THYROID DISORDERS Sarah Chaudhry and Eugenia Gisin 10/21/13.

THYROID DISORDERS

Sarah Chaudhry and Eugenia Gisin

10/21/13

LECTURE OVERVIEW

Review of normal thyroid function

Thyroid disorders Hyperthyroidism

Causes, effects, treatmentGraves’ Disease

HypothyroidismCauses, effects, treatmentHashimoto’s Disease

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

Thyroglobulin is

made/secreted

Iodination occurs on tyrosine residue

of thyroglobulin

Proteolysis occurs resulting

in T4 and T3 being cleaved

off of thyroglobulin

PRODUCTION OF T4 AND T3

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

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

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

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

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

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

GRAVES’ DISEASE: EFFECT

HYPERTHYROIDISM!

TRAb

Normal Graves’ Disease

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

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

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)

DISORDERS: HYPOTHYROIDISM

Under production of T3 and T4What 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

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

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

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

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

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

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

HASHIMOTO’S: TREATMENT

Thyroid Hormone replacement agents Levothyroxine (synthetic T4) Triiodothyronine (T3) Desiccated Thyroid extract

(usually from pork or beef)- ex. Armour Thyroid

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

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

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

SUMMARY!

T3 and T4: increase the basal metabolic rate

↑ body temperature↑ pulse↑ attention and reflexes

THYROID DISORDER SUMMARY

Questions?????

Thank You!