Management of Thyroid Disorders Handout

Management of Thyroid Disorders Devada Singh-Franco, PharmD, CDCES Associate Professor, Pharmacy Practice [email protected] 1 Objectives 1. 2. 3. 4. 5. 6. 7. 8. Describe signs/symptoms of hyper- and hypothyroidism. Outline changes seen in thyroid function tests. Describe mode of action, patient selecti...

Management of Thyroid Disorders Devada Singh-Franco, PharmD, CDCES Associate Professor, Pharmacy Practice [email protected] 1 Objectives 1. 2. 3. 4. 5. 6. 7. 8. Describe signs/symptoms of hyper- and hypothyroidism. Outline changes seen in thyroid function tests. Describe mode of action, patient selection, initial, maintenance and maximal doses, drug interactions, and adverse effects for thionamides, beta blockers. Compare and contrast products available for thyroid supplementation in hypothyroidism; describe drug of choice. Outline starting and maintenance doses and adverse effects for levothyroxine and monitoring of therapy. Provide goals for treating thyroid disorders, including TSH and FT4 values. Construct rational therapeutic regimens for treatment of thyroid disorders for all patients, including pregnant women. Provide monitoring parameters and frequency of monitoring for patients treated for thyroid disorders. 2 1 Guidance on material for exam       All slides are for your information/reference…except for slides with  Please study the information on the slides with  Please go through all slides to see which ones have Please only know generic names, as only generic names of drugs will be on the exam Please know how to dose levothyroxine based on age and cardiac status and TSH values **For online assignments/quizzes, please review/use ALL slides** 3 Which of the following laboratory parameters indicate that a patient may have hypothyroidism? A. B. C. D. ↑TSH, ↑FT4 ↓TSH, ↓FT4 ↓TSH, ↑FT4 ↑ TSH, ↓FT4 4 2 Thyroid gland  An endocrine gland that uses iodine to create thyroid hormones  Located in the middle of the neck  Releases thyroid hormones (THs) that regulate the body's physiological functions https://www.merckmanuals.com/home/hormonal-and-metabolic-disorders/thyroid-glanddisorders/overview-of-the-thyroid-gland 5 1. Hypothalamus detects when circulating THs are low and will release TRH 2. TRH instructs pituitary to release TSH 3. TSH instructs thyroid gland to secrete THs (Brain) (Brain) (Neck) Arbl.cvmbs.colostate.edu/ …/control.html 6 3 TSH: Thyroid Stimulating Hormone  Increased TSH levels in primary hypothyroidism  Hypothalamus will detect persistently low levels of thyroid hormones and secrete TRH (thyrotropinreleasing hormone) which will instruct pituitary to secrete TSH (which will unsuccessfully try to stimulate thyroid gland to secrete thyroid hormones)   Low or undetectable TSH levels in hyperthyroidism  Hypothalamus will detect persistently elevated levels of thyroid hormones and no longer secrete TRH and so pituitary gland will not receive instructions to secrete TSH.  Thyroid gland is functioning independently to secrete THs 7 T4 (Thyroxine) & T3 (Triiodothyronine)   Thyroid gland (TG) will secrete greater amounts of T4 than T3 into circulation  T4 is solely produced by the TG; it is significantly less biologically active than T3  T3 is more biologically active than T4  99% proteinbound and binds more tightly to proteins than T3)  T3 has a T1/2 of 1 day (>99% protein-bound but binds less tightly to proteins) 8 4 Thyroid Function Tests (TFTs)  FT4 (ng/dL) TSH (mIU/L) FT4= Free T4 Normal 0.8-2.7 0.5-4.7 Hyper   TSH= Thyroid stimulating hormone Hypo   9 Hypothyroidism 10 5 Thyroid Function Tests (TFTs) FT4 (ng/dL) TSH (mIU/L) Normal 0.8-2.7 0.5-4.7 ?   ?    FT4= Free T4 TSH= Thyroid stimulating hormone 11 What is hypothyroidism?  Condition characterized by decreased activity of the thyroid gland with compensatory increase in TSH  Primary hypothyroidism  Hashimoto’s Disease: antibodies attack various parts of the thyroid gland including the thyroid peroxidase (TPO) enzyme (very important enzyme to produce thyroid hormones) 12 6 Signs & Symptoms          Dry, thin, cool, coarse skin and hair Diffuse alopecia Puffy face, hands, feet Brittle nails Cool peripheral extremities Slowed reflexes/speech Bradycardia Weight gain with poor appetite Tiredness, weakness, low energy level          Memory impairment Muscle aches/stiffness Carpal tunnel syndrome Cold intolerance Hoarseness Constipation Menstrual irregularities ± Goiter Gradual Onset! 13 Diagnosis of hypothyroidism Signs & symptoms  Labs (bloodwork)   FT4   TSH  Positive TPO antibodies  14 7 Goals of Thyroid Replacement Therapy (TRT) 1. 2. 3. 4. Restore thyroid hormone levels within tissue Provide symptomatic relief Prevent neurologic deficits in newborns and children Normalize labs 15 Who should be treated?  TSH > 11 mIU/L   What should they receive? T4 versus T3 replacement    TSH 5-10 mIU/L AND symptoms   TSH 5-10 mIU/L AND TPO antibodies T4 metabolizes into T3 T3 much more potent replacement Combination T4 (Synthroid®) with T3 (liothyronine or Cytomel®) has been used in patients with normalized TSH, but still complain of symptoms of hypothyroidism 16 8 Synthetic thyroid hormone (T4) Levothyroxine (Synthroid®)    Provides patient with a stable pool of T4 Adults ≤60 years of age without evidence of cardiac disease: 1.6 mcg/kg/day IBW Adults ≥ 61 years of age without evidence of CHD: 25 to 50 mcg once daily  Any patient with known cardiac disease    12.5-25 mcg/day and titrate up based on tolerability Any patient with TSH 5-10 (as noted on previous slide)  25-50 mcg/day and titrate up based on tolerability https://www.synthroidpro.com/pharmacy/protected-unprotected.aspx 17 Calculate full replacement dose for a 37 YO female (5’5”, 79 Kg); no significant PMH; TSH = 15mIU/L; FT4 0.7ng/dL 18 9 Synthetic T4 Replacement 1. 2. When to take: 60 minutes before breakfast or 3 hours after dinner, with water Obtain TSH and FT4 6 weeks later  Target TSH: 0.4 to 4 mIU/L  Adjust dose by 12.5 to 25 mcg increments at 6- or 8-week intervals as needed 1.  Effects Hypo- symptoms begin to 1. resolve (hopefully) 2. Look for hyper- symptoms as we want to avoid overreplacement.  Atrial fibrillation  Immediately report palpitations, chest pain  Immediately report excessive sweating, heat intolerance, nervousness  Osteoporosis risk is increased with overreplacement 19  Indicated for patients ≥6 years of age  Available as an amber oral gel capsule and as a liquid (Tirosint-SOL)  Administered once-daily 30-60 minutes before breakfast  If patient requires frequent dose adjustments and/or has poor symptom control while on levothyroxine tablets, switching to Tirosint may be considered 75 mcg 88 mcg 100 mcg 112 mcg 125 mcg 137 mcg 150 mcg 175 mcg 200 mcg 50 mcg 25 mcg 13 mcg Synthetic T4 20 10 Which of the following laboratory parameters indicate that a patient has been successfully treated with levothyroxine? A. B. C. D. ↑TSH, ↑FT4 ↓TSH, ↓FT4 ↓TSH, ↑ FT4 ↑ TSH, ↓FT4 21 Armour Thyroid: T4 & T3 Freeze-dried porcine gland  Contains T4 & T3 in 4:1 or 3:1 or 2:1 ratio  Starting dose: 30 mg daily; can increase by 15 mg every 2-3 weeks    Most patients will need 60-120 mg/day T3 adverse effects  Immediately report chest pain, palpitations, excessive sweating, heat intolerance, nervousness 22 11 Cytomel®: T3 Only Preparation (Liothyronine)    Synthetic T3 (PO & IV) Oral absorption = 90% High incidence of adverse effects    Immediately report chest pain, palpitations, excessive sweating, heat intolerance, nervousness Not recommended first-line due to adverse events Initial dose: 25 mcg daily   Can titrate up by 25 mcg every 1-2 weeks Maintenance: 25-75 mcg daily 23 Hypothyroidism & Pregnancy  Effect of maternal HOT     Miscarriage, spontaneous abortion Congenital defects, impaired cognitive development Maternal THs provide fetus with THs for up to 18 weeks  fetus forms their own thyroid gland If mom-to-be is on levothyroxine, will need a 3050% increase in levothyroxine pre-pregnancy dosage to maintain euthyroid status  Levothyroxine is DOC during pregnancy   Take 2 additional tablets weekly as soon as patient knows they are pregnant Counsel patient to see HCP/obstetrician for further follow-up and dosage adjustments Thyroid. 2017;27:315-389. 24 12 Drug Interactions with T4   Take T4 at least 4 hours apart from iron, calcium, antacids, magnesium, cholestyramine, soy Obtain TSH and FT4 ≥ 6 weeks after a potential interacting drug is started with T4 dosage adjustment as necessary 25 Patient counseling 1. 2.  3.  5. 6. 7. Symptom resolution may take months/years Lab improvement in 6-8 weeks  4.  Treatment will be life-long 2-3 weeks for symptoms to lessen, not completely resolve Monitor TSH, FT4 levels ≥ 6 weeks after initiation or any dose adjustments or starting any interacting medications When TSH is WNL, monitor 1-2x/year Know the name and dose of medication Take on an empty stomach (AM or PM) If you become pregnant, you may need more thyroid hormones (e.g., take 2 extra tabs per week) Know the signs/symptoms of HYPERTHYROIDISM to tell if you are taking too much thyroid hormone 26 13 Questions? 27 Selected References 1. 2. 3. 4. 5. 6. 7. 8. American Thyroid Association. Guidelines for the treatment of hypothyroidism. Thyroid. 2014;24(12):1670-1751. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017;27:315-389. Synthroid [package insert]. North Chicago, IL. Abbott Laboratories; July 2020. Tirosint [package insert]. Parsippany, NJ. IBSA Pharma Inc.; June 2018. Skelin M, Lucijanic T, Klaric DA, et al. Factors affecting gastrointestinal absorption of levothyroxine. Clinical Therapeutics. 2017:39:378-403. 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, 12e. McGraw Hill; 2023. https://accesspharmacy-mhmedical-com. Thyroid Gland. In: Molina PE. eds. Endocrine Physiology, 5e. McGraw Hill; 2018. https://accessmedicine-mhmedical-com.e Ross DS. Treatment of primary hypothyroidism in adults. UpToDate.com 28 14 Hyperthyroidism 29 Which of the following laboratory parameters indicate that a patient has hyperthyroidism? A. B. C. D. ↑TSH, ↑FT4 ↓TSH, ↓FT4 ↓TSH, ↑ FT4 ↑ TSH, ↓FT4 30 15 Graves’ Disease    Accounts for 85% of all cases of hyperthyroidism Formation of thyrotropin receptor antibodies (TRAb) stimulate the TSH receptors in the thyroid gland to produce and secrete thyroid hormones regardless of the amount of thyroid hormones in circulation TSH level is low to undetectable 31 Hyperthyroidism: Signs & Symptoms        Nervousness Anxiety Insomnia Increased sweating Palpitations Chest pain SOB / Dyspnea       Weakness / Fatigue Light/no menstrual period Heat intolerance Increased bowel movements Weight loss despite good appetite Physical Findings      Goiter Warm smooth velvety skin; moist palms Fine, resting tremor Tachycardia Vision changes   Proptosis: bulging of the eyes Irritation or grittiness Endocrine Society."Goiter | Endocrine Society." Endocrine.org, Endocrine Society, 18 February 2022, https://www.endocrine.org/patientengagement/endocrine-library/goiter (Reproduced with permission from Fauci AS, Kasper DL, Longo DL, et al., eds. Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill; 2005:2114.). 32 16 Diagnosis of Graves’ Disease 1. 2. Signs and symptoms Labs  FT4  TSH  Positive TRAb 33 Treatment Options 1. 2. 3. 4.  Thionamides (MMI and PTU) Radioactive iodine ablation therapy:  Uses radiation to destroy the thyroid gland  Good choice for patients with thyroid nodules or who are unable to take thionamides Thyroidectomy  Surgical removal of the thyroid gland  Good choice for those with very large goiters or who are unable to take thionamides Adjunctive therapy to all the above: beta blockers (propranolol, atenolol)  Anxiety, tremor, palpitations, heat intolerance  Goal HR