6 SURGERY II 8 - Thyroid and Parathyroid Glands

Surgery II 6.8

THYROID AND PARATHYROIDS OUTLINE I. Congenital Lesions II. Evaluation of Thyroid Disease III. Goiter IV. Hyperthyroidism/Thyrotoxicosis V. Toxic Goiter VI. Non-toxic Goiter VII. Thyroiditis VIII. Thyroid Cyst IX. Being Tumors X. Malignant Tumors XI. Parathyroid Glands

Dr. Ampil Not Lectured

PYRAMIDAL LOBE  50 % of individuals  Distal end of thyroglossal duct persists  Projecting up from the isthmus, lying just to the left or right of the midline.  Very common, and of no clinical significance, unless a surgeon decides to do a total thyroidectomy  No pathologic problem most of the time  When the thyroid gland enlarges, the pyramidal lobe can also enlarge

REFERENCES 1. PPT (2015 Lecture) 2. 2016A Trans 3. 2015B Trans 4. Schwart’z/Sabiston

CONGENITAL LESIONS  Unlike the abdomen and thoracic cavity, the neck is a relatively superficial so it’s easier to diagnose thyroid disease, usually presenting with an ANTERIOR NECK MASS  Normally, the thyroid gland should not be palpated  Embryologic life of the thyroid gland: it starts at the base of the tongue and goes 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 THYROGLOSSAL DUCT ANOMALIES (Cyst, Sinus, Fistula) Thyroglossal duct (lifted from 2015B Trans) o The tract from the base of the tongue all the way to the neck o Supposed to disappear after the thyroid goes down  Thyroglossal duct cysts are the most commonly encountered CONGENITAL CERVICAL anomalies  Typically midline masses in childhood  80% below hyoid bone  ELEVATES with tongue protrusion o Upon protrusion, the thyroid gland goes up through the patent thyroglossal duct  During the embryologic life, the thyroid gland originates from the foramen cecum at the base of the tongue. From there, it will descend and will split into two forming the 2 lobes of the thyroid gland. The thyroglossal duct is supposed to degenerate upon birth. If it persists → thyroglossal duct problems  Clinical Importance: distinguish thyroglossal duct from simple cyst because they have different treatment  Cyst → excise  Thyroglossal duct cyst → Sistrunk Procedure ▫ If the thyroglossal duct cyst is simply excised, it will recur  No external sinuses but may infect  Treatment: SISTRUNK Procedure – removal of the mass and the entire tract all the way to the base of the tongue, until the hyoid bone  This procedure consists of en bloc cystectomy and excision of the central hyoid bone to minimize recurrence 

Figure 2. Pyramidal Lobe  

ECTOPIC THYROID Failure of the thyroid to descend completely into the neck Results to thyroid tissue anywhere along the tract

LINGUAL / SUBLINGUAL THYROID  Mass or thyroid found at the base of the tongue  If you excise it, the patient will no longer have a thyroid  Represents a failure of the median thyroid anlage to descend normally and may be the only thyroid tissue present  S/Sx: o Hypothyroid symptoms o Obstructive symptoms o Choking, dysphagia, airway obstruction  Treatment:  If small in size, Exogenous thyroid hormone to suppress TSH  Radioactive iodine (RAI) ablation followed by hormone replacement  Surgical excision is 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 (If big)

Figure 3. Lingual or Sublingual Thyroid

Figure 1. Thyroglossal Duct The L-team | Kheita, Jean, Renan, Ikey, Bea, James, Sher, Lori, Aleya

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Surgery II 6.8 o

EVALUATION OF THYROID DISEASE  Thyroid problems usually appear as anterior neck masses  Usually, a thyroid mass moves up with swallowing

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 Figure 4. 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. 

THYROID FUNCTION TESTS MOST ACCURATE TESTS of thyroid function o SERUM TSH (Thyroid Stimulating Hormone)  The most sensitive and specific test for determining thyroid function  Reflect the ability of the anterior pituitary to detect free T4 levels  There is an inverse relationship between free T4 levels and the logarithm of TSH concentration – small changes in in free T4 lead to a large shift in TSH levels o 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 TSH FT4 AND FT3 ASSAY DIAGNOSIS High Low Hypothyroid High Normal Subclinical Hypothyroid Low High Hyperthyroid Low Normal Subclinical Hyperthyroid *If the patient can only avail one test, request for TSH

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Others: o 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

The L-team | Kheita, Jean, Renan, Ikey, Bea, James, Sher, Lori, Aleya

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Thyroid antibodies  Include anti-Tg, antimicrosomal, or anti-TPO and thyroidstimulating 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

INITIAL WORK-UP Initial diagnostic modality is thyroid function test o TSH, FT4, FT3 If euthyroid o Ultrasound o FNABC If hyperthyroid o Thyroid scan  Hot / warm nodule: treat as toxic nodule  Cold nodule: FNABC

ULTRASOUND Main advantage: determine consistency of mass o Simple cyst = thyroid cyst (purely fluid) o Complex cyst = goiter (has both cystic and solid components) o Solid nodule = tumor  Noninvasive, no radiation exposure  Monitoring nodule size (for non-operative tx)  Size & multicentricity: can detect masses even 1mm  Detects non-palpable masses  Cervical lymphadenopathy  Guide fine-needle aspiration (FNA) biopsy  Evaluating substernal goiters (extent, tracheal compression)  Characteristics associated w/ CA o Hypoechogenicity o Irregular margins o Increased nodular flow (Doppler)  Hypervascular → increased blood flow o Invasion / regional lymphadenopathy 

SOLID

COMPLEX

CYST

Figure 5. Ultrasound Results

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Surgery II 6.8     

FINE NEEDLE ASPIRATION BIOPSY CYTOLOGY (FNABC) Performed after ultrasound Single most useful diagnostic modality for diagnosing thyroid nodules in euthyroid patients 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 FNABC in “toxic” patients (hyperthyroid), not accurate  More vascular which can lead to Increased bleeding, 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 o Increased false positive result o Hypertrophic cells mistaken for CA

RADIONUCLIDE IMAGING / THYROID SCAN Iodine-123 (123I), iodine-131 (131I), or Technetium-99m (99mTc) pertechnetate  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  Thyroid gland is the only organ in the body that takes up iodine. If you give radioactive iodine, expect all of the iodine to be imbibed in the thyroid.  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 

OTHER DIAGNOSTICS Not routinely used, only for completion Neck CT Scan o For lesions of borderline resectability  If not sure if mass is resectable (preferably use double contrast)  Laryngoscopy o Hoarseness or s/s of compression of recurrent laryngeal nerve  Metastatic Work-Up o 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.  PET-CT scans - for Tg-positive, RAI-negative tumors  

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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 7. (Left) Nodular Goiter: unilateral enlargement (Right) Diffuse Goiter: bilaterally symmetrical enlargement; like a “scrotum” in the neck  Any enlargement of the thyroid gland  Endemic goiter - occurrence of a goiter in a significant proportion of individuals in a particular geographic region o In the past, dietary iodine deficiency was the most common cause of endemic goiter o Dietary goitrogens (kelp, cassava, and cabbage) also participate in formation  Elevated TSH levels induce diffuse thyroid hyperplasia, 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.

Figure 6. Thyroid Scan  More recently, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography (CT) is being increasingly used to screen for metastases in patients with thyroid cancer in whom other imaging studies are negative. The L-team | Kheita, Jean, Renan, Ikey, Bea, James, Sher, Lori, Aleya

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Surgery II 6.8 TOXIC GOITER

Figure 8. Toxic Goiter  Despite the normal thyroid hormone levels, there’s still production by either a tumor or the thyroid itself  S/Sx: Thyrotoxic symptoms NON-TOXIC GOITER

 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  Diagnostic Tests o Patients are usually 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 Most euthyroid patients with 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 Surgical resection is reserved for goiters that: a. Continue to increase despite T4 suppression b. Cause obstructive symptoms c. Have substernal extension d. Have malignancy suspected or proven by FNAB e. Are cosmetically unacceptable  Near-total or total thyroidectomy is the treatment of choice, and patients require lifelong T4 therapy

CLASSIFICATION Endemic Medications Thyroiditis Familial Neoplasm Figure 9. Non-Toxic Goiter  Most are thought to result from TSH stimulation secondary to inadequate thyroid hormone synthesis and other paracrine growth factors  Signs and Symptoms: o ASYMPTOMATIC (80%)  There’s just a mass that moves up with swallowing  Pressure sensation at the back (in the neck from the book) o Compressive Symptoms (as they become large)  Dysphagia, orthopnea (dyspnea in the book)  Catarrh - frequent clearing of throat  Dysphonia – hoarseness  From RLN injury is rare, except when malignancy is present  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  Sudden enlargement of nodules or cysts due to hemorrhage may cause acute pain The L-team | Kheita, Jean, Renan, Ikey, Bea, James, Sher, Lori, Aleya

Table 2. Etiology of Non-Toxic Goiter SPECIFIC ETIOLOGY Iodine Deficiency, Dietary Goitrogens (Cassava, Cabbage) Iodide, Amiodarone, Lithium Subacute, Chronic (Hashimoto’s) Impaired Hormone Synthesis From Enzyme Defects Adenoma, Carcinoma Resistance to Thyroid Hormone

HYPERTHYROIDISM/THYROTOXICOSIS  Clinical manifestations result from an excess of circulating thyroid hormone  Clinical Manifestations o Heat intolerance, sweating & thirst, weight loss, palpitations, atrial fibrillation o Resting Tachycardia : most reliable sign o Nervousness, fatigue, emotional lability, hyperkinesis, fine tremors, muscle wasting, proximal muscle group weakness with hyperactive tendon reflexes o Amenorrhea, decreased fertility o Facial flushing, warm & moist skin o Ophthalmopathy (eye signs) o Dermopathy (thickened skin in pretibial region)  It is important to distinguish disorders such as Graves’ disease and toxic nodular goiters that result from increased production of thyroid hormone from those disorders that lead to a release of stored hormone from injury to the thyroid gland (thyroiditis) or from other non-thyroid gland–related conditions.  Graves’ disease, toxic multinodular goiter, and solitary toxic nodule are most relevant to the surgeon

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Surgery II 6.8

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Table 3. Differential Diagnosis of Hyperthyroidism INCREASED HORMONE RELEASE OF PREFORMED SYNTHESIS (INCREASED RAIU) HORMONE (DECREASED RAIU) Graves’ Disease (Diffuse Toxic Goiter) Toxic Multinodular Goiter  Thyroiditis - Acute Phase of Hashimoto’s Thyroiditis, Toxic Adenoma Drug Induced—Amiodarone,  Subacute Thyroiditis Iodine  Factitious (Iatrogenic) Thyroid Cancer  Thyrotoxicosis Struma Ovarii  “Hamburger Thyrotoxicosis” Hydatidiform Mole TSH-Secreting Pituitary Adenoma RAIU = radioactive iodine uptake; TSH = thyroid-stimulating hormone TOXIC GOITER 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 o Autoimmune o Antibodies directed against the thyroid hormone receptor o Stimulate thyrocytes to produce excessive thyroid hormone  Etiology is autoimmune that stimulates the thyroid to produce excessive hormone  Clinical Features: o Can be divided into those related to hyperthyroidism and those specific to Graves’ disease. o Hyperthyroid symptoms:  Heat intolerance  Increased sweating and thirst  Weight loss despite adequate caloric intake o Symptoms of increased adrenergic stimulation o The most common GI symptoms include increased frequency of bowel movements and diarrhea o 50% of patients will develop clinically evident ophthalmopathy  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 10. Thyroid Radionuclide Scan of Graves’ Disease 

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) The L-team | Kheita, Jean, Renan, Ikey, Bea, James, Sher, Lori, Aleya

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Definitive treatment: o Radioactive Iodine Ablation Therapy (RAI)  Mainstay treatment in North America  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 breastfeeding o Surgery (thyroidectomy)  Surgery is recommended when RAI is contraindicated: ▫ Confirmed cancer or suspicious thyroid nodule ▫ Young ▫ Pregnant ▫ Had severe reactions to anti-thyroid medications ▫ Have large goiters with compressive symptoms ▫ Reluctant to undergo RAI therapy Indications for Treatment o Surgery  Compressive symptoms (e.g. dysphagia, orthopnea)  Large nodules  Require high amounts of RAI  Resistant to treatment  Suspicions for malignancy  Immediate resolution of thyrotoxicosis is needed  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 o RAI  Small goiters (