REVIEW OF STRUMA

PREPARED BY: Stefano Leatemia 11.2012.031

SURGERY CLERKSHIP AIR FORCE HOSPITAL OF DR.ESNAWAN ANTARIKSA FACULTY OF MEDICINE UKRIDA PERIOD MAY 6th JULY 13th 2013

TABLE OF CONTENTS

Preface ...................................................................................................................................i Content ..........................................................................................................................................1 CHAPTER I Introduction .3 CHAPTER II Anatomy and Physiology of Thyroid .....................................................................4 CHAPTER III 3.1 Struma Difusa ....9 3.2 Struma Nodosa Toxic .......................................................10 3.3 Struma Difusa ...11 3.4 Struma Nodosa Non Toxic ..12 3.5 Carcinoma 14 3.6 Enforcement Measures Struma Diagnosis ...............................................................18 CHAPTER IV Conclusion .. 22 REFERENCES .. .23

CHAPTER I INTRODUCTION

Struma is the enlargement of the thyroid gland caused by the addition of thyroid gland tissue itself. Enlargement of the thyroid gland that causes changes in the body's functions and some that did not affect function. Struma is a disease common day-to-day, with a history and a thorough physical examination, struma with or without metabolic dysfunction can be diagnosed accurately. Epidemiological Survey for struma endemik often found in mountainous regions such as the Alps, Himalayas, Bukit Barisan and other mountain areas. For toxic struma prevalence is 10 times more common in women than men. In the case of a woman found 1,000 women 20-27, while the men 1-5 of 1,000 men.

CHAPTER II Thyroid Gland Anatomy and physiology

To understand disease and thyroid disorders, to remember back about the anatomy of the thyroid. Anatomy and normal physiologic must be known and remembered back before the change of anatomy and physiology that may progress to a disease or disorder. 2.1 Anatomy of the Thyroid The thyroid gland consists of three lobes, which dextra lobe, the left lobe and the isthmus which lies in the middle. It can sometimes be found all four parts namely the pyramidal lobe is located on the isthmus slightly to the left of the center line. This lobe is residual thyroid tissue that remains embryonic. The thyroid gland has a weight of about 25-30 grams and is located between the thyroid and sixth tracheal rings. The entire thyroid tissue wrapped by a layer called the true capsule.

Vascularity of the thyroid gland derived from: . 1) A. Superior thyroid which is a branch of A. Carotid externa 2) A. Inferior thyroid which is a branch of A. Subclavian 3) A. Ima thyroid which is a branch of the Arcus Aorta

Nerve that passes through the thyroid is the recurrent nerve. It is located in the dorsal neural thyroid before entering the larynx.

2.2 Physiology of Thyroid The thyroid gland is an endocrine gland that secretes hormones Thyroxine or T4, triiodothyronine or T3 and calcitonin. In the blood of most of the T3 and T4 are bound by plasma proteins are albumin, Thyroxin Binding Pre Albumin (TBPA) and Thyroxin Binding Globulin (TGB). Fraction T3 and free T4 circulates in the blood and play a role in regulating the secretion of TSH. HORMON thyroid is controlled by hyroid-stimulating hormone (TSH) produced by the anterior lobe of the gland and release hypofise influenced by thyrotropine-releasing hormone (TRH). Thyroid glands also secrete calcitonin of parafolicular cell, which can lower serum calcium affect bone. Thyroid hormone function, among others: 1) increase the metabolic rate

2) 3) 4)

cardiogenic effects simpatogenik growth and nervous system

CHAPTER III DISCUSSION Enlargement of the thyroid gland or struma classified according to its physiological effects clinical, and changes in shape that occur. Struma can be divided into: 1) Toxic struma, struma which raises the clinical symptoms in the body, based on changes in shape can be subdivided into a. Diffusa, ie if the enlargement of the thyroid gland covering the entire lobe, like those found in Grave's disease. b. Nodosa, ie if the enlargement of the thyroid gland only on one lobe, like those found in Plummer's disease. 2) Nontoxic struma, the struma that does not cause clinical symptoms in the body, based on the change in shape can be subdivided into a. Diffusa, such as those found in endemic struma b. Nodosa, such as those found in thyroid malignancy

Enlargement of the thyroid gland can be caused by: 1) Hyperplasia and hypertrophy

Each organ is triggered when the work will have to compensate by increasing the number of cells and multiply. Likewise, when the thyroid gland will be encouraged to work pertumnuhan produce the hormone thyroxine and will have m embesar, such as puberty and pregnancy. 2) Inflammation or infection Processes such as inflammation of the thyroid gland in acute thyroiditis, subacute thyroiditis (de Quervain) and chronic thyroiditis (Hashimoto) 3) Neoplasms Benign and malignant Struma cause clinical symptoms caused by changes in thyroid hormone levels in the blood. The thyroid gland can result in excessive levels of thyroid hormone or commonly called hyperthyroidism and in levels of normal or less than normal is called hypothyroidism. Symptoms in hyperthyroidism are: Increased appetite and weight loss Can not stand the heat and hyperhidrosis Palpitations, high systolic and diastolic pressure is low resulting in a high pulse (pulsus celler) and in the long term could be atrial fibrillation Tremor Diarrhea Infertility, amenorrhae in women and testicular atrophy in men Exophtalmus

Symptoms in hypothyroidism is the opposite of hyperthyroidism: Decreased appetite and weight gain 8

Can not stand the cold and dry scaly skin Bradycardia, low systolic pressure and pulse pressure are weak Gestures become sluggish and edema of the face, eyelids and limbs

3.1 Difusa Toxic Struma 3.1.1 Definition Difusa toxic struma can be found in Grave's Disease. The disease is also called Basedow. Trias Basedow include diffuse enlargement of the thyroid gland, and eksoftalmus hipertiroidi. Disease is more common in younger people with symptoms such as excessive sweating, hand tremors, decreased heat tolerance terhafap, weight loss, emotional instability, menstrual disorders such as amenorrhea, and polidefekasi (often defecation). Clinical often found in the thyroid gland enlargement, sometimes there is also a manifestation of the eye and miopatia exophthalmus ekstrabulbi. Although the etiology of Graves' disease is not known for sure, it seems there is a role of an antibody that can be captured TSH receptor, leading to increased thyroid hormone stimulus. The disease is also characterized by increased absorption of radioactive iodine by the thyroid gland.

Image: Graves disease

3.1.2 Pathophysiology Grave's Disease is a disease caused by abnormalities in the body's immune system, where there is a substance called Thyroid Receptor Antibodies. This substance occupies TSH receptor in thyroid cells and stimulate them in berlebiham, so it can not occupy the TSH receptor and thyroid hormone levels in the body is increased. 3.1.3 Clinical Symptoms Symptoms and signs that arise is a manifestation of increased metabolism in all body systems and organs that may be clinically apparent. Increased metabolism causes increased caloric needs, and often intake (intake) insufficient caloric needs, causing drastic weight loss. Increased metabolism in the cardiovascular system visible in the form of an increase in blood circulation, among others, with an increase in cardiac output / cardiac output up to twothree times normal, and also in a resting state. Rhythm pulse rise and pulse pressure increases, so be pulsus Celer; patients will experience tachycardia and palpitations. Burden on myocardial, and autonomic nerve stimulation can result in a heart rhythm disorder ektrasistol, atrial fibrillation, and ventricular fibrillation. Gastrointestinal secretion and peristalsis increases often resulting polidefekasi and diarrhea. Hipermetabolisme nervous system usually causes tremors, sleeplessness sufferers, often waking in the night. Patients experience emotional instability, anxiety, thought disorder, and unwarranted fear that very disturbing. In the airways, causing dyspnea and tachypnea hipermetabolisme are not too distracting. Muscle weakness mainly proximal muscles, usually quite disturbing and often appear suddenly. This is caused by electrolyte disturbances triggered by the hipertiroidi.

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Menstrual disorders can be secondary amenorrhoea or metrorhagia. Eye disorders caused by an autoimmune reaction in the form of antibodies binding to receptors on muscle and connective tissue in the eye socket ekstrabulbi. Connective tissue and fat tissue to hyperplastic so eyeball pushed to the outer eye muscles and pinched. The result is eksoftalmus which can cause eye damage due to keratitis. Impaired muscle movement will cause strabismus.

Figure: Schematic pathogenesis of Graves' disease

3.1.4 Treatment Graves disease therapy aimed at controlling the state tirotoksisitas / hipertiroidi with antithyroid administration, such as propyl-tiourasil (PTU) or karbimazol. Definitive therapy can be selected between anti-thyroid medication long-term, detachments with radioactive iodine, or thyroidectomy. Surgery of the Thyroid with hipertiroidi done especially if treatment with the 11

thyroid gland fails medikamentosa great.Surgery usually provides a good permanent cure although sometimes encountered the hipotiroidi and minimal complications.

3.2 Struma Nodosa Toxic 3.2.1 Definition Nodosa toxic struma is an enlarged thyroid gland on one lobe is accompanied by signs of hyperthyroidism. Nodular enlargement occurs in young adulthood as a nontoxic goiter. When untreated, in 15-20 years can be toxic. Was first distinguished from Grave's disease by Plummer, then known as Plummer's disease.

3.2.2 Pathophysiology The disease begins with the onset of nodular enlargement of the thyroid gland that does not cause symptoms of toxicity, but if not treated immediately, within 15-20 years can cause hyperthyroidism. The factors that affect the change of nontoxic be toxic include these nodules turn out to be its own autonomous (associated with autoimmune diseases), thyroid hormone from the outside, as the radioactive iodine treatment. 3.2.3 Clinical Symptoms When history, it is difficult to distinguish between Grave's disease with Plummer's disease because both showed symptoms of hyperthyroidism. The difference is when a physical examination at the time of palpation where we can feel the enlargement affects only one lobe. 3.2.4 Treatment Therapy given to Plummer's Disease Grave's also the same as that aimed at controlling the state tirotoksisitas / hipertiroidi with antithyroid administration, such as propyl-tiourasil (PTU) or karbimazol. Definitive therapy can be selected between antithyroid medication long-term, detachments with radioactive iodine, or 12

thyroidectomy. Surgery of the Thyroid with hipertiroidi done especially if treatment with the thyroid gland fails medikamentosa great. Surgery usually provides a good permanent cure although sometimes encountered the hipotiroidi and minimal complications.

3.3 Struma Difusa nontoxic 3.3.1 Definition Endemic goitre endemic goitre is a disease that i signed with ti roid gland enlargement that occurs in a population, and is expected to relate to deficiencies in the daily diet. Endemic goiter epidemiology is estimated there are approximately 5% in a population of primary school children / preadolescent (6-12 years), as is evident from several studies. Endemic goitre occurs due to deficiency of iodine in the diet.Frequent incidence of endemic goiter in derah pegnungan, such as in the Himalayas, alpens, areas with the availability of natural iodine and iodine additional coverage has not done well 3.3.2 Pathophysiology Generally, the mechanism of occurrence of goiter caused by a

deficiency intake iodine by the body. In addition, goiter can also be caused by congenital abnormalities of thyroid hormone synthesis or goitrogen (goiter-causing agents such as intake Excessive calcium and Brassica family vegetables). Lack of iodine causes a lack of thyroid hormone can be synthesized. This will lead to an increase in the release of TSH (thyroid-stimulating hormone) into the blood as kompensatoriknya effect. The effect causes hypertrophy and hyperplasia of thyroid follicular cells, resulting in enlargement of the thyroid macroscopically. This enlargement can normalize body of work, because on the kompensatorik effects of thyroid hormone needs are met. However, in some cases, such as iodine deficiency is endemic, this enlargement will not be able to compensate for the existing disease. The condition known as goiter hypothyroidism. The degree of enlargement of the thyroid following levels and duration of thyroid hormone deficiency that occurs in a person.

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Diffuse Goiter Diffuse Goiter is a form like piece that forms a visible enlargement without forming nodules. Form is usually found with non-toxic properties (normal thyroid function), hence this form is also called simple goiter. Can also be referred to as colloid goiter due to an enlarged follicle cells are generally met by colloidal proficiency level. This disorder appears in endemic and sporadic goiter. Endemic goiter appeared in a soil, water, and food supply contains less iodine, so the iodine deficiency is widespread in the area teresebut. Examples region is mountainous Alps, the Andes or Himalayas. Meanwhile, sporadic goiter appeared less frequently and can be caused by many things, the consumption of which inhibit the synthesis of thyroid hormones or enzymes for impaired thyroid hormone synthesis dropped hereditary. On simple goiter, there are two phases of evolution, namely hyperplastic and colloid involution. In the hyperplastic phase, the thyroid gland is diffusely enlarged and symmetrical, although not too large magnifying power (up to 100-150 grams). Follicle-folikelnya coated by columnar cells are numerous and crowded. Accumulation of these cells is not the same in the whole gland. If after the consumption of iodine the body needs increased or decreased thyroid hormone, follicle epithelial cell involution occurs, forming large follicles filled with colloid. Thyroid would normally macroscopically visible brown and translucent, while histologically will be seen that the follicles filled with colloid and epitelnya flattened and cuboidal cells.

3.3.3 Clinical Symptoms Most of the clinical manifestations associated with enlargement of the thyroid gland. Most patients remained euthyroid state shows, but some circumstances having hypothyroidism. Hypothyroidism is more common in children with biosynthetic defect as the cause, including defects in the transfer of iodine. 3.3.4 Procedures

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The goal of treatment is to shrink the goitre endemic goitre and hypothyroidism resolve possible, namely by giving SoL Lugoli for 4-6 months. If there is improvement, treatment was continued until a year and then tapering off in 4 weeks. When the 6 months after treatment of goitre is not also shrink the medical treatment is not successful and should be operative action.

3.4 Struma nodosa nontoxic

3.4.1 Definition Goitre nodosa is non toxic ti roid gland enlargement to the clinically palpable nodules without one or more signs hypertiroidisme. The term struma nodosa indicates the existence of a process, either physiological or pathological cause asymmetrical enlargement of the thyroid gland. Because it is not accompanied by signs of toxicity in the body, it is referred to as asymmetric enlargement nodosa nontoxic goiter.This disorder is very common everyday, and to watch out for signs of possible malignancy.

3.4.2 Pathophysiology SNNT can also be referred to as sporadic goiter. If endemic goitre occurs 10% of the population in areas with iodine deficiency, the sporadic goiter occurs in someone who does not live in an area endemic low iodine. The cause is as yet unknown, there can be interference enzyme important in the synthesis of thyroid hormones or consumption of drugs containing lithium, propiltiourasil, fenilbutazone, or aminoglutatimid. 3.4.3 Clinical Symptoms In general, non-toxic struma nodosa had no complaints because there was no hypo-or hyperthyroidism. SNNT diagnosis is important in the absence of toxic symptoms caused by changes in thyroid hormone levels, and felt on palpation of the enlarged thyroid gland on one lobe. Usually thyroid began to swell at a young age and developed into multinodular in adulthood. Due to gradual growth, goitre may be asymptomatic unless large lump in the neck. 15

majority of patients with struma nodosa can live with strumanya without complaint. Although most of struma nodosa does not interfere with breathing due to jut forward, others can cause narrowing of the trachea when bilateral enlargement. Goitre nodosa unilateral stimulation can lead the way into contra lateral direction. Thus may not lead to the promotion of respiratory disorders. Significant narrowing cause respiratory until finally happened with stridor inspiratoar larynx and epiglottis so heavy dispn because fixed to the ea. trachea. Complaints that there is a sense of weight in the neck. Trachea during swallowing to cover up the

3.4.4 Treatment Operative action is still the main option on SNNT. Various techniques of operations include: a. Lobectomy, which is the lobe lift, when the gland is left subtotal weighing 3 grams b. Isthmolobektomi, the removal of one lobe followed by the isthmus c. Total thyroidectomy, which is removal of the entire thyroid gland d. Bilateral subtotal thyroidectomy, the partial removal of the right lobe and the left part, the rest of the network in the posterior 2-4 grams taken to prevent damage to the parathyroid glands or N.Recurrent Laryngeus 3.5 Carcinoma of the Thyroid 3.5.1 Definition Thyroid carcinoma is a malignancy (uncontrolled growth of cells) that occur in the thyroid gland. Cancer is a depressing thyroid malignancy in thyroid which has 4 types: papillary, follicular, medullary and anaplastic. Thyroid cancer rarely causes enlargement of the gland, often causing small growth (nodule) in the gland. The majority of thyroid nodules are benign, thyroid cancer usually can be cured Thyroid Cancer often limit the ability to absorb iodine and limit the ability to produce thyroid hormone, but sometimes produce enough thyroid hormone, causing hyperthyroidism. 16

3.5.2

Classification of thyroid carcinoma

2) Papillary carcinoma, This carcinomas derived from thyroid cells and is the most common type of thyroid carcinoma. More often found in children and young adults and is more common in females. Exposed to radiation during childhood helped to cause this malignancy. First appeared in the form of a palpable lump in the thyroid gland as enlarged lymph nodes or neck area. Metastases may occur via the lymph to other areas in the thyroid or, in some cases, to the lungs. 3) Follicular carcinoma, carcinoma is derived from follicular cells and is 20-25% of thyroid carcinoma. Follicular carcinoma primarily affects on age above 40 tahun.Karsinoma follicular also attacked 2 women up to 3 times more often than men. Exposure to X-rays during childhood increases the risk of this type of malignancy. This type is more invasive than the papillary type. 4) Anaplastic carcinoma, This highly malignant carcinoma and constitute 10% of thyroid cancers. Slightly more often in women than men. Metastasis occurs in rapid, early around it and then other parts of the body. At first people were just complaining about the presence of thyroid tumor area. With this cancer infiltration around, arising hoarseness, stridor, and difficulty swallowing. Life expectancy after diagnosis is established, usually only a few months. 5) Parafolikular carcinoma, carcinoma parafolikular or medul l er is unique among thyroid cancer. This carcinoma more commonly in women than men and is most often over 50 years. Carcinoma is rapidly metastasize, often to the place much like the lungs, bones, and liver. His trademark is his ability to secrete calcitonin because of origin. Carcinoma is often said to be hereditary.

3.5.3 Differences Benign and Malignant Thyroid Nodules Approximately 5% had malignant struma nodosa. In the clinic should be differentiated thyroid nodules are benign and malignant nodules that have these characteristics: 1. Consistency hard on some parts or the whole nodules and hard-driven, although malignant nodules may undergo cystic degeneration and then become soft. 17

2. In contrast to the consistency of soft nodules more often benign, although calcified nodules can be found in adenomatous hyperplasia longstanding. 3. Infiltration into the surrounding tissue nodules merupaka sign of malignancy, although not always malignant nodules infiltrating. If found ptosis, miosis, and enoftalmus a sign of infiltration into surrounding tissue 4. 20% are malignant solitary nodules whereas multiple nodules are rarely malignant. 5. Nodules that appear suddenly or rapidly growing needs, especially malignant suspicion that is not accompanied by pain. Or nodules old suddenly enlarged progressively 6. Suspected malignant nodules when accompanied by regional lymph node enlargement or change in voice became hoarse. 7. Carotid artery pulsation is palpable from the rear edge of the sternocleidomastoid muscular enlargement due to pressure nodules (Berry's Sign) 3.6 Enforcement Measures Diagnosis Struma 3. 5. 1 Anamnesis On history, major complaints expressed by the patient may be a lump in the neck that has lasted a long time, and the symptoms of hyperthyroidism or hipotiroidnya. If the patient complained of a lump in the neck, then it should be further explored whether or progressive enlargement occurs very slowly, accompanied with swallowing disorders, impaired breathing and voice changes. After that asked whether or not there symptoms of hyper and hypofunction of thyroid kelenjer. Need a place to stay were also asked patients and salt intake to see if there are trends towards endemic goitre. Conversely, if patients present with symptoms towards hyper or hypofunction of the thyroid, should be explored further to hyper or hypo and whether there is a lump in the neck. 3. 5. 2 Physical Examination

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On physical examination localist status at the anterior region coli, the most first carried out an inspection, symmetrical enlargement seen whether or not, arise respiratory signs or not, part moves while swallowing or not. On palpation it is important to determine whether the right is bejolan thyroid gland or lymph nodes. The difference was at the time the patient is asked to swallow. If true then enlarged thyroid lumps will also move when swallowing, while if not moving then to think about the possibility of enlarged cervical lymph nodes. Palpable enlargement should be described: Location: right lobe, left lobos, isthmus Size: in centimeters, length diameter The number of nodules: one (uninodosa) or more than one (multinodosa) Consistency: cystic, soft, chewy, hard Pain: there is pain or not at the time of palpation Mobility: no or no attachment to the trachea, muscular sternokleidomastoidea Lymph nodes around the thyroid: no enlargement or not

3.5.3 Examination Support Laboratory tests used in the diagnosis of thyroid disease is divided into: 1. Examination to measure thyroid function. Examination to determine levels of T3 and T4 and TSH most often using radioimmunoassay technique (RIA) and ELISA in serum or blood plasma. Normal levels of total T4 in adults is 50-120 ng / dl. Normal levels of T3 in adults is 0.65 to 1.7 ng / dl. 2. Examination to indicate the cause of thyroid disorders. Antibodies to various thyroid antigens found in the serum of patients with autoimmune thyroid disease. Such as thyroglobulin antibodies and thyroid stimulating hormone antibodies 3. Radiological examination

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 X-rays can clarify the deviation of the trachea or retrosternal goitre enlargement is generally clinically was to be expected. X-ray neck AP and lateral position is usually an option. Thyroid ultrasound is useful to determine the number of nodules, differentiate between solid and cystic lesions, detect the presence of cancerous tissue that does not capture iodine and can be seen by scanning the thyroid. Thyroid scanning is essentially a presentation of I 131 uptake thyroid distributed. Uptake can be determined from the impression the size, shape and location of the main parts is thyroid function (distribution within the gland). Normal uptake of 15-40% within 24 hours. From the results of thyroid scanning can distinguish three forms, namely cold nodule uptake when nil or less than normal compared with the surrounding region, this suggests that the function of low and often occurs in neoplasms. The second form is when uptakenya warm nodule with surrounding, showing the function of the thyroid nodule with other parts. If the latter is the hot nodule uptake more than normal, meaning excessive activity and rarely in neoplasms. 4. FNAB. Histopathologic examination of 80% accuracy. It is worth remembering that not to determine the only definitive therapy based on the results of FNAB alone. 3.5.4 Measures Surgery Indications operations on goitre is: 1. 2. 3. 4. Toxic diffuse goiter who fail to medical therapy Struma uni or multinodosa with the possibility of malignancy Struma with compression disorders Cosmetics 20

Contraindicated in goiter surgery: 1. Struma toksika that have not prepared in advance 2. Goitre with cardiac decompensation and other systemic diseases that have not been controlled 3. Large goitre which cling tightly to the neck tissues that are normally difficult to move because of carcinoma. Such carcinomas are usually of poor prognosis anaplastic type. Attachment to the trachea or larynx or trachea may well dilakukanreseksi laringektomi, but attachment with extensive soft tissue neck excision is difficult to do well. First clinical examination for menentuka n whether the suspected malignant thyroid nodules or suspected to be benign. When the suspected malignant nodules, it is distinguished whether the case is operable or inoperable. When the case at hand is inoperable then performed an act of incisional biopsy for histopathological examination purposes. Debulking followed by action and external radiation or chemoradiotherapy. When suspected malignant thyroid nodules or suspected benign operable can be taken isthmolobektomi or lobectomy. If after the PA results prove that the lesion is benign then the operation is complete, but if malignant it must be determined beforehand which type of carcinoma occurred. Complications of thyroid surgery: a. Bleeding from A. Superior thyroid b. Dispneu c. Paralysis N. Recurrent Laryngeus. Consequently oto-laryngeal muscle weakness occurs d. Paralysis N. Laryngeus Superior. As a result, patients become lenih sound weak and difficult to control the high pitch sound, due to the

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shortening of the vocal cords due to relaxation of M. Cricothyroid. Possibility terligasi nerve during surgery

CHAPTER IV CONCLUSION

Goitre is a disease that often we encounter daily. It's important to do a history and physical examination are thorough and meticulous to determine the presence or absence of signs of toxicity caused by changes in thyroid hormone levels in the body. So also with signs of malignancy that can be detected in time. Next is to determine the appropriate tests to determine the exact diagnosis of the existing types of goitre. With a definite diagnosis then we can mnentukkan appropriate for treatment of goitre experienced by pasie. Does it require surgery, or simply given treatment within a certain period.

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REFERENCES 1. Widjosono, Garitno, Endocrine System: Textbook of Surgery. Editor Syamsuhidayat R.Jong WB, Revised Edition, EGC, Jakarta, 1997: 925-952. 2. Kariadi KS Sri Hartini, Sumual A., Struma nodosa Non Toxic & Hyperthyroidism: Textbook of Pneyakit In, Keiga Edition, Publisher Faculty of Medicine, Jakarta, 1996: 757-778. 3. Schteingert David E., Thyroid Disease, Pathophysiology, Fourth Edition, Book Two, EGC, Jakarta, 1995: 1071-1078. 4. Liberty Kim H, Thyroid Glands: Textbook of Surgery, Volume One, Publisher Binarupa script, Jakarta, 1997: 15-19.

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