Endocrine System: Thyroid gland

Where is the thyroid gland located?

below the Adam's apple

What is the structure of the thyroid gland?

left and right lobe

-lobes are are divided into lobules

What are the thyroid lobules composed of?

-thyroid follicles

-parafolicular cells

What are thyroid follicles made of?

-outer layer of cuboidal cels

-inner colloid

What connects the lobes of the thyroid?

isthmus

What is the site of thyroid hormone synthesis?

thyroid follicles

Where are the receptors for thyroid stimulating hormone located?

follicular cells

What type of hormone is thyroid hormone?

amine

What is the precursor to thyroid hormone?

tyrosine

What are the types of thyroid hormone? What differentiates them?

T3, rT3, and T4

-the number of iodine atoms

-rT3 is negligable because it is biologically inactive and there is only a small amount

What is the most biologically active form of thyroid hormone?

T3

What form of thyroid hormone is secreted most?

T4

What is the mechanism of action for thyroid hormone?

-hydrophobic molecule that penetrates membrane to access receptors

-binds to nuclear receptors

(simillar mechanism of action to steroid hormones)

What is thyroglobulin?

a glycoprotein located within the colloid on which thyroid hormones are synthesized and stored

How is iodide transported into follicular cells?

pump on surface of follicular cuboidal cells actively transport iodide from blood stream into the cell

-iodide comes from the diet because we can not synthesize it

What inhibits iodide pump activity?

-perchlorate

-thiocyanate

What is the role of thyroid peroxidase?

-oxidize iodide to iodine

-iodinate tyrosine to form MIT and DIT

-coupling reactions between MIT and DIT to form thyroid hormone

What is organification of thyroglobulin?

1. Binding to Iodine to Thyroglobulin.

2. Tyrosine is iodized to monoiodotyrosine (MIT) then to diiodotyrosine(DIT).

3. 2 DIT couple to form thyroxine (T4) or one MIT and 2 DIT form triiodthyronine (T3) and a small amount is Reverse T3 (RT3) with no function in humans.

What happens when follicular cells are stimulated by thyroid stimulating hormone?

1) thyroglobulin complex is endocytosed

2) T3, T4, MIT, and DIT are cleaved off by proteolytic mechanism

3) T3 and T4 are secreted into the blood

4) MIT and DIT are deiodinated and iodide is recycled

What is the target of drugs used to block thyroid hormone secretion? WHich is most effective?

-block iodide transfer into thyroid follicles

-block thyroid peroxidase receptors (most effective because of its multiple functions)

What is used to block the activity of thyroid peroxidase?

propylthiouracil

How is thyroid hormone transported in the blood? In what form is it active?

-bound to plasma proteins

-free state (active state)

What proteins does thyroid hormone bind to?

-thyroxine binding globulin (majority is bound to this)

-albumin

What is the purpose of thyroid hormone binding to circulating hormones?

serves as reservoir for thyroid hormone

How does changing levels of thyroxine binding globulin (TBG) affect free thyroid hormone levels?

-if TBG is high then total thyroid hormone levels will increase to increase free thyroid hormone

-if TBG is low then total thyroid hormone levels will decrease to decrease free thyroid hormone

What determines the activity of thyroid hormone secretion?

level of free hormone (not bound to protein)

What is the active form of thyroid hormone?

T3

How is T4 transformed into active thyroid hormone?

5'- iodinase in target tissue

How is the secretion of thyroid hormone regulated?

hypothalamic-pituitary axis

1) hypothalamus releases thyrotopin releasing hormone

2) stimulates tyrotropes in anterior pituitary to secrete thyroid stimulating hormone (TSH)

3) TSH stimulates follicular cells to secrete T3 and T4

What does the negative feedback loops for thyroid hormone target?

based on levels of free T3

-hypothalamus

-pituitary gland

What is thyroid stimulating immunoglobulin?

-mimic TSH to activate TSH receptors in thyroid

-levels of this will not be affected by negative feedback

Why is thyroid stimulating immunoglobulin potentially bad?

levels of this will not be affected by negative feedback

-this can lead to hyperthyroidism

What is Grave's disease?

hyperthyroidism caused by increased thyroid stimulating immunoglobulins

-TSH levels will be low in this disease

What are stimulating factors for thyroid hormone?

-TSH

-thyroid stimulating immuoglobulins

-increasd thyriod binding globulin (TBG) levels

What are inhibitory factors for thyriod hormone?

-iodide deficiency

-deiodinase deficiency

-excessive iodide intake

-perchlorate and thiocyanate

-propylthiouricil

-decreased TBG

What are the functions of thyroid hormone?

multiple effects on growth and metabolism

-increase expression of Na/K ATPase

-increased utilization of substrates for energy

What is the effect of increased Na/K ATPase by thyroid hormone?

-increase energy demand

-increase basal metabolic rate

--increase thermogenesis, sweating, and blood flow

--increase respiration

--increase cardiac output

What is another name for hyperthyroidism?

thyrotoxicosis

What is hyperthyroidism?

hypermetabolic state caused by elevated levels of T4 and T3

What are causes of hyperthyroidism?

-pituitary ademomas

-thyroid adenomas (rare)

-graves disease

-neonatal thyrotoxicosis

-excesive thyroid hormone therapy to treat hypothyroidism

-thyroid carcinomas (rare)

What is neonatal thyrotoxicosis?

mother has grave's disease and that exposes the baby to excess thyroid hormone

What are symptoms of hyperthyroidism?

-increased BMR

-weight loss

-negative nitorgen balance from protein breakdown

--thermogenesis and sweating

-increased cardiac output

-myxedema

-hyperrelexia

What are ocular manifestations of Grave's disease?

-axial proctosis

-dalrymple sign (lid retraction)

-lagophtalmos

-EOM restriction

-corneal dryness

What are treatments for Graves disease?

-restoration of euthyroid status (normal thyroid)

-sodium and water restriction

-systemic steroids

-orbital decompression

-eye lubricant and lid taping

-surgical repairs

What are treatments for hyperthyroidism?

-propythiouracyl

-thryoidectomy

-radiolabeled iodine

-beta adernergic blockers

What is hypothyroidism?

reduced action of thyroid hormne

What causes hypothyroidism?

-genetic defect

-thyroud stimulating hormone resistance

-post-ablative (after surgury)

-autoimmune

-iodide deficiency

-drug induced

-pituitary failure

-hypothalamic failure

What is Hashimoto's thyroiditis?

Autoimmune destruction of the thyroid gland leading to hypothyroidism

What are symptoms of hypothyroidism?

-decreased BMR

-weight gain

-positive nitrogen balance

-growth retardation if postnatal

-mental retardation if prenatal

-lethargy

-myxedema

-exophthalmos

What is treatment for hypothyroidism?

hormone replacement therapy

What is myxedema?

mucoploysaccharide deposits in lower limbs and behind the eyes seen in both hyper and hypothyroidism

Is a goiter associated with hyper or hypothyroidism?

both