Thyroid Disorders: Causes, Physiology, and Treatment - PDF

Thyroid Disorders Dr. Marian Sobhy Assistant professor of clinical pharmacy Beni-Suef University  Thyroid physiology The thyroid gland consists of two lobes connected with isthmus and is situated in the lower neck. The follicular cells of...

Thyroid Disorders Dr. Marian Sobhy Assistant professor of clinical pharmacy Beni-Suef University  Thyroid physiology The thyroid gland consists of two lobes connected with isthmus and is situated in the lower neck. The follicular cells of the gland synthesises, stores and releases two major metabolically active hormones: Tetra-iodothyronine (Thyroxine, T4) and tri-iodothyronine (T3) that are primarily responsible for regulation of metabolism. Most of the T4 is changed to T3 outside of the thyroid Thyroid hormones are essential for proper fetal growth and development, particularly of the central nervous system (CNS). After delivery, the primary role of thyroid hormone is in regulation of energy metabolism. Thyroid gland  Thyroid physiology These hormones can affect the function of virtually every organ in the body. The parafollicular cells of the thyroid gland produce calcitonin. T4 and T3 are produced by the organification of iodine in the thyroid gland. Iodine is actively transported into the thyroid follicular cells. This inorganic iodine is oxidized by thyroid peroxidase and covalently bound to tyrosine residues of thyroglobulin. These iodinated tyrosine residues, monoiodotyrosine and diiodotyrosine, couple to form T4 and T3.  Thyroid physiology Eighty percent of thyroid hormone is synthesized as T4.Thyroid hormones are released from the gland when needed, primarily under the influence of TSH. T4 and T3 are transported in the blood by three proteins ( albumin, thyroid binding globulin, transthyretin). T4 is 99.97% protein bound, and T3 is 99.7% protein bound, with only the unbound or free fractions physiologically active. The high degree of protein binding results in a long half-life of these hormones: approximately 7 to 10 days for T4 and 24 hours for T3.  Thyroid physiology Most of the physiologic activity of thyroid hormones is from the actions of T3. T4 can be thought of primarily as a prohormone. Eighty percent of needed T3 is derived from conversion of T4 to T3 in peripheral tissue under the influence of tissue deiodinases. These deiodinases allow end organs to produce the amount of T3 needed to control local metabolic functions.  Thyroid physiology Regulation of thyroid hormone synthesis The production and release of thyroid hormones are regulated by the hypothalamic–pituitary–thyroid axis. Hypothalamic thyrotropin-releasing hormone (TRH) stimulates the release of thyrotropin or thyroid- stimulating hormone (TSH) when there are physiologically inadequate levels of thyroid hormones. TSH promotes production and release of thyroid hormones. As circulating thyroid hormone levels rise to needed levels, negative feedback results in decreased release of TSH and TRH. Thyroid physiology Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates the anterior pituitary gland to release thyroid- stimulating hormone (TSH), which stimulates the thyroid gland to release hormones. These thyroid hormones reduce the secretion of TSH and TRH.  Hormones of thyroid glands Function of thyroid Function of calcitonin hormones Lowers blood calcium Increase rate of energy and phosphate ion release from concentration by carbohydrate, increase inhibiting bone rate of protein resorption and by synthesis, stimulate increasing excretion of activity in nervous these ions by kidney system Source of control : Source of control :TSH blood calcium hormone concentration  Thyroid disorders Thyroid disorders includes: Hypothyroidism Hyperthyroidism Goiter Thyroid nodules Thyroid cancer  Goiter Goiter is a swelling in the neck resulting from an enlarged thyroid gland. A goiter can be associated with a thyroid that is not functioning properly. A goiter may be associated with hypothyroidism, hyperthyroidism, or normal thyroid function  What causes goiter? Goiters have different causes, depending on their type. Simple goiters develop when the thyroid gland does not make enough hormones to meet the body's needs. Endemic goiters occur in people in certain parts of the world who do not get enough iodine in their diet (iodine is necessary to make thyroid hormone). Sporadic goiters, in most cases, have no known cause. In some cases, certain drugs can cause this type of goiter. For example, the drug lithium  Diseases and conditions that can cause goiter Graves' disease: is an autoimmune disease.In this case, the immune system attacks the thyroid gland and the thyroid grows larger. Hashimoto's disease This is another autoimmune disease. In this case, the disease causes inflammation (swelling) of the thyroid gland. This causes it to produce fewer thyroid hormones, resulting in a goiter.  Diseases and conditions that can cause goiter Nodular goiter. In this condition, growths called nodules occur on one or both sides of the thyroid gland, causing it to grow larger Thyroid cancer. Cancer of the thyroid gland often enlarges the thyroid. Pregnancy. Human chorionic gonadotropin, a hormone that a woman produces during pregnancy, can cause the thyroid to grow. Thyroiditis. Inflammation of the thyroid gland itself can cause the thyroid gland to grow. This can happen after the person has an illness caused by a virus, or after a woman gives birth.  Other risk factors for goiter Other risk factors for goiter include the following: Hereditary (inherited from family) Female gender Age over 40  Thyroid nodules Nodule refers to an abnormal growth of thyroid cells that may be solid or fluid- filled lumps within the thyroid. The vast majority of thyroid nodules are benign (noncancerous) and don't cause symptoms, but a small proportion of thyroid nodules do contain thyroid cancer. In order to diagnose and treat thyroid cancer at the earliest stage, most thyroid nodules need some type of evaluation. Thyroid nodules  Thyroid cancer Thyroid cancer is more common among women than men. About 2/3 of cases occur in people under age 55. Most cases of thyroid cancer have a good prognosis and high survival rates, especially when diagnosed in its early stages  Hypothyroidism Etiology Primary: gland related Secondary: Hypopituitarism Tertiary: Hypothalamic dysfunction (rare)  Etiology Primary Hypothyroidism is most common; it is due to disease in the thyroid, and thyroid- stimulating hormone (TSH) levels are high. Causes of Primary Hypothyroidism Autoimmune thyroiditis (Hashimoto disease) Iatrogenic (irradiation, surgery) Drugs (amiodarone, radiocontrast media, lithium, interferon-α, tyrosine kinase inhibitors) Silent thyroiditis (including postpartum) Iodine deficiency  Etiology Secondary hypothyroidism is less common; it is due to pituitary disease, and TSH levels are low Tertiary hypothyroidism occurs when insufficient TRH from the hypothalamus leads to insufficient release of TSH, which in turns causes inadequate thyroid stimulation Etiology  Risk Factors Age (older than 50) Female gender Obesity Thyroid surgery X-ray or radiation treatments to the neck  Clinical features Cardiovascular signs: Bradycardia CNS symptoms: Pericardial effusion Fatigue, lethargy, depression, inability to concentrate Cardiomegaly Hyperlipidemia Renal function: Constipation, ascites Impaired ability to excrete a water load Weight gain Cold intolerance Anemia: Rough, dry skin Impaired Hb synthesis Puffy face and hands Fe deficiency due to menorrhagia and Hoarse, husky voice impaired intestinal absorption Respiratory failure Folate def. due to impaired intestinal Menorrhagia, infertility, hyper- prolactinemia absorption Pernicious anemia Neuromuscular system: Muscle cramps Slow reflexes Carpal tunnel syndrome  Hashimoto’s Thyroiditis It is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on there may be no symptoms. Over time the thyroid may enlarge, forming a goiter. Hashimoto's thyroiditis is thought to be due to a combination of genetic and environmental factors. Risk factors include a family history of the condition and having another autoimmune disease. Hashimoto’s thyroiditis is about seven times more common in women than in men  Hashimoto’s Thyroiditis With this condition, the immune system attack the thyroid gland. Over time, this attack causes the thyroid to stop producing hormones which leads to hypothyroidism. The autoimmune inflammatory response results in a lymphocytic infiltration of the thyroid gland and its eventual destruction Patients with autoimmune thyroiditis (Hashimoto disease) have circulating antithyroid peroxidase antibody (anti-TPOAbs).  Hashimoto’s Thyroiditis Hashimoto’s thyroiditis is a commom cause of hypothyroidism and goiter especially in teens and young women. Diagnosis is confirmed with elevated blood TSH level, decreased T4 level and elevated anti-thyroid autoantibodies titres  Related Complications Myxedema coma is rare life-threatening clinical condition that represents severe hypothyroidism This condition usually occurs in patients with long- standing, undiagnosed hypothyroidism. Myxedema is also used to describe the dermatologic changes that occur in hypothyroidism and occasionally hyperthyroidism. In this setting, myxedema refers to deposition of mucopolysaccharides in the dermis, which results in swelling of the affected area.  Related Complications Myxedema Coma Symptoms Weakness. Confusion or non- responsiveness. Feeling cold. Low body temperature. Swelling of the body, especially the face, tongue, and lower legs. Difficulty breathing. low blood pressure, low blood sugar Management of Myxedema Coma Medical Treatment Support ventilation as respiratory failure is the major cause of death in myxedema coma Intravenous fluids Electrolytes replacement as necessary Thyroid hormones are usually administered intravenously to quickly correct the low thyroid hormone blood level. Oral thyroid hormone is usually not used for severe myxedema because it may take days or weeks to obtain the proper blood level, and swallowing pills may not be safe. L-thyroxine 0.2-0.5 mg IV bolus, followed by 0.1 mg IV until oral therapy is tolerated. This results in clinical response in hours Management of Myxedema Coma IV glucose if the blood sugar level is low Antibiotics if an infection is present Patients should be in ICU setting: following the start of treatment, careful monitoring, in the intensive care unit, is necessary.  Screening/Diagnosis Normal value of TSH level is (0.4-4.5mIU/L) A TSH level of 4.5 to 10 mIU/L may constitute mild or subclinical hypothyroidism. A TSH level greater than 10 mIU/L signifies overt hypothyroidism. Normal value of free T4 is (0.7–1.9 ng/dL ). Free T4 level less than (0.7 ng/dL) indicate hypothyrodism.  Diagnosis of Hypothyroidism Low freeT4 and high TSH is diagnostic of primary hypothyroidism Serum T3 levels are variable (maybe in normal range) Positive test for thyroid autoantibodies (anti- TPOAbs). PLUS an enlarged thyroid gland suggest Hashimoto’s thyroiditis TRH test may be done to differentiate pituitary from hypothalamic disease. Absence of TSH response to TRH indicates pituitary deficiency. In tertiary hypothyroidism administration of TRH produces increase in TSH. MRI of brain is indicated if pituitary or hypothalamic disease is suspected. Need to look for other pituitary deficiencies.  Treatment of Hypothyroidism There are three major goals in the treatment of hypothyroidism: replace the missing hormones (treatment with thyroxine to ensure that patients receive a dose that will restore well-being and that usually returns the TSH level to the lower end of the normal range relieve signs and symptoms achieve a stable biochemical euthyroid state.  Treatment of Hypothyroidism Despite the availability of a wide array of thyroid hormone products, it is clear that synthetic Levothyroxine (LT4) is the treatment of choice for almost all patients with hypothyroidism. LT4 mimics the normal physiology of the thyroid gland, which secretes mostly T4 as a prohormone. Peripheral tissues convert T4 to T3 as needed based on metabolic demands. If T3 is used to treat hypothyroidism, the peripheral tissues lose their ability to control local metabolic rates  Treatment of Hypothyroidism The initial dose of L-thyroxine. will depend on the patient's age, severity and duration of disease. In young, healthy patients with disease of short duration, L-thyroxine. may be commenced in a dose of 50–100 μcg daily. As the drug has a long half-life, it should be given once daily. The most convenient time is usually in the morning. After 6 weeks on the same dose (not a shorter interval as TSH takes this time to stabilise after a dose change), thyroid function tests should be checked. The TSH concentration is the best indicator of the thyroid state, and this should be used for further dosage adjustment.  Treatment of Hypothyroidism A raised TSH concentration indicates inadequate treatment. The majority of patients will be controlled with doses of 100–200 μcg daily, with few patients requiring more than 200 μcg. During pregnancy, an increase in the dose of thyroxine by 25–50% is needed to maintain normal TSH levels. Check TSH concentration every month during pregnancy as L-thyroxine dose requirement tends to go up as the pregnancy progresses.