Thyroid Gland Disorders PDF

Thyroid Gland Disorders By: Sahar Mamoun Mohamed Ali BCPS, BCCS, MBA, ICT, Msc Clinical Pharmacy/United Kingdom THYROID DISORDERS  Thyroid disorders Hyperthyroid Hypothyroid disorder...

Thyroid Gland Disorders By: Sahar Mamoun Mohamed Ali BCPS, BCCS, MBA, ICT, Msc Clinical Pharmacy/United Kingdom THYROID DISORDERS  Thyroid disorders Hyperthyroid Hypothyroid disorder disorder Subclinical Subclinical Thyroid Storm Myxedema Coma Hyperthyroidism Hypothyroidism Hyperthyroid disorder Thyrotoxicosis  Hyperthyroid Disorder Classification A. Toxic diffuse goiter (Graves’ disease): Most common hyperthyroid disorder i. Autoimmune disorder ii. Thyroid-stimulating antibodies directed at thyrotropin receptors mimic TSH and stimulate triiodothyronine/thyroxine (T3/T4) production. b. Pituitary adenomas: Produce excessive TSH secretion that does not respond to normal T3 negative feedback c. Toxic adenoma: Nodule in thyroid, autonomous of pituitary and TSH d. Toxic multinodular goiter (Plummer disease): Several autonomous follicles that, if large enough, cause excessive thyroid hormone secretion b.Painful subacute thyroiditis: Self-limiting inflammation of the thyroid gland caused by viral invasion of the parenchyma, resulting in the release of stored hormone c.Drug induced (e.g., excessive exogenous thyroid hormone doses, amiodarone therapy)  Diagnosis ⚫ Elevated free T4 serum concentrations. ⚫ Suppressed TSH concentrations (except in TSH- secreting adenomas). T4 TSH  Clinical presentation 1) Weight loss/increased 8) Menstrual disturbances appetite. (lighter or more infrequent 2) Heat intolerance menstruation, amenorrhea) caused by hypermetabolism of 3) Goiter estrogen. 4) Fine hair 5) Heart 9) Sweating or warm, moist palpitations/tachycardia skin 7) Nervousness, anxiety, 10) Exophthalmos, insomnia 11) Rare: pretibial myxedema in Graves’ disease.  Therapy goals a. Minimize or eliminate symptoms, improve quality of life. b.Minimize long-term damage to organs (heart disease, arrhythmias, sudden cardiac death, bone demineralization, and fractures). c. Normalize free T4 and TSH concentrations.  Pharmacotherapy of Thyroid disorders A. Ablative therapy: Treatment of choice for Graves disease, toxic nodule, multinodular goiter: Radioactive iodine ablative therapy or surgical resection for adenomas based on patient preferences or comorbidities. ⚫ Ablative therapy often results in hypothyroidism. B. Anti-thyroid pharmacotherapy usually reserved for: i. Awaiting ablative therapy or surgical resection (a) Depletes stored hormone. (use antithyroid those block synthesis but not the release). (b) Minimizes risk of post-treatment hyperthyroidism. ii. Not an ablative or surgical candidate (e.g., serious CVS disease, candidate not likely to be adherent to radiation safety) iii. When ablative therapy or surgical resection fails to normalize thyroid function  Drugs 1. Thioureas (i.e., PTU, and methimazole) i. Dosing (a) Propylthiouracil or PTH (1) Initial: 100 mg by mouth 3 times/day (2) block both, hormone synthesis and peripheral conversion of T4 into T3. (3) Once euthyroid, may reduce to 50 mg 2 or 3 times/day  (b) Methimazole (1)Preferred agent for Graves disease according to the American Association of Clinical Endocrinologists (AACE) for most patients unless in first trimester of pregnancy; then use PTU (2) Initial: 10–20 mg by mouth once daily (3) Maximal: 40 mg 3 times/day (4) Once euthyroid, may reduce to 5–10 mg/day ❖ Adverse effects of Thioureas: (a) Hepatotoxicity issue with PTU (black box warning): AACE recommends baseline Liver function tests (b) Rash (c) Arthralgias, lupus-like symptoms (d) Fever (e) Agranulocytosis early in therapy (rare): AACE recommends baseline CBC. May repeat to be used if patient becomes febrile or develops pharyngitis 2. Nonselective β-blockers (primarily propranolol, sometimes nadolol ) i. Mechanism of action: Blocks many hyperthyroidism manifestations mediated by β- adrenergic receptors. Also may block T4 (less active) conversion into T3 (more active) ii.Dosing of Non-selective β-blockers: (a) Initial: 20–40 mg by mouth 3 or 4 times/day (b) Maximal: 240–480 mg/day Efficacy of Non-selective β-blockers: (a) Primarily used for symptomatic relief (e.g., palpitations, tachycardia, tremor, anxiety) (b) Guidelines recommend use in elderly, symptomatic patients, and others with heart Rates greater than 90 beats/minute. Consider in all symptomatic patients only. (c) not recommended in asymptomatic pts. (d) Primary role is treatment of thyroiditis, which is usually self- limiting, and for acute management of thyroid storm. (e) Alternatives: Clonidine, and non- dihydropyridine CCBs. 3. Iodines (e.g., Lugol’s solution, saturated solution of KI) i. Mechanism of Iodines action: Inhibits the release of stored thyroid hormone. Minimal effect on hormone synthesis. Helps decrease vascularity and size of gland before surgery ii. Adverse effects of Iodines (a)Hypersensitivity (b) Metallic taste (c) Soreness or burning in mouth or tongue Subclinical Hyperthyroidism  Subclinical Hyperthyroidism 1. Definition: a situation of Low or undetectable TSH with normal T4 2. Risk of Subclinical Hyperthyroidism? a. Associated with increased risk of atrial fibrillation in patients older than 60 years b. Associated with increased risk of bone fracture in postmenopausal women c. Conflicting data regarding mortality risk 3. Treatment similar to treating overt hyperthyroidism a. Oral antithyroid drug-therapy is alternative to ablative therapy in young patients with Graves disease b. β-Blockers may be of benefit to control cardiovascular morbidity, especially with atrial fibrillation. 4. If untreated, screen regularly for the development of overt hyperthyroidism (increased free T4 Concentrations in addition to already decreased TSH). Thyroid storm  Thyroid Storm 1. Severe and life-threatening decompensated thyrotoxicosis. Mortality rate may be as high as 20%. 2. Precipitating causes: Trauma, infection, antithyroid agent withdrawal, severe thyroiditis, Post-ablative therapy (especially if not adequate pretreatment) 3. Presentation: Fever, tachycardia, vomiting, dehydration, coma, tachypnea, delirium. Pharmacotherapy a. Propylthiouracil (PTU)… rapid onset than other thioureas. b. Iodide therapy 1 hour after PTU initiation (dosed as above) to block hormone release c. β-Blocker therapy: Esmolol commonly used (can use other agents [e.g., propranolol]) to control symptoms and blocks conversion of T4 to T3 d. Acetaminophen as antipyretic therapy if needed (avoid NSAIDs because of displacement of protein-bound thyroid hormones) e. Corticosteroid therapy: Prophylaxis against relative adrenal insufficiency Hypothyroid Disorders  Hypothyroid Disorders Classification A. Hashimoto’s disease: Most common hypothyroid disorder in areas with iodine sufficiency ⚫ i. Autoimmune-induced thyroid injury resulting in decreased thyroid secretion ⚫ ii. Disproportionately affects women B. Iatrogenic: Thyroid resection or radioiodine ablative therapy for treatment of hyperthyroidism C. Iodine deficiency most common cause worldwide D. Secondary causes i. Pituitary insufficiency (failure to produce adequate TSH secretion, referred to by some as central or secondary hypothyroidism) ii. Drug induced (e.g., amiodarone, lithium)  Diagnosis 1) Decreased free T4 serum concentrations. 2) Elevated TSH concentrations, usually above 10 mIU/L (normal or low if central hypothyroidism is the etiology). T4 TSH  Clinical presentation ⚫ Cold intolerance ⚫ Coarse skin and hair ⚫ Periorbital swelling ⚫ Dry skin ⚫ Menstrual disturbances (more ⚫ Fatigue, lethargy, frequent or longer weakness menstruation, painful menstruation, menorrhagia) ⚫ Weight gain caused by hypometabolism of ⚫ Bradycardia estrogen ⚫ Slow reflexes Pharmacotherapy of Hypothyroidism a. Levothyroxine or T4 (drug of choice)….synthetic T4 i. Dosing (a) In otherwise healthy adults, 1.6 mcg/kg (use ideal body weight) per day. (b) In patients 50–60 years of age, consider 50 mcg/day (c) Initiate with (12.5 - 25 mcg) once daily in the elderly or in those with existing cardiovascular disease) (c) Dose titration based on response (control of symptoms, normalization of TSH and free T4)  (d) Usually dosed in the morning on an empty stomach 30–60 minutes before breakfast or at bedtime 4 hours after last meal; dosed separately from other medications (e) Daily requirements will be higher in pregnancy. iv. Adverse effects of thyroxin (a) Hyperthyroidism (b) Cardiac abnormalities but less than T3 because of slow absorption. (c) Linked to risk of fractures (usually at higher doses or over- supplementation) ii. Monitoring (a)(4 – 8) weeks is appropriate to assess patient response (about a 7-day half-life for T4). May take longer for TSH to achieve steady- state concentrations (b) Use free T4 rather than TSH if secondary hypothyroidism.. (Use both if primary hypothyroid) (c) Some concurrent drug therapy may need to be adjusted (e.g., warfarin, phenytoin, insulin, sedatives) Subclinical Hypothyroidism  Subclinical Hypothyroidism 1. Definition: a situation of Elevated TSH with normal T4. 2. Risk? a. TSH greater than 7.0 mIU/L in the elderly associated with increased risk of heart failure b. TSH greater than 10 mIU/L associated with increased risk of coronary heart disease. 3. Treatment of subclinical hypothyroidism is controversial. 4. Whom to treat a. TSH between 4.5 and 10 mIU/L and i. Symptoms of hypothyroidism ii. History of cardiovascular disease, HF, or risk factors. b. Initial daily doses of 25–75 mcg recommended 5. If untreated, screen regularly for the development of overt hypothyroidism (decreased free T4 Concentrations in addition to already increased TSH). Myxedema Coma 1. Severe and life-threatening decompensated hypothyroidism. Mortality rate 30%–60% 2. Precipitating causes: Trauma, infections, heart failure, medications (e.g., sedatives, narcotics, anesthesia, lithium, amiodarone) 3. Presentation: Coma is not required and is uncommon despite terminology, altered mental state (very common), hypothermia, and hypoventilation. Pharmacotherapy a. Intravenous thyroid hormone replacement i. T4: 100- to 500-mcg loading dose, followed by 75–100 mcg/day, until patient can tolerate oral therapy. Lower the initial dose in frailer patients or in patients with established CVS disease. ii. Some advocate the use of T3 over T4 because conversion may be suppressed in myxedema coma. Cost and availability limit I.V T3 use. b. Antibiotic therapy: some advocate empiric broad antibiotics. c. Corticosteroid therapy i. Hydrocortisone 100 mg every 8 hours (or equivalent steroid) ii. Can be discontinued if random cortisol concentration not found to be depressed