Thyroid hormones 2.

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Presentation transcript:

Thyroid hormones 2

Remember! TSH glycoproteins consisting of alpha and beta subunits, the alpha subunit is similar to that found in three glycoproteins hormones LH, FSH, HCG is in turn regulated by thyrotropin releasing hormone TRH from hypothalamus. TRH is a tripeptide which has been synthesized and is available for exogenous administration.

Thyroid hormones Hormones (T4, T3, and RT3), once released into the bloodstream, exist either as protein bound or in a free form. The T3 and T4 hormones help regulate the body's metabolic rate. An excess of T3 and T4 will make you feel overactive and you may lose weight. If you don't have enough of these hormones, you'll feel sluggish and you may gain weight. T4 is produced entirely by the thyroid, T3 is also produced by peripheral conversion from T4 in cells of the kidney, liver, heart, anterior pituitary and other tissue. T4 is deiodinated to the active metabolite T3 or an inactive metabolite reverse T3(rT3). The mechanism controlling these conversions is poorly understood

Measurement of total thyroid hormones includes protein-bound and free fractions. Alterations in the concentration of serum proteins (high levels of estrogens “birth control pills, non-bio-identical hormone replacement, or pregnancy”) will affect total T4 and total T3 levels. Such changes in proteins may result in misleading elevation or reduction of total thyroxine and tri-iodothyronine. Because over 99% of released thyroid hormone is attached to proteins in the blood, it is believed that measuring the amount not attached to proteins (i.e., free thyroid hormone) is a more accurate measurement of thyroid hormone levels. Measuring the total hormone level is generally less reliable. Techniques which measure free fractions of T4 or T3 are not usually influenced by the amount of TBG present.

Triiodothyronine (T3) T3 is typically measured in cases of hyperthyroidism where the T4 levels are normal. In healthy individuals, T4 is largely converted to T3 but in severely ill people suffering from a variety of acute or chronic illnesses, less T3 and more reverse T3 is produced.

RT3 Reverse triiodothyronine (rT3) differs from triiodothyronine (T3) in the positions of the iodine atoms attached to the aromatic rings. The majority of rT3 found in the circulation is formed by peripheral deiodination (removal of an iodine atom) of T4 (thyroxine). rT3 is believed to be metabolically inactive. The rT3 level tends to follow the T4 level: low in hypothyroidism and high in hyperthyroidism. Additionally, increased levels of rT3 have been observed in starvation, anorexia nervosa, severe trauma and hemorrhagic shock, hepatic dysfunction, postoperative states, severe infection, and in burn patients (ie, "sick euthyroid" syndrome). This appears to be the result of a switchover in deiodination functions with the conversion of T4 to rT3 being favored over the production of T3.

The approximate value can be estimated from knowing T4 and T3 values since we know that T4 will become either T3 or RT3. For example, if the T4 is elevated and the T3 is low, we know that RT3 (what the rest of the T4 becomes) will be relatively elevated. Cortisol decreases TSH, lowering thyroid hormone production. Cortisol inhibits the conversion of T4 to active T3, and increases the conversion of T4 to reverse T3.

Hypothyroidism In primary hypothyroidism, serum total T4 is low and serum TSH raised. Serum T3 levels are of no diagnostic value as they are frequently in the normal range even when T4 is low. In primary hypothyroidism the ECG may reveal bradycardia. In hypothyroidism secondary to pituitary disease, T4 values and FTI are low and there is no TSH response to TRH, but with lesser degrees of pituitary impairment the pattern of the TSH response to TRH is variable. In hypothalamic disease, TSH response to TRH is typically delayed.

Hyperthyroidism The clinical diagnosis of hyperthyroidism is confirmed by finding an elevated serum T3. If T4 is normal but thyrotoxicosis is still suspected, then T3 should be measured. T3 is often elevated before T4 in hyperthyroidism (T3 toxicosis).

Note: In states of thyroid hormone resistance, the concentrations of the thyroid hormones and thyroid-stimulating hormone TSH are typically elevated, but the affected patients are usually euthyroid or even possibly hypothyroid.

Antithyroid antibodies Antithyroid antibodies are created when the body's immune system attacks parts of the thyroid with antibodies. There are several different types of antithyroid antibodies: TSH-R Ab is a TSH receptor antibody, and is present in most of patients who have Graves' disease. The antibodies stimulate the TSH-receptor which causes the thyroid to make more thyroid hormone (T4 and T3). Antithyroglobulin antibodies (Anti-TG Ab) are present in patients with Hashimoto's thyroiditis. Antibodies against the protein thyroglobulin can result in destruction of thyroid cells. This destruction can lead to hypothyroidism. Antithyroid peroxidase antibodies (Anti-TPO Ab) are similar to antithyroglobulin antibodies. They are found in high levels in patients with Hashimoto's thyroiditis, and can lead to destruction of thyroid cells.

Autoimmune thyroid disease Autoimmune thyroid disease falls into two main categories: Hashimoto’s Thyroiditis: Hashimoto’s Thyroiditis is typically identified by checking antibodies that attack the thyroid tissue. Grave’s Disease: Is typically diagnosed using Thyroid-Stimulating Immunoglobulin (TSI), Long Acting Thyroid Stimulator (LATS) and TSH-Binding Inhibiting Immunoglobulin (TBII). These are different names for the same test.

Hashimoto’s patient Hashimoto’s patient who is taking replacement hormones but still suffers from hypothyroid symptoms – often in spite of repeated changes in the dose and type of medication. In these patients, inflammation is depressing thyroid receptor site sensitivity and producing hypothyroid symptoms, even though lab markers like TSH, T4 and T3 may be normal.

Confounding factor When exogenous T4 is ingested, the T4 (or free T4) measurements can become discordant from the TSH measurements. For example, suppose a patient has primary hypothyroidism with a low FT4 level and an elevated TSH level. With oral administration of thyroxine, the FT4 can return to the reference interval far more quickly than can the TSH, which may not return to the reference interval for several weeks

Tumor in thyroid gland The important points to remember are that cancers arising in thyroid nodules generally do not cause symptoms, thyroid tests are typically normal even when cancer is present, and the best way to find a thyroid nodule is to make sure your doctor checks your neck! Acromegaly a rare condition where the body produces too much growth hormone can be considered as risk factor for thyroid cancer. The primary therapy for all forms of thyroid cancer is surgery. After surgery, patients need to be on thyroid hormone for the rest of their life. If your doctor recommends radioactive iodine therapy, your TSH will need to be elevated prior to the treatment.

Thyroid cancer that spreads (metastasizes) to distant locations in the body occurs rarely but can be a serious problem. Surgery and radioactive iodine remain the best way to treat such cancers as long as these treatments continue to work. However, for more advanced cancers, or when radioactive iodine therapy is no longer effective, other means of treatment are needed. All patients who have undergone thyroidectomy require thyroid hormone replacement with levothyroxine once the thyroid is removed. The dose of levothyroxine prescribed by your doctor, determined by the extent of your thyroid cancer.

Thyroglobulin Thyroglobulin is a protein produced by thyroid tissue . Thyroglobulin Levels are increased in all types of thyrotoxicosis, except thyrotoxicosis factitia. The thyroid gland is the only organ which makes Tg. Therefore, Tg is a good test to tell if there are thyroid cells in the body. Once the whole thyroid is taken out, the thyroglobulin level should go down to close to zero. Thyroglobulin is used as a tumor marker (i.e. test to see how much cancer is in the body) for thyroid cancer. If thyroglobulin levels go up after removing the whole thyroid, there is concern that the cancer may have come back (i.e. recurred) or spread (i.e. metastasized). caused by self-administration of thyroid hormone.

Detectable thyroglobulin levels may require additional tests and possible further treatment with radioactive iodine and surgery. In addition to routine blood tests, your doctor may want to periodically repeat a whole-body iodine scan to determine if any thyroid cells remain. Whole body scanning is also done after your TSH level is raised, either by stopping your thyroid hormone or by administering Thyrogen® injections. Increasingly, these scans are only done for high risk patients and have been largely replaced by routine neck ultrasound and thyroglobulin measurements that have a higher diagnostic sensitivity especially when done together.

Calcitionin Calcitonin is produced by the parafollicular, or C cells in the thyroid gland. It helps in control of blood calcium levels. Calcium is a mineral that performs a number of important functions, such as building strong bones. Calcitonin isn't essential for maintaining good health because your body also has other ways of controlling calcium. This test is used as a tumor marker for a rare type of thyroid cancer known as medullary thyroid cancer.

Appropriate use of thyroid tests comment Test use Most sensitive test for primary hypothyroidism and hyperthyroidism Excellent test serum TSH Screening High in primary and low in secondary hypothyroidism decreased Elevated in Hashimoto thyroiditis Serum TSH FT4 Anti-thyroglobulin and anti-thyroperoxidase antibodies For hypothyroidism Suppressed except in TSH-secreting pituitary tumor or pituitary hyperplasia(rare) Elevated Increase uptake; diffuse versus (hot) foci on scan Elevated in Graves disease Ususally (65%) positive in Graves disease T3 or FT3 I123 uptake and scan TSH-R-Ab (stim) For hyperthyroidism

Best diagnostic method for thyroid cancer. Useful in assessing the risk of malignancy(multinodular goiter or pure cysts are less likey to be malignant). Useful to mointor nodules and patients after thyroid surgery for carcinoma Fine-needle aspiration biopsy I123 uptake and scan 99mTC scan ultrasonography For thyroid nodules

QUIZ THYROID part 1 & 2 الثلاثاء 11/4/2017 الساعة 11:00

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