1. Malignant Thyroid Disease
Ong, Edilisa – Onilla, John Christopher
3 Medicine C

2. 39 y/o Female CC: Anterior Neck Mass Ong, Vicar
39 y/o Female from Bicol
With a Chief Complain of Anterior Neck Mass
History of Present Illness
!0 year history of slowly growing nodular Anterior Neck mass. No other accompanying symptoms

3. 10 years PTC 2 years PTC 6 months PTC HISTORY OF PRESENT ILLNESS:
Ong, Vicar
HISTORY OF PRESENT ILLNESS:
10 years PTC
Slowly growing nodular Anterior Neck Mass
No other accompanying symptoms
2 years PTC
Rapid Increase in the size of the mass
6 months PTC
hoarseness
Difficulty in swallowing
 – 

4. NO REVIEW OF SYSTEMS: Fever Weight Loss Tremors Chest Pain
Ong, Vicar
REVIEW OF SYSTEMS: NO
Fever
Weight Loss
Tremors
Chest Pain
Easy Fatigability
Abdominal Pain

5. PAST MEDICAL HISTORY Unremarkable FAMILY HISTORY
Ong, Vicar
PAST MEDICAL HISTORY Unremarkable FAMILY HISTORY

6. PHYSICAL EXAM
Ong, Vicar
PR = 100/min RR = 20/min T = 370C No Exopthalmos Neck: 25X20cm multinodular, firm, right anterolateral neck mass which moves with deglutination there is a mass 5X3cm hard nodule within the big mass Palpable cervical adenopathies posterior to the SCM

7. Salient features 39 y/o Female Lives in Bicol
Ong, Keno
Salient features
39 y/o
Female
Lives in Bicol
Ten year history of a slow growing nodular anterior neck mass
2 years prior to consult- rapid increase in size of mass; 25x20 firm, right, anterolateral, moves with deglutition. 5x3cm hard nodule within the big mass
6mos PTC- hoarseness and difficulty swallowing
Palpable cervical adenopathies posterior to the sternocleidomastoid

8. Clinical Impression Papillary Carcinoma
Ong, Keno
Clinical Impression
Papillary Carcinoma
accounts for 80% of all thyroid malignancies
occurs more often in women, with a 2:1 female:male ratio
mean age at presentation is 30 to 40 years
euthyroid and present with a slow-growing painless mass in the neck
Dysphagia, dyspnea, and dysphonia are usually associated with locally advanced invasive disease
Lymph node metastases are common

9. Differential diagnosis
Ong, Keno
Differential diagnosis
Goiter
may be diffuse, uninodular, or multinodular
asymptomatic, although patients often complain of a pressure sensation in the neck, particularly with motion
compressive symptoms, such as dyspnea and dysphagia
Dysphonia from recurrent laryngeal nerve injury is rare, except when malignancy is present
soft, diffusely enlarged gland (simple goiter) or nodules of various size and consistency in case of a multinodular goiter

10. Common in iodine deficient areas
Ong, Keno
Follicular Carcinoma
10% of thyroid cancers
Common in iodine deficient areas
Women have a higher incidence of follicular cancer, with a female:male ratio of 3:1, and a mean age at presentation of 50 years
solitary thyroid nodules, occasionally with a history of rapid size increase, and long-standing goiter
cervical lymphadenopathy is uncommon at initial presentation approximately 5%

11. Hurthle Cell 3% of all thyroid malignancies
more often multifocal and bilateral (approximately 30%)
usually do not take up RAI (approximately 5%),
more likely to metastasize to local nodes (25%) and distant sites
associated with a higher mortality rate (approximately 20% at 10 years)

12. Ong, Keno
Medullary Carcinoma
5% of thyroid malignancies and arise from the parafollicular or C cells of the thyroid
present with a neck mass that may be associated with palpable cervical lymphadenopathy (15 to 20%)
Local pain or aching is more common in patients with these tumors, and local invasion may produce symptoms of dysphagia, dyspnea, or dysphonia
female:male ratio is 1.5:1
Most patients present between 50 and 60 years of age
frequently develop diarrhea, which may result from increased intestinal motility and impaired intestinal water and electrolyte flux

13. Women are more commonly affected
Ong, Keno
Anaplastic Carcinoma
Women are more commonly affected
majority of tumors present in the seventh and eighth decades of life
long-standing neck mass, which rapidly enlarges and may be painful
Associated symptoms, such as dysphonia, dysphagia, and dyspnea, are common
Lymph nodes usually are palpable at presentation

14. 2. What work-ups are needed if any?
Ong, Nicodemus
2. What work-ups are needed if any?
Fine needle aspiration biopsy (FNAB)
needle is placed into the nodule several times and cells are aspirated into a syringe
Viewed by pathologist
Complete neck ultrasound
To evaluate lymph node metastasis and the contralateral lobe

17. 3. INDICATIONS FOR THYROIDECTOMY
Onilla, Arianne
3. INDICATIONS FOR THYROIDECTOMY
1. As therapy for some individuals with thyrotoxicosis, both those with Graves’ disease and others with hot nodules 2. To establish a definitive diagnosis of a mass within the thyroid gland, especially when cytologic analysis after fine-needle aspiration (FNA) is either nondiagnostic or equivocal 3. To treat benign and malignant thyroid tumors 4. To alleviate pressure symptoms or respiratory difficulties associated with a benign or malignant process 5. To remove an unsightly goiter. 6. To remove large substernal goiters, especially when they cause respiratory difficulties
“Chapter 21. Surgery of the Thyroid Gland”, Edwin L. Kaplan, MD et. al., Revised 20 Jul 2010, retrieved from last November 27, 2011

18. Standard Treatment of Most Papillary Carcinomas
Onilla, Arianne
Total Thyroidectomy
Near Total Thyroidectomy
“Chapter 21. Surgery of the Thyroid Gland”, Edwin L. Kaplan, MD et. al., Revised 20 Jul 2010, retrieved from last November 27, 2011

19. Onilla, Arianne
MRND
 with appropriate central and lateral neck dissection when nodes are involved. The so-called cherry-picking operations, which remove only the enlarged lymph nodes, should not be performed.Rather, when tumor is found in the lateral triangle, a modified radical neck dissection should be performed27(Fig. 12). At the conclusion of a modified radical neck dissection, the lymph node–bearing tissue from the lateral triangle is removed, whereas the carotid artery, jugular vein, phrenic nerve, sympathetic ganglia, brachial plexus, and spinal accessory nerve are spared and left in place. Many times sensory nerves can be retained as well. Prophylactic neck dissection of the lateral triangle should not be performed for papillary cancer; such dissections should be done only when enlarged nodes with tumor are found.
Central lymph nodes (level VI) are frequently involved with metastases from ipsilateral thyroid cancers as are levels III, IV, and V which are removed in most lateral neck dissections.
“Chapter 21. Surgery of the Thyroid Gland”, Edwin L. Kaplan, MD et. al., Revised 20 Jul 2010, retrieved from last November 27, 2011

20. Onilla, Arianne
Radioiodine Therapy
Radioiodine therapy with I131 has been commonly used in order to ablate any remaining normal thyroid remnant that is present in the thyroid bed after near- total or total thyroidectomy or to treat local or distant metastatic thyroid cancer.
More recently, there has been a trend to use radioiodine more sparingly in low risk patients with small tumorsbecause this treatment has not been shown to decrease mortality in such individuals. Hence, radioiodine is now recommended postoperatively in high riskpapillary cancer and in patients with metastatic disease, gross extrathyroidal extension, or when tumors are greater than 4 cm. It is recommended for selected patients with tumors 1 cm to 4 cm in diameter, but it is not recommended in low risk patients with tumors less than 1 cm in diameter.25a
“Chapter 21. Surgery of the Thyroid Gland”, Edwin L. Kaplan, MD et. al., Revised 20 Jul 2010, retrieved from last November 27, 2011

21. Ong, Edilisa
4. How would you manage the patient? Immediate postop? In the next 4-6 weeks? Long term plans?

22. Postoperative Management of Differentiated Thyroid Cancer
Ong, Edilisa
Postoperative Management of Differentiated Thyroid Cancer
Radioiodine Therapy
Reduces recurrence and provides a small improvement in survival, even in low-risk patients
More sensitive screening tool than CXR or CT scan for detecting metastasis
Less sensitive than thyroglobulin (Tg) for detecting metastatic disease (except Hΰrtle cell tumors)
Metastatic diff. thyroid CA can be detected and treated by 131I in about 75% of patients
Treats>70% of lung micrometastases at are detected by RAI scan in the presence of a normal CXR
Success rates drop to <10% with pulmonary metastases
Schwartz’s Principle of Surgery, 9th edition

24. Postoperative Management of Differentiated Thyroid Cancer
Ong, Edilisa
Postoperative Management of Differentiated Thyroid Cancer
I. Radioiodine Therapy - RAI Ablation
All patients with stage III or IV disease
All patients with stage II disease < 45 y/o
Most patients with stage II disease ≥ 45 y/o
Patients with stage I disease who have aggressive histologies, nodal metastases, multifocal disease, and extrathyroid or vascular invasion
Schwartz’s Principle of Surgery, 9th edition

25. Postoperative Management of Differentiated Thyroid Cancer
Ong, Edilisa
Postoperative Management of Differentiated Thyroid Cancer
Cont. Radioiodine Therapy
Discontinue T4 therapy for approx. 6 weeks before scanning with 131I. T3 should be given to decrease the period of hypothyroidism.
T3 discontinued for 2 weeks to allow TSH levels to rise before treatment (>30mU/L)
Low iodine diet
Screening dose: 1-3 mCi of 123I; mx uptake 24 hours later
Should be <1% after a total thyroidectomy
If there is significant uptake: therapeutic dose of 131I, 30 to 100 mCi to low risk Px; mCi for high risk patients
Some wants to omit screening dose to minimize thyrocyte stunning and subsequent requirement for higher treatment doses.
Schwartz’s Principle of Surgery, 9th edition

26. Postoperative Management of Differentiated Thyroid Cancer
II. External Beam Radiotherapy
To control unresectable, locally invasive or recurrent disease; treat metastases in support bones to decrease the risk of fractures
Of value for treatment and control of pain from body metastases when minimal and no RAIU
III. Chemotherapy
Most frequently used: Doxorubicin (Adriamycin) and paclitaxel (Taxol)
Doxorubicin – used as radiosensitizer, consider for Px undergoing external beam radiotherapy
Schwartz’s Principle of Surgery, 9th edition

27. Postoperative Management of Differentiated Thyroid Cancer
IV. Thyroid Hormone
A replacement therapy with additional effect of suppressing TSH and reducing the growth stimulus for any possible residual thyroid cancer cells.
Administer T4 to ensure patient is euthyroid, with circulating TSH levels of about 0.1μU/ml in low-risk Px and < 0.1μU/ml for high risk Px.
Balance between risk of tumor recurrence with the side effects associated with prolonged TSH suppression – osteopenia and cardiac problems
Schwartz’s Principle of Surgery, 9th edition

28. Follow-Up of Patients with Differentiated Thyroid Cancer
Thyroglobulin (Tg) Measurement
Tg levels after total thyroidectomy should be:
< 2ng/mL (if Px is taking T4)
<5 ng/mL (if Px is hypothyroid)
Tg levels with > 2ng/mL is highly suggestive of metastatic disease or persistent normal thyroid tissue, esp. if it increases when TSH levels increase when hypothyroid during preparation for RAI scanning or after recombinant TSH
Schwartz’s Principle of Surgery, 9th edition

29. Ong, Edilisa
95% of patients with persistent or recurrent follicular cell carcinoma will have Tg levels > 2ng/mL
Tg and anti-Tg antibody levels should be measured initially at 6-month intervals and then annualy if Px is clinically disease free
Schwartz’s Principle of Surgery, 9th edition
Harrison’s Principles of Internal Medicine, 17th edition

30. Follow-Up of Patients with Differentiated Thyroid Cancer
Ong, Edilisa
Follow-Up of Patients with Differentiated Thyroid Cancer
II. Imaging
For low risk patients
(-) TSH-stimulated Tg and cervical ultrasound
Don’t require routine Dx whole body RAI scans
For high-intermediate risk patients
Whole body scans 6-12 months after remnant ablation may be of value
Cervical ultrasound recommended to evaluate thyroid bed and central & lateral cervical nodal compartments at months postthyroidectomy and then annualy for at least 3-5 years
If RAI and ultrasound scans are (-) but Tg remains elevated – FDG PET scan may help localize the disease
Schwartz’s Principle of Surgery, 9th edition

31. Survival Rate Ong, Edilisa
A. Papillary cancer, cohort of 1851 patients. I, 1107 (60%); II, 408 (22%); III, 312 (17%); IV, 24 (1%); n = 1185.
B. Follicular cancer, cohort of 153 patients. I, 42 (27%); II, 82 (54%); III, 6 (4%); IV, 23 (15%); n = 153.
Harrison’s Principles of Internal Medicine, 17th edition

32. 5. What are the possible complications of treatment?
Ong, Edilisa
5. What are the possible complications of treatment?

33. Complications of Thyroid Surgery
Minor
Postoperative surgical site seromas
Poor scar formation
Major
Bleeding
Injury to the Recurrent Laryngeal Nerve
Injury to the Superior Laryngeal Nerve
Hypoparathyroidism
Thyrotoxic Storm
Infection
Hypothyroidism

34. Major Complications - Bleeding
Intraoperative bleeding
stains the tissues and obscures important structures
Postoperative bleeding
 unrecognized or rapidly expanding hematoma can cause airway compromise and asphyxiation
Presentation
neck swelling, neck pain, and/or signs and symptoms of airway obstruction (eg, dyspnea, stridor, hypoxia)
Evaluation
Physical examination
 Imaging studies (CT scanning and ultrasonography)
Prevention
Sound surgical technique
Treatment
If a neck hematoma is compromising the patient's airway, open the surgical incision at the bedside to release the collection of blood, and immediately transfer the patient to the operating room.

35. Major complications – Injury to the Recurrent Laryngeal Nerve
Mechanisms of injury to the RLN include complete or partial transection, traction, contusion, crush, burn, misplaced ligature, and compromised blood supply
True vocal-fold paresis or paralysis
Presentation
Patients with unilateral vocal fold paralysis present with postoperative hoarseness or breathiness
Patients with bilateral vocal-fold paralysis may present with biphasic stridor, respiratory distress, or both
Evaluation
Indirect and fiberoptic laryngoscopy
Prevention
Deliberate identification of the RLN minimizes the risk of injury

36. Treatment
Two surgical treatment options are available for patients with unilateral vocal-fold paralysis: medialization and reinnervation.
Medialization is most commonly performed
Medialization of the impaired vocal fold improves contact with the contralateral mobile fold
Reinnervation - primary neurorrhaphy using phrenic nerve, ansa cervicalis, and preganglionic sympathetic neurons
In bilateral vocal-cord paralysis, initial treatment involves obtaining an adequate airway
Emergency tracheotomy may be required
Cordotomy and arytenoidectomy are the most common procedures

37. Major complications – Injury to the SuperiorLaryngeal Nerve
The external branch provides motor function to the cricothyroid muscle involved in elongation of the vocal folds
Trauma to the nerve results in an inability to lengthen a vocal fold and, thus, an inability to create a high-pitched sound
The external branch of the SLN is probably the nerve most commonly injured in thyroid surgery (0-25%)
Presentation
mild hoarseness or decreased vocal stamina, loss of the upper register
Evaluation
Laryngeal EMG
Prevention
Deliberate identification of the SLN minimizes the risk of injury
Treatment
Speech Therapy

38. Major complications: Hypoparathyroidism
Inadequate production of PTH leads to hypocalcemia
Hypoparathyroidism, and the resulting hypocalcemia, may be permanent or transient
The rate of permanent hypoparathyroidism is %.
The condition may be due to direct trauma to the parathyroid glands, devascularization of the glands, or removal of the glands during surgery
Presentation
Initially asymptomatic
Symptoms and signs of hypocalcemia include circumoral paresthesias, mental status changes, tetany, carpopedal spasm, laryngospasm, seizures, QT prolongation on ECG, and cardiac arrest
Prevention
The best way to preserve parathyroid gland function is to identify the glands and to maintain their blood supply
Treatment
Patients who have symptomatic hypocalcemia in the early postoperative period or whose calcium levels continue to fall rapidly require treatment
In symptomatic patients, replace calcium with intravenous calcium gluconate

39. Major complications: Thyrotoxic storm
May result from manipulation of the thyroid gland during surgery in the patients with hyperthyroidism
Presentation and evaluation
Signs of thyrotoxic storm in the anesthetized patient include tachycardia and hyperthermia
in the awake patient - nausea, tremor, and altered mental status, cardiac arrhythmias
Intraoperative management
Stop the procedure. Intravenous beta-blockers, PTU, sodium iodine, and steroids are administered to control sympathetic activity, release of thyroid hormone, hyperthermia
Postoperative management
Removal of the thyroid gland does not immediately relieve thyrotoxicosis because the half-life of circulating T4 is 7-8 days
As thyroid hormone levels decrease and as symptoms resolve, medications should be gradually weaned over the weeks after surgery

40. Major complications: Infection
Presentation
Postthyroidectomy infection may manifest as superficial cellulitis or as an abscess
Evaluation
Gram staining and culturing to direct the choice of antibiotics
CT imaging - deep neck abscess
Prevention
sterile surgical technique
Treatment
Antibiotics that provide good coverage against gram-positive organisms (eg, against staphylococci and streptococci)
If patients have deep neck abscesses, begin with broad- spectrum antibiotics 
Drain abscesses, and direct antibiotic coverage according to culture findings

41. Major complications: Hypothyroidism
Untreated hypothyroidism causes symptoms such as cold intolerance, fatigue, constipation, muscle cramping, and weight gain
Evaluation
Measurement of thyrotropin (thyroid-stimulating hormone [TSH]) levels
Prevention
Hypothyroidism is an expected sequela of total thyroidectomy
Treatment
For hypothyroid patients, start levothyroxine (about 1.7 mcg/kg/d)
Check their thyrotropin level in approximately 4-6 weeks, and adjust the dosage appropriately

42. Table 38-7 Complications of Radioactive Iodine Therapy (131I) and Doses at Which They Are Observed
Acute
Long-Term
Neck pain, swelling, and tenderness
Hematologic
Thyroiditis (if remnant present)
  Bone marrow suppression (>500 mCi)
Sialadenitis (50–450 mCi), taste dysfunction
  Leukemia ( >1000 mCi)
Hemorrhage (brain metastases)
Fertility
Cerebral edema (brain metastases, 200 mCi)
  Ovarian/testicular damage, infertility
Vocal cord paralysis
Increased spontaneous abortion rate
Nausea and vomiting (50–450 mCi)
Bone marrow suppression (200 mCi)
Pulmonary fibrosis
Chronic sialadenitis, nodules, taste dysfunction
Increased risk of cancer
  Anaplastic thyroid cancer
  Gastric cancer
  Hepatocellular cancer
  Lung cancer
  Breast cancer (>1000 mCi)
  Bladder cancer
Hypoparathyroidism

43. Prognosis

44. Papillary Carcinoma >95% 10-yr survival
AGES Scoring System (age, histologic grade, extra thyroidal invasion and metastasis, tumor size)
MACIS (completeness of surgical resection, invasion and metastasis)
AMES (age, metastasis, extra thyroidal spread and tumor size)
TNM system
(+) BRAF mutations
Associated with LN mets and higher tumor grade
DNA Aneuploidy, dec. CAMP response to TSH, inc. EGF binding, (+) N-ras and gsp mutations, overexpression of c-myc, (+) p53 mutations
WORSE PROGNOSIS

45. 5 year survival 10 YEAR SURVIVAL
Thyroid CA type
5 year survival
10 YEAR SURVIVAL
Stage I
Stage II
Stage III
Stage IV
OVERALL
PAPILLARY
100%
93%
51%
96-97%
FOLLICULAR
71%
50%
91%
85%
MEDULLARY
100
98%
81%
28%
80-86%
75%
ANAPLASTIC - 7%
7-14%
NO DATA

46. Follicular Carcinoma Mortality: 15% at 10 years, 30% at 20 years
Age > 50 at presentation, >4 cm, high tumor grade, vascular invasion, extrathyroidal invasion, distant mets
POOR PROGNOSIS

47. Medullary Carcinoma Depends on disease stage
Approx. 80% 10-year survival rate
45% in patients with LN involvement
Non-MEN (familial) >> MEN2A >> sporadic MTC >> MEN 2B

48. Anaplastic Carcinoma Most aggressive
Few patients survive 6 months after diagnosis