Clinics and Grand Rounds in Surgery SK Kochar
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ThyroidCHAPTER 1

SK Kochar
 
MULTINODULAR GOITER
 
Case Study 1
32-yr-old female, housewife, a resident of Rewari complains of swelling in front of neck, duration 7 years.
 
History of Present Illness
Patient complains that she noticed a small swelling in front of the neck 7 yr back. Insidious in onset the swelling was around 1.5 cm x 1.5 cm when first noticed and located in the midline. No appreciable increase in the swelling for around 6 ½ yr. Swelling was painless. About 5 months back the swelling began to increase rapidly and attained the present size. The increase was not associated with pain at any time. There is no history of difficulty in breathing, swallowing or hoarseness of voice. There is no history of preference to cold or hot climate, excessive sweating, palpitation, exhaustion on straining, chest pain, nervous excitability, irritability, insomnia, gain or loss of weight and weakness of muscles. She does not give any history of evening rise of fever, cough, and hemoptysis. Her sleep is normal, appetite is normal and bowel habit is regular. She does not give any history of irradiations in the past, drug intake or any history of bony pain.
Past history A sinus in the suprasternal region operated 8 yr back. Tubectomy 6 yr back. No history of diabetes mellitus 2(DM), pulmonary tuberculosis (TB), hypertension (HTN) or coronary artery disease (CAD).
Personal history Mixed diet
Menstrual history Regular
Obstetric history Para 3 Gravida 3.
Family history No history of similar disease in the family or neighborhood.
On examination Averagely built and nourished. No pallor, icterus, pulse 84/minute, palms are not moist. Blood pressure (BP) 110/70 mm of Hg. No cervical lymphadenopathy. No eye signs. No wasting of muscles. No tremors.
 
Local Examination
A well-healed scar in the suprasternal notch area. Swelling in front of neck, more prominent on the right side about 8 cm x 6 cm. Swelling extends from the thyroid cartilage superiorly to the suprasternal notch below. From side to side it is located between the two sternocleidomastoid muscles (SCM). It moves with deglutition. Does not move with protrusion of the tongue. No dilated veins.
Palpation A bilobed swelling, right side measures 5 x 5 cm rounded shaped, smooth. Left side measures 4 x 3 cm nodular surface and nontender. It is firm in consistency. It is slightly mobile in side-to-side and craniocaudal direction. One is able to get below the swelling. Kocher’s test is negative. No other swelling palpable in the neck. Trachea is central and both carotids are felt. No lymph nodes palpable in the vicinity or in the cervical region.
Percussion No retrosternal extension.
Auscultation No bruit heard.
Chest, CVS and abdomen NAD
Provisional diagnosis Multinodular goiter, clinically euthyroid.
3 Q. How do you say that it is euthyroid?
A. There is no history suggestive of toxicity. Pulse is in normal range and there are no eye signs.
Q. How would you like to confirm this?
A. T3 T4 and TSH estimation are reliable indicators of toxicity.
Q. What could be cause of sudden increase in the size of the gland?
A. Haemorrhage in a nodule and malignant changes may be the causes.
Q. How will you confirm this?
A. FNAC of the representative area is diagnostic in most lesions.
Q. Can it predict follicular carcinoma?
A. No. In follicular carcinoma capsular invasion is a distinguishing point from follicular adenoma and this aspect cannot be ascertained in FNAC.
Q. What is the role of USG?
A. USG can demonstrate multinodularity in a clinically solitary nodular lesion. It may be helpful in taking a USG-guided needle biopsy in suspected lesion/clinically non-palpable lesions It may be of use to evaluate retrosternal extension. It does not form the part of routine protocol for thyroid evaluation.
Q. Would you like to do thyroid scan?
A. No. It can demonstrate cold nodule but neither does it gives tissue diagnosis nor is it preferred test for evaluation of thyrotoxicosis.
Q. What is the natural history of the nodular goiter?
A. All goiters start as colloid goiters and over the passage of time due to fluctuating requirements of thyroid hormones involution and evolution takes place thus there is irregularity giving rise to nodule formations (Fig. 1.1).
Q. What complications can takes place?
A. Hemorrhage can take place in the nodules giving rise to sudden increase in size, pain and pressure symptoms. Toxicity may take place either due to a nodule becoming autonomous or internodular tissue hyperfunctioning. Malignant changes may also take place.
4
zoom view
Fig. 1.1: A case of multinodular goiter (Contributed by Dr GR Joshi)
Q. How will you manage this patient?
A. Since the patient has come with sudden increase in the size I will like to rule out the malignant changes. If FNAC shows nodular goiter and no evidence of malignancy I will offer sub-total thyroidectomy.
Q. Why subtotal?
A. Although a school of thought is gaining popularity of doing total thyroidectomy but it has got certain disadvantages. The injury to recurrent laryngeal nerve is more. Tetany is more common and patient has to be on replacement therapy.
Q. Then why it has been advocated?
A. Recurrence is practically not known (following total thyroidectomy) and in certain cases if lesion turns out to be malignant, the treatment is already provided. Injury to recurrent laryngeal nerve is not more than subtotal in expert hands and the tetany can be avoided by saving a parathyroid.
Q. Following subtotal thyroidectomy would you like to give any more treatment?
A. There is no requirement of any further treatment except followup. There are few surgeons who will prefer to give thyroxin for a period of two to three years to avoid recurrence but this is not universally accepted.
5Q. What are the indications of surgery in a case of multinodular goiter?
A. The indications for treatment of a multinodular goiter include compression-induced symptoms, hyperthyroidism, suspected malignancy, and, in some instances, cosmetic concerns.1 Recently there is trend towards total thyroidectomy for multinodular goiter.2,3 The total thyroidectomy can be performed safely and with morbidity comparable to that of lesser resections. A subtotal thyroidectomy has the potential for the development of recurrent goiter and the increased surgical morbidity associated with re-operation, or, in the case of an unsuspected malignancy, the possibility of performing a less than adequate resection.
 
SOLITARY NODULE THYROID
 
Case Study 2
26 years old lady comes with complains of swelling in front of neck. Duration 4 months.
 
History of Present Illness
Patient was apparently well till around 4 months back when she noticed a small swelling in front of neck on the right side, insidious in onset and has since been growing in size to attain the present size of 6 x 6 cm. There has been no history of fever or pain in the swelling at the onset of the swelling. No history of sudden increase in size. No history of dyspnea, difficulty in deglutition, change in voice. No history of weight loss, appetite, diarrhea or preference to cold or hot climate. No history of easy fatigability, tremors or any nervous instability or disorder. No history of weight gain, lethargy, constipation or hair loss. No history of menstrual irregularities. No history of bone pain chest pain, hemoptysis.
Past history No past history of similar swelling in the neck. No history of antithyroid drugs/ irradiation exposure. No history of major surgical/medical illness. Not a known case of TB, HTN, DM.
6 On examination Averagely built and nourished lady. Heart rate 88/min, regular with normal volume. No water hammer pulse. BP 130/86 mm of Hg casual. No pallor, clubbing, pedal edema/ pretibial myxedema. Skin is normal. Facial expression is normal.
 
Local Examination of Neck
Patient examined in sitting position and hands above her head and behind her head pushing forward.
On inspection: 6 x 5 cm ovoid swelling seen in the region of right lobe of thyroid extending from just below the thyroid cartilage to 4 cm above suprasternal notch in craniocaudal direction and from midline to the medial borders of SCM. It moves up on deglutition but not on protrusion of tongue. Skin over the swelling is normal. No dilated veins, scar /sinus. No other swelling seen.
On palpation 6 x 5 cm ovoid swelling palpable in the region of right lobe thyroid extending from just below thyroid notch to 4 cm above the suprasternal notch craniocaudally and from medial border of right SCM muscle to midline from side to side.
It is not tender, firm in consistency, smooth surface, margins well felt, not adherent to skin. Left lobe not felt. Carotid pulsations are felt in normal location. Trachea is central. No other swelling palpable in the neck. No cervical lymph nodes palpable. On auscultation there is no bruit audible over the superior pole. No signs of thyrotoxicosis in the form of eye signs/exopthalmos noted. No ophthalmoplegia/diplopia.
Provisional diagnosis Solitary nodular goiter, euthyroid.
Differential diagnosis
  • Colloid goiter
  • Multinodular goiter
  • Mitotic lesion.
7 Q. Is prior neck irradiation a risk factor?
A. Prior neck irradiation is a risk factor for thyroid malignancy. Any irradiation above 0.5 Gy to the thyroid during the first 3 or 4 years of life has been associated with a 1% to 7% incidence of thyroid cancer occurring 10 to 30 years later.4
Q. What are clinical features suggestive of malignancy?
A. If there is one area within a multinodular goiter that is distinctly different from the remainder of the gland on the basis of palpation or function or has demonstrated rapid growth, or if there are two discrete nodules in a gland that is otherwise normal, then there is the possibility of a malignant neoplasm rather than a benign multinodular goiter.5 The association of a thyroid nodule with enlarged lymph nodes, particularly anterior triangle adenopathy, suggests malignant disease. Fixation of the nodule to strap muscles or the trachea also suggests malignancy. Pain, tenderness, or sudden swelling of the nodule usually indicates hemorrhage into the nodule but can also indicate an invasive malignancy. Hoarseness may arise from pressure or by infiltration of a recurrent laryngeal nerve by a neoplasm and is usually associated with malignancy. Symptoms of brachial plexus irritation suggest malignancy. 14% to 20% of thyroid cancer specimens contain diffuse or focal thyroditis.
Q. What is the role of X-ray neck?
Soft-tissue radiographs of the neck may disclose indentation or deviation of the trachea if the tumor is more than 3 or 4 cm in diameter. Fine, stippled calcifications through the tumor (psammoma bodies) are virtually pathgnomonic of papillary cancer. Patchy or “signet ring” calcification occurs in old cysts and degenerating adenomas The diagnostic accuracy was nearly 98%, with less than 2% false-positive and false-negative results in one of the series.
Q. How will you confirm that it is not multinodular goiter?
A. USG can demonstrate whether it is multi/solitary nodular goiter.
Q. What are the implications if it is solitary nodule?
A. It has been seen that solitary nodular goiter has malignancy rate of 12.5%.
8 Q. How will you rule out malignancy in a solitary nodular goiter?
A. FNAC is diagnostic in all lesions except in follicular lesions as this needs paraffin sections to conclude.
Q. Why so?
A. In follicular lesions capsule invasion is pathognomic and this cannot be assessed by FNAC.
Q. How do you manage a case of follicular neoplasm/disease of thyroid?
A: Most surgeons recommend a total thyroid lobectomy with isthmusectomy for “follicular or Hürthle cell neoplasms.” When the lesion is benign, no further therapy is needed. When the tumor is malignant, completion (total) thyroidectomy may be indicated to facilitate subsequent radioactive iodine (RAI) scanning and therapy. Risk-group classification (AMES, AGES, TNM, EORTC, or MACIS)(see infra) is also considered by many surgeons as a criterion before completion thyroidectomy is recommended.6-12 Ipsilateral lymph node metastatic lesions occur in only about 10% of patients with follicular thyroid cancer (FTC) and in about 25% of patients with Hürthle cell cancer.13 Enlarged lymph nodes in the central neck area should be removed. A functional lateral neck dissection is indicated for patients with clinically palpable nodes. Patient is placed on thyroid suppression therapy with L-thyroxin and after 6-8 weeks thyroid scan is performed. Thyroxin therapy is stopped 6-8 days before thyroid scan. Residual thyroid tissue thus demonstrated on scan is ablated with radioactive Iodine 131. Following this patient is put on thyroxin therapy and observed in follow-up clinic.14-16
Q. How do you manage papillary carcinoma of thyroid gland?
A. Most surgeons agree that total or near-total thyroidectomy is the preferred operation for high-risk patients with PTC —as defined by the AMES (age of patient, presence of distant metastatic lesions, and extent and size of the primary cancer), AGES (patient age and tumor grade, extent, and size), TNM 9(tumor characteristics, lymph node involvement, and distant metastatic lesions), EORTC (European Organization for Research and Treatment of Cancer), or MACIS (metastatic lesions, patient age, completeness of resection, invasion, and size of tumor) classification system.7-12,17 A total or near-total thyroidectomy is also recommended in a patient with PTC when bilateral nodules are present, when cancer is bilateral, when the primary tumor extends beyond the thyroid capsule, or when local or distant metastatic disease is present. The following arguments are advanced in favor of total or near-total thyroidectomy. PTC is often multifocal and may spread throughout the thyroid by lymphatic drainage. Total or near-total thyroidectomy facilitates the postoperative use of 131I to ablate residual thyroid tissue and to identify and treat residual or distant tumor. After total thyroidectomy, Tg (Thyroglobin) is a more sensitive indicator of residual disease. Many retrospective studies have reported a lower recurrence rate and tumor-free survival rate6,10,18 after bilateral than unilateral resection. For several reasons, however, opinions differ about the extent of thyroid resection for patients with low-risk PTC. Minimal PTCs are defined as cancers smaller than 1cm, which do not extend beyond the thyroid capsule and are not metastatic or angioinvasive. Patients with such cancers have a death rate of about 0.1%and a recurrence rate of approximately 5%.3 Unilateral total lobectomy may be an appropriate definitive procedure for patients with minimal thyroid cancers.18
Q. What is the role of measuring thyroglobulin?
A. When serum thyroglobulin is undetectable, the absence of anti-Tg antibodies can confirm the absence of disease, whereas measurable anti-Tg antibodies may serve as a tumor marker. Similarly, Park and colleagues19 found evidence of recurrent disease in 63.6% (21/33) of patients with undetectable serum Tg but positive anti-Tg antibodies. The authors concluded that a finding of low serum Tg at the first annual follow-up evaluation was highly predictive of absence of disease, and that routine diagnostic scans could be omitted in these patients.
10 Q. How do you manage recurrence in a case of a well-differentiated thyroid malignancy?
A. Recurrence in local or regional lymph nodes after initial surgery should be treated with completion thyroidectomy, if residual tissue exists, plus regional lymph node dissection (i.e. modified radical neck dissection).20 Radio iodine therapy should be used as adjuvant therapy. Local recurrence in the central neck should be treated surgically with postoperative 131I ablation and TSH suppression therapy. External radiation treatment is helpful when tumors cannot be removed surgically.
Q. What are the markers for follow up of well-differentiated thyroid cancer?
A. The serum thyroglobulin is valuable in the follow up of patients with well-differentiated thyroid cancer and that increasing serum levels are often the first sign of recurrence.26
Q. How do you manage metastasis to lung and bone?
A. Lung metastases from differentiated thyroid cancers have shown to accumulate more radioactive iodine than bone metastases, such that patients with lung metastases respond better to radioactive iodine than those with bone metastases. For patients with isolated bone metastasis, the management is surgical resection followed by radioiodine treatment and, if there is no uptake, external radiotherapy usually relieves pain and is occasionally curative.
Q. How do you manage MTC?
Most endocrine surgeons agree that total thyroidectomy is the treatment of choice for patients with MTC due to the high incidence of multicentricity and the more aggressive course of this tumor.21 In addition, the central compartment of nodes from the carotid sheath to the trachea should be meticulously cleared along with the peritracheal nodes (central neck node dissection), which allows for appropriate staging of the disease process. Any palpable lymph nodes in the lateral areas require a modified radical neck dissection. Some surgeons will perform an ipsilateral neck dissection in patients with an MTC larger than 2 cm due to the fact that 60% of these patients will have nodal metastases.2
11 Q. What is work-up for MTC?
A. Sporadic MTC presents in the fourth decade typically as a thyroid mass, emphasizing the importance of appropriate work-up with fine-needle aspiration. Despite cytological variability in MTC, fine-needle aspiration with calcitonin immunohistochemical staining is highly sensitive and specific for medullary carcinoma. Regional lymph nodes are positive in more than 50% of patients, with distant metastasis present in 10% to 20% of patients.22 MTC of any type that presents as a palpable mass implies regional nodal involvement.23
In the presence of symptoms associated with pheochromocytoma (nervousness, headache, and palpitations) and hypercalcemia, as well as symptoms of hoarseness, dysphagia, and diarrhea, both basal and stimulated calcitonin levels should be obtained. Basal calcitonin levels are elevated in only approximately two-thirds of patients who present with MTC.22,24 Carcinoembryonic antigen (CEA) levels should be obtained preoperatively and have a role along with calcitonin testing in postoperative follow-up. In addition, calcium, parathyroid hormone, and 24-hour urine collection should be obtained for urinary catecholamines, vanillyl mandelic acid, and metanephrines in all patients preoperatively.
Medullary carcinoma tends to spread initially within the thyroid, metastasizing through regional lymphatics to cervical and mediastinal nodal groups and eventually hematogenously metastasizing to lung, liver, bone, and other sites.22 Approximately one-third of MTC recurs clinically after surgery, with up to 50% of patients having elevated calcitonin levels postoperatively. For all types of MTC, the 5-year survival rate is between 78% and 91%, and the 10-year survival is between 61% and 75%. Regional metastasis was present in only 11% of patients who had thyroid primaries less than 1 cm and in 40% of patients with primaries greater than 3 cm. Presentation with a thyroid mass strongly correlates with regional nodal disease. Preoperative calcitonin levels predicted the incidence of regionally involved nodes at surgery as well as postoperative calcitonin levels. Because of the tendency for nodal regional 12involvement, a prophylactic central neck dissection is required in all patients at the time of total thyroidectomy. The central neck dissection should extend from hyoid to innominate and laterally to the jugular veins and should include Delphian pre-and para-tracheal nodal groups as well as superior mediastinal nodes. In patients with palpable thyroid disease with no preoperative neck examinations, strong consideration should be made for bilateral functional neck dissections encompassing regions II through V. In patients with nonpalpable thyroid disease identified by screening, total thyroidectomy and central neck dissection should be adequate in most cases.
Q. What is the role of calcitonin levels in postoperative period?
A. Calcitonin levels should be checked approximately 2 months postoperatively. Normal basal and stimulated calcitonin levels are excellent indications that resection has been curative.25 Calcitonin and CEA levels should be followed postoperatively to help identify patients who are at risk for recurrence or metastasis.
 
TOXIC GOITER
 
Case Study 3
Neelam Roy Age 28 yr, resident of Chhapra district of North Bihar presented with complaints of Swelling in front of neck for 3 years.
 
History of Present Illness
Patient states that she was apparently asymptomatic till 3 years ago when during her last pregnancy she noticed a small swelling in front of her neck without pain or fever which has gradually increased over this period. However she has noticed that during last one year the size has increased faster than the earlier. No history of regression of the swelling, or any other swelling in neck or the body. No history of difficulty in swallowing and breathing. Patient does give history of heat intolerance, with increased sweating, moist palms, palpitation, and dyspnea on excretion, easy 13fatigability, nervous excitability and recent change in menstrual cycle in form of oligomenorrhea. No history of prominence of eyeball or loss of weight. No history of chest pain or ankle swelling. No history of constipation, failing memory, increased sleepiness, change in voice. Patient is mother of two children, had her menarche at 12 yr of age 0-4 days of flow monthly, but since last one year it occurs only for one day and is scanty.
Patient is not a known case of HTN/TB and has not received any treatment for her complaints.
On examination Patient is an averagely built and nourished lady, having anxious look, no pallor/cyanosis/ generalized lymphadenopathy or ankle swelling. Pulse 100/min, resp18/min and BP 130/94 mm of Hg. There is no lid retraction. No exophthalmos, lid lag, staring look. No difficulty in convergence and no diplopia on looking upwards and outwards. No conjunctival edema. Her palms are hot and moist. Fine tremors of out stretched hand are present.
 
Local Examination
On inspection of the neck with the patient sitting on a stool with neck slightly hyperextended.
There is a large butterfly shaped swelling in front of the neck extending across the whole of the horizontal aspect of neck, approximately 8 cm to the right of midline to approximately 7 cm to the left of midline. Overlying skin is normal without any redness, edema, scar or sinus. No distended veins seen on the neck. The swelling moves on deglutition but not on protrusion of tongue. When the swelling rises lower border of the swelling is not seen. No visible pulsation. On raising both arms above the head there is no congestion of face.
On palpation. No local rise of temperature and no local tenderness. Swelling has bosselated surface with soft consistency. Margins are merging imperceptibly beneath the swelling. Lower border is extending upto sternoclavicular joint. Although swelling moves up on deglutition but the tracheal rings cannot be palpated in suprasternal space. No fixity to skin. No restriction of the 14mobility in horizontal or vertical direction. No palpable thrill at the upper pole of the swelling. Carotid pulsations are bilaterally well felt at the posterior aspect of the swelling. Trachea could not be palpated. No cervical lymph node palpable. Percussion node over the sternum is resonant. On auscultation, there is no systolic bruit.
Chest. NAD.
Abdomen. NAD.
Provisional diagnosis Multinodular goiter with toxicity without any airway obstruction.
Q. What is the cause of goiter?
A. Simple goiter is sometimes due to a definable cause of impaired thyroid hormone synthesis, such as iodine deficiency, ingestion of a goitrogen, or a defect in a hormone biosynthetic pathway, but the cause is usually unknown.
Q. What is Graves’ disease?
A. Thyroid enlargement, hyperactivity of the thyroid gland and presence of antibodies against different fraction of the thyroid gland. It may be accompanied by infiltrative ophthalmopathy and less commonly by infiltrative dermopathy.
Q. What is the cause of Graves’ disease?
A. The central disorder is a disruption of homeostatic mechanisms that normally control hormone secretion. This disruption results from the presence in plasma of thyroid-stimulating immunoglobulins (TSIs) of the IgG class that are elaborated by lymphocytes. When human thyroid tissue is used as the assay system, the end points are stimulation of colloid droplet or cyclic AMP generation (for thyroid-stimulating antibodies, TSAbs) and inhibition of the binding of TSH to its receptors in human thyroid tissue (TSH-binding inhibitory immunoglobulins, TBIIs). These factors represent antibodies against the thyroid TSH receptor (TRAbs)
Q. What are clinical features in this patient suggestive of toxicity?
A. Palpitation, dyspnea on accustomed exertion, heat intolerance, sweating in the palm, excitability, nervousness, irregular menstruation and fine finger tremors.
15 Q. How will you confirm it?
A. Serum TSH, free T4, T3 (RIA) are the laboratory tests required to arrive at diagnosis. In Graves’ disease antithyroglobulin and antimicrosomal antibodies are helpful in confirming the diagnosis. TSH receptor antibody (TSH-R Ab [stim] are often elevated.
Q. What is primary thyrotoxicosis and secondary thyrotoxicosis?
A. In primary thyrotoxicosis, thyroid enlargement and features of thyrotoxicosis appear at the same time while in secondary thyrotoxicosis there is long standing goiter and features of thyrotoxicosis appear later. The later could be as result of autonomous nodule or interglandular tissue in multinodular goiter as the seat of hyperactivity.
Q. What is difference between term thyrotoxicosis and hyperthyroidism?
A. In thyrotoxicosis the cause may not necessarily be the thyroid gland. It could be ectopic thyroid tissue in ovarian dermoid tumour, high levels of hCG seen in molar pregnancy, choriocarcinoma, testicular malignancies and, rarely metastatic functioning thyroid carcinoma.
Q. What is the effect of thyroid hormone on the heart?
Thyroid hormones increase the number and affinity of β-adrenergic receptors in the heart and consequently increase its sensitivity to the ionotropic and chronotropic effects of catecholamines. There is a decrease in the peripheral resistance as a result of cutaneous vasodilatation and it predisposes patients to high output failure.
Q. What is Pemberton’s sign?
A. Signs of compression can be induced with large retrosternal goiters when the patient’s arms are raised above the head; they may include suffusion of the face, giddiness, and syncope.
Q. What is the minimum quantity of iodine required to maintain normal thyroid function.
A The minimum daily iodine intake that will maintain normal thyroid function is 150 mg in adults.
16 Q. Beside thyroid gland what other tissue transport iodide against concentration gradient
A. The salivary glands, the gastric mucosa, the placenta, the cilliary body of the eye, the choroids plexus and the mammary glands also transport iodide against a concentration gradient, but their uptake is not affected by TSH. The mammary glands also bind the iodine: di-iodotyrosine is formed in mammary tissue, but T3 and T4 are not.
Q. What is the isotope used and why that is preferred?
A. The isotopes of iodine that is most commonly used is 123 I because it has a half-life of 0.55 days, compared with 131I which has a half-life of 8.1 days and 125I, which has a half-life of 60 days.
Q. How does thiocarbamides act?
A. The thiocarbamides, a group of compounds related to thiourea, inhibit the iodination of monoiodotyrosine and block the coupling reaction. The two used clinically are propyl-thiouracil and methimazole.
Q. How does Lugol’s iodine act?
A. In normal individuals, large doses of iodides act directly on the thyroid to produce a mild and transient inhibition of organic binding of iodide and hormone synthesis. This inhibition is known as the Wolff-Chaikoff effect. The effect is greater and more prolonged when iodide transport is increased, and that is why patients with thyrotoxicosis are more responsive to iodide than normal individuals. It reduces the effect of TSH on the gland by reducing the camp response to this hormone, and it inhibits the proteolysis of thyroglobulin. In thyrotoxicosis, iodide cause colloid to accumulate, and the vascularity of the gland is decreased, making iodide treatment of considerable value in preparing thyroid patients for surgery. Iodine affects all facets of thyroid function. Endocytosis of colloid and proteolysis of thyroglobulin comes to a halt. Excess iodide inhibits its own transport in thyroid cells and may alter the redox potential of cells thus interfering with iodination thus reducing T3 and T4 synthesis.
17Lugol’s solution (5% iodine in10% potassium iodine solution. 5-10 drops/day)
Collossal—8 mg iodine/5 ml liquid.
Iodide—100-300 mg/day.
Q. What is the role of RAIU?
A. One valuable application of the RAIU test occurs when thyrotoxicosis is associated with a low RAIU. Causes include iodineinduced hyperthyroidism, thyrotoxicosis factitia, inadvertent ingestion of ground meat containing thyroid glands (“hamburger toxicosis”), and the spontaneously resolving thyrotoxicosis associated with painless chronic thyroiditis, postpartum thyroiditis, or subacute thyroiditis.
Q. What is the role of scintiscan?
A. Imaging by scintiscan permits localization of sites of accumulation of radio iodine or sodium [99mTc] pertechnate. Unlike iodide, little pertechnate is organically bound; hence, its duration of stay in the thyroid is short. This property, together with its short physical half-life, makes pertechnate a valuable radionuclide for imaging the thyroid by scintillation scanning.
This technique is useful for defining areas of increased or decreased function within the thyroid and for detecting retrosternal goiter, ectopic thyroid tissue, hemiagenesis of the thyroid, and functioning metastases of thyroid carcinoma.
Q. What is the role of USG?
A. Ultrasonic examination of the thyroid is also useful for differentiating cystic from solid nodules. Since ultrasonic scans provide an accurate indication of size, are noninvasive, and apparently have no injurious effects, sequential scans can be employed to assess changes in the size of the thyroid as a whole or of discrete nodules over time or in response to treatment.
Q. What is the pathogenesis of ophthalmopathy of Graves’ disease?
A. An antigen in orbital tissues that cross-reacts with the thyroid has been postulated, and fibroblasts from orbital tissues contain a material that reacts with antibodies to the TSH receptor. Both cellular and humoral immunity may play a role in the 18ophthalmopathy. Cytokines and/or growth factors released by T cells may lead to production of an inflammatory reaction with proliferation of more fibroblasts and glycosaminoglycans production, thereby initiating the edema and increase in muscle volume and retro-orbital fat. The ophthalmopathy is characterized by an inflammatory infiltrate of the orbital contents, exclusive of the globe, with lymphocytes, mast cells, and plasma cells. The orbital musculature is often enlarged owing to infiltration with lymphocytes, muco-polysaccharides, and edema, which with fat largely account for the increased volume of the orbital contents that causes the globe to protrude. Muscle fibers show degeneration and loss of striations, with ultimate fibrosis.
Q. What is the characteristic of dermopathy of Graves’ disease?
A. The dermopathy of Graves’ disease is characterized by thickening of the dermis, which is infiltrated with lymphocytes and with hydrophilic, meta-chromatically staining mucopolysaccharides.
Q. What are common manifestations of thyrotoxicosis?
Common manifestations include nervousness, emotional labiality, and inability to sleep, tremors, frequent bowel movements, excessive sweating, and heat intolerance. Weight loss is usual despite a well-maintained or increased appetite. Proximal muscle weakness with loss of strength is often manifested by difficulty in climbing stairs. In premenopausal women, oligomenorrhea and amenorrhea tend to occur. Dyspnea, palpitations, and, in older patients, enhancement of angina pectoris or cardiac failure may be present. In general, nervous symptoms dominate the clinical picture in younger individuals, whereas cardiovascular symptoms predominate in older subjects. Usually, the patient appears anxious, restless, and fidgety. The skin is warm and moist with a velvety texture, and palmer erythema is present. Separation of the fingernail from the nailbed (onycholysis, Plummer’s nail) is common, especially on the ring finger. The hair is fine and silky. A fine tremor of the fingers and tongue, together with hyper-reflexia, is characteristic.
19Ocular signs include a characteristic state with widened palpebral fissures, infrequent blinking, lid lag, and failure to wrinkle the brow on upward gaze. These signs result from sympathetic over stimulation and usually subside when the thyrotoxicosis is corrected.
The mechanical component includes proptosis of varying degrees with ophthalmologic and congestive oculopathy characterized by chemosis, conjunctivitis, periorbital swelling, and the potential complications of corneal ulceration, optic neuritis, and optic atrophy. When exophthalmos progresses rapidly and becomes the major concern in Graves’ disease, it is termed progressive and, if severe, malignant exophthalmos. The term exophthalmia, ophthalmologists refers to, is the ocular muscle weakness that results in impaired upward gaze and convergence and strabismus with varying degrees of diplopia. Exophthalmos may be unilateral initially but usually becomes bilateral with time.
Cardiovascular features include a wide pulse pressure, sinus tachycardia, atrial arrhythmias (especially atrial fibrillation), systolic murmurs, increased intensity of the apical first sound, cardiac enlargement, and, at times, overt heart failure. A to and fro, high-pitched sound may be audible in the pulmonary area and may simulate a pericardial friction rub (Means-Lerman scratch).
Q. What factors falsely increase T4 levels?
A. Factors increasing T4 (False +)
Laboratory error
Autoimmunity
Acute illness
High estrogen state
Contraceptives
Pregnancy
HRT
Tamoxifen
Acute psychiatric problems
Hyperemesis gravidarum
Drugs
Amiodarone
Amphetamines
Clofibrate
Q. What factors falsely decrease T4 levels?
A. Factors decreasing T4 levels (false –ve)
Laboratory level
Severe illness
Cirrhosis
Nephrotic syndrome
20Drugs
Androgens
Carbamazepine
Fluorouracil
Phenyl butazone
Q. How do you manage ophthalmopathy?
A. Standard therapeutic approaches to ophthalmopathy include corticosteroids given either orally, by retrobulbar injection, or by pulse intravenous injection. In some cases, greater benefit has been seen with combined oral steroids and external radiotherapy. Based upon the existence of an inflammatory response in ophthalmopathy, Stamato and colleagues27 investigated whether treatment with anti-inflammatory agents such as colchicine might be beneficial. They treated a total of 20 patients with active inflammatory ophthalmopathy with 10 receiving colchicine and 10 receiving corticosteroids. All patients exhibited some clinical improvement on magnetic resonance imaging (MRI) and clinical activity scores, with amelioration of the inflammatory response in 100% of the colchicine-treated patients and in 85% of the steroidtreated patients.
Q. What are the factors which influence post-radiation hypothyroidism?
A. The most significant influences are higher dosages of RAI, relatively younger age, or prior administration of lithium, which has been found to increase intrathyroidal RAI retention.28
21 Q. How long antithyroid drugs are to be administered
A. Although there was a reciprocal relationship between TSH-receptor titers and duration of therapy, with the lowest levels seen after 36 months, it is suggested that treatment for longer than 18 months should not be necessary.29 By contrast, cigarette smoking and titers of TSH receptors were found to be independent predictors of recurrence after the withdrawal of thiourea.30
Q. What is the role of radiotherapy in toxic nodule?
Toxic nodules may also be treated by administration of single 30 to 60 mCi doses of 131I. The ease and convenience of 131I, lower expense, avoidance of a scar, and avoidance of hospitalization make it the preferable approach in older patients and those with coincident serious illness. Results are to some extent unpredictable. Smaller doses may be ineffective or may need to be repeated, and the remainder of the gland receives 10 to 80 Gy, which induces hypothyroidism in approximately 10% of cases.31
Q. What are the effects of hyperthyroidism in pregnancy?
A. In pregnant women, inadequately treated hyperthyroidism can lead to pre-eclampsia, maternal heart failure, thyroid storm, pre-term delivery, miscarriage, and stillbirth. Antithyroid drugs are the optimal treatment choice, with propyl-thiouracil preferred because less medication crosses the placenta. The therapeutic goal is to control the mother’s hyperthyroidism using the least possible amount of medication, to avoid suppressing the fetus’ thyroid gland. Patients should be followed every few weeks and six weeks postpartum, as the disease may worsen after delivery. If low-dose antithyroid drugs are ineffective or intolerable, patients may undergo bilateral subtotal thyroidectomy during the second trimester.
Q. What remission rate can be achieved with antithyroid drugs?
A. When combined with thyroxin for two years’ treatment, anti thyroid drugs have been credited with remission in 40% to 65% of patients.32
22 Q. Can you have T4 raised and TSH not suppressed?
A. If free T4 is elevated and TSH is not suppressed, a TSH-producing pituitary adenoma should be suspected.
Q. What are the advantages of surgery?
A. Surgery is safe, removes the lesion, provides histologic diagnosis, avoids leaving a hard nodule in the thyroid gland, and avoids irradiation and possible hypothyroidism. In Graves’ disease surgery still remains the treatment of choice during pregnancy and in patients with large goiters, signs of compression or in presence of scintigraphic “cold” area.
Q. How do you prepare the patient for surgery?
A. The aim of preoperative preparation of a case of thyrotoxicosis is to achieve:
  • Euthyroid state
  • Protect the target organ
  • Decrease the vascularity
  • Make gland firmer
  • Decrease the size.
Single drug/single protocol may not achieve all the desired effects. Antithyroid drugs takes minimum three weeks to show clinical response and near euthyroid stage is achieved in 8-12 weeks. The beneficial effects of Iodine start waning after 10-15 days due to escape phenomenon. Beta-blockers do protect the target organ but does not decrease the circulating hormones levels.
Patients are ordinarily rendered euthyroid with a thiourea drug. Propranolol is given until the T3 is normal preoperatively. Thyroid vascularity is reduced by preoperative treatment with either ipodate sodium or iopanic acid (500 mg twice daily for 3 days) or Iodine (e.g. Lugol’s solution, 2 or 3 drops orally daily for 7-10 days).
Some surgeons also advocate the addition of thyroxin in the preoperative preparation, as it will suppress TSH and the decrease in size, which might occur with antithyroid drugs.
Q. Where do you ligate superior thyroid vessels and why?
A. Superior thyroid artery is ligated close to the superior pole. Infact experienced surgeons ligate its ant and posterior branches to avoid damage to external laryngeal nerve.
23 Q. What happens if external laryngeal nerve is injured?
A. Injury to external laryngeal nerve results in easy voice fatigability and loss of timbre.
Q. What happens when recurrent laryngeal nerve is injured?
A. Bilateral recurrent laryngeal nerve palsy is an occasional and very serious complication of thyroidectomy. Acute dyspnea occurs as a result of the paramedian position of both vocal cords folds which reduce the airway to 2-3 mm and which tend to get sucked together on inspiration. In severe cases tracheotomy or intubation is necessary immediately otherwise death occurs from asphyxia. Unilateral recurrent laryngeal nerve palsy of sudden onset produces hoarseness, which is most notable for lack of volume to the voice and occasionally may be associated with difficulty in swallowing liquids and weakening of the cough.
Q. Where do you ligate inferior thyroid artery and why?
A. It is ligated as close to the gland as possible. The aim is to ligate it after it has given blood supply to parathyroid. This can be achieved if recurrent laryngeal nerve is identified and then all the vessels in front of recurrent laryngeal nerve are ligated.
Q. What are complication of thyroid surgery?
A. Hemorrhage, respiratory obstruction, recurrent laryngeal nerve palsy, parathyroid insufficiency, thyroid storm, and thyroid insufficiency, wound infection, hypertrophic scar and stitch granuloma.
Q. How do you manage thyroid storm?
A. The management is symptomatic and supportive, propylthiouracil is given 150-250 mg every 6 hours. Iodide is given 1 hour later as Lugol’s solution drops three times daily orally or sodium iodide (1 gm IV slowly). Propranolol is given (cautiously in the presence of heart failure) in a dosage of 0.5-2 mg IV every 4 hours. Hydrocortisone is usually given in doses of 50 mg every 6 hours, with rapid reduction as the clinical situation improves.
24 APPENDIX
 
Characteristics of Thyroid Cancer
Papillary
Follicular
Medullary
Anaplastic
Incidence
Most common
Common
Uncommon
Rare
Average age
30
40
50
57
Female
70%
72%
56%
56%
Death due to thyroid cancer
6%
24%
33%
98%
Invasion
Juxtanodal
+++++
+
++++++
+++
Blood Vessels
+
+++
+++
+++++
Distant sites
+
+++
++
++++
Resemblance to normal thyroid
+
+++
+
+-
123I uptake
+
++++
0
0
Degree of malignancy
+
++ To +++
+ To ++++
++++++++
Pathologic pTNM staging and survival rates for adult well differentiated thyroid carcinoma following appropriate treatment.
Description
Five-year survival
Ten-year survival
Stage 1
Under 45: Any T, any N, no M Over 45: T< 1 cms, no N, no M
100%
98%
Stage 2
Under 45: Any T, any N, any M Over 45 T > 1cm limited to thyroid, no N, no M
99%
85%
Stage 3
Over 45: T beyond thyroid capsule, no N, no M; or any T, regional N, no M
95%
70%
Stage 4
Over 45: Any T any N, any M
80%
61%
Loh KC, et al. J Endocrinol Metab 1997;82:3553; and Hay ID: Endocrinol Metabol Clin North Am 1990;19;545
25
Symptoms and signs of hyperthyroidism
Organ system
Symptoms
Signs
Nervous system
Nervousness
Emotional lability
Sleeplessness
Tremors
Anxious
Restless
Hyperreflexia
Fine tremors of fingers and tongue.
Eye
Prominent eyes
Spastic
Stellwags: infrequent blinking
Dalrymple’s: widened palpebral fissure.
von Grafe’s: lid lag
Joffroy ’s: failure to wrinkle the brow on upward gaze.
Cardiovascular
Palpitations
Dyspnea
Angina
Sinus tachy-arrhythmias
Hyperdynamic circulation: loud S1, systolic murmurs, wide pulse pressure Heart failure
Means-Lerman Scratch: To and fro high-pitched sound in pulmonary area.
Gastro-intestinal
Weight loss despite increased appetite
Frequent bowel movements.
Decreased BMI.
Menstrual
Oligomenorrhoea/amenorrhea
Musculoskeletal
Inability/difficulty to climb or do works requiring proximal muscles.
Proximal muscle weakness.
Integumentary/Metabolic
Excessive sweating Heat intolerance
Warm, moist and velvety skin with palmer erythema.
Plummer nails: separation of nail from nailbed, especially of ring finger.
 
Features of Graves’ other than Hyperthyroidism
 
Ophthalmopathy
  1. 26Exophthalmos
  2. Chemosis
  3. Myopathy and neuropathy
  4. Mobius sign: inability to converge.
 
Dermopathy and Acropathy
Pretibial myxedema and clubbing
 
Differential Diagnosis of the Thyroid Nodule
zoom view
 
Thyroid Nodule
27
zoom view
 
Patient with Well-differentiated Thyroid Cancer (80-90% papillary, 10-20% follicular)
28
zoom view
 
American Joint Committee on Cancer Staging System for Thyroid Cancer
TNM classification
Tumor
T0 No evidence of tumor
T1 Tumor< 1 cm
T2 Tumor more than 1 cm but less than 4 cm
T3 Tumor more than 4 cm but limited to thyroid
T4 Tumor of any size extending beyond thyroid capsule
Node involvement
Nx Nodes cannot be assessed
N0 No nodal metastases
N1 Regional node metastases
N1a Ipsilateral node involvement
N1b Bilateral cervical or mediastinal lymph nodes.
29Metastases
Mx Distant metastases cannot be assessed
M0 No distant metastases
M1 Distant metastases
 
Arguments for and against Conservative or More Radical Surgery for Well-differentiated Thyroid Cancer
Issue
Conservative surgery
Radical surgery (TT)
Safety of surgery
Risk of permanent hypocalcemia and recurrent laryngeal nerve injury greatly reduced with lobar or subtotal thyroidectomy.
Experienced surgeon can perform these procedures with very minimal or no long-term complications
Postoperative iodine
If necessary 131I ablation of thyroid remnant can be accomplished with no morbidity
Thyroid ablation with 131I is complicated by pain if gross thyroid remnant exists; decrease efficacy of 131I with residual thyroid
Anaplastic cancer
Local recurrence able to be managed; risk of conversion to anaplasia is <1%
Potential to local recurrence with possible dedifferentiation to a more aggressive tumor.
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