THYROID ENDOCRINOLOGY Anatomy of the Thyroid gland -centered around the trachea, bilobular butterfly shape and each

lobe is connected by isthmus -composed of two types of cells : FOLLICULAR CELLS and PARAFOLLICULAR CELLS -Follicular cells are arranged in spheres called FOLLICLES. Each sphere consists of single layer of epithelial cells that a more narrow apical end facing the interior of the follicle and broader end -Follicular cells produce thyroglobulin and is stored in the center portion of the follicle called colloid. Physiologic Effect of Thyroid Hormones: -increase in metabolic processes and energy expenditures (increased heart rate, increased gastric mobility, growth and maturation) Synthesis of thyroid hormones: 1. Trapping of iodide from the diet into the follicular cells(active transport) 2. Iodide is oxidized and is attached to the tyrosine residues of the thyroglobulin upon the action of peroxidase 3. Monoiodotyrosine (MIT) and Diiodotyrosine (DIT) are formed. 4. MIT and DIT are enzymatically coupled to form T3 and T4 5. Newly formed thyroid hormones are attached into the thyroglobulin and are stored Release and Transport 1. 2. 3. 4. Stored T3 and T4 diffuse back into the follicular cells. T3 and T4 are released from the thyroglobulin by the enzyme protease The hormones are released in the circulation. T3 and T4 binds to transport proteins TBG, TBPA and albumin

Note: over 99% percent of hormones are bound to proteins, leaving only a minute amount of free hormones.

Thyroid Stimulating Hormones

-Blood levels of TSH are significantly elevated in primary hypothyroidism and T4 and T3 levels are low. If the TSH remains to be low in the presence of decreased thyroid function, a pituitary malfunction is usually suspected. This condition is known as secondary hypothyroidism.

Thyroxine (T4)
-elevated in cases of overt hyperthyroidism and decreased in overt hypothyroidism -the difficulty in using T4 to assess thyroid function is that approximately 99.97% is bound to transport proteins -Total T4 = T4 bound to proteins plus the free, metabolically active T4 -Total T4 is reflective of the TBG levels in the blood. -Free T4 accounts for 0.02% of the total T4 in the blood. It is the free T4 that can enter the cells and undergo conversion to the metabolically potent T3.

Triidothyronine (T3)
-useful in diagnosing mild hyperthyroidism because T3 rises earlier and more markedly than T4 in all cases of hyperthyroidism -Total T3 and FT3 are compared to assess problems with TBG levels

Reverse T3- metabolically inactive form of T3 and is present in serum almost entirely as a result of the generation from T4 in peripheral tissues. Removal of the iodide from an inner phenyl ring of thyroxine produces rT3, whereas the removal of an outer iodide produces the active T3. Estimation of Free Thyroid Hormones Thyroid Hormone-Binding Ratio- formerly known as T3 uptake test

T3 uptake test Serum is incubated with 125Iodine-labelled T3. Binder is added to the sample to remove unbound T3. The binder is then separated from the sample and the amount of label in the binder is determined. Results are expressed as a percentage of the total label originally added. If result is high, it indicates ________________________ If result is low, it indicates _________________________

Thyroid Autoimmunity
Autoantibody Antithyroglobulin Thyroid peroxidase (formerly antimicrosomal) Anti-TSH receptor or Thyroid Stimulating Immunoglobulins (TSHIg) Graves disease 12-30% 45-80% 70-100% Hashimotos thyroiditis 35-60% 80-99% 6-60%

Clinical Applications Hyperthyroidism

-Subclinical Hyperthyroidism typically shows a normal level of thyroid hormone and a low TSH -Overt hyperthyroidism- associated with increased elevated T3 and T4 accompanied by low TSH -Thyrotoxicosis the term used to describe the condition that occurs when excessive amount of thyroid hormones in circulation affect the tissue, elevated T3 -Graves Disease- hyperthryroidism, goiter and exopthalmos (bulging of the eyes) -caused by presence of TSHIg produced by B cells stimulated self-reactive T cells -Toxic Nodular Goiter/Toxic Adenomas- presence of palpable thyroid nodules that has autonomous activity -Toxic Multinodular Goiters there are multiple areas within the thyroid gland that are autonomously producing thyroid hormones Symptoms include: Decreased weight, nervousness, sweating, palpitations, heat intolerance, enlarged thyroid gland How to assess hyperthyroidism? TSH -------- High --------- with High FT4 and FT3 -------- ______________________________ TSH -------- Normal ----- with Normal FT4 and FT3 ---- ______________________________ TSH -------- Low --------- with Normal T4 but High T3 -- ______________________________ TSH -------- Low --------- with Normal T4 and T3 -------- ______________________________ TSH -------- Greatly Low or Undetected ----- High T4 and positive autoantibodies: ______________________________ TSH -------- Greatly Low or Undetected ------ High T4 and negative autoantibodies: _____________________________ _____________________________ Hypothyroidism -Subclinical Hyperthyroidism typically shows a normal level of thyroid hormone and a high TSH -Overt hyperthyroidism- associated with increased low T3 and T4 accompanied by high TSH -Hashimotos thyroiditis presence of antibodies against the thyroidal peroxidase and thyroglobulin -Congenital Hypothyroidism- thyroid hypofunction due to deficiency in thyroid tissue -Iodine deficiency How to assess hypothyroidism?

TSH -------- Low --------- with Low FT4 and FT3 -------- ______________________________ TSH -------- Normal ----- with Normal FT4 and FT3 ---- ______________________________ TSH -------- High --------- with Normal T4 and T3 -------- ______________________________ TSH -------- High --------- with Low T4 and T3 -------- ______________________________ TSH -------- ____ ------- with ___ T4 and T3 --------------- Hashimotos throiditis