Thyroid Disorders PDF January 2025

Thyroid Disorders Kyle Palmer, PharmD January 2025 Today’s date 1 Objec...

Thyroid Disorders Kyle Palmer, PharmD January 2025 Today’s date 1 Objectives Describe the physiology of thyroid hormones Explain the pathophysiologic processes and complications with imbalances Interpret thyroid laboratory values and classify the disorder Review the most common etiologies of hyperthyroidism and hypothyroidism Recognize common signs and symptoms of hyperthyroidism and hypothyroidism 2 Thyroid Disorders 3 Thyroid Disorders The thyroid hormones affect many organ functions within our body In kids it's used for growth and development In adults in helps metabolic stability 4 Thyroid Gland The largest endocrine gland in the body 5 Thyroid Gland The thyroid gland consists of follicular and parafollicular cells. Follicular cells produce thyroid hormones, specifically thyroxine (T4) and triiodothyronine (T3). Parafollicular cells produce calcitonin. 6 Thyroid Hormones Thyroxine (T4) Triidothyronine (T3) Potency Less potent 4x more potent Plasma T1/2 7 days 1.5 days 20% from thyroid; Formation 100% from thyroid gland 80% from peripheral conversion from T4 Protein Binding 99.96% protein bound 99.6% protein bound Precursor to t3 ~80% comes from Conversion the conversion from T4 7 Thyroid Hormones Thyroxine (T4) Triidothyronine (T3) Potency Less potent 4x more potent Plasma T1/2 7 days 1.5 days 20% from thyroid; Formation 100% from thyroid gland 80% from peripheral conversion from T4 Protein Binding 99.96% protein bound 99.6% protein bound Precursor to t3 ~80% comes from Conversion the conversion from T4 8 Thyroid Hormone Biosynthesis (The six steps) Hormone secretion Proteolysis liberates T3 and T4 from tyrosine The coupling of 2 residue iodinated tyrosine Free T3 and T4 enter molecules forms circulation Iodination of either T4 or T3 thyroglobulin MIT+DIT= T3 and Iodinated tyrosine DIT+DIT= T4 → coupling Oxidation of iodide residues form is catalyzed by thyroid to iodine monoiodotyrosine (MIT) peroxidase and diiodotyrosine (DIT)→ Uptake and organification. concentration of iodide Thyroglobulin synthesized from tyrosine 9 Thyroid Hormone Regulation T4 and T3 release from the thyroid is HIGHLY regulated Hypothalamic-pituitary-thyroid axis Negative feedback loop When the level of circulating (free) T4 increases, the circulating T4 inhibits the secretion of TSH and TRH Less TSH will decrease T4 production 10 Testing 11 Labs Reference Test Measures Comments Range (Varies) Gold standard for screening, diagnosis, and dose titration Anterior Most sensitive and specific lab for TSH pituitary TSH 0.5-4.7 mIU/L thyroid function level Sensitivity: 98% specificity: 92% Screening test for thyroid function Direct measure Used with TSH for initial diagnosis Free T4 of free 0.8-2.7 ng/dL Monitoring hyperthyroidism thyroxine treatment Confirm diagnosis Direct measure For conversion abnormalities Free T3 of free 145-348 pg/dL Determine hyperthyroidism severity triiodothyronine Limited utility / rarely used 12  13 Hypothyroidism 14 Background Clinical syndrome results from inadequate thyroid hormone secretion from thyroid gland Most common disorder of thyroid dysfunction Affects females > males Incidence increases with age 15 Etiology Primary Hashimoto’s disease (“autoimmune thyroiditis”) Presences of anti-TPOAbs inhibit thyroid peroxidase Iatrogenic Due to thyroid irradiation, surgery, or high doses of antithyroid drugs Iodine deficiency Most common cause worldwide 16 Etiology cont. Secondary Pituitary disease Caused by tumors, surgery, external pituitary radiation, trauma, autoimmune conditions Hypothalamic disease TRH deficiency as result of cranial irradiation, trauma, neoplastic disease Medication-Induced Amiodarone, lithium, interleukin-2, checkpoint inhibitors , etc. 17 Signs and Symptoms 18 Treatment Overview Levothyroxine (T4) = drug of Brand names: Synthroid, Levoxyl, Unithroid choice Thyroid, desiccated USP Brand names: Amour Thyroid, Nature-Throid, (T4 and T3) = animal derived NP Thyroid Liothyronine (T3) Brand name: Cytomel Liotrix (T4 and T3) Brand name: Thyrolar 19 Myxedema Coma Rare, but potentially fatal complication of hypothyroidism Occurs when hypothyroidism left untreated for a long time, or when hypothyroidism decompensates Life-threatening medical emergency Poor circulation, hypothermia, hypometabolism, delirium, multiple organ abnormalities Initial treatment = intravenous levothyroxine 20 Hyperthyroidism 21 Background Much less common than hypothyroidism Characterized More common by thyroid More common in women than hormone in smokers men (5:1 ratio) excess of T4, T3, or both 22 Etiology Primary Graves’ disease (genetic) Most common cause Presence of TSHR-SAb that stimulate thyroid hormone synthesis and release Toxic adenoma Benign tumor that produces thyroid hormone independent of pituitary and TSH control Thyroid cancer Iodine excess (ex: radiocontrast dye) 23 Etiology Secondary Defect in anterior pituitary gland or hypothalamus TSH-secreting pituitary tumors Medication-Induced Amiodarone, interferon-alpha, iodine, lithium, etc. 24 Signs and symptoms 25 Antithyroid Beta-blockers Drugs Iodides (propranolol) (Methimazole, Propylthiouracil) Radioactive Surgery Iodine 26 Thyroid Storm Also referred to as thyrotoxic crisis Rare, but life-threatening, hypermetabolic state induced by excessive release of thyroid hormones Signs and symptoms Fever, tachycardia, tachypnea, dehydration, profuse sweating, agitation, delirium, psychosis, coma Treatment = propylthiouracil + iodide + beta blocker + systemic steroid + aggressive cooling 27 Goiters Enlargement of the Thyroid gland Most common cause worldwide is iodine deficiency Lower levels of T4 and T3  leads to more TSH secretion The increased TSH cause a increase in thyroid cells production leading to hyperplasia of the gland Thyrotoxicosis - Occurs when the goiter mass is large enough to produce more thyroid hormone than needed - Symptoms will typically seen over years due to this process - Detected by inspection, palpations or ultrasound 28 Take Home Points Thyroid disorders are Thyroid hormones common and may Thyroid hormone regulate cellular cause significant biosynthesis is a metabolism in morbidity and complex process essentially every cell mortality Diagnosis and treatment are based In hypothyroidism, In hyperthyroidism, on clinical physiological physiological presentation and processes are slower processes are faster laboratory values, primarily TSH and T4 29 Questions? Thank You 30 References Kane MP, Bakst G. Thyroid Disorders. In: DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L. eds. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition. McGraw Hill; 2023. Accessed January 23, 2025. https:// accesspharmacy.mhmedical.com/content.aspx? bookid=3097&sectionid=265902604 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016; 26(10):1343-1422. Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014; 24(12): 1670-1751. Can AS, Rehman A. Goiter. [Updated 2023 Aug 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https:// www.ncbi.nlm.nih.gov/books/NBK562161/ 31