WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

SJIF Impact Factor 5.210

Volume 5, Issue 1, 244-258

Review Article

ISSN 2278 – 4357

A REVIEW ON THYROID GLAND AND RELATED DISORDERS *Gopala Krishna Ch, Aparna S, Gopi M, Ashok Kumar D, Nagababu P, Swarna Latha P, Sudhakar Babu A M S *Department of Pharmacology, A M Reddy Memorial College of Pharmacy, Petlurivaripalem, Narasaraopet, Guntur [District], Andhra Pradesh. 522601.

Article Received on 28 Oct 2015, Revised on 19 Nov 2015, Accepted on 12 Dec 2015

ABSTRACT In the present paper, we review about the thyroid gland which is one of the examples of endocrine system. The endocrine system and endocrine organs, like the thyroid, undergo important functional changes. The prevalence of thyroid disorders increases with numerous

*Correspondence for Author

morphological and physiological changes of the thyroid gland. In this,

Gopala Krishna Ch

we review on the thyroid gland structure, and the hormones related or

Department of

released by the thyroid gland, the thyroid evaluation, hyperthyroidism,

Pharmacology, A M

hypothyroidism, including their sign and symptoms, thyroid carcinoma

Reddy Memorial College

and goiter.

of Pharmacy, Petlurivaripalem, Narasaraopet, Guntur [District], Andhra Pradesh. 522601.

KEYWORDS: Thyroid gland, hyperthyroidism, hypothyroidism, thyroid evaluation, thyroid carcinoma, goiter. INTRODUCTION

Thyroid is a small gland found at the base of neck. Thyroid makes thyroid hormone. Thyroid hormone controls many activities in body, including how fast calories can burn and how fast the heart beats. Diseases of the thyroid cause it to make either too much or too little of the hormone. Women are more likely than men to have thyroid diseases. Thyroid gland is brownish-red and soft during life Usually weighs about 25- 30g (larger in women) Surrounded by a thin, fibrous capsule of connective tissue External to this is a ―false capsule‖ formed by pretracheal fascia Right and left lobes United by a narrow isthmus, which extends across the trachea anterior to second and third tracheal cartilages In some people a third ―pyramidal lobe‖ exists, ascending from the isthmus towards hyoid bone. The thyroid gland is composed of 2 lobes connected by an isthmus. It is surrounded by a dense irregular collagenous connective tissue capsule, in which (posteriorly) the parathyroid glands are www.wjpps.com

Vol 5, Issue 1, 2016.

244

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

embedded. The thyroid gland is subdivided by capsular septa into lobules containing follicles. These septa also serve as conduits for blood vessels. Lymphatic vessels & nerves. Figure 1

Synthesis of thyroid hormones Dietary iodine is essential for synthesis of thyroid hormones. Iodine, after conversion to iodide in the stomach, is rapidly absorbed from the gastrointestinal tract and distributed in the extracellular fluids. After active transport from the blood stream across the follicular cell basement membrane, iodide is enzymatically oxidized by thyroid peroxidase, which also mediates the iodination of the tyrosine residues in thyroglobulin to form monoiodotyrosine and diiodotyrosine. The iodotyrosine molecules couple to form T4 (3,5,3¢,5¢tetraiodothyronine) or T3 (3,5,3¢-triiodothyronine). Once iodinated, thyroglobulin containing newly formed T4 and T3 is stored in the follicles. Secretion of free T4 and T3 into the circulation occurs after proteolytic digestion of thyroglobulin, which is stimulated by thyroidstimulating hormone (TSH). Deiodination of monoiodotyrosine and diiodotyrosine by iodotyrosine deiodinase releases iodine, which then reenters the thyroid iodine pool.

www.wjpps.com

Vol 5, Issue 1, 2016.

245

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Figure 2

Structures of T3 and T4 hormones Figure 3

THYROID HORMONE TRANSPORT T4 and T3 are tightly bound to serum carrier proteins: thyroxine-binding globulin (TBG), thyroxine-binding pre-albumin, and albumin. The unbound or free fractions are the biologically active fractions and represent only 0.04% of the total T4 and 0.4% of the total T3.

www.wjpps.com

Vol 5, Issue 1, 2016.

246

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Thyroid Evaluation Thyroid gland function and structure can be evaluated by (1) serum thyroid hormone levels, (2) imaging of thyroid gland size and architecture, (3) measurement of thyroid autoantibodies, and (4) thyroid gland biopsy (by fine-needle aspiration [FNA]). TESTS OF SERUM THYROID HORMONE LEVELS Total serum T4 and T3 measure the total amount of hormone bound to thyroid-binding proteins by radioimmunoassay. Total T4 and total T3 levels are elevated in hyperthyroidism and low in hypothyroidism. Increase in TBG (as with pregnancy or estrogen therapy) increases the total T4 and T3 measured in the absence of hyperthyroidism. Similarly, total T4 and T3 are low despite euthyroidism in conditions associated with low thyroid-binding proteins (e.g., cirrhosis or nephrotic syndrome). Thus, further tests to assess the free hormone level that reflects biologic activity must be performed. Free T4 level can be estimated by calculating the free T4 index or can be measured directly by dialysis. The free T4 index is an indirect method of assessing free T4. It is derived by multiplying the total T4 by the T3 resin uptake, which is inversely proportional to the available T4 binding sites on TBG. Free T4 can be measured directly by dialysis or ultrafiltration. This is more accurate and is preferred to the free T4 index. Serum TSH is measured by a third-generation immunometric assay, which employs at least two different monoclonal antibodies against different regions of the TSH molecule, resulting in accurate discrimination between normal TSH levels and levels below the normal range. Thus, the TSH assay can diagnose clinical hyperthyroidism (elevated free T4 and suppressed TSH) and subclinical hyperthyroidism (normal free T4 and suppressed TSH). In primary (thyroidal) hypothyroidism, serum TSH is supranormal because of diminished feedback inhibition. In secondary (pituitary) or tertiary (hypothalamic) hypothyroidism, the TSH is usually low but may be normal. Serum thyroglobulin measurements are useful in the follow-up of patients with papillary or follicular carcinoma. After thyroidectomy and iodine-131 (131I) ablation therapy, thyroglobulin levels should be less than 2mg/L while the patient is on suppressive levothyroxine treatment. Levels in excess of this value indicate the presence of persistent or metastatic disease. Calcitonin is produced by the medullary cells of the thyroid. Calcitonin measurements are invaluable in the diagnosis of medullary carcinoma of the thyroid and for following the effects of therapy for this entity.

www.wjpps.com

Vol 5, Issue 1, 2016.

247

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Comparison of serum concentrations of T3 and T4. Table: 1

Serum concentration

T4

T3

100 nmol/l

2 nmol/1

20 pmol/l (0.02%)

5 pmol/l (0.4%)

Total Free (%)

Physiologic Effects of Thyroid Hormone 

Cardiovascular Effects



Increased heart rate and cardiac output



Gastrointestinal Effects



Increased gut motility



Skeletal Effects



Increased bone turn over and resorption



Pulmonary Effects



Maintenance of normal hypoxic and hypercapnic drive in the respiratory center



Neuromuscular Effects



Increased muscle protein turnover and increased speed of muscle contraction and relaxation



Lipids and Carbohydrate Metabolism Effects



Increased hepatic gluconeogenesis and glycogenolysis as well as intestinal glucose absorption Increased cholesterol synthesis and degradation Increased lipolysis



Sympathetic Nervous System Effects



Increased numbers of b-adrenergic receptors in the heart, skeletal muscle, lymphocytes, and adipose cells Decreased cardiac a-adrenergic receptors Increased catecholamine sensitivity



Hematopoietic Effects



Increased red blood cell 2,3-diphosphoglycerate, facilitating oxygen dissociation from hemoglobin with increased oxygen available to tissues.

Hyperthyroidism Hyperthyroidism, or overactive thyroid, causes the thyroid gland to produce more thyroid hormone than the body needs. Hyperthyroidism occurs when the thyroid makes too much t4, t3, or both. A variety of conditions can cause hyperthyroidism. Graves' disease, an autoimmune disorder, is the most common cause of hyperthyroidism. It causes antibodies to www.wjpps.com

Vol 5, Issue 1, 2016.

248

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

stimulate the thyroid to secrete too much hormone. Graves’ disease occurs more often in women than in men. It tends to run in families, which suggests a genetic link. Excess iodine, a key ingredient in T4 and T3 inflammation of the thyroid (thyroiditis) that causes T4 and T3 to leak out of the gland tumors of the ovaries or testes benign tumors of the thyroid or pituitary gland large amounts of tetraiodothyronine taken through dietary supplements or medication causes hyper thyroidisam. Figure 4

Signs and symptoms Symptoms can include weight loss, eating more than usual, rapid heartbeat, feeling nervous or anxious, irritability, trouble sleeping, trembling hands, increased sweating, feeling hot more easily, muscle weakness, diarrhea or more bowel movements than normal, and fewer and lighter menstrual periods than usual, frequent bowel movements. increased appetite, nervousness, restlessness, inability to concentrate, weakness, Irregular heartbeat ,difficulty sleeping, fine, brittle hair, itching, hair loss, nausea and vomiting, breast development in men. Diagnose of Hyperthyroidism The first step in diagnosis is to get a complete history and physical exam. This can reveal these common signs of hyperthyroidism are weight loss, rapid pulse, elevated blood pressure, protruding eyes and enlarged thyroid gland. Cholesterol Level Test Low cholesterol can be a sign of an elevated metabolic rate, in which your body is burning through cholesterol quickly.

www.wjpps.com

Vol 5, Issue 1, 2016.

249

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

T4 and T3 Resin Uptake (T3RU) Tests These tests measure how much thyroid hormone (T4 and T3) is in blood. Thyroid Stimulating Hormone (TSH) Level Test Thyroid stimulating hormone (TSH) is a pituitary gland hormone that stimulates the thyroid gland to produce hormones. When thyroid hormone levels are normal or high, your TSH should be lower. Triglyceride Level Test The triglycerides level may also be tested. Similar to low cholesterol, low triglycerides can be a sign of an elevated metabolic rate. Thyroid Scan and Uptake This allows knowing the thyroid is overactive. In particular, it can tell if the entire thyroid or just a single area of the gland is causing the over activity. Ultrasound Ultrasound can measure the size of the entire thyroid gland, as well as any masses within it. Doctors can also use ultrasound to know 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. Treat of Hyperthyroidism: Medication Antithyroid medications, such as methimazole (Tapazole), stop the thyroid from making hormones. Radioactive Iodine Radioactive iodine effectively destroys the cells that produce hormones. Antithyroid medications and radioactive iodine are common treatments. The downside is that these medications can have severe side effects, such as low white blood cell count. White blood cells are crucial to immune function.

www.wjpps.com

Vol 5, Issue 1, 2016.

250

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Surgery A section or all of your thyroid gland may be surgically removed. You will then have to take thyroid hormone supplements to prevent hypothyroidism, which occurs when you have an underactive thyroid that secretes too little hormone. Also, beta blockers, such as propranolol, can help control your rapid pulse, sweating, anxiety, and high blood pressure. Most people respond well to this treatment. Hypo thyroidisam Hypothyroidism, or underactive thyroid, is when your thyroid does not make enough thyroid hormones. Hypothyroidism is a clinical syndrome caused by defi- ciency of thyroid hormones. In infants and children, hypothyroidism causes retardation of growth and development and may result in permanent motor and mental retardation. Congenital causes of hypothyroidism include agenesis (complete absence of thyroid tissue), dysgenesis (ectopic or lingual thyroid gland), hypoplastic thyroid, thyroid dyshormogenesis, and congenital pituitary diseases. Adult-onset hypothyroidism results in a slowing of metabolic processes and is reversible with treatment. Hypothyroidism (Table 65–4) is usually primary (thyroid failure), but it may be secondary (hypothalamic or pituitary deficiency) or due to resistance at the thyroid hormone receptor. In adults, autoimmune thyroiditis (Hashimoto’s thyroiditis) is the most common cause of hypothyroidism. This may be isolated or part of the polyglandular failure syndrome type II (Schmidt’s syndrome), which also includes insulin-dependent diabetes mellitus, pernicious anemia, vitiligo, gonadal failure, hypophysitis, celiac disease, myasthenia gravis, and primary biliary cirrhosis. Iatrogenic causes of hypothyroidism include 131I therapy, thyroidectomy, and treatment with lithium or amiodarone. Iodine deficiency or excess can also cause hypothyroidism. Figure 5

www.wjpps.com

Vol 5, Issue 1, 2016.

251

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Causes of hypothyroidism Hypothyroidism results when the thyroid gland fails to produce enough hormones. Hypothyroidism may be due to a number of factors, including. 

Autoimmune disease. People who develop a particular inflammatory disorder known as Hashimoto's thyroiditis suffer from the most common cause of hypothyroidism. Autoimmune disorders occur when your immune system produces antibodies that attack your own tissues. Sometimes this process involves your thyroid gland. Scientists aren't sure why the body produces antibodies against itself. Some think a virus or bacterium might trigger the response, while others believe a genetic flaw may be involved. Most likely, autoimmune diseases result from more than one factor. But however it happens, these antibodies affect the thyroid's ability to produce hormones.



Treatment for hyperthyroidism. People who produce too much thyroid hormone (hyperthyroidism) are often treated with radioactive iodine or anti-thyroid medications to reduce and normalize their thyroid function. However, in some cases, treatment of hyperthyroidism can result in permanent hypothyroidism.



Thyroid surgery. Removing all or a large portion of your thyroid gland can diminish or halt hormone production. In that case, you'll need to take thyroid hormone for life.



Radiation therapy. Radiation used to treat cancers of the head and neck can affect your thyroid gland and may lead to hypothyroidism.



Medications. A number of medications can contribute to hypothyroidism. One such medication is lithium, which is used to treat certain psychiatric disorders. If you're taking medication, ask your doctor about its effect on your thyroid gland.

Less often, hypothyroidism may result from one of the following 

Congenital disease. Some babies are born with a defective thyroid gland or no thyroid gland. In most cases, the thyroid gland didn't develop normally for unknown reasons, but some children have an inherited form of the disorder. Often, infants with congenital hypothyroidism appear normal at birth. That's one reason why most states now require newborn thyroid screening.



Pituitary disorder. A relatively rare cause of hypothyroidism is the failure of the pituitary gland to produce enough thyroid-stimulating hormone (TSH) — usually because of a benign tumor of the pituitary gland.

www.wjpps.com

Vol 5, Issue 1, 2016.

252

Gopala et al.



World Journal of Pharmacy and Pharmaceutical Sciences

Pregnancy. Some women develop hypothyroidism during or after pregnancy (postpartum hypothyroidism), often because they produce antibodies to their own thyroid gland. Left untreated, hypothyroidism increases the risk of miscarriage, premature delivery and preeclampsia — a condition that causes a significant rise in a woman's blood pressure during the last three months of pregnancy. It can also seriously affect the developing fetus.



Iodine deficiency. The trace mineral iodine — found primarily in seafood, seaweed, plants grown in iodine-rich soil and iodized salt — is essential for the production of thyroid hormones. In some parts of the world, iodine deficiency is common, but the addition of iodine to table salt has virtually eliminated this problem in the United States. Conversely, taking in too much iodine can cause hypothyroidism.

Signs and symptoms Symptoms can include feeling cold more easily, constipation, muscle weakness, weight gain, joint or muscle pain, feeling sad or depressed, feeling very tired, dry skin, thinning hair, sweating less than usual, a puffy face, hoarse voice, and more menstrual bleeding than usual. Hypothyroidism is treated with medicine that gives the thyroid hormone it needs to work normally There are no symptoms that are unique to hypothyroidism. There may be no symptoms early in the disease process. Long standing, untreated hypothyroidism can cause obesity, joint pain, heart disease, and infertility. Other symptoms can include. 1. Increased sensitivity to cold 2. Depression 3. Fatigue 4. Weakness 5. Heavier menstrual flow 6. Brittle hair and nails If left untreated, the following symptoms can occur: 1. hoarseness 2. puffiness of the face, hands, and feet 3. slowed speech 4. decreased taste and smell 5. thin eyebrows 6. thickened skin

www.wjpps.com

Vol 5, Issue 1, 2016.

253

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

7. coma (called ―myxedema coma‖) Diagnose of Hypothyroidism Primarily a physical exam is conducted and reviews of medical history is known. This can reveal any procedures like thyroid surgery or radiation treatments connected to hypothyroidism. Family history might reveal a close relative with autoimmune disease. Medication history might be positive for drugs, such as lithium and amiodarone that can cause the condition. Because hypothyroidism is most often found in women over age 50, some doctors advocate thyroid function screening for this group. Blood tests also are common. These include 1. thyroid function tests: T4, T3RU and TSH 2. tests for pituitary function: TSH 3. cholesterol (can be elevated) 4. CBC (may show anemia) 5. liver enzymes (can be elevated) 6. prolactin (can be elevated) 7. electrolytes (sodium can be low) In hypothyroidism, T4 is low and TSH is high. This means the pituitary is sending more TSH to stimulate the thyroid, but the thyroid does not respond. A low TSH indicates the pituitary may be the cause of hypothyroidism. Treatment of Hypothyroidism A common treatment is to replace thyroxine with a specific synthetic thyroid hormone (levothyroxine). This hormone is safe and affordable, but determining the right dosage often takes time. Your metabolic rate has to be returned to normal. Raising it too quickly can cause palpitations and make some medical problems like coronary artery disease and atrial fibrillation worse. Symptoms of thyroid hormone excess are. 1. shakiness or tremors 2. palpitations 3. insomnia 4. increased appetite

www.wjpps.com

Vol 5, Issue 1, 2016.

254

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

5. Diets rich in soy and high fiber can interfere with levothyroxine absorption. Medications and supplements also can reduce absorption. These include: 6. calcium supplements 7. iron supplements 8. cholestyramine 9. aluminum hydroxide (present in some antacids) Thyroid cancer. Most people with thyroid cancer have a thyroid nodule that does not cause any symptoms. If you do have symptoms, you may have swelling or a lump in the neck, problems swallowing, or a hoarse voice. Thyroid cancer is most often treated with surgery to remove the whole thyroid gland. Figure 6

Goiter A goiter is an unusually enlarged thyroid gland. Usually, the only symptom of a goiter is a swelling in your neck. But a very large goiter can cause a tight feeling in your throat, coughing, or problems swallowing or breathing. Medicine may help the goiter shrink back to near normal size. Figure 7

www.wjpps.com

Vol 5, Issue 1, 2016.

255

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Thyroiditis Thyroiditis is inflammation of the thyroid. It happens when your immune system attacks your thyroid. A common type of thyroiditis is postpartum thyroiditis. Postpartum thyroiditis may be treated with medicine. Thyroiditis can cause symptoms of either hyperthyroidism or hypothyroidism. Figure 8

Thyroid nodules A thyroid nodule is a swelling in one section of the thyroid gland. Most thyroid nodules do not cause symptoms and are not cancerous. But some thyroid nodules make too much thyroid hormone, causing hyperthyroidism. Sometimes, nodules grow so big that they cause problems with swallowing or breathing Figure 9

Thyroid problems in women’s In women, thyroid diseases can cause.

www.wjpps.com

Vol 5, Issue 1, 2016.

256

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Problems with your menstrual period. Your thyroid helps control your menstrual cycle. Too much or too little thyroid hormone can make your periods very light, heavy, or irregular. Thyroid disease also can cause your periods to stop for several months or longer, a condition called amenorrhea. If your body’s immune system causes thyroid disease, other glands, including your ovaries, may be involved. This can lead to early menopause (before age 40). Problems getting pregnant. When thyroid disease affects the menstrual cycle, it also affects ovulation. This can make it harder for you to get pregnant. Problems during pregnancy. Thyroid disease not treated with medicine can cause health problems for the mother, including premature delivery (before 39 weeks of pregnancy), preeclampsia, or miscarriage. Untreated thyroid disease can also cause health problems for the baby, including heart failure or problems with growth and brain development. CONCLUSION Diseases of the thyroid gland are common in primary care medicine and most can be diagnosed and treated satisfactorily by the primary care physician. In some instances thyroid disease may present in patients in a subtle manner and these clinical signs and symptoms are often mistaken for the natural course of ageing especially when they manifest in the elderly. It is for this reason that a correct diagnosis is imperative. Correct diagnosis of thyroid disease enables the clinician to effectively manage the patient and thus vastly improve the patient’s quality of life. The importance of the use of correct thyroid function tests are not only required for the diagnosis of the condition but also for the long- term management of the patient. It is a fundamental tool in monitoring patient response to treatment as well as guiding the clinician with regard to dose titration. REFERENCES 1. Cooper DS: Clinical practice. Subclinical hypothyroidism. N Engl J Med., 2001; 345: 260–265. 2. Dabon-Almirante CL, Surks MI: Clinical and laboratory diagnosis of Thyrotoxicosis. Endocrinol Metab Clin North Am., 1998; 27: 25.

www.wjpps.com

Vol 5, Issue 1, 2016.

257

Gopala et al.

World Journal of Pharmacy and Pharmaceutical Sciences

3. Dillman WH: The thyroid. In Goldman L, Bennett JC (eds): Cecil Textbook of Medicine, 21st ed. Philadelphia, WB Saunders, 2000; 1231–1250. 4. Hermus AR, Huysmans DA: Treatment of benign nodular Thyroid Disease. N Engl J Med., 1998; 338: 1438. 5. Weetman AP, McGregor AM: Autoimmune thyroid disease: Further developments in our understanding. Endocr Rev., 1994; 15: 788. 6. 29 CHAPTER 5 5.1 CONCLUSION Diseases of thyroid…. wiredspace.wits.ac.za/bitstream/handle/10539/1575/05Chapter5.pdf 7. Hyperthyroidisms: Causes, Symptoms, &Treatment-Health line www.healthline.com/health/hyperthyroidism 8. Hyporthyroidism: Causes-mayo Clinic www.mayoclinic.org/diseases.../hypothyroidism/.../causes/con-20021179 9. Thyroid symptoms That Signal Thyroid Problems…Web MD www.webmd.com/women/understanding-thyroid-problems-symptoms 10. The Thyroid gland-Endocrinology-NCBI Bookshelf www.ncbi.nlm.nih.gov › NCBI › Literature › Bookshelf

www.wjpps.com

Vol 5, Issue 1, 2016.

258