Hyperthyroidism PDF Lecture Slides

HYPERTHYROIDISM Dr. Marian Sobhy Assistant professor of clinical pharmacy Beni-Suef University  Hyperthyroidism/thyrotoxicosis Hyperthyroidism is defined as the production of excessive amounts of thyroid hormones by the thyroid gland and accelerated metabolism in the periphera...

HYPERTHYROIDISM Dr. Marian Sobhy Assistant professor of clinical pharmacy Beni-Suef University  Hyperthyroidism/thyrotoxicosis Hyperthyroidism is defined as the production of excessive amounts of thyroid hormones by the thyroid gland and accelerated metabolism in the peripheral tissues. Thyrotoxicosis refers to the clinical syndrome associated with prolonged exposure to elevated levels of thyroid.  Hyperthyroidism/thyrotoxicosis The secretion of thyroid hormone is no longer under the regulatory control of the hypothalamic-pituitary center. Having this conditions also means that there is a low level of thyroid stimulating hormone) TSH) in bloodstream, because the pituitary gland senses that there is“enough” thyroid hormone in the blood.  What causes hyperthyroidism? Thyroiditis: inflammation of the thyroid leads to irritation of thyroid allowing too much thyroid hormone to enter blood. This can lead to pain and discomfort. Pregnancy can also lead to thyroiditis that is usually short-term. Tyroid nodules: they are common in both hypothyroidism and hyperthyroidism. In hyperthyroidism, these nodules can lead to an increase in thyroid’s size and production of too much thyroid hormone. There is no known cause of this.  What causes hyperthyroidism? An autoimmune condition : known as Graves’ disease is the most common cause of hyperthyroidism. It causes antibodies to stimulate the thyroid to secrete too much hormone. Benign tumors of the thyroid Large amounts of tetraiodothyronine taken through dietary supplements or medication Excess iodine, a key ingredient in T4 and T3 Trophoblastic (hCG-secreting) tumors  Graves’ disease Graves’ disease is an autoimmune disorder. It causes thyroid gland to create too much thyroid hormone in the body causing hyperthyroidism. In Graves’ disease, immune system creates antibodies known as thyroid-stimulating receptor antibodies (TSHR ab) that bind to the TSHr and chronically stimulate it causing the thyroid to create too much thyroid hormone. Graves’ disease occurs more often in women than in men. It tends to run in families, which suggests a genetic link.  Clinical symptoms High amounts of T4 and T3 can cause an excessively high metabolic rate. This is called a hypermetabolic state. When in a hypermetabolic state, heart may experience a rapid heart rate, increased cardiac output (due to increased oxygen demand) , heart failure, elevated blood pressure, and hand tremors. sweat a lot and develop a low tolerance for heat.  Clinical symptoms GI System  Hyperthyroidism can cause more frequent bowel movements, weight loss, due to increased calorigenesis  Malabsorption  Steatorrhea Women  irregular menstrual cycles  Anovulatory infertility Men  Gynecomastia( development of breast in men)  Decreased libido( sexual desire)  Decreased or abnormal sperm Serum Lipids Low total cholesterol  Clinical symptoms Eyes Exophthalmos : bulging of the eye as the immune system attacks the muscles and fatty tissues around and behind the eye, making them swollen anteriorly out of the orbit Impaired eye muscle function (Diplopia: the simultaneous perception of two images of a single object) conjunctival edema and pain in the eyes Corneal ulceration Optic neuritis and even blindness Clinical symptoms Exophthalmos  Clinical symptoms Skin Warm May be erythematous (due to increased blood flow) Sweating and heat intolerance Onycholysis: loosening of nail beds and softening of nails resulting in painless detachment of the nail from the nail bed Clinical symptoms Onycholysis  Clinical symptoms Other symptoms of weakness hyperthyroidism irregular heartbeat include: difficulty sleeping increased appetite fine, brittle hair nervousness itching restlessness hair loss inability to concentrate  Diagnosis The first step in diagnosis is to get a complete medical history and physical exam. This can reveal these common signs of hyperthyroidism: weight loss rapid pulse elevated blood pressure protruding eyes enlarged thyroid gland  Diagnosis Other tests may be performed to further evaluate diagnosis. These include:  Cholesterol test Low cholesterol can be a sign of an elevated metabolic rate, in which body is burning through cholesterol quickly.  Free T4, T3 These tests measure the increase in thyroid hormone (T4 and T3) in the blood.  Diagnosis  Thyroid stimulating hormone level test When thyroid hormone levels are normal or high, TSH should be lower. An abnormally low TSH can be the first sign of hyperthyroidism.  Triglyceride test Triglyceride level may also be tested. Similar to low cholesterol, low triglycerides can be a sign of an elevated metabolic rate.  Diagnosis Ultrasound Ultrasounds can measure the size of the entire thyroid gland, as well as any masses within it. Doctors can also use ultrasounds to determine if a mass is solid or cystic. CT or MRI scans A CT or MRI can show if a pituitary tumor is present that’s causing the condition.  Treatment of hyperthyroidism β-Blockers Because many of the manifestations of hyperthyroidism appear to be mediated by the β-adrenergic system, β-adrenergic blockers (such as propranolol) can rapidly relieve tremor, anxiety, and heat intolerance and control rapid pulse, sweating, and high blood pressure. Because β-blockers do not reduce the synthesis of thyroid hormones, they are used only until more specific antithyroid therapy is effective.  Treatment of hyperthyroidism Methods to Reduce Thyroid Hormone Synthesis Excess production of thyroid hormone can be reduced in four ways: Iodides Antithyroid drugs Radioactive iodine Surgery.  Treatment of hyperthyroidism 1- Iodide Potassium iodide is administered either as a saturated solution (SSKI) that contains 38 mg iodide per drop or as Lugol solution, which contains 6.3 mg iodide per drop. The usual dose of Lugol’s solution is 3 to 5 drops three times daily, and that of SSKI is 1 to 3 drops three times daily.  Treatment of hyperthyroidism Large doses of iodide inhibit the synthesis and release of thyroid hormones. Serum T4 levels may be reduced within 24 hours, and the effects may last for 2 to 3 weeks. Acute iodide excess results in decreased intrathyroidal organification and release of thyroid hormones from the thyroid gland, a process known as the Wolff–Chaikoff effect, that is a presumed reduction in thyroid hormone levels caused by ingestion of a large amount of iodine.  Treatment of hyperthyroidism This is due to inhibition of the peroxidase enzyme organification of iodide. It is proposed that iodopeptide(s) are formed that temporarily inhibit thyroid peroxidase (TPO) mRNA and protein synthesis and, therefore, thyroglobulin iodinations. The acute Wolff-Chaikoff effect lasts for few days and then, through the so-called "escape phenomenon ", the organification of intrathyroidal iodide resumes and the normal synthesis of thyroxine (T4) and triiodothyronine (T3) returns.  Treatment of hyperthyroidism Escape phenomenon occur as a result of autoregulatory mechanisms that inhibit thyroid iodide transport, and decrease inorganic iodine concentration inside the thyroid follicle below a critical threshold (falls below the level required for inhibition of organification) secondary to down- regulation of sodium-iodide symporter (NIS) on the membrane of the thyroid follicular cell.  Treatment of hyperthyroidism Failure to escape results in hypothyroidism, which occurs in the presence of underlying thyroid disease, such as chronic autoimmune thyroiditis, postpartum thyroiditis or surgical therapy. Preterm babies are particularly susceptible to iodine-induced hypothyroidism because of the immaturity of the autoregulation of the thyroid gland.  Treatment of hyperthyroidism These effects are, however, transient and last a few days or weeks, after which the antithyroid action of pharmacologic iodine is lost and thyrotoxicosis recurs or worsens. Short-term iodide therapy is used to prepare patients for surgery, usually in combination with a thionamide drug. Iodine is also used in the management of severe thyrotoxicosis (thyroid storm) because of its ability to inhibit thyroid hormone release acutely.  Treatment of hyperthyroidism 2- Antithyroid Drugs The thionamide agents propylthiouracil (PTU) and methimazole (MMI) are used to treat hyperthyroidism. Carbimazole, an MMI prodrug, is used in some countries (10 mg carbimazole = 6 mg MMI). These drugs inhibit thyroid hormone synthesis by interfering with thyroid peroxidase–mediated iodination of tyrosine residues in thyroglobulin.  Treatment of hyperthyroidism PTU has the added effect of inhibiting the conversion of T4 to T3. The thionamides also have immunosuppressant effects. In patients with Graves disease treated with thionamides, TSHr-Ab levels and other immune mediators decrease over time. Both drugs are well absorbed from the gastrointestinal (GI) tract. PTU has a half-life of 1 to 2.5 hours, whereas the half-life of MMI is 6 to 9 hours.  Treatment of hyperthyroidism MMI use has increased dramatically since the mid-1990s compared to PTU. Although PTU has the advantage of inhibiting T4-to-T3 conversion, MMI can be given as a single daily dose and may have a better overall safety profile, particularly less hepatotoxicity. Antithyroid drugs are used as primary therapy for Graves disease or as preparative therapy before surgery or radioactive iodine administration.  Treatment of hyperthyroidism Remission of Graves disease occurs in 40% to 60% of patients after 1 to 2 years of therapy. Antithyroid therapy may be stopped or tapered after 12 to 24 months. Relapse usually occurs in the first 3 to 6 months after stopping antithyroid therapy.  Treatment of hyperthyroidism Side effects of Antithyroid drugs Antithyroid drugs are associated with an overall low rate of adverse effects, although serious adverse effects can occur. Skin rash, arthralgias, and GI upset are seen in 5% of patients. Hepatotoxicity is an uncommon but potentially serious or fatal adverse effect, occurring in 0.1% to 0.2% of patients. However, transient rises in aminotransferase enzyme levels are seen in up to 30% of patients treated with PTU. Agranulocytosis is one of the most serious adverse effects of antithyroid drug therapy.  Treatment of hyperthyroidism 3- Radioactive Iodine Radioactive iodine, typically I, produces thyroid ablation without surgery. I is well absorbed after oral administration. The iodine is concentrated in the thyroid gland and has a half-life of 8 days. Over a period of weeks, thyroid cells that have taken up the I begin to develop abnormalities and necrosis. Eventually, thyroid cells are destroyed, and hormone production is reduced.  Treatment of hyperthyroidism After a single dose, 40% to 70% of patients will be euthyroid in 6 to 8 weeks, and 80% will be cured. In most patients, hypothyroidism will develop, and long-term LT4 replacement will be necessary. Because I has a slow onset of action, most patients are treated initially with β-blockers and antithyroid drugs to prevent I-induced thyroid storm. MMI is the preferred agent before the administration of I.  Treatment of hyperthyroidism MMI is discontinued 3 to 5 days before the administration of I (otherwise, the isotope will not be trapped by the thyroid). Since the ablative effect of radioiodine usually commences within 2–3 months, many patients with mild or moderate disease will not need to restart their drug treatments, though close patient monitoring is required. Treatment of hyperthyroidism Patients with severe thyrotoxicosis should restart their antithyroid drugs on day 3. MMI is then withdrawn periodically over the next 4 to 6 weeks as thyroid function normalizes to assess the effects of the radioiodine. β-Blockers can be continued during I therapy. Radioactive iodine therapy is contraindicated during pregnancy and breastfeeding. Common side effects include dry mouth, dry eyes, sore throat, and changes in taste.  Treatment of hyperthyroidism 4- Surgery Subtotal thyroidectomy is indicated in patients with very large goiters and thyroid malignancies and those who do not respond or cannot tolerate other therapies. Patients must be euthyroid before surgery, and they are often administered iodide preoperatively to reduce gland vascularity.  Treatment of hyperthyroidism Postoperative hypothyroidism occurs in 10% of patients who undergo subtotal thyroidectomy. After thyroidectomy, serum calcium and intact parathyroid hormone levels should be monitored for early identification of postoperative hypoparathyroidism. Postoperative administration of calcium and calcitriol may be given and then tapered over 1 to 2 weeks if the patient does not develop hypoparathyroidism. Graves Disease and 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 TSHr-abs.  Graves Disease and Pregnancy Because radioactive iodine is contraindicated and surgery is best avoided during pregnancy, most patients are treated with antithyroid drugs. PTU is considered the treatment of choice, particularly in the first trimester. While MMI is thought to have greater teratogenic potential versus PTU. Patients receiving prepregnancy MMI should be switched to PTU as soon as the pregnancy is confirmed.  Graves Disease and Pregnancy The lowest possible dose of PTU to maintain maternal euthyroidism should be used. Given the potential maternal adverse effects of PTU (eg, hepatotoxicity), it may be preferable to switch from PTU to MMI for the second and third trimesters. Antithyroid therapy in excessive doses may suppress fetal thyroid function.  Graves Disease and Pregnancy Although PTU and MMI are found in breast milk, nursing mothers should be switched to MMI after delivery because of the risk of hepatotoxicity from PTU in the mother and infant.  Pediatric Hyperthyroidism Pediatric Hyperthyroidism β-Blockers are administered to children who are symptomatic or have a heart rate greater than 100 beats/min. MMI is the preferred antithyroid drug therapy in children at a dose of 0.2 to 0.5 mg/kg/day. Once a euthyroid state is achieved, the MMI dose can be reduced by 50% or more to maintain euthyroidism.  Pediatric Hyperthyroidism As in adults, antithyroid drugs are administered to children with Graves disease for 1 to 2 years.  Thyroid Storm Thyroid storm is a life-threatening condition caused by severe thyrotoxicosis. Signs and symptoms include high fever, tachycardia, tachypnea, dehydration, delirium, coma, and GI disturbances. Thyroid storm is precipitated in a previously hyperthyroid patient by infection, trauma, surgery, and sudden withdrawal from antithyroid drugs.  Thyroid Storm Patients with thyroid storm are treated with a short-acting β-blocker such as intravenous (IV) esmolol, IV or oral iodide large doses of PTU (500–1000 mg load; then 250 mg every 4 hours) or MMI (60–80 mg/day). Supportive care with acetaminophen to suppress fever fluid and electrolyte management  Thyroid Storm antiarrhythmic agents are important components of therapy. IV hydrocortisone 300 mg initially and then 100 mg every 8 hours is used often because of the potential presence of adrenal insufficiency.