Physiology PA2 Thyroid and Parathyroid Function PDF

Physiology PA 2 Thyroid and parathyroid function assessment: laboratory tests, external radionuclide scan, ultrasonography Thyroid gland is located in anterior neck, lying like a small bow tie across the front of the trachea. Adult thyroid weight = 20g It is composed of...

Physiology PA 2 Thyroid and parathyroid function assessment: laboratory tests, external radionuclide scan, ultrasonography Thyroid gland is located in anterior neck, lying like a small bow tie across the front of the trachea. Adult thyroid weight = 20g It is composed of left and right lobes and a small connecting branch or isthmus Thyroid glands produce 2 types of hormones: Thyroid hormones (T4,T3) Calcitonin The thyroid hormones are the only ones that require an essential trace element, iodine, for the production of active hormone The hormone is stored in an extracellular site within a highly proteinaceous material called thyroid colloid Major protein: Thyroglobulin which contains thyroid hormones: Tetraiodothyronine (T4 or thyroxine) Triiodothyronine (T3) Thyroglobulin is surrounded by thyroid follicular cells, which are responsible for the synthesis of thyroid hormones The C cells (parafollicular cells) of the thyroid, which are not part of the follicular unit synthesize Calcitonin Calcitonin play a role in Ca2+ and phosphate The thyroid hormons production Thyroid-stimulating hormone (TSH) It binds to specific receptors and signals the follicular cell to ingest a microscopic droplet of colloid by endocytosis. Inside the follicular cell, these droplets are digested by intracellular lysosomes into T4 , T3 , and other products. T4 and T3 are then secreted by the thyroid cell into the circulation. and signals the follicular cell to ingest a microscopic droplet of colloid by endocytosis. Inside the follicular cell, these droplets are digested by intracellular lysosomes into T4 , T3 , and other products. T4 and T3 are then secreted by the thyroid cell into the circulation. Free T4 and T3 diffuse into target cells, and within the cells the T4 (80%) is converted to T3 (35%) by 5′-deiodinase T3 is three to eight times more active than T4, considered to be the active form of thyroid hormone, with T4 considered the “pre”-hormone Four steps are involved in the synthesis of these hormones: Inorganic iodile from the circulating blood is trapped Iodile is oxidized to iodine Iodine is added to tyrosine to produce monoiodotyrosine and diiodotyrosine (organification) One monoiodotyrosine is coupled with one diiodotyrosine to yield T3 and two diiodotyrosines are coupled to yield T4 (coupling). Thyroid hormones T4,T3 Secreted T4 and T3 circulate in the bloodstream almost entirely bound to proteins Free T3 is biologically active and mediates the effects of thyroid hormone on peripheral tissues The major binding protein is thyroxine-binding globulin (TBG). TBG is synthesized in the liver and binds one molecule of T4 or T3. The regulation of T3 and T4 occurs in: 1) Thyroid-releasing hormone (TRH) is released by the brain and stimulates the release of TSH (thyrotropin) from the pituitary gland. 2) TSH stimulates iodine uptake by the thyroid gland and also causes the release of T3 and T4 from the thyroid gland. 3) High serum levels of free T3 and T4 “shut off” the release of TSH from the pituitary gland, whereas decreased levels induce TSH release. Screening High-risk persons that should be screened are: neonates pregnant and postpartum females elderly family history of autoimmune disease or thyroid disease Diagnosis of hyperthyroidism and hypothyroidism should include TSH and free thyroxine (fT4). FT4 is the most reliable indicator of thyroid status in sick individuals Disorders characterized depending on the site of the defect: Primary: Disease originates in the thyroid gland Secondary: Disease originates in the pituitary gland Tertiary: Disease originates in the hypothalamus Laboratory tests for thyroid function Sample Collection and Handling Serum or plasma Preferable free from hemolysis and lipemia Newborn screening is whole blood collected by heel puncture within 48 to 72 hours after birth Sample should be stored at 2 to 8 C if not analyzed within 24 hours Tests is available to assess thyroid function: TSH free thyroxine (fT4) total thyroxine (TT4) free triiodothyronine (fT3) total triiodothyronine (TT3) thyroglobulin thyroid antibodies thyroxine binding globulin (TBG) Immunoassays are used for determination of hormone levels The plasma concentrations of most hormones are extremely low RIA (radioimmunoassay) Top: After a specific antibody (Y) is mixed with the labeled hormone (H*), a radioactive antigen-antibody complex is formed. Middle: The patient’s serum is added. The unlabeled hormone in the patient’s serum (H) competes with the labeled hormone for binding to the antibody: Antibody · H* + H ⇌ Antibody · H + H*. Bottom: Free hormone and antibody-hormone complex are separated from each other. The radioactivity of the free, unbound hormone is measured. A large amount of hormone in the patient’s serum leads to a high specific radioactivity of the free hormone.  1. TSH TSH is used as a screening test for thyroid status: Hypersecretion increased TSH joined by increased fT4 - secondary (pituitary) causes of thyrotoxicosis and result in hyperactivity of the thyroid. Hypersecretion increased TSH joined by low fT4 – primary hypothyroidism. Hyposecretion low TSH and low fT4 is secondary hypothyroidism. Hyposecretion low TSH and high fT4 is primary hyperthyroidism. 2. Serum total T4 and T3 levels Serum total T4 and T3 levels are usually measured by radioimmunoassay (RIA), chemiluminometric assay, or similar immunometric technique. Serum total T4 and T3 levels are usually measured by radioimmunoassay (RIA), chemiluminometric assay, or similar immunometric technique. Because more than 99.9% of thyroid hormone is protein bound, alteration in thyroid hormone–binding proteins frequently leads to total T4 and T3 levels outside of the normal range without representing true clinical thyroid dysfunction. Because of this, assays to measure free T4 and T3 , the biologically active hormone forms, were developed. Current method includes measurement of fT4 using immunometric assays. In the laboratory evaluation of: hypothyroidism, the earliest abnormality is increased TSH, followed by decreased serum levels of T4 and T3. hyperthyroidism in the initial evaluation reveals elevated thyroid hormone serum levels and decreased serum TSH. 4. Thyroglobulin Thyroglobulin is a protein synthesized and secreted exclusively by thyroid follicular cells. Thyroglobulin is a protein made only by thyroid cells. If it’s found in the blood, it means thyroid tissue is present. This makes it a useful marker for monitoring thyroid cancer after treatment. In patients successfully treated with surgery and radioactive iodine, thyroglobulin levels should be undetectable, if not, it may indicate remaining or returning cancer. It is measured using different lab techniques like RIA, ELISA, IRMA, and ICMA to ensure accurate detection. 5. Thyroid antibodies Many diseases of the thyroid gland are related to autoimmune processes In autoimmune thyroid disease, antibodies are directed at thyroid tissue with variable responses A. TRAb (TSH receptor antibodies) Cause of hyperthroidism = autoimmune disorder called Graves disease The AB are directed at TSH receptor, stimulating the receptor and leading to growth of the thyroid gland and production of excessive amounts of thyroid hormone. This condition can be diagnosed with tests that detect TSHR stimulating antibodies. B. TPO Antibodies TPO (thyroid peroxidase) is an enzyme that helps make thyroid hormones. It adds iodine to a protein (thyroglobulin) and links the pieces together to form T3 and T4. Autoantibodies directed against thyroid peroxidase (TPO) in thyroid microsomes are the most important autoantibodies detected in the serum of patients with autoimmune thyroiditis. The immune system can mistakenly attack TPO by producing autoantibodies. These antibodies can block TPO’s function, damage thyroid cells, and lead to thyroid disorders like Hashimoto’s thyroiditis or hypothyroidism. Range: >100 IU/ml = Positive 60-100 IU/ml = Equivocal 60IU/ml = Negative High thyroid antibodies = hypothyroidism C. Antithyroglobuline antibody Antithyroglobulin (TgAb) was the first antibody discovered against a thyroid protein, thyroglobulin. The frequency of positive titers gradually increases in the female population with aging. Normal value ranges may vary among different laboratories. 6. Thyroxine binding globulin (TBG) In the blood, most of the T3 and T4 is bound to proteins including albumin and thyroxine-binding globulin (TBG). Acts as a plasma reservoir for T4, because T4 will only be active when it is released from the plasma proteins and enters the target cells. Thyroid hormones travel in the blood mostly bound to proteins. If these binding proteins increase or decrease, total T3 and T4 levels can change, but free T3, T4, and TSH stay normal, meaning thyroid function remains unchanged. Pregnancy and oral contraceptive pills raise concentrations of thyroid-binding proteins Cirrhosis, nephrotic s. cause lower concentrations of thyroid-binding proteins Parathyroid glands Has 3 effects on kidney: Increase the reabsorption of renal tubular calcium Increase phosphate excretion Enhance 1α-hydroxylation of 25-hydroxy vitamin D PTH, vitamin D and calcitonin, brings about: the mobilization of calcium and phosphate from the skeletal system increases the uptake of calcium in the intestine the excretion of phosphate via the kidneys. Secretion of PTH is inhibited by: High calcium concentrations and is promoted by low calcium concentrations. Immunoassay methods are used for in vitro quantitative determination of intact parathyroid hormone in human serum and plasma. The ratios of intact hormone to peptide fragments may vary from individual to individual as well as between patients with hyperparathyroidism or chronic renal failure The concentration of metabolically inactive PTH fragments increases in renal failure Imagistic investigations Thyroid ultrasound Advantages High-resolution ultrasonography (US) is the most sensitive imaging modality for examination of the thyroid gland and associated abnormalities. Ultrasound scanning is non-invasive, widely available, less expensive, and does not use any ionizing radiation. real time ultrasound imaging helps to guide diagnostic and therapeutic interventional procedures in cases of thyroid disease. Limits Ultrasound is useful for examining the structure of the thyroid but cannot assess its function (whether it’s overactive, underactive, or normal). To check function, blood tests or a radioactive uptake test are needed. While ultrasound can help evaluate thyroid nodules by looking at features like size, shape, blood flow, and calcifications, it cannot confirm or rule out cancer with certainty. A biopsy may be needed for a definite diagnosis. Indications To Confirm presence of thyroid nodule when physical exam is equivocal To Characterize a thyroid nodule To Identify suspect malignant thyroid masses To differentiate between thyroid nodules and other cervical masses like lymphadenopathy, thyroglossal cyst To evaluate diffuse changes in thyroid parenchyma To Detect post-operative residual or recurrent tumor To screen high risk patients for thyroid malignancy. To guide diagnostic FNA cytology/biopsy and therapeutic interventional procedures Normal thyroid glands = 2 lobes & bridging isthmus Thyroid size shape volume varies in = Age & Sex Volume Female= 10-15 ml Volume Male= 12-18 ml Elastography For virtual palpation of the thyroid nodule Gives information on tissue stiffness noninvasively Most malignant tumors are characterized by the presence of abnormally firm stroma due to the presence of collagen and myofibroblasts, which is the desmoplastic transformation. To differentiate benign from malignant thyroid nodules. By elastography elasticity assessments can be obtained. Visual scoring of colors within and around the nodules can be assessed, using 4-5- scale scoring systems. The likelihood of malignancy increases with an increase in the strain ratio, where 1 is the most elastic, and 5 the firmest. Thyroid scan and uptake – Nuclear medicine investigation Non invasive Painless IV These tests use radioactive materials called radiopharmaceuticals or radiotracers, molecules linked to, or "labeled" with, a small amount of radioactive material that can be detected on the PET scan A special camera and a computer provides information about thyroid's size, shape, position and function Imagistic investigations – thyroid radionuclide scan Thyroid Scan and Uptake Procedure Thyroid hormone supplements, Iodine-containing solutions, vitamins, and medications should not be taken 1–2 weeks before the study. Patients should not have radiological studies involving iodine contrast in the last 4–8 weeks. Thyroid scintigraphy is commonly performed with Tc-99m pertechnetate, thyroid scintigraphy, Iodine-131, thyroid uptake or Iodine 123 uptake Indications Used for localization of parathyroid adenoma or hyperplasia in patients with biochemically proven hyperparathyroidism Procedure Tc-99m sestamibi is currently the preferred radiotracer for parathyroid imaging. Parathyroide radionuclide scan Combined Thyroid and Parathyroid Imaging Radiopharmaceuticals: I—Technetium-99m pertechnetate or I-123 for thyroid phase II—Technetium-99m MIBI or Tc-99m tetrofosmin or thallium-201 chloride Principles: The examination is based on the differential washout of Tc-99m MIBI from the thyroid tissue compared with abnormal parathyroid tissue. The rate of washout from the abnormal parathyroid tissue, such as parathyroid adenoma, is much slower than that of the normal thyroid tissue. The distributions of the two tracers can be visually compared Brown tumor Black arrows in the midshaft of tibia Also called osteoclastomas are benign lesions that represent the osteoclastic resorption