroidism.
Early apoptosis may cause thyroid follicular disruption and thyroid hormone release, causing transient hyperthyroidism sometimes referred to as Hashitoxicosis

20. Hashimoto’s: Causes Still very unclear!!! Genetics?
Clusters in families and higher occurrence in siblings
30 to 60% in identical twins
The thyroglobulin gene has been linked to autoimmune thyroid disease and has been suggested to code for Tg forms with different immune reactivity
Increased frequency in patients with Turner’s and Down’s syndrome
Theories: molecular mimicry and bystander activation
Molecular Mimicry: immune response to a foreign antigen that is structurally similar to an endogenous substance
Bystander activation: The arrival of a thyroid-cell virus or activated non- specific lymphocytes within the thyroid may cause the local release of cytokines, which may activate resident local thyroid-specific T cells

21. HASHIMOTO’s: Diagnosis
Some clinicians consider the presence of serum thyroid autoantibodies as sufficient evidence for Hashimoto's disease.
This logic is based upon the observation that thyroid antibodies correlate well with the presence of a lymphocytic infiltrate in the thyroid gland at autopsy examination of individuals with no history of thyroid failure
High levels of TSH (which eventually lead to goiters in some patients)
Low levels of T3 and T4
Ultrasound of thyroid
Often misdiagnosed, because the symptoms resemble many other disorders

22. Hashimoto’s: encephalopathy
Very rare condition associated with Hashimoto’s
2.1/100,000 with a male to female ratio of 1:4
Immune-mediated disorder rather than representing the direct effect of an altered thyroid state on the central nervous system
Elevated antithyroid antibodies, an essential feature of this disorder, are consistent with an active autoimmune process
Symptoms:
personality changes
aggression
delusional behavior
concentration and memory problems
coma
Disorientation
headaches
partial paralysis on the right side
psychosis

23. Hashimoto’s: Treatment
Thyroid Hormone replacement agents
Levothyroxine (synthetic T4)
Triiodothyronine (T3)
Desiccated Thyroid extract (usually from pork or beef)- ex. Armour Thyroid

24. Hypothyroidism: Other Causes
Iodine Deficiency
Most common in developing world- remote inland areas and semi-arid equatorial climates where no marine foods are eaten
Used to synthesize thyroid hormones
Leads to goiters- which are caused from low levels T3 and high levels of TSH which stimulate cell proliferation in the thyroid
Leads to cretinism- increased mental retardation

25. Hypothyroidism: Other Causes
Secondary or Tertiary hypothyroidism- related to problems with the pituitary and hypothalamus
Examples:
Sheehan’s Syndrome (postpartum hypopituitarism) – rare complication of child birth
Tumors and head injury can result in decreased TSH production

26. Anatomy
Gland is located below larynx, and consists of two lobes – one on each side of trachea
Lobes connected by isthmus
Two types of cells:
Follicular cells
Majority
Secrete iodine-containing hormones: triiodothyronine (T3) and tetraiodothyronine or thyroxine (T4)
Parafollicular cells
Secrete calcitonin

27. Summary! T3 and T4: increase the basal metabolic rate
↑ body temperature
↑ pulse
↑ attention and reflexes

28. Thyroid Disorder summary

29. Questions?????

30. Thank You!