Thyroid Disease                                                Part 1
                         by H. David Bergman, Ph.D.
Introduction                                         gland, it is rapidly converted to iodine and
Hypothyroidism and hyper...
neck symptoms, family history of thyroid             diffusely enlarged goiter, infiltrative
dysfunction, and/or a history...
results in cutaneous thickening and pigmentation     and has been implicated in hyperthyroidism. This
over the tibial aspe...
A common cause of hypothyroidism is                  The tricyclic antidepressants (i.e., imipramine)
associated with ther...
Table 1
                                     Examples of Thyroid Function Tests
                       Tests              ...
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Thyroid Disease Part 1


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Thyroid Disease Part 1

  1. 1. Thyroid Disease Part 1 by H. David Bergman, Ph.D. Dean, College of Pharmacy, Southwestern Oklahoma State University GOALS AND OBJECTIVES Goals: To provide the pharmacist with information regarding hypothyroidism and hyperthyroidism their symptoms, signs, diagnosis and etiologies. Objectives: After completing this article, the pharmacist should be able to: 1. List the major signs and symptoms of hypothyroidism and hyperthyroidism. 2. Discuss the diagnostic procedures involved with hypothyroidism and hyperthyroidism. 3. Describe the major causes of hypothyroidism and hyperthyroidism. 4. Discuss the primary laboratory procedures associated with hypothyroidism and hyperthyroidism. E.L.F. Publications, Inc. is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmaceutical education. This program has been approved for 1.5 contact hour (0.15 CEU). Universal Program Number 406-000-07-001-H01. The expiration date for this program is 2/05/10. 1
  2. 2. Introduction gland, it is rapidly converted to iodine and Hypothyroidism and hyperthyroidism are incorporated with tyrosine molecules to form common diseases of the thyroid gland which monoiodotyrosine (MIT) and diiodotyrosine affect about 1% to 4% of the population in the (DIT). Combinations of these molecules (i.e., United States. Females account for 75% of the DIT and MIT; DIT and DIT) form T3 and T4. thyroid disorders. The primary form of treatment These hormones are highly protein bound in the for these chronic disorders is pharmacological circulation. Only 0.2% of T3 and 0.02% of T4 intervention. Consequently, the pharmacist is are in the unbound form and active. often the health professional that can optimize Diagnostic Procedures patient care by appropriate counseling, detecting A variety of diagnostic procedures have been adverse effects and potential drug interactions, developed to evaluate thyroid function as well as and participating in the selection and evaluation aid in the diagnosis of thyroid disorders. Several of drug therapy. laboratory tests can assess thyroid homeostasis The Thyroid Gland and metabolic function. These tests evaluate The thyroid gland is located on top of the circulating hormone levels, glandular activity, trachea and is a highly vascular organ which hypothalmis-pituitary function, autoimmunity, consists of two lobes connected by a middle and various nonspecific metabolic indices. Initial section known as the isthmus. The thyroid gland screening tests for thyroid disorders should aids in the regulation and maintenance of normal include the resin triiodothyronine and thyroxine body metabolism, homeostasis and development. uptake and the free thyroxine index (FT4I). If The thyroid gland is responsible for synthesizing, hypothyroidism is suspected, then a thyroid storing and releasing triiodothyronine (T3; half- stimulating hormone (TSH) level as well as life = 1.5 days) and thyroxine (T4; half-life - 7 antibodies to thyroglobulin and the microsomal days), which are active hormones. antigen should be assessed. Conversely, triiodothyronine by RIA and the thyrotropin The activities involved with these processes releasing hormone (TRH) are of significant value occur via a complex negative feedback in determing the presence of hyperthyroid state. mechanism involving the thyroid gland and the Antibodies confirm the presence of an hypothalmic-pituitary axis. The negative autoimmune thyroid disorder, while radioactive feedback mechanism is associated with changing iodine uptake (RAIU) and thyroglobulin values levels of thyroid hormone. Low circulating levels are useful in evaluating a malignancy and of thyroid hormone initiate the release of TSH nodular disease. (thyroid stimulating hormone) from the pituitary and appear to influence the secretion of TRF A variety of nonspecific tests are associated with (thyrotropin releasing factor) from the thyroid function. Serum cholesterol, carotene, hypothalmus. These increased levels of TSH lactic dehydrogenase, and creatine enhance increased iodide trapping by the gland phosphokinase levels may be decreased in which eventually results in an increase in individuals with hyperthyroidism and elevated in synthesis and circulating thyroid hormone levels. those with hypothyroidism. As the thyroid hormone levels increase, the In addition, to thyroid function tests, an pituitary and hypothalmic centers impede release evaluation of individuals for thyroid disorders of TRF and further thyroid hormone must include an examination of the thyroid gland biosynthesis. As thyroid hormone levels to indicate any abnormalities (i.e., enlargement, decrease, the process is repeated. nodules) as well as an examination of other Both T4 and T3 synthesis occur in the thyroid organ systems to assess any effects associated gland, while T3 production also occurs as a with thyroid hormone functions. In addition, a result of monodeiodination of secreted T4. After complete history, including any symptoms the dietary inorganic iodide is trapped by the related to thyroid hormone functions, history of 2
  3. 3. neck symptoms, family history of thyroid diffusely enlarged goiter, infiltrative dysfunction, and/or a history of any chest or ophthalmopathy, dermopathy and acropathy. All neck irradiation as a child, must be completed. of these findings may not be present for any one case. The exact cause of Graves disease is As indicated, the thyroid gland is very complex unknown, but it is primarily a disease of females, and is associated with many normal physiological the average age of occurrence is between 30 and functions. The wide variety of complex thyroid 40 years, it has a familial association and stress function tests are very beneficial, but can be appears to be a factor in its occurrence. affected by other factors (i.e., drugs, diseases). For example, starvation, acute depression, and Many of the underlying factors appear to have chronic disorders affecting major organs may be an autoimmune component involving both associated with the appearance of thyroid humoral and cellular mechanisms. The diagnosis dysfunction as indicated by thyroid function of Graves disease is confirmed by elevated tests. However, thyroid hormone levels of various laboratory parameters, such as supplementation is usually not needed and may T3 and T4 and RAIU. In addition, antibodies are cause harm. In most of these situations, the present in approximately 80% of patients with reversal of apparent thyroid abnormality is Graves disease. associated with a control of normal physiological The thyroid gland in Graves disease is processes. Tables I and II provide information frequently diffusely enlarged and symmetric, regarding some thyroid function tests and the with a firm but rubbery consistency. Thrills (a drugs that alter them. vibration felt on palpitation) and bruits (a sound Symptoms of Hyperthyroidism heard in ausculation) may be found in the Hyperthyroidism or thyrotoxicosis is hyperfunctioning goiter. Bruits are more characterized by increased metabolism of all common and may be found over the entire gland. body systems which can be attributed to Both will disappear as a euthyroid state is excessive quantities of thyroid hormone. The reached. symptoms include muscle weakness, fatigue, Ocular manifestations vary from the palpitations, nervousness, insomnia, flushing, characterictic infiltration opthalmopathy of diarrhea, abnormal menstrual flow, and weight Graves disease to the noninfiltrative. The loss despite increased appetite. These symptoms noninfiltrative ocular problems result from are reflective of increased physiological effects. hyperactivity of the sympathetic system and can However, not all symptoms will be present in be found in any thyrotoxic condition. They are each patient. In some patients, particularly the usually reversible with control of the elderly with chronic disease, many of the typical thyrotoxicosis. The infiltrative ocular findings symptoms will not be present, but other are the most obvious in Graves disease. They symptoms such as low grade fever, delayed may be unilateral or bilateral and may not be speech and congestive heart failure will obscure reversible. Edema and swelling, photophobia, the diagnosis. This disorder is known as masked and conjunctivitis are common problems. hyperthyroidism. If this problem is not treated, Protrusion of the cornea more than normal coma and death can occur. (proptosis) results in a wide-eyed staring expression. Blindness resulting from venous Causes of Hyperthyroidism congestion and hemorrhage of the retina and Although the primary features of excessive optic nerve can occur. Ocular symptoms occur production of thyroid hormone and accelerated in approximately half the patients, while only five metabolism are common to hyperthyroid states, percent have severe problems. thyroxicosis is a disorder of multiple etiologies. Pretibial myxedema is an uncommon Graves disease or toxic diffuse goiter is mucopolysaccharide infiltration of the skin which characterized by symptoms of hyperthyroidism, a 3
  4. 4. results in cutaneous thickening and pigmentation and has been implicated in hyperthyroidism. This over the tibial aspects of the leg. Although appears to be related to the iodine content rather usually asymptomatic, this dermopathy can be than any pharmacological activity. treated with a topical corticosteroid. Hypothyroidism or myxedema is a state The least common of the major causes of characterized by a decrease in all body processes hyperthyroidism is toxic nodular disease or because of a lack of thyroid hormone. The Plummer s disease. It is characterized by an clinical features of hypothyroidism are often autonomous hyperfunctioning nodule of obscure and nonspecific. They include weight approximately five centimeters in diameter which gain despite limited intake, decreased sweating, produces larger than normal doses of hormone fatigue, mental and physical sluggishness, and suppression of normal thyroid tissue. This constipation, cold intolerance, muscle aches, and etiology is more common in patients in their fifth tingling. In addition, diminished sympathetic or sixth decade of life and is the most common tone may lead to drooping of the eyelids, form in the elderly. The nodule(s) may remain delayed deep tendon reflexes, dry brittle hair and asymptomatic for many years. However, toxicity nails, and cool, coarse skin. can occur in the later years. Since the conversion of carotene to vitamin A is Subacute thyroiditis is an inflammatory condition impeded in hypothyroidism, a yellowish tint may of the thyroid that is believed to have a viral be present on the palms of the hands. Both etiology. The symptoms are very similar to a cardiovascular and neurological manifestations viral infection and include malaise, flu-like indicate a slowing or low output effect. The symptoms and fever as well as localized swelling former may appear as angina or congestive heart of the gland and hyperthyroidism or failure, while the latter may be reflected in ECG hypothyroidism symptoms. Typically, conditions findings. associated with hyperthyroidism occur initially, Although renal disease is not apparent, but chronic inflammation eventually results in alterations in renal function, such as changes in hypothyroidism features. Subacute thyroiditis is antidiuretic hormone secretion and glomerular usually self-limiting and treatment consists of filtration rate, may occur. A comparison of the symptomatic measures (i.e., heat, rest, clinical features associated with hyperthyroidism analgesics). and hypothyroidism appears in Table III. Triiodothyronine toxicosis is characterized by Hypothyroidism can be goitrous or nongoitrous. normal levels of thyroxine and elevated levels of The goiters or enlargements of the thyroid result triiodothyronine. It is associated with Graves from excessive thyroid stimulating hormone disease, toxic goiters, and carcinomas. Elevated activity in response to reduced thyroid levels. levels of triiodothyronine often precede elevated Goitrous hypothyrodism disorders include thyroxine levels. endemic, multinodular, drug induced, Iatrogenic thyrotoxicosis has occurred with dyshormonogenesis, and Hashimoto s chemicals. Iodine has caused thyrotoxicosis in thyroiditis, while non-goitrous conditions are individuals who live in iodine deficient areas, caused by cretinism, iatrogenic and idiopathic then receive iodine supplementation. This has atrophy, and secondary hypothyroidism of been the most common mechanism associated pituitary or hypothalmic origin. with iodine, but thyrotoxicosis has occurred in Pituitary hypothyroidism can occur as a result of individuals following injection of radio contrast trauma, pituitary tumors or other diseases material. Lithium acts similarly to iodine in associated with abnormal pituitary gland preventing hormone release. Consequently, function. Hypothalmic hypothyroidism appears hyperthyroidism can occur after its withdrawal. to be a rare disease which results in part from Amiodarone contains large amounts of iodine inadequate thyrotropin releasing factor secretion. 4
  5. 5. A common cause of hypothyroidism is The tricyclic antidepressants (i.e., imipramine) associated with therapy for hyperthyroidism. have also been associated with the development Iatrogenic hypothyroidism occurs in some of the of goiter. Tolbutamide has been shown to inhibit patients receiving radioactive iodine and/or iodide binding which can result in a reduction of surgery. thyroid hormone. Dietary goitrogens, such as cabbage, normally do not produce any significant Iodiopathic atrophy of the thyroid gland appears degree of hypothyroidism unless large quantities to be associated with antibodies involved in a are consumed for long periods of time. destructive immune process. Dyshormonogenesis refers to a specific group of Cretinism or congenital hypothyroidism is familial thyroid disorders which are associated attributed to an in utero deficiency of thyroid with abnormalities in synthesis, delivery, or hormone or may result from defective hormone peripheral action of thyroid hormones. These synthesis, incomplete development of the thyroid disorders can result from a variety of gland, or pituitary or hypothalmic dysfunction in impairments (i.e., lack of converting enzyme, the newborn. The clinical features vary with impaired release processes) and are detected regard to the amount, age of onset, and duration primarily by elimination of other causes. of thyroid hormone deficiency. The initial features include prolonged jaundice, Chronic thyroiditis or Hashimoto s thyroiditis is constipation, drooling, hypothermia, a heavy characterized by diffuse enlargement and expression, umbilical hernia, hoarseness, and a lymphocytic infiltration of the thyroid, an protruding abdomen. After three to six months, immunological abnormality and hypothyroidism. poor appetite, growth retardation and It is a frequent cause of hypothyroidism and is development, and failure to thrive become more 10 to 20 times more common in females, with apparent. However, neurological damage may the middle ages the peak for occurrence. Like already be irreversible. In many cases, an early Graves disease, there appears to be familial recognition of the problem may be possible by a factors involved in its development. Evidence radioimmune assay of thyroid stimulating indicates that many of the major factors and hormone in cord blood. processes associated with Hashimoto s thyroiditis have an autoimmune basis or Endemic goiter is the general term used to component. describe thyroid enlargement associated with iodine deficiency which is encountered in a significant amount of the population. As with other thyroid diseases, females are affected more frequently than males. The quantity of dietary iodine will usually determine the degree of enlargement which becomes nodular with advancing years. Goiters may occur as a result of drug use. Drugs used to treat hyperthyroidism, such as iodides or thioamides, may cause goiter if excessive doses are employed. Lithium has been implicated as a goitrogen when administered to individuals with abnormal glands. This effect may appear after several months to several years of therapy. If the disease is treated with thyroxine (T4) or lithium is discontinued, the goiters usually respond. 5
  6. 6. Table 1 Examples of Thyroid Function Tests Tests Hyperthyroidism Hypothyroidism Protein Bound Iodine (PBI) Increase Decrease Thyroxine (T4) Increase Decrease Resin Triiodothyronine Uptake (RT3U) Increase Decrease Thyroxine Uptake (RT4) Increase Decrease Free Thyroxine Index (FT4I) Increase Decrease Triiodothyronine (T3) Increase Decrease Free Triiodothyronine Index (FT3I) Increase Decrease Radioactive Iodine Uptake (RAIU) Increase Decrease Thyrotropin Stimulating Hormone (TSH) Decrease Increase Triiodothyronine Suppression Test Nonsuppression Nonsuppression Thyrotropin Releasing Hormone Test (TRH) No response Response Thyroid Scan Enlarged Hypofunction Table 2 Examples of Drugs Which May Affect Thyroid Function Test Drugs Suspected Mechanism Estrogens Increase serum thyroxine Binding Oral Contraceptives Globulin (TBG) concentrations Clofibrate Anabolic Steroids Decrease Serum TBG Concentrations Danazol Glucocorticoids Phenylbutazone Displacement of T4 and T3 from TBG Mitotane Chloral Hydrate 5 - FU Tincture of Iodine Dilute Total Body Iodide Pools SSK I Lugol s Solution Iodide Compounds Furosemide Decrease Total Iodide Pools Ethacrynic Acid Phenobarbital Hepatic Enzyme Induce of T4 Metabolism Amiodarone Impair Conversion of T4 to T3 Table 3 Clinical Features Associated With Hyperthyroidism & Hypothyroidism Feature Hypothyroidism Hyperthyroidism Hair Dry, brittle, sparse Thinning, fine texture Eyes Ptosis, Edematous eyelids Prominence of the eyes Temperature Cold intolerance Heat intolerance Weight Weight gain despite decreased appetite Weight loss despite increased appetite Cardiac Cardiac enlargement, low output CHF Palpitations, High output CHF Emotional Depressed; lethargic; increased sleep Nervous, irritable, insomnia needs Neuromuscular Delayed deep tendon reflexes Rapid deep tendon reflexes Gastrointestinal Constipation Diarrhea Genitouinary Dysmenorrhea, Menorrhagia Amenorrhea, decreased length of menstrual flow Extremities cold and dry skin hot and moist skin 6