Surgery 1.04 Surgical Diseases of the Thyroid Gland

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Surgery II 1.04

1 Sem/A.Y. 2016-2017

Surgical Diseases of the Thyroid Gland Dr. Ampil

I. II. III. IV. V. VI. VII.

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August 30, 2016  

OUTLINE Diseases of the Thyroid Gland Evaluation of thyroid diseases Goiter Thyroiditis Thyroid cyst Benign tumors Malignant tumors a. Papillary carcinoma b. Follicular carcinoma More aggressive neoplasms Parathyroids

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I. DISEASES OF THE THYROID GLAND Thyroid diseases are easy to diagnose unlike the abdomen and thoracic cavity, where you barely see the lesions. Usual presentation is anterior neck mass Skin  subcutaneous thyroid gland Normally, the thyroid gland should not be palpable Congenital Lesions Embryologic life of the thyroid gland: it starts at the base of the tongue (foramen cecum), pierces the hyoid bone and migrates down the neck where it lies during the adult life Any problem with the descent of the thyroid gland to the neck will cause congenital abnormalities

Figure 2. Pyramidal lobe. Distal end of the thyroglossal duct persists thus resulting to a third lobe of the thyroid. 3.

Ectopic Thyroid

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Failure of the thyroid to descend completely into the neck Results to thyroid tissue anywhere along the tract Lingual/Sublingual Thyroid o Mass or thyroid found at the base of the tongue o Represents a failure of the median thyroid anlage to descend normally and may be the only thyroid tissue present o Signs and Symptoms  Hypothyroid- if the thyroid gland is small  Obstructive symptoms- if the thyroid gland is big (choking, dysphagia, airway obstruction)  Hemorrhage o Treatment:  Radioactive iodine (RAI) ablation followed by hormone replacement.  If small: Exogenous thyroid hormone to suppress TSH  If large: Surgical excision; rarely needed but, if required, should be preceded by an evaluation of normal thyroid tissue in the neck to avoid inadvertently rendering the patient hypothyroid.

Figure 1. Embryonic Migration of the Thyroid Gland. 1.

Thyroglossal Duct Anomalies

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Cyst, sinus, fistula Typically midline masses in childhood 80% below hyoid bone Elevates with tongue protrusion o Because embryologically, the thyroid gland originates from the foramen cecum (base of the tongue). From there, the thyroid gland goes down and splits into two. The thyroglossal duct should degenerate upon birth. If the thyroglossal duct persists thyroglossal duct problems Treatment: It is important to recognize thyroglossal duct cyst from a simple cyst because treatment is different o Simple cyst  excise o Thyroglossal duct cyst  Sistrunk procedure (remove the tract and part of the hyoid bone) since it will recur if simply excised!

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Distal end of thyroglossal duct persists Projecting up from the isthmus, lying just to the left or right of the midline No pathologic problem most of the time When the thyroid gland enlarges, the pyramidal lobe can also enlarge.

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Pyramidal Lobe

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50% of individuals

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Figure 3. Lingual/Sublingual Thyroid 

II. EVALUATION OF THYROID DISEASES Thyroid problems usually appear as anterior neck mass that moves up with deglutition

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Surgery II 1.04

Figure 5. Hypothalamus – Pituitary – Thyroid Axis. The hypothalamus releases TRH, stimulating the anterior pituitary gland to secrete TSH, which stimulates the thyroid to produce thyroid hormones with iodine. Excess in thyroid hormones will produce a negative feedback mechanism which suppresses the production of TSH. Also, If TSH is increased, there is a negative feedback to the hypothalamus which will decrease TRH secretion.

Figure 4. Thyroid nodule

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Initial Work-up Thyroid function test: Initial diagnostic modality - TSH, FT4, FT3 serum levels If euthyroid: Ultrasound, Fine Needle Aspiration Biopsy Cytology (FNABC) If hyperthyroid: Thyroid scan - Hot/warm nodule: treat as toxic nodule - Cold nodule: FNABC

1. Thyroid Function Test MOST ACCURATE TESTS of thyroid function  SERUM TSH (Thyroid Stimulating Hormone)  The most sensitive and specific test for determining thyroid function  Reflect the ability of the anterior pituitary to detect FT4 levels  There is an inverse relationship between FT4 levels and the logarithm of TSH concentration: small changes in FT4 lead to a large shift in TSH levels  FREE T4 & FREE T3 ASSAY (FT4 & FT3)  Measure the biologically active thyroid hormones which cause the clinical manifestations  FT4 is not performed as a routine screening tool in thyroid disease. Use of this test is confined to cases of early hyperthyroidism  FT3 is most useful in confirming the diagnosis of early hyperthyroidism Table 1. Interpreting Thyroid Function Tests (Memorize) SERUM FT4 AND FT3 DIAGNOSIS TSH ASSAY High Low Hypothyroid Subclinical Normal High Hypothyroid Low High Hyperthyroid Subclinical Normal Low Hyperthyroid  If the patient can only avail one test, request for TSH

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Other thyroid function test (Non-routine):  Total T4 & T3  Both are measured by radioimmunoassay  Measure both the free and bound components of the hormones  T4 levels reflect the output from the thyroid gland  T3 levels in the non-stimulated thyroid gland are more indicative of peripheral thyroid hormone metabolism; not generally suitable for as a general screening test  Thyroid antibodies  Include anti-Tg, antimicrosomal, or anti-TPO and thyroid-stimulating immunoglobulin  indicate underlying disorder, usually an autoimmune thyroiditis  High in 80% of patients with Hashimoto’s thyroiditis and may also be elevated in Grave’s disease, multinodular goiter, and thyroid neoplasms (occasionally)  Thyroglobulin  Increases dramatically in destructive processes of the thyroid gland (i.e. thyroiditis, Grave’s disease, toxic multinodular goiter)  Most important use is in monitoring patients with differentiated thyroid cancer for recurrence 2.

Ultrasound

 Helpful in the evaluation of thyroid nodules, distinguishing 

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solid from cystic ones, and providing information about size and multicentricity. Major advantage: determine consistency of mass o Simple cyst: thyroid cyst (purely fluid) o Complex cyst: goiter (mixed) o Solid nodule: tumor Monitoring nodule size (for non-operative treatment) o Can detect masses even if 1mm o Detects non-palpable masses Size and multicentricity Cervical lymphadenopathy Guides FNAB

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Evaluating substernal goiters (extent, compression) Characteristics associated with carcinoma: o Hypoechogenicity o Irregular margins o Increased nodular flow (Doppler)  Hypervascular  increased blood flow o Invasion/ regional lymphadenopathy

tracheal

Figure 6. Ultrasound of Thyroid Nodule 3.     

Fine Needle Aspiration Biopsy Cytology (FNABC) Single most useful diagnostic modality for diagnosing thyroid nodules in euthyroid patients Performed after ultrasound Diagnostic: Cytopathologic Diagnosis (cells) Therapeutic: Thyroid Cyst o If it’s a thyroid cyst, you can just aspirate the contents then the cyst will be gone Limitations o Technical expertise of the surgeon and the pathologist o Differentiating Follicular CA vs Benign Adenoma o Small nodule (hard to hit)  Do ultrasound-guided FNA o Drawbacks of FNA in “toxic” patients (hyperthyroid): not accurate since…  They are more vascular which can lead to Increased bleeding  Increased false positive result - Cells are actively dividing and can be mistaken for CA, so you do not do FNA for nodules that are hot or warm - If hyperthyroid – you do a thyroid scan  Hypertrophic cells mistaken for CA

Figure 7. Fine Needle Aspiration Biopsy Cytology (FNABC). Stick a needle through the mass then aspirate cells to get a cytopathologic diagnosis. 4.

Radionuclide Imaging/Thyroid Scan

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Iodine-123 (123I), iodine-131 (131I), or Technetium-99m (99mTc) pertechnetate

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Iodine is preferred because it is more accurate o Preferably I123 or 131 because 3-8% of warm nodules are cold on pertechnetate scan  Iodine-123 - emits low dose radiation, half-life of 12 to 14 hours, and is used to image lingual thyroids or goiters  Iodine-131 - half-life of 8 to 10 days and leads to higher-dose radiation exposure, used to screen and treat patients with differentiated thyroid cancers for metastatic disease  Technetium-99m pertechnetate  Increasingly being used for thyroid evaluation  Taken up by the mitochondria, but is not organified  Advantage of having a shorter half-life and minimizes radiation exposure  Particularly sensitive for nodal metastases  Shows size and shape of the gland and distribution of functional activity  COLD o Areas that trap less radioactivity than the surrounding gland  MALIGNANCY IS HIGHER (20%)  HOT o Areas that demonstrate increased activity

Figure 8. Radionuclide Imaging/Thyroid Scan 5.

Other Diagnostics

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Not routinely used, only for completion Neck CT Scan: For lesions of borderline resectability. If one is not sure if mass is resectable (preferably use double contrast).  Laryngoscopy: Hoarseness or s/s of compression of recurrent laryngeal nerve  Metastatic Work-Up: Symptom-Directed  Chest / Liver / Bone / Brain  Work-up for MEN: for medullary cancer o Suspect if w/ family history of Multiple Endocrine Neoplasia Type 2 (MEN 2A) or Medullary Thyroid Cancer (MTC) o High basal serum CALCITONIN: virtually diagnostic for MTC o Further work-up for primary hyperparathyroidism & pheochromocytoma  CT/MRI provide excellent imaging of the thyroid gland and adjacent nodes and are particularly useful in evaluating the extent of large, fixed, or substernal goiters (which cannot be evaluated by ultrasound) and their relationship to the airway and vascular structures.  Non-Contrast CT Scans should be obtained for patients who are likely to require subsequent RAI therapy.

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Surgery II 1.04  PET-CT scans: for Tg-positive, RAI-negative tumors    

III. GOITER Most common thyroid disease in Filipinos More than 80% of thyroid nodules of Filipinos turn out to be goiter Moves with swallowing Can be classified whether nodular vs diffuse and toxic vs nontoxic Nodular vs Diffuse

Figure 9. (Left) Nodular Goiter: Unilateral enlargement (Right) Goiter: Bilaterally symmetrical enlargement; like a “scrotum” in the neck

 Elevated TSH levels induce diffuse thyroid hyperplasia,

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followed by focal hyperplasia, resulting in nodules that may or may not concentrate iodine, colloid nodules, or microfollicular nodules. The TSH-dependent nodules progress to become autonomous In the past, dietary iodine deficiency was the most common cause of endemic goiter Dietary goitrogens (kelp, cassava, and cabbage) also participate in formation Toxic vs Non-Toxic

Figure 10. Toxic vs Non-Toxic Goiter 1.

Non-Toxic Goiter

 Most are thought to result from TSH stimulation secondary   

to inadequate thyroid hormone synthesis and other paracrine growth factors May also be caused by problems of thyroid hormone resistance Nowadays, it’s very hard to have iodine deficiency since a lot of food are fortified May be diffuse, uninodular, or multinodular

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Familial goiters result from inherited deficiencies in enzymes necessary for thyroid hormone synthesis Endemic goiter refers to the occurrence of a goiter in a significant proportion of individuals in a particular geographic region

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Signs and Symptoms o Asymptomatic (approx. 80% of the time)  There’s just a mass that moves up with swallowing  Pressure sensation at the back o Compressive symptoms  Dysphagia, orthopnea  Catarrh: frequent clearing of throat  Dysphonia (hoarseness)  Pemberton sign – facial flushing and dilatation of cervical veins on raising the arms above the head – rarely seen  Caused by obstruction of venous return at the thoracic inlet from a substernal goiter – MEMORIZE! Came out in the board exam  Physical Exam: o Soft, diffusely enlarged gland (simple goiter) or nodules of various size and consistency in case of a multinodular goiter. o Deviation or compression of the trachea may be apparent.  Diagnosis: o Euthyroid with normal TSH and low-normal or normal free T4 levels. o RAI uptake often shows patchy uptake with areas of hot and cold nodules. o FNAB is recommended in patients who have a dominant nodule or one that is painful or enlarging, as carcinomas have been reported in 5% to 10% of multinodular goiters. o CT scans are helpful to evaluate the extent of retrosternal extension and airway compression  Treatment: o Small, diffuse goiters do not require treatment o Exogenous thyroid hormone to reduce the TSH stimulation of gland growth for large goiters  May result in decrease and/or stabilization of goiter size  Most effective for small diffuse goiters o Endemic goiters are treated by iodine administration o TSH suppression  Give high-dose exogenous thyroid hormone at levels that suppress serum TSH o Thyroidectomy: Surgical resection is reserved for goiters that:  Continue to increase despite T4 suppression  Cause obstructive symptoms  Have substernal extension  Have malignancy suspected or proven by FNAB  Are cosmetically unacceptable  Near-total or total thyroidectomy is the treatment of choice and patients require lifelong T4 therapy Table 2. Indications of TSH Suppression and thyroidectomy as treatment options for Non-Toxic Goiter. TSH suppression Thyroidectomy  Patients from geographic  Large goiters areas with iodine  Compressive symptoms deficiency  Suspicious nodules  Young patients with small  Contraindications to TSH thyroid nodules suppression

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Surgery II 1.04  Nodular goiters with no evidence of functional autonomy

1. Post-menopausal 2. Older than 60 y/o 3. Osteoporosis 4. Cardiovascular disease  Failure of medical treatment

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Table 3. Etiology of Non-toxic Goiter CLASSIFICATION SPECIFIC ETIOLOGY Endemic Iodine deficiency, dietary goitrogens (cassava, cabbage) Medications Iodide, amiodarone, lithium Thyroiditis Subacute, chronic (Hashimoto’s) Familial Impaired hormone synthesis from enzyme defects Neoplasm Adenoma, carcinoma 2. Toxic Goiter  Despite the normal thyroid hormone levels, there’s still production by either a tumor or the thyroid itself  Graves’ disease, toxic multinodular goiter and solitary toxic nodule are most relevant to the surgeon  Clinical manifestations result from an excess of circulating thyroid hormone Hyperthyroidism/Thyrotoxicosis Clinical Manifestations:  Heat intolerance, sweating & thirst,  Weight loss  Palpitations, atrial fibrillation  RESTING TACHYCARDIA: most reliable sign – patients may not present with other manifestation but this is always present; indicates that patient is clinically hyperthyroid (2017A)  Nervousness, fatigue, emotional lability, hyperkinesis, fine tremors, muscle wasting, proximal muscle group weakness with hyperactive tendon reflexes  Amenorrhea, decreased fertility  Facial flushing, warm & moist skin  Ophthalmopathy (eye signs)  Dermopathy (thickened skin in pretibial region) i. 

Graves Disease Diffuse toxic goiter o Familial predisposition o Females 40-60 yrs  Possible “triggers” o Postpartum state, iodine excess, lithium therapy, and bacterial & viral infections  Etiology: Autoimmune o Antibodies directed against the thyroid hormone receptor o Stimulate thyrocytes to produce excessive thyroid hormone o Etiology is autoimmune that stimulates the thyroid to produce excessive hormone  Clinical Manifestations  Can be divided into those related to hyperthyroidism and those specific to Graves’ disease.  Hyperthyroid symptoms: o Heat intolerance o Increased sweating and thirst o Weight loss despite adequate caloric intake  Symptoms of increased adrenergic stimulation  The most common GI symptoms include increased frequency of bowel movements and diarrhea  50% of patients will develop clinically evident ophthalmopathy

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Diagnosis o High FT4 and/or FT3 o Low TSH o Diffusely “Hot” uptake on radionuclide scan o Auto-antibodies against  Thyrotropin receptor  Thyroglobulin  Peroxidase

Figure 11. Grave’s Disease on Radionuclide Scan 

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Treatment o Anti-Thyroid drugs  To prepare patient for definitive treatment  High relapse rate if discontinued  Types: - Propylthiouracil (PTU, 100-300mg TID) - Methimazole (10-30mg TID) – more potent than PTU Definitive treatment o Surgery (thyroidectomy) – recommended when RAI is contraindicated o Radioactive Iodine Ablation Therapy (RAI)  Causes progressive development of hypothyroidism (over 70% in 11 years), requiring lifelong thyroxine  Has been shown to lead to progression of opthalmopathy  Takes 3-6 months to achieve Euthyroid  Absolute contraindications include women who are pregnant and breastfeeding

Table 4. Comparison of Surgery and RAI SURGERY RAI  Immediate ablation  Gradual ablation (40% decrease in 1 yr)  Complete relief of symptoms  Relief of most toxic symptoms in 3-6 mos except  Definite histologic diagnosis ophthalmopathy  Need to render euthyroid  Permanent hypothyroidism in first 10 yrs  Surgical risks  “Radiation” effects (Not for pregnant/breastfeeding) Table 5. Indications for Surgery or RAI SURGERY RAI  Compressive symptoms  Small goiters (volume < 100mL)  Large nodules - Require high amounts of  Without suspected RAI malignant potential - Resistant to tx  Previous thyroidectomy  Immediate resolution of  High surgical risk thyrotoxicosis needed  Suspicious nodule or confirmed cancerous For surgery, the patient needs to be euthyroid before surgery (through anti-thyroid drugs for 3-4 week) to prevent thyroid storm and decrease vascularity of the gland.

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Surgery II 1.04 Table 6. Adverse Effects of Surgery and RAI SURGERY RAI  Hemorrhage (