Hypothyroidism Year 4 Paediatrics Notes OmpathStudy

Hypothyroidism Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Munge / ENDOCRINOLOGY -- Slide 1 Thyroid Disease Dr Rose Munge Slide 2 The main function of the thyroid gland is to synthesize T4 and T3.\nThe only known physiologic role of iodine is in the synthesis of these hormones.\nThe daily recommended dietary allowance of iodine is 110-130 μg for infants, 90-120 μg for children, and 150 μg for adolescents and adults. Thyroid tissue has an avidity for iodide and is able to trap, transport, and concentrate it in the follicular lumen for synthesis of thyroid hormone.\nEntry of iodide from the circulation into the thyroid follicular cell is carried out by the sodium–iodide symporter (NIS).\nIodide diffuses across the cell to the apical membrane where it is transported into the colloid via pendrin. Slide 3 To form thyroid hormone inorganic iodide must be organified onto tyrosine residues of thyroglobulin in the follicular lumen. Thyroglobulin is a large homodimeric glycoprotein with a molecular weight of approximately 660 kDa that contains 138 tyrosine residues.\nIodination of about 14 of these tyrosines forms monoiodotyrosine (MIT) or diiodotyrosine (DIT).\nTwo molecules of DIT then couple to form one molecule of T4, or one molecule of DIT and one of MIT couple to form T3.\nOnce formed, hormones remain stored as part of thyroglobulin in the colloid of the follicular lumen until ready to be secreted from the thyroid.\nT4 and T3 are liberated when the follicular cell endocytoses colloid and the thyroglobulin is degraded by endosomal proteases and peptidases. Slide 4 In adults, the thyroid secretes approximately 85 μg of T4 and 6-7 μg of T3 daily.\n 20% of circulating T3 is secreted by the thyroid, the remainder is produced by deiodination of T4 in extrathyroidal tissues by iodotyrosine deiodinases (types 1 and 2).\n T3 is the physiologically active thyroid hormone because it binds the thyroid hormone receptor with 10- to 15-fold greater affinity than T4. Slide 5 Thyroid hormones increase oxygen consumption, stimulate protein synthesis, influence growth and differentiation, and affect carbohydrate, lipid, and vitamin metabolism.\nEntry of T4 and T3 into cells is facilitated by specific thyroid hormone transporters. Once inside the cell, T4 is converted to T3 by type 1 or 2 deiodinase.\nIntracellular T3 then enters the nucleus and binds to thyroid hormone receptors.\nThyroid hormone receptors are members of the steroid hormone receptor superfamily that includes receptors for glucocorticoid, androgen, estrogen, progesterone, vitamin D, and retinoids. Slide 6 Four thyroid hormone receptor isoforms (α1, α2, β1, and β2 ) are expressed in different tissues and consist of a ligand-binding domain that binds T3, a hinge region, and a DNA-binding domain (zinc finger) that binds to thyroid hormone receptor response elements.\n Binding of T3 to the thyroid hormone receptor causes recruitment of co-activator molecules, transcription of messenger RNA, and protein synthesis.\n Multiple levels of regulation of thyroid hormone signaling, including deiodination, transmembrane transport, and thyroid hormone receptor expression allow tissue-specific modulation of thyroid hormone action in the face of a given level of circulating T4. Slide 7 70% of circulating T4 is bound to thyroxine-binding globulin (TBG), and most of the remainder is bound to albumin and prealbumin.\n 0.03% of serum T4 is unbound and comprises free T4. 50% of circulating T3 is bound to TBG and 50% is bound to albumin, while only 0.3% of T3 is unbound or free T3.\n Because the concentration or binding of TBG is altered in many clinical circumstances, its status must be considered when interpreting total T4 or T3 levels. Slide 8 Thyroid Regulation The thyroid is regulated by TSH, secreted by the anterior pituitary.\n Binding to the TSH receptor activates adenylate cyclase in the thyroid gland and stimulates all steps of thyroid hormone biosynthesis, from uptake of iodine to release of thyroid hormones.\n TSH synthesis and release are stimulated by TRH, synthesized in the hypothalamus and secreted into the pituitary. Slide 9 In states of decreased thyroid hormone, TSH and TRH are increased, while increased thyroid hormone inhibits TSH and TRH production.\n In many nonthyroidal illnesses, circulating T3 levels fall induced by factors such as fasting, chronic malnutrition, acute illness, and certain drugs.\n The decreased levels of T3 may be a physiologic adaptation, resulting in decreased rates of oxygen consumption, of substrate use, and of other catabolic processes. Slide 10 Thyroid Function Tests Methods are available to measure all the thyroid hormones in serum: T4, free T4, T3, and free T3.\nDirect free T4 assays are widely available and are generally reliable in healthy patients; however, these assays may be unreliable during acute illness or with severe abnormalities of thyroid hormone binding.\nMany free T3 assays are poorly standar