Module I 2 - Thyroid Gland Disorders PDF

PHAM 422 (Pharmacotherapy III) Thyroid Gland Disorders Prepared By: Ph. Omar Alsamani, PharmB, Rph, CPHQ, CSSYB, BLS, mDip Pharmacoeconomic, TeamSTEPPS Master Trainer  Objectives Discuss the prevalence of common thyroid disorders. Discuss the re...

PHAM 422 (Pharmacotherapy III) Thyroid Gland Disorders Prepared By: Ph. Omar Alsamani, PharmB, Rph, CPHQ, CSSYB, BLS, mDip Pharmacoeconomic, TeamSTEPPS Master Trainer  Objectives Discuss the prevalence of common thyroid disorders. Discuss the relationship between serum TSH levels and primary thyroid disease, and the advantages for use of TSH levels over serum T4 & T3 in assessment of diseases. Recognize classical clinical manifestations of hypothyroidism and the consequences of inadequate treatment. Describe the importance of levothyroxine (LT4) in the treatment of hypothyroidism. Discuss the LT4 product bioequivalency and the importance of maintaining patients on the same product. Describe the management of thyroid disorders during pregnancy. Identify classical signs and symptoms of hyperthyroidism and consequences of suboptimal treatment. Discuss different modalities for pharmacotherapy of hyperthyroidism, including their advantages and  Introduction Large number of people around the world have low or high intake of iodine that could result in thyroid disorder Most common thyroid disorders are hypothyroidism and hyperthyroidism (often require long-term pharmacotherapy). Thyroid disorders, if undetected or improperly treated can result in long-term complications, including increased mortality. Incidence of hypothyroidism is more than hyperthyroidism Hypothyroidism 3.7% Hyperthyroidism 0.5% Prevalence of hypothyroidism was found to be correlated with age (incidence increases with age) Pregnant women were also found to have higher prevalence of hypothyroidism. Many patients with hypothyroidism are not being managed successfully.  Thyroid Physiology. The thyroid gland consists of two lobes in the lower neck. The gland synthesizes, stores, and releases two major metabolically active hormones: 1.Tetra- iodothyronine(Thyroxine, T4). 2.Tri-iodothyronine (T3). Both T4 and T3 are produced within the follicular cells in the thyroid.  Thyroid Physiology. The ratio of T4:T3 secreted by the thyroid gland is 10:1. The gland secretes 80–100 μcg of T4 and 10 μcg of T3 daily. 10% of circulating T3 from direct thyroidal secretion, and 90% is produced by peripheral conversion from T4. The half-life of T4 in plasma is about 6– 7 days and that of T3 24–36h in adults. Investigations/Diagnosis  Testing Thyroid Function. The laboratory investigation of hypothyroidism is straightforward. Clinical assessment combined with a single estimation of thyroid hormones and TSH, is sufficient to make the diagnosis. In primary disease, the levels of free T4 and T3 are low/high and the TSH level decrease/rises markedly. Hypothyroidism  Etiology. Primary hypothyroidism accounts for more than 95% of adult cases. It is usually due to: 1. Failure of the thyroid gland “autoimmune destruction” (Hashimoto disease). 2. Treatment of thyrotoxicosis. Secondary disease is due to hypopituitarism. Tertiary disease due to failure of the hypothalamus. Peripheral hypothyroidism is due to tissue insensitivity to the action of thyroid hormones. Drug-induced hypothyroidism. Amiodarone and lithium cause hypothyroidism in around 10% of patients treated.  Clinical Manifestations Hypothyroidism can affect multiple body systems, but symptoms are mainly non-specific and gradual in onset. Hypothyroidism is often confused with simple obesity and  Therapy Minimize Goals. or eliminate symptoms; improve quality of life. Minimize long-term damage to organs (myxedema coma, heart disease). Normalize free T4 and TSH concentrations.  Treatment All patients with symptomatic hypothyroidism require replacement therapy. T4 (Levothyroxine) is usually the treatment of choice except in myxoedema coma where T3 may be used in the first instance. Initial dose of T4 will depend on the patient’s: 1. Age. 2. Severity. 3. Duration of disease. 4. Coexistence of cardiac disease.  Treatment Young, Adults Pregnancy Elderly Cardiac healthy patients patients 50–100 μcg 125 μcg Daily Increase by 25 μcg daily 12.5–25 daily (1.6mcg/kg 25–50% and increased mcg/day. IBW) slowly by 25 μcg every 4–6 weeks Most Checkpatients TSHwilllevel be controlled everywith 6 doses weeksof 100–200 μcg daily. to adjust the patient’s dose. Interval should not be shorter than 6 weeks as TSH takes this time to stabilize after a dose change. For optimal bioavailability, dosed in the morning 30–60m before breakfast or at bedtime 3–4 hours after the last meal; dosed separately from other medications.  Drug holiday: The conscious decision to stop using a regularly prescribed medication for some time. Hypothyroidism requires lifelong Drug treatment with T4. Holidays Patients on long-term drug therapy have a low adherence to their medication regimen. Often terminated because patients feel well and think that treatment is no  Adverse Effects. Hyperthyroidism. Cardiac abnormalities (tachyarrhythmias, angina, myocardial infarction). Linked to risk of fractures.  Bioequivalence Guidelines recommend brand-name levothyroxine or consistent use of specific generic products. Although legal, guidelines recommend against changing from brand to generic and vice versa. It is recommended to stay with one product throughout therapy.  Myxoedema Coma Myxoedema coma is a rare but potentially fatal complication of severe, untreated hypothyroidism. The condition is a medical emergency and should be treated rapidly and aggressively. Mortality rate 30%–60%. Pharmacotherapy:  Intravenous thyroid hormone replacement (Some advocate the use of T3 over T4, given that T3). Hyperthyroidism (Thyrotoxicosis)  Etiology Thyrotoxicosis (increased hormone synthesis): 1. Graves’ disease. 2. Multinodular goiter. 3. Toxic single adenoma. 4. Iodine induced. Thyroiditis (thyroid destruction and leakage of stored thyroid hormones). 1. Acute. 2. Silent. 3. Amiodarone induced.  Graves’ Disease. Is the commonest cause of thyrotoxicosis. It is an autoimmune condition, results from production of an abnormal IgG immunoglobulin which can occupy the TSH receptor on the thyroid follicular cell.  Nodular disease Also known as Toxic multinodular goiter (Plummer disease). Several autonomous follicles that, if large enough, cause excessive thyroid hormone secretion. Clinically, the thyrotoxicosis is generally less severe and more gradual in onset.  Also called Painful subacute thyroiditis. Due to inflammation by a viral Thyroiditi infection or rapid autoimmune attack, resulting in follicular cell s death will result in the release of pre-formed thyroid hormones. Self-limiting, there is a brief period of hyperthyroidism before thyroid hormone levels fall to subnormal.  Clinical Manifestations. Characterized by increases in metabolic rate and activity of many systems. The signs and symptoms reflect increased adrenergic activity, especially in the cardiovascular and neurological systems  Treatment Three forms of therapy are available: 1. Anti-thyroid drugs. 2. Surgery. 3. Radioactive iodine. There is no general agreement as to the specific indications for each form of therapy, and none of them is ideal.  Treatment In children, surgery may be difficult and the complication rate is higher. Also, radioiodine has been avoided due to potential thyroid malignancy. In pregnancy, radioiodine is not used due to the likelihood of producing a hypothyroid neonate. Surgery during pregnancy should be deferred to the second trimester. Most patients can be controlled with drugs.  Ablative Therapy Treatment that uses heat or cold to destroy, or ablate, cancer tumors. It is required for all patients with toxic multinodular goiters. Thyroid ablation can be achieved by 1. Radioiodine. 2. Surgery.  Radioactive iodine Radioiodine therapy is administered orally and is very effective for a large majority of patients. it is absorbed into the bloodstream in the gastrointestinal (GI) tract. It will concentrate in the thyroid gland, where it begins destroying the gland's cells. Contraindicated in pregnancy and breastfeeding.  Surgery Surgery is required for those patients with very large goiters.  β-Blockers Patients need to have their symptoms addressed and their thyrotoxicosis controlled. β-Blockers in standard antihypertensive doses are effective within hours and should be offered to patients with severe thyrotoxicosis. Mechanism of action: Blocks many hyperthyroidism manifestations mediated by β-adrenergic receptors; also may block (less active) T4 conversion to (more active) T3 when used at high. Non-selective agents (e.g. propranolol & nadolol) are preferred because they can impair the conversion of T4 to T3. Propranolol dosing (target resting HR ˂ 90 bpm). I. Initial: 20–40 mg by mouth three or four times daily. II. Maximal: 240–480 mg/day.  Iodide Iodine (I₂) refers to the neutral element, and iodide (I⁻) is its negatively charged ion form. It treats hyperthyroidism through a process known as the Wolff-Chaikoff effect. Wolff–Chaikoff is effective of rejecting a large quantity of imbibed iodide, and therefore preventing the thyroid from synthesizing large quantities of thyroid hormone.  Iodide Serum T4 levels may be reduced within 24 hours, and the effects may last for 2 - 3 weeks. Iodides are used most commonly in Graves disease before surgery and to quickly reduce hormone release in patients with thyroid storm. Potassium iodide is administered either as a saturated solution (contains up to 50 mg iodide/drop) or as Lugol’s solution (contains up to 8 mg iodide /drop) The typical starting dose is 120 - 400 mg iodide/day.  Iodide Iodide should not be given before radioactive iodine treatment because it inhibits concentration of the radioactivity in the thyroid gland. The most frequent toxic effects of iodide: hypersensitivity reactions, iodism (characterized by palpitations, depression, weight loss & pustular skin eruptions), and gynecomastia.  Antithyroid Drugs The thionamide agents use to treat hyperthyroidism Carbimazole (a prodrug for Propylthiour Methimazol methimazole - acil (PTU) e (MMI) available in some countries including Bahrain) They inhibit thyroid hormone synthesis. PTU has the added benefit of inhibiting the conversion of T4 to T3. They have immunosuppressant effects - in patients with Graves disease treated with thionamides, Ab levels and other immune mediators were found to decrease over time. Initial doses of antithyroid medications are high, then the dose can be reduced as the thyroid tests normalize Antithyroid drugs are used as primary therapy for Graves disease or as preparative therapy before surgery or radioactive iodine.  Antithyroid Drugs In most patients, there is no clear efficacy advantage of one thionamide over the other Thyroid function testing should be performed every 4 -to 6 weeks until stable. After initiating treatment, thyroid hormone levels drop within 2 - 3 weeks, and after 6 weeks, 90% of patients with Graves disease become euthyroid. The major SE of antithyroid drugs is agranulocytosis, which should be monitored by CBC and patients advised to seek medical help if severe mouth ulcers, sore throat or febrile illness occur. Hepatotoxicity (more with PTU) was also reported and hence LFTs need to be monitored  Thyroid Storm Thyroid storm is a life- threatening condition caused by severe thyrotoxicosis. S & S: high fever, tachycardia, tachypnea, dehydration, delirium, coma, and GI disturbances. Thyroid storm is precipitated in a previously hyperthyroid patient by infection, trauma,  Thyroid Storm Treatment: Short-acting β- Large doses of blocker such as IV or oral iodide PTU or MMI. IV esmolol – to – decrease Decrease reduce CA release of synthesis and activity on the thyroid release of thyroid periphery and hormones hormones CVS Supportive care might also be IV hydrocortisone is used needed: often because of the Paracetamol to suppress potential presence of fever adrenal insufficiency. Fluid and electrolyte Pharmacological dose of replacement steroids suppresses serum T3 levels Antiarrhythmic drugs  Nodular Goiters Thyroid nodules can present as hot (hyperfunctioning), cold (hypofunctioning), or multinodular. Malignancy should be considered if there is recent growth in a “cold” nodule Clinically suspicion for cancer should be raised in case of a firm nodule, a history of thyroid irradiation, or a strong family history of medullary thyroid carcinoma.  Nodular Goiters Acute pain within a goiter suggests an acute viral thyroiditis, which may be associated with transient hyperthyroidism. Thyroid function tests, including TSH and FT4 levels, and antibodies should be obtained. Treatment options: – Hyperthyroidism: Surgery, radioactive iodine – Hypothyroidism: thyroid-replacement therapy, if needed to correct. Thyroid-suppression therapy is not recommended for benign nodules.  Hyperthyroidism during Pregnancy Pregnancy may worsen or precipitate thyrotoxicosis in women with underlying Graves disease owing to the TSH agonist effect of β- hCG. Untreated maternal thyrotoxicosis may result in increased rates of miscarriage, premature delivery, eclampsia, and low-birth-weight infants. Fetal and neonatal hyperthyroidism may occur as a result of transplacental passage of TSH receptor antibodies with stimulatory activity Because radioactive iodine is contraindicated and surgery is best avoided during pregnancy,  Hyperthyroidism during Pregnancy PTU is considered the treatment of choice, particularly in the 1st trimester. MMI is believed to have greater teratogenic potential, so should be avoided. Patients receiving pre-pregnancy MMI should be switched to PTU as soon as pregnancy is confirmed. Lowest dose of PTU to maintain maternal euthyroidism should be used. Given the potential maternal adverse effects of PTU (e.g. hepatotoxicity), it may be preferable to switch to MMI in the 2nd & 3rd trimesters. Excessive doses of antithyroid therapy may suppress fetal thyroid function. Both PTU & MMI are secreted in breast milk, MMI is preferred in nursing mothers because of hepatotoxicity risk from PTU in the mother & infant. Thank You