The L-team | Kheita, Jean, Renan, Ikey, Bea, James, Sher, Lori, Aleya Page 1 of 11
THYROID AND PARATHYROIDS
Not LecturedOUTLINE
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
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 1. Thyroglossal Duct
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
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)
The L-team | Kheita, Jean, Renan, Ikey, Bea, James, Sher, Lori, Aleya Page 2 of 11
EVALUATION OF THYROID DISEASE
Thyroid problems usually appear as anterior neck masses Usually, a thyroid mass moves up with swallowing
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
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
o 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)
o 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
Figure 5. Ultrasound Results
SOLID COMPLEX
The L-team | Kheita, Jean, Renan, Ikey, Bea, James, Sher, Lori, Aleya Page 3 of 11 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
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.
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
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.
The L-team | Kheita, Jean, Renan, Ikey, Bea, James, Sher, Lori, Aleya Page 4 of 11 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
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
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
Table 2. 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
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
The L-team | Kheita, Jean, Renan, Ikey, Bea, James, Sher, Lori, Aleya Page 5 of 11 Table 3. Differential Diagnosis of Hyperthyroidism
INCREASED HORMONE SYNTHESIS (INCREASED RAIU)
RELEASE OF PREFORMED HORMONE (DECREASED RAIU) Graves’ Disease (Diffuse Toxic
Goiter)
Toxic Multinodular Goiter Toxic Adenoma Drug Induced—Amiodarone, Iodine Thyroid Cancer Struma Ovarii Hydatidiform Mole
TSH-Secreting Pituitary Adenoma
Thyroiditis - Acute Phase of Hashimoto’s Thyroiditis, Subacute Thyroiditis Factitious (Iatrogenic) Thyrotoxicosis
“Hamburger Thyrotoxicosis” 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)
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 (<100mL)
Without suspected malignant potential Previous thyroidectomy
High surgical risk
Table 4. Comparison of Surgery and RAI
SURGERY RAI
Immediate ablation Gradual ablation (40% in 1 year)
Complete relief of symptoms Relief of most toxic symptoms in 3-6 months
(except ophthalmopathy) Definitive histologic diagnosis
Need to render euthyroid first Permanent hypothyroidism in 10 years
Surgical risk “radiation” effects Table 5. Adverse Effects of Surgery vs RAI
SURGERY RAI Hemorrhage <5% RLN (recurrent laryngeal nerve) injury 3-8% Hypo-parathyroidism 2-5% Hypothyroidism 10% in 5 yrs Neck edema, thyroiditis 5-10% Sialadenitis 11.5%
Vocal cord paralysis <5% GIT complaints 67%
Acute radiation sickness 30-50% Impaired fertility 10-45% Bone marrow suppression 3-35% Taste dysfunction 37%
Parathyroid dysfunction 5-60% Leukemia, bladder cancer <5% Nodule consistency hardening
The L-team | Kheita, Jean, Renan, Ikey, Bea, James, Sher, Lori, Aleya Page 6 of 11 TOXIC MULTI-NODULAR GOITER
Usually older than 50 years of age
Often has; prior history of a non-toxic multi-nodular goiter
Over several years the thyroid nodules become autonomous to cause hyperthyroidism
Diagnosis:
o TSH, FT4, FT3, thyroid scan Treatment:
o Thyroidectomy
Figure 11. Toxic Multi-Nodular Goiter
NON-TOXIC GOITER
Result from iodine deficiency and/or TSH stimulation, or idiopathic Nowadays, it’s very hard to have iodine deficiency since a lot of food
are fortified
Most of the time idiopathic
May be diffuse, uninodular, multinodular
Familial goiters result from enzyme deficiencies necessary for thyroid hormone synthesis
Endemic goiter refers to occurrence of a goiter in a significant proportion on individuals in a particular geographic region (*you should know - mountain area where no seafood)
Diagnosis: o TSH, FT4, FT3 o Ultrasound o FNAB
If multinodular do FNAB on dominant nodule and/or any suspicious nodule on ultrasound
Treatment (Suppression vs. Surgery):
o TSH suppression (conservative treatment)
Give high dose exogenous thyroid hormone at levels that will suppress TSH
o Thyroidectomy
Table 6. Indications for TSH suppression vs. Thyroidectomy
TSH SUPPRESSION THYROIDECTOMY
Patients from geographic areas
with iodine deficiency Large goiters Young patient with small nodule Compressive symptoms Nodular goiter with no evidence
of functional anatomy Suspicious nodules Contraindication of TSH suppression
Post-menopausal Older than 60 y/o Osteoporosis
Cardiovascular disease Failure of medical treatment
SUMMARY – GOITER
Most common thyroid disease in Philippines (85% of thyroid disease) Types o Diffuse nontoxic o Nodular nontoxic o Diffuse toxic o Nodular toxic Diagnosis o TSH, FT4, FT3
If toxic : Thyroid scan Non-toxic : Ultrasound, FNAB Treatment
o Toxic: surgery, RAI, anti-thyroid drug o Non-toxic: none, TSH suppression, surgery
THYROIDITIS
Inflammatory disorder of the thyroid gland
May cause initial hyperthyroidism, then progress over time to hypothyroidism
Thyroiditis usually is classified into acute, subacute, and chronic forms, each associated with a distinct clinical presentation and histology
ACUTE (SUPPURATIVE) THYROIDITIS Infectious cause
The thyroid gland is inherently resistant to infection due to its extensive blood and lymphatic supply, high iodide content, and fibrous capsule. Infectious agents can seed it via:
o Hematogenous or lymphatic route
o Direct spread from persistent pyriform sinus fistulae or thyroglossal duct cysts
o Result of penetrating trauma to the thyroid gland o Immunosuppression.
Streptococcus and anaerobes account for about 70% of cases
More common in children often preceded by an upper respiratory tract infection or otitis media
Characterized by
o Severe neck pain radiating to the jaws or ear, fever, o Chills
o Odynophagia o Dysphonia Diagnosis
o Established by leukocytosis on blood tests and FNAB for Gram’s stain, culture, and cytology
o CT scans may help to delineate the extent of infection
o A persistent pyriform sinus fistula should always be suspected in children with recurrent acute thyroiditis
o Barium swallow demonstrates the anomalous tract with 80% sensitivity
Treatment
o Parenteral antibiotics and drainage of abscesses
o Patients with pyriform sinus fistulae require complete resection of the sinus tract, including the area of the thyroid where the tract terminates, to prevent recurrence.
SUBACUTE THYROIDITIS Self-limiting
o Remission in 2-4 months Subtypes
o Granulomatous (De Quervain’s) o Lymphocytic
o Postpartum
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PAINFUL PAINLESS
ONSET Gradual
AGE 30-40 years old women 30-60 years old women HISTORY Upper respiratory tract
infection Autoimmune; occurs in postpartum period (<6 weeks) PE Gland is enlarged, exquisitely tender, and firm
Normal sized or minimally enlarged, slightly firm,
non-tender gland
DIAGNOSIS
Early stages: TSH decreased; Tg, T4, and T3 levels are elevated due to the release of preformed thyroid hormone from
destroyed follicles TREATMENT
Aspirin and steroids; Thyroidectomy if non responsive to medical
treatment
B-blockers and thyroid hormone replacement for
symptomatic CHRONIC THYROIDITIS
LYMPHOCYTIC (HASHIMOTO’S) THYROIDITIS Autoimmune
MOST COMMON INFLAMMATORY DISORDER OF THE THYROID and the leading cause of hypothyroidism
Antibodies develop against thyroid antigens o Anti-thyroid peroxidase (anti-TPO) antibodies o Anti-thyroglobulin (anti-Tg) antibodies
o Must check for serum assays of anti-TPO and anti-TG antibodies Others
o TSH receptor-blocking antibodies, Thyroid stimulating Ab, Cytotoxic Ab
Clinical Presentation
o More common in women between ages of 30 and 50
o Most common presentation is that of a minimally or moderately enlarged firm granular gland discovered on routine physical examination or the awareness of a painless anterior neck mass o 20% of patients present with hypothyroidism
o 5% presents with hyperthyroidism
o Classically, presents with diffusely enlarged, firm gland, which also is lobulated.
Diagnostic Studies
o When suspected clinically, an elevated TSH and the presence of thyroid autoantibodies usually confirm the diagnosis.
o FNAB is indicated in patients who present with a solitary nodule or a rapidly enlarging goiter
Treatment
o Thyroid hormone replacement
RIEDEL’S THYROIDITIS
Chronic inflammatory disease causing dense fibrosis of the gland Fibrosis may extend beyond thyroid capsule to the neck
May be mistaken for CA
Causes intense fibrosis and presents as a hard mass on the neck, so this is the one most operated on
The Etiology of this disorder is controversial, and it has been reported to occur in patients with other autoimmune diseases.
This association, coupled with the presence of lymphoid infiltration and response to steroid therapy, suggests a primary autoimmune etiology. Typically presents as a painless, hard anterior neck mass, which
progresses over weeks to years to produce symptoms of compression, including dysphagia, dyspnea, choking and hoarseness.
Physical exam reveals a hard, “woody” thyroid gland with fixation to surrounding tissues.
Diagnosis is confirmed by open thyroid biopsy, because the firm and fibrous nature of the gland renders FNAB inadequate.
Surgery is the mainstay of the treatment TREATMENT OF THYROIDITIS Medical Treatment
Indications for surgery
o Malignancy cannot be ruled out o Significant signs of compression o Failure of medical treatment
Serial monitoring of thyroid function as indicated
THYROID CYST
Exact cause is unknown Theories:
o Lack of iodine in the diet
o Autoimmune disorder that causes inflammation of the thyroid (Hashimoto’s disease)
o Genetic defect
o Exposure to radiation in childhood
Treatment: needle aspiration +/- TSH suppression
BENIGN TUMORS
FOLLICULAR ADENOMA Hard to differentiate from follicular carcinoma
o Only histologic difference from follicular carcinoma is absence of capsular & blood vessel invasion
o Do a preoperative biopsy
PLUMMER DISEASE (TOXIC ADENOMA) Hyperthyroidism from a single hyperfunctioning nodule Typically occurs in younger patients
Diagnostics: RAI scan; “hot” nodule
Treatment: Thyroidectomy after control of hyperthyroidism
MALIGNANT TUMORS Well-differentiated o Papillary o Follicular Medullary Anaplastic Others
Table 8. Frequency of Thyroid Carcinomas. 90-95% of thyroid carcinomas are well differentiated cancers
PATHOLOGY FREQUENCY (%) *Papillary 80 Follicular 10 Hurthle cell 3 Medullary 5 Anaplastic 1 Others 1 CLINICAL MANIFESTATIONS Initially asymptomatic Usually euthyroid Progressive growth Invasion of structures
o Recurrent laryngeal nerve, esophagus, trachea, Neck node enlargement
The L-team | Kheita, Jean, Renan, Ikey, Bea, James, Sher, Lori, Aleya Page 8 of 11 PAPILLARY CARCINOMA
Relatively benign course Compatible with long life
30-45% metastasis to lymph nodes (but this had no impact on survival) Accounts for 80% of all thyroid malignancies in iodine-sufficient areas
and is the predominant thyroid cancer in children and individuals exposed to external radiation
Papillary carcinoma is the MOST COMMON OF THE THYROID NEOPLASMS and is usually associated with an excellent prognosis, particularly in female patients younger than 40 years
2:1 female-to-male ratio, and the mean age at presentation is 30 to 40 years
Most patients are euthyroid and present with a slow-growing painless mass in the neck
Diagnosis: FNAB
o If malignant, complete neck ultrasound is strongly recommended to evaluate the contralateral lobe and for lymph node metastases in the central and lateral neck compartments
Preference for LYMPHATIC SPREAD 1-2% distant metastasis
Common radiation induced CA 90-95% cure rate
Cells with intranuclear cytoplasmic inclusions = ORPHAN ANNIE NUCLEI Calcified deposits = PSAMOMMA BODIES
Most patients with papillary carcinoma can expect an excellent prognosis, with the 10-year survival rate approaching 95% for the most favorable stages
SUBTYPES
The pathologic diagnosis of papillary carcinoma depends on the cytologic findings of well-recognized papillary cytomorphology
Pure papillary, papillary follicular, follicular variant
Tall cell, columnar, diffuse sclerosing, clear cell, trabecular, Hurthle cell variant and poorly differentiated
o They are trying to find out which types are aggressive compared to the rest, which is why there are so many subtypes
FORMS Minimal/Occult/Microcarcinoma
o < 1cm o Non-palpable
o Detected only by ultrasound
Intrathyroidal has NOT gone beyond the thyroid capsule Extrathyroidal has extended into the neck and nearby structures
TREATMENT
Total or near-total thyroidectomy for high risk or bilateral tumors and for primary cancers >1 cm unless with contraindications.
The 2009 ATA guidelines for thyroid cancer management suggest that prophylactic (ipsilateral or bilateral) dissection may be performed in patients with advanced (T3 or T4) papillary thyroid carcinoma, whereas the procedure is not needed for small (T1 and T2) tumors that are clinically node negative
Biopsy-proven lymph node metastases – modified radical or functional neck dissection
FOLLICULAR CARCINOMA Relatively benign course
Common in iodine-deficient areas
Malignancy is defined by presence of capsular and vascular invasion 5-20% metastasis to lymph nodes
Spreads via BLOODSTREAM/HEMATOGENOUS SPREAD (in comparison to papillary which spreads via lymphatic system)
2-5% distant metastasis Associated with goiter in 10-15%
70-80% cure rate (papillary type still has a higher cure rate) Follicular and Papillary are relatively indolent
3:1 female-to-male ratio (2015B)
Mean age presentation: 50 years old (2015B)
Cumulative mortality: 15% at 10 years and 30% at 20 years
PROGNOSTIC INDICATORS FOR WELL-DIFFERENTIATED CARCINOMA DAMES (Cady and Rossi)
D DNA content measured by flow cytometry A Age: men <40 years old, women <50 years old M Metastases
E Extrathyroid spread
S Size of tumors (less than or >5 cm) AGES (Hay)
A Age
G Histologic Grade E Extrathyroidal invasion S Metastatic tumor size MACIS (Hay)
M Metastases A Age of presentation
C Completeness of original resection I Extrathyroidal invasion
S Size of original lesion Laudico, dela Peña, De Vera PGH
o Age
o Histology (nodal metastasis had no impact)
Predictors of thyroid nodules malignancy, Ampil, Cortex, SIRF 1998 Age 56 +/- 15 years
Size 4.5 +/-1.4 cm especially if solitary
Consistency Hard especially if solitary (Histology and multicentricity had no impact)
o There is no consensus on methods to classify which are aggressive and which are not
Table 9. Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (AMES or AGES)
LOW RISK HIGH RISK
AGE <40 years >40 years
SEX Female Male
EXTENT No local extension, intrathyroidal, no capsular invasion Capsular invasion, extrathyroidal extension
METASTASIS None Regional or distant
SIZE <2 cm >4 cm
GRADE Well differentiated Poorly differentiated E. STAGING FOR WELL-DIFFERENTIATED CARCINOMA Primary tumor (T)
Tx Primary tumor cannot be assessed T0 No evidence of primary tumor
T1 Tumor ≤2 cm in diameter, limited to thyroid
T2 Tumor >2 cm but <4 cm in diameter, limited to thyroid
T3 Tumor >4 cm in diameter, limited to thyroid, or any tumor with minimal extrathyroidal invasion
T4a
Any size tumor extending beyond capsule to invade subcutaneous soft tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve, or intrathyroidal anaplastic cancer
T4b Tumor invading pre-vertebral fascia, or encasing carotid artery or mediastinal vessels; or extrathyroidal anaplastic cance
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mediastinal nodes
Nx Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis
N1a Metastases to level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes)
N1b Metastases to unilateral, bilateral, or contralateral cervical or superior mediastinal lymph nodes
Distant metastasis (M)
Mx Distant metastases cannot be assessed M1 No distant metastasis
Table 10. TNM Classification of Thyroid Tumors PAPILLARY OR FOLLICULAR TUMORS (WELL-DIFFERENTIATED)
STAGE TNM < 45 years I Any T, any N, M0 II Any T, any N, M1 ≥ 45 years I T1, N0, M0 II T2, N0, M0 III T3, N0, M0; T1–3, N1a, M0 Iv a T4a, N0–1a, M0; T1–4a, N1b, M0 IV b T4b, any N, M0
IV c Any T, any N, M1
Notice that in younger than age 45 years, the staging is only up to stage II
In younger than age 45 years old, notice that even if there is a metastasis it is still considered as stage II
It signifies that it isn’t that aggressive when it is present for ages <45 years old
This is the only cancer that has age as a factor
TREATMENT OF WELL-DIFFERENTIATED CARCINOMA Surgery
o < 1.0 cm (microcarcinoma), solitary: Total lobectomy + Isthmusectomy
o >1.0 cm, multicentric: Total Thyroidectomy (Schwartz’s it is >4 cm) Extrathyroidal Spread
o Total thyroidectomy + Central neck dissection (+) Lymph Node Metastasis
o Total thyroidectomy + Modified radical neck dissection Extent of Thyroidectomy
Figure 12. A diagram showing thyroid lobectomy to be done on <1cm WDC adenoma with a contralateral normal lobe. For all other types especially if
there are bilateral nodules, we do total thyroidectomy. Subtotal thyroidectomy is not indicated anymore.
COMPLICATION OF THYROIDECTOMY Bleeding - because it is a vascular area
Recurrent Laryngeal nerve injury – causes hoarseness. If both recurrent laryngeal nerve injury the vocal cords will both close necessitating tracheostomy
Superior Laryngeal nerve injury – decrease volume of voice Hypocalcaemia – inadvertent involvement of the parathyroids Thyroid storm – occurs if the patient was not euthyroid to begin with
Figure 13. Location of the parathyroid glands on the thyroid. Proximity of the parathyroid causes it to be excised along with thyroid upon thyroidectomy
causing symptoms of hypocalcaemia. You only need ½ -1 to maintain parathyroid function.
Figure 14. Borders of the Central Neck. Superior: Thyroid Cartilage. Medial: TE Groove. Lateral: Carotid Sheath. Inferior: Suprasternal Notch
ADJUVANT THERAPY Radioactive iodine ablation
TSH suppression (Target serum TSH = 0) NO ROLE: Chemotherapy/radiation therapy
MONITORING AND FOLLOW-UP
Figure 15. Algorithm for Monitoring
We monitor Serum Thyroglobulin (Tg) after thyroidectomy. Ideally it should be decreased or 0 after the procedure because it is produce by the thyroid gland
Tg levels in patients who have undergone total thyroidectomy should be <2 ng/mL when the patient is taking T4 , and <5 ng/mL when the patient is hypothyroid
A Tg level >2 ng/mL is highly suggestive of metastatic disease or persistent normal thyroid tissue
Approximately 95% of patients with persistent or recurrent thyroid cancer of follicular cell origin will have Tg levels >2 ng/mL
Tg and anti-Tg antibody levels should be measured initially at 6-month intervals and then annually if the patient is clinically disease free
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If it is still positive, we work up the patient with a whole body can. Areas with iodine will light up
WHOLE BODY IODINE-131 SCAN
In cases where there is still positive serum thyroglobulin (Tg) 6-12 months after total thyroidectomy for a high risk well-differentiated carcinoma, one must suspect recurrence since Tg is produced only by the thyroid
When this happens, work up the patient and what is usually done is Whole Body Iodine-131 Scan. It works in a similar principle to RAI scan, but it is applied for the whole body. The distant metastatic lesions will imbibe iodine and will light up
Treatment for metastatic sites: Radioactive Iodine Tablets HURTHLE CELL CARCINOMA
Subtype of follicular CA
More often multifocal and bilateral (30 %), usually do not take up RAI (5 %), more likely to metastasize, associated with higher mortality rate (20% at 10 years).
It DOES NOT respond to RAI.
Treatment: lobectomy and isthmusectomy MEDULLARY CARCINOMA More aggressive than papillary/follicular carcinoma Arise from parafollicular or C cells of the thyroid
o C cells secrete calcitonin
o 25% occur within the spectrum of several inherited syndromes (germline mutations in the RET ) proto-oncogene
Familial medullary thyroid cancer, MEN2A & B Diagnosis
o Raised serum calcitonin levels – this finding clinches the diagnosis o FNA cytology – confirms the diagnosis
o Once diagnosed, all new patients with MTC should be screened for RET point mutations, pheochromocytoma, & hyperparathyroidism Treatment
o Minimum is total thyroidectomy + central neck dissection ANAPLASTIC CARCINOMA
Most aggressive of all Rapidly enlarging
o Doctor’s experience: A patient with anaplastic carcinoma was admitted once, but whose surgery was delayed for 1 month because of financial constraints. The tumor was observed to be growing bigger and bigger every day before their very eyes Treatment:
o Tracheostomy + Radiotherapy (RT provides only 30% success rate)
Most of the time, because of the immense size of the mass, thyroidectomy/resection may not be possible. Thus, tracheostomy is done to address the obstruction of airways. o Total thyroidectomy / Chemotherapy / Radiotherapy Done if the tumor is still resectable o Palliative treatment
J. OTHER RARE CANCERS Sarcoma
Lymphoma
The diagnosis is considered in patients with a goiter, especially one that has apparently grown significantly in a short period.
Other initial symptoms include hoarseness, dysphagia, and fever. There is also an increased association between lymphoma and
Hashimoto's thyroiditis.
Ultrasound may demonstrate a classic pseudocystic pattern.
FNA can be diagnostic
The use of flow cytometry for monoclonality can confirm diagnosis Neck, chest, abdominal CT or MRI to assess extrathyroidal spread. Most thyroid lymphomas are B cell in origin
Use of the CHOP regimen (cyclophosphamide, hydroxydaunomycin [doxorubicin], vincristine, and prednisolone) has been associated with excellent survival.
Metastatic cancer
o Kidney, breast, lung, and melanoma FNAB usually provides definitive diagnosis.
Resection of the thyroid, usually lobectomy, may be helpful in many patients, depending on the status of their primary tumor
PARATHYROID GLANDS
CALCIUM HOMEOSTASIS Parathyroid hormone (PTH): increases serum calcium
Vitamin D: increases serum calcium by stimulating the absorption of calcium and phosphate from the gut.
o The first hydroxylation at carbon 25 occurs in the liver
o The second hydroxylation at carbon 1 occurs in the kidney in response to increased PTH levels.
o 1,25(OH)2D3 increases calcium and phosphate resorption from the
gastrointestinal tract and stimulates bone resorption, which raises calcium levels
Calcitonin: decreases serum calcium
Table 10. Actions of Major Calcium-Regulating Hormones
BONE KIDNEY INTESTINE
PARA-THYROID HORMONE Stimulates resorption of calcium and phosphate Stimulates resorption of calcium and conversion of
25(OH)D3; inhibits resorption of phosphate and bicarbonate No direct effects VITAMIN D Stimulates transport of calcium Inhibits resorption of calcium Stimulates calcium and phosphate absorption CALCITONIN Inhibits resorption of calcium and phosphate Inhibits resorption of calcium and phosphate
No direct effects
Figure 16. Calcium homeostasis and parathyroid hormone (PTH). 1,25(OH)2D3, 1,25-dihydroxycholecalciferol.
HYPERPARATHYROIDISM There is excess PTH, thus there is hypercalcemia Primary (PHPT)
o From abnormal parathyroid glands, usually due to a tumor Secondary
o A compensatory response to hypocalcemic states Chronic renal failure
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o Chronically stimulated glands become autonomous, resulting in persistence or recurrence of hypercalcemia after successful renal transplantation
o Even though serum calcium is elevated, PTH is still being continuously secreted.
PRIMARY HYPERTHYROIDISM (PHPT)
Arises from increased PTH production from abnormal parathyroid glands and results from a disturbance of normal feedback control exerted by serum calcium.
PHPT is characterized by increased parathyroid cell proliferation and PTH secretion that is independent of calcium levels
Causes
o Parathyroid hyperplasia (20%)
o Adenoma (80% single if single adenoma) o Carcinoma (1%)
o Low dose ionizing radiation Latency: 30 to 40 years
Higher PTH levels and a higher incidence of concomitant thyroid neoplasms than those who did not have exposure o Family history
MEN1, MEN2A, isolated familial HPT, and familial HPT with jaw-tumor syndrome
PHPT is the most common primary presentation of MEN1 (80%)
Signs and Symptoms
o Due to increased serum calcium o “Classic” pentad of symptoms
Kidney stones (80%), painful bones(15 to 20%), abdominal groans, psychic moans & fatigue
o Minimally symptomatic
Weakness, fatigue, polydipsia, polyuria, nocturia, bone & joint pain, constipation, decreased appetite, nausea, heartburn, pruritus, depression, & memory loss
o Asymptomatic Diagnosis
o High serum calcium
First done if suspicion of PHPT is raised because of signs and symptoms. If serum calcium is high, do serum PTH.
o High serum PTH assay
A high serum PTH suggests the pathology is indeed primarily located in the parathyroids. Thus perform a parathyroid scan. o Parathyroid scan
Presence of abnormal growth confirms the diagnosis, thus, do parathyroidectomy.
o Radiology
Bone involvement
Pathognomonic signs seen best on hand X-ray: Subperiosteal resorption (most apparent on the radial aspect of the middle phalanx of the second and third fingers), bone cysts, and tufting of the distal phalanges
Treatment: Parathyroidectomy o Subtotal
If dealing with an adenoma, usually, just one needs to be removed, since not all parathyroids will be enlarged.
If dealing with hyperplasia, the problem is that all 4 glands will be enlarged. You can’t remove all four. Thus, do a three-and-one-half parathyroidectomy, leaving ½ of one
parathyroid in place.
o Total parathyroidectomy with autotransplantation or transfer of a gland to a neck or forearm muscle
Alternative to 3 ½ parathyroidectomy.
HYPOPARATHYROIDISM Causes
o Di George’s syndrome - congenitally absent parathyroid o Neonatal hypoparathyroidism - from hyperparathyroid mother o THYROID SURGERY: leading to injury to the parathyroid, most
common cause, 95% of cases (total thyroidectomy)
Temporary hypoparathyroidism – occurs in 90% of all thyroidectomy cases. In the course of thyroid gland dissection, edema of the parathyroids is unavoidable thus it temporarily becomes dysfunctional and cannot produce PTH. Permanent hypoparathyroidism – remaining 5-10%. Means
the surgeon has inadvertently removed the parathyroids. Signs and Symptoms
o Hypocalcemia causing increased neuromuscular excitability o Circumoral and fingertip numbness and tingling
o Mental symptoms: anxiety, confusion, and depression
o (+) CHVOSTEK SIGN: Contraction of facial muscles elicited by tapping on the facial nerve anterior to the ear
o (+) TROUSSEAU SIGN: Carpopedal spasm, which is elicited by occluding blood flow to the forearm with a blood pressure cuff for 2–3 min
o Tetany
o These signs and symptoms must be monitored in a patient who has undergone thyroidectomy.
Diagnosis
o Decreased serum ionized calcium levels Treatment
o Calcium tablets or IV infusion o Vitamin D supplements
I can't think of a single reason why I should be a surgeon, but I can think of a thousand reasons why I should quit. They make it hard on purpose. There are lives in our hands. There comes a moment when it's more than just a game, and you either take that step forward or turn around and walk away. I could quit but here's the thing, I love the playing field. –Dr. Meredith Grey (Grey’s Anatomy)
LAST TRANS FOR SURGERY!!! The L-team now signing off :)) See you clerkship! God bless for the upcoming exams!! :D
Editor’s note: Good luck to everyone!! Last push for third year!!