THYROID

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THYROID

• James Taclin C. Banez, M.D., FPSGS, FPCS

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• ANATOMY
• Location / Parts
• Arteries / Venous drainage
• Nerve Supply
• Sympathetic (cervical ganglion)
• Parasympathetis (vagus)
• Histology
• Thyroid follicle (thyroglobulin)
• C cells (neuroectoderm 4th and 5th ultimo
  brachial bodies).

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• PHYSIOLOGY
• Synthesis secrets thyroid hormone (thyroid
  follicle)
• Iodide uptake
• Oxidation of iodide to iodine
• Organification (thyroxin-iodine) MIT / DIT
• Coupling of inactive iodotyrosine T4 /T3
• Stored ----gt released by protease / peptidase
• Calcium Level
• Calcitonin (C cell)

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Evaluation of Thyroid Diseases

1. Clinical history and physical examination
2. Serum T3 T4, TSH determination
3. Thyroid scan
4. Thyroid ultrasound
5. CT scan / MRI
6. FNAC

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HYPERTHYROIDISM (Thyrotoxicosis)

• With increase thyroid hormone secretion
• Graves disease
• Toxic nodular goiter
• Toxic thyroid adenoma
• With out increased thyroid hormone secretion
• Sub-acute thyroiditis
• Functioning metastatic thyroid cancer
• Struma ovarii

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HYPERTHYROIDISM

• GRAVES Disease (Diffuse Thyroid Goiter)
• Most common form of thyrotoxicosis
• Autoimmune
• Female gt male most prevalent 20-40 y/o
• Thyroid stimulating antibody (immunoglobulin)
• directed at the TSH receptor or the thyroid
  follicular cells.
• LATS (long acting thyroid stimulating antibody)
• TRAb (thyroid receptor antibody)

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HYPERTHYROIDISM

• GRAVES Disease (Diffuse Thyroid Goiter)
• Manifestations
• Signs/symptoms of thyrotoxicosis
• heat intolerance
• sweating
• weight loss, muscle wasting
• tachycardia/atrial fibrillation
• fine tremors
• easy fatigability
• hypoactive tendon reflexes
• amenorrhea
• decrease fertility
• easy fatigability, agitation and excitability
• diarrhea

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HYPERTHYROIDISM

• GRAVES Disease (Diffuse Thyroid Goiter)
• Triad
• diffuse goiter
• thyrotoxicosis
• exopthalmos
• Other
• hair loss
• pretibial myxedema
• gynecomastia
• splenomegally

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HYPERTHYROIDISM

• GRAVES Disease
• Exopthalmos
• Due to increase retro-bulbar tissue
• Spasm of the upper eyelid, revealing the sclera
  above the corneoscleral limbus (Dalrymples
  sign)
• Lid lag (von graefes sign)
• External ophthalmoplegia (inability to move the
  eyeball)
• Supra and infraorbital swelling
• Congestion and edema of the conjunctiva and
  sclera (chemosis) ----gt ulceration
• Progression --gt damage of optic nerve --gt
  decreases visual acuity and impairment of color
  vision (malignant exopthalmos) not corrected
  surgically --gt blindness

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HYPERTHYROIDISM

• Diagnosis
• Autonomous thyroid function
• Low TSH
• Elevated T3 / T4
• Thyroid scan ---gt diffuse elevated iodine uptake
• Treatment
• Choices
• Antithyroid drugs
• Radioactive iodine therapy
• Surgery
• Choice depends on
• Age
• Severity of the disease
• Size of the gland
• Coexistent pathology (Ophthalmoplegia)
• Other factors
• Patients preference

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HYPERTHYROIDISM

• Antithyroid Drugs
• Propyl thiouracil (PTU) 100-300mg TID
• Methimazole (Tapazole) 10-20 TID then OD
• Carbimazole 40mg OD
• Inhibits the organic binding of iodine and
  coupling of iodotyrosine
• PTU can also lower conversion of T4 to T3 it can
  also decrease thyroid autoantibody levels
• Disadvantage of these drugs.
• Crosses the placenta --gt inhibits fetal thyroid
  function
• Excreted in breast milk
• Side effects
• Skin rashes
• Fever
• Peripheral neuritis
• Polyarteritis
• Granulocytopenia (reversible)
• Agranulocytosis / aplastic anemia (poor
  prognosis)

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HYPERTHYROIDISM

• Beta blockers (propranolol) to alleviate
  peripheral adrenergic effects
• Advised medical management
• Small diffusely enlarge gland or larger glands
  that decreases in size due to antithyroid drugs
• Toxic nodule goiters or large diffuse glands or
  hyperthyroidism when drug was discontinued ---gt
  thyroidectomy / radioactive iodine

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HYPERTHYROIDISM

• Radioactive Iodine Therapy
• Advantages
• Avoidance of surgery (no injury to nerve /
  parathyroid gland)
• Reduce cost ease of treatment
• Disadvantages
• Lifelong thyroxin replacement therapy
• Slower correction of hyperthyroidism
• Higher relapse rate
• Adverse effect of ophthalmopathy
• Suitable treatment
• Small or moderate size goiter
• Relapse after medical and surgical therapy
• Antithyroid drug and surgery are contraindicated
• Contraindicated
• Pregnant / breast feeding
• Ophthalmopathy (progression of eye signs)
• Isolated nodular goiter or toxic nodular goiter
• Young age (children/adolescence ----gt Infertility
  / carcinoma

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HYPERTHYROIDISM

• Radioactive Iodine Therapy
• Pt. is placed in euthyroid state with
  anti-thyroid drugs. Then discontinue the drugs
  for 2-3 wks before RAI tx is started (I 131
  sodium iodide)
• Complication of RAI tx
• Exacerbations of thyrotoxicosis with arrhythmia
• Overt thyroid storm
• Hypothyroidism
• Risk of fetal damage
• Worsening of eye sign
• Hyperparathyroidism

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HYPERTHYROIDISM

• Thyroid Surgery
• Indicated to
• Young patient
• With Grave ophthalmopathy
• Pregnant
• With suspicious thyroid nodule in Graves gland
• Large nodular toxic goiter w/ low level of
  radioactive iodine uptake.
• Placed patient to euthyroid state prior to
  thyroid surgery
• Antithyroid drugs
• Lugols iodine solution (3 drops BID)
• Propranolol
• Thyroidectomy
• Bilateral subtotal thyroidectomy
• Total lobectomy subtotal lobectomy
  contra-lateral (Hartley-Dunhill)
• Total thyroidectomy
• Advantages over RAI
• Immediate cure of the disease
• Low incidence of hypothyroidism
• Potential removal of coexisting thyroid carcinoma

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HYPERTHYROIDISM

• Recurrent thyrotoxicosis after surgery---gt RAI
• Treatment of Exopthalmos
• Tape eyelids at night
• Wear eyeglasses
• Steroid eye drop / systemic steroid (60mg
  prednisone OD) alleviate chemosis.
• Lateral tarsorrhaphy to oppose eyelids
• Radio-orbital radiation or orbital decompression

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HYPERTHYROIDISM

• Toxic Nodular Goiter (Plummers disease)
• No extrathyroidal manifestation
• Milder than Graves disease
• Treatment
• Propranolol
• Thyroidectomy (lobectomy with isthmectomy)
• Toxic adenoma
• Solitary toxic nodule (Follicular) tumor
• Thyrotoxicosis is uncommon unless it is 3 cm in
  size or more.

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• Thyroid storm
• Life threatening
• Precipitated by
• Infection (pharyngitis / pneumonitis)
• Iodine 131 treatment
• Prophylactic treatment --- Surgery in euthyroid
  state
• Treatment
• Fluid replacement
• Antithyroid drug
• Beta blocker
• Lugols iodine solution
• Hydrocortisone
• Cooling blanket
• Sedation
• Extreme cases ----gt peritoneal dialysis or
  hemofiltration to lowe T4T3
• Avoid ASPIRIN ---gt increases free thyroid hormone
  levels

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HYPOTHYROIDISM

• Causes
• Primary
• Autoimmune thyroiditis
• Hashimotos thyroiditis
• Primary myxedema
• Iatrogenic
• Thyroidectomy
• Iodine 131 tx
• Antithyroid drugs
• Congenital (Cretinism)
• Thyroid dysgenesis
• Dyshormonogenesis
• Inflammatory
• Subacute thyroiditis
• Riedels thyroiditis
• Metabolism
• Iodine deficiency
• Secondary
• Hypopituitarism

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THYROIDITIS

• Acute Suppurative Thyroiditis
• Uncommon
• Associated with URTI
• Staphylococcuc, Streptococcus and Pneumococci
• E. Coli
• Sx - acute thyroid pain
• - dysphagia
• - fever
• Dx - FNA ----gt smear and CS
• Tx - IV antibiotics / drain (abscess)

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THYROIDITIS

• Nonsuppurative Thyroiditis
• Hashimotos disease (Autoimmune lymphocytic
  thyroiditis)
• Most common form of chronic lymphocytic
  thyroiditis
• Autoimmune disease
• Antithyroglobulin / antimicrosomal antibodies
• 10 x more in females 30 60y/o
• Familial 50 in first degree relatives
• Predisposing factors
• Down syndrome
• Familial Alzheimers disease
• Turner syndrome
• Can co-exist with papillary CA
• S/Sx - Tightness in the throat (most common)
• - Painless, nontender enlargement of gland
• Dx - Increase TSH, decrease T3 T4
• - () Anti-thyroid antibodies
• - FNA ---gt rule out CA (confirmatory)
• Tx - Medical if w/o compression ----gt thyroid
  hormone
• - Surgical 1. Obstructive

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THYROIDITIS

• Nonsuppurative Thyroiditis
• Subacute Thyroiditis (De Quervans Thyroiditis /
  Giant Cell Thyroiditis)
• Exact cause unknown
• Female 5x more the males
• 20 40 y/o
• S/Sx - Tender enlargement of the gland
• - Fever, malaise w/ unilateral or bilateral
  thyroid pain
• Dx - FNA
• - ESR (increase)
• - Neutrophilia
• Tx - NSAIDS
• - Prednisone

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THYROIDITIS

• Nonsuppurative Thyroiditis
• Riedels Thyroiditis
• Marked dense invasive fibrosis that may involve
  surrounding structures
• Can cause hypoparathyroidism
• Unknown cause ( maybe part of fibrosclerosis
  retroperitoneum, mediastinum, lacrimal gland and
  bile duct)
• S/Sx - Compression symptoms
• - Hoarseness - dyspnea
• - stridor - dysphagia
• Tx - Tamoxifen
• - Steroid
• - Isthmectomy to relieve
• compression symptom
• - Thyroxine replacement

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GOITER

• Enlargement of the thyroid gland in a euthyroid
  pt not associated with neoplasm or inflammation
• Familial
• Inherited enzymatic defect (dyshormonogenesis)
• Autosomal recessive
• Hypothyroidism / euthyroid
• Endemic
• Iodine deficiency
• Sporadic
• No definite cause, excludes goiter caused by
  thyroiditis and neoplasm as well as endemic goiter

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GOITER

• Pathology
• May be diffusely enlarged and smooth, or enlarged
  markedly nodular
• Nodules are filled w/ gelatinous, colloid rich
  material and scattered between areas of normal
  thyroid tissues
• With areas of degeneration, hemorrhage and
  calcification.

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GOITER

• S/Sx
• Asymptomatic usually
• Pressure symptoms usually
• Dysphagia
• Dyspnea
• Paralysis of recurrent laryngeal nerve
• Sudden pain associated with rapid enlargement of
  the gland ---gt hemorrhage into a colloid nodule
  or cyst
• Superior mesenteric syndrome due retro-sternal
  extension causing facial flushing that is
  accentuated by raising his arm above the head
  (Pembertons sign).

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GOITER

• Dx
• FNAC ---gt specially if one nodule predominates,
  or painful or has recently enlarged. To rule out
  CA
• TSH, T3 T4 ---gt usually normal
• ---gt pts gt 60y/o w/ long standing multinodular
  goiters (gt17yrs) develops thyrotoxicosis
  (Plummers dse). Low TSH w/ increased T3 but
  normal T4 (T3 toxicosis)
• Tx
• No tx for euthyroid, small, diffuse goiter
• Thyroxine ---gt for large diffuse goiter to
  depress TSH stimulation and reduce hyperplasia
• Iodine ---gt for endemic goiter
• Surgery
• Cosmetically acceptable
• Compression symptoms
• Suspicion for malignancy

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Solitary or Dominant Thyroid Nodule

• Most are benign (colloid nodule/adenomas)
• Physician should
• Perform an accurate clinical assessment
• Appreciate the risk factors for thyroid carcinoma
• Which pts would benefit from surgery
• Risk factors for thyroid CA
• Low-dose radiation to head neck (lt2000 rad)
• - gt2000rads causes destruction of thyroid gld.
• - tends to be papillary type, multi-focal w/
  higher incidence of LN metastases.
• Family hx of thyroid CA
• - Medullary CA inherited as an autosomal
  dominanat trait
• - Papillary CA 6 familial dse.
• Age
• - thyroid nodule in children and elderly are
  more likely to be malignant.
• Signs
• Rapid enlargement of an old or new nodule
• Symptoms of local invasion or compression
  symptoms
• Consistency Hard, gritty or fixed to surrounding
  structures
• Palpable cervical lymphadenopathy

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Solitary or Dominant Thyroid Nodule

• Work up for Thyroid nodule
• FNAC procedure of choice
• benign - 65 false () - 1
• malignant - 5 false (-) - 5
• Suspicious - 15
• Non-diagnostic 15
• Limitation of FNAC
• Follicular or Hurtle cell neoplasm (needs
  vascular and capsular invasion)
• Hx of head and neck radiation and family hx of
  thyroid CA usually has multifocal lesions.
• If FNAC encountered a cyst ---gt drain completely
  75 is curative if cyst persist after 3 attempts
  ---gt unilateral lobectomy

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Solitary or Dominant Thyroid Nodule

• Work up for Thyroid nodule
• Thyroid ultrasonography
• Use to a) follow up the size of suspected
  benign nodules diagnosed by FNAC
• b) to detect presence of non-palpable
• nodules to locate and differentiate it for
  cyst or solid
• MRI / CT scan
• For large retro-sternal extension
• For recurrent or persistent thyroid tumor and to
  differentiate recurrence from postoperative
  fibrosis
• Detect the presence of invasion, sign of CA.

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Solitary or Dominant Thyroid Nodule

• Work up for Thyroid nodule
• Thyroid isotope imaging
• Check the function and locate small lesions
• Cold -----------gt 10 25 malignant
• Hot -----------gt 1 malignant
• Laboratory
• Thyroid function test
• Not useful in assessing thyroid nodule
• Serum thyroglobulin level
• To detect presence of metastatic lesions
• Check completion of thyroidectomy
• Not used in medullary and anaplastic thyroid CA
• Serum calcitonin
• Follow up in medullary CA
• RET oncogens () pt should have 24 hrs urine
  determination of VMA, metanephrine and
  cathecolamine to rule out a coexisting
  pheochromocytoma (for medullary CA)

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Solitary or Dominant Thyroid Nodule

• Approach for Thyroid Nodule

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MALIGNANT THYROID

• 90 95 are differentiated tumor w/ follicular
  origin
• Papillary thyroid adenocarcinoma
• Follicular adenocarcinoma
• Hurtle cell carcinoma
• 6 arise from parafollicular cells
• Medullary carcinoma of thyroid
• 1 poorly differentiated
• Anaplastic thyroid carcinoma

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MALIGNANT THYROID

• Oncogene associated w/ Thyroid carcinoma
• RET oncogene
• Seen in papillary and medullary thyroid CA
• Located in chromosome 10
• TRK A
• Chromosome 1
• Mutated ras oncogenes
• Follicular thyroid carcinoma, thyroid adenoma and
  multinodular goiter
• Mutated p53 gene
• Anaplastic thyroid carcinoma

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MALIGNANT THYROID

• Papillary Thyroid Carcinoma
• Most common (80)
• Predominant thyroid CA in children (75)
• Usually due to radiation exposure of the neck
  (85-90)
• Multi-focal (30-88) has LN spread
  (para-tracheal cervical LN).
• Can invade trachea, esophagus and recurrent
  laryngeal nerve late hematogenous spread.
• Mixed tumor (papillary follicular) variant of
  papillary CA, but classified as papillary for it
  biologically acts as papillary CA.
• Orphan Annie Nuclei
• Characteristic cellular feature
• Abundant cytoplasm, crowded nuclei
• and intra-nuclear cytoplasmic inclusion

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MALIGNANT THYROID

• Papillary Thyroid Carcinoma
• 3 forms of papillary CA (based on size and
  extent)
• Minimal or occult / micro carcinoma
• 1 cm or less, no capsular invasion
• Non-palpable and usually an incidental finding
  intra-op or autopsy
• Recurrence rate ----gt 7
• Mortality ------------gt 0.5
• Intra-thyroidal Tumors
• gt 1cm and confined to the thyroid gland
• (-) extra thyroidal invasion
• Extra-thyroidal Tumors
• Locally advanced with invasion through the
  thyroid capsule into adjacent structures.
• All types can be associated w/ LN metastases and
  intra-thyroidal blood vessel invasion or
  occasionally metastases

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MALIGNANT THYROID

• Papillary Thyroid Carcinoma
• S/Sx
• Euthyroid, slow growing painless mass
• Signs of local invasions
• Dysphagia
• Dyspnea
• Hoarseness of voice
• Palpable cervical LN more apparent than primary
  lesion (lateral aberrant thyroid)
• Uncommon distant metastases (lung metastases in
  children)
• Diagnosis
• FNAC (specific and sensitive for papillary,
  medullary and anaplastic)
• CT/MRI in pts w/ extensive local or sub-sternal
  extension

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MALIGNANT THYROID

• Papillary Thyroid Carcinoma
• Prognostic indicators (85 10yrs survival)
• AGES scale
• A- age G- grade E- extent S- size
• MACIS scale
• M- metastases A- age C-
  completeness of resection
• I- extra thyroidal invasion S- size
• AMES
• TNM
• Distant metastases (bone) most significant
  prognostic indicator overall

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MALIGNANT THYROID

• Papillary Thyroid Carcinoma (SURGERY)
• Lobectomy with isthmectomy acceptable for minimal
  papillary thyroid CA
• Total thyroidectomy (near total) if
• Size if tumor gt 3cm
• Age male gt 40y/o female gt 50y/o
• Angioinvasion
• Distant metastases
• Thyroidectomy w/ modified radical neck
  dissection
• If with clinically palpable cervical
  lymphadenopathy
• Not done for prophylaxis
• Reasons for total thyroidectomy
• 85 is multifocal
• To decrease incidence of anaplasia in any
  residual tissue
• Facilitate the diagnosis of unsuspected
  metastatic disease by RAI scanning or treatment
• Greater sensitivity of blood thyroglobulin level
  to predict recurrent or persistent of the disease.

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MALIGNANT THYROID

• Follicular Thyroid Carcinoma
• 10 Female gt Male (31), mean age 50y/o
• More frequent in Iodine deficiency area
• Vascular invasion hematogenous spread is more
  common (bone, lung and liver).
• Types
• Minimally invasive tumor
• Invasion into but not through the tumor capsule
• Previously called atypical adenoma
• Invasive tumors (capsular/vascular)
• 1 thyrotoxic
• Dx / Tx
• FNAC not helpful ----gt lobectomy and isthmectomy
  (frozen section) ----gt () total thyroidectomy
  ----gt iodine 131 to detect distant metastases and
  for ablation.
• Prognosis
• Age over 50y/o
• gt 4cm size
• Higher tumor grade
• Marked vascular invasion
• Marked extra-thyroidal invasion
• Distant metastasis

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MALIGNANT THYROID

• HURTLE CELL THYROID TUMOR
• 3 5, intermediate, uni-focal
• Male Female (21), spread by lymphatics
• Derived from oxyphilic cells of the thyroid gld.
• Possess TSH receptors and produces thyroglobulin
• Only 10 takes up iodine hence thallium scan is
  used to localize distant metastasis
• Often multifocal and bilateral
• Dx FNAC ----gt 20 malignant
• Tx - total thyroidectomy for RAI ablation
  usually fails
• - mod radical neck dissection if with palpable
• cervical LN
• - Thyroid suppression is suggested
• Prognosis 60 ------gt 5yr survival

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MALIGNANT THYROID

• MEDULLARY THYROID CARCINOMA
• 5-7 Aggressive tumor 50-60y/o
• Arise from parafollicular or C cells of the
  thyroid (neuroectodermal-ultimobrachial bodies
  4th 5th branchial pouches.
• Secrets calcitonin (95) 85 secrets
  carcinoembryonic antigen (CEA)
• Sporadic 90
• unifocal, usually 45y/o
• worse prognosis
• Familial 10
• Associated with
• MEN IIA or Sipples syndrome (MTC, hyperplastic
  parathyroid and pheochromocytoma
• MEN IIB (MTC, pheochromocytoma,
  ganglioneuromatosis and Marfan,s syndrome)
• Multifocal, usually 35 y/o
• Better prognosis

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MALIGNANT THYROID

• MEDULLARY THYROID CARCINOMA
• Does not concentrate Iodine 131, Thallium scan is
  used to localized distal metastasis.
• Spread
• Lymphatics (neck and superior mediastinum)
• Blood ---gt liver, bone (osteoblastic) and lung
• Local invasion
• Can secrets
• Calcitonin
• Histamine
• Serotinin (causes diarrhea)
• ACTH 2-4 causing Cushing syndrome
• CEA
• Prostaglandin E2 and F2 alpha
• Dx
• Hx PE serum calcitonin, CEA, FNAC, Serum
  calcium

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MALIGNANT THYROID

• Tx
• Total thyroidectomy
• Radiotherapy and chemotherapy ---gt failure
• MRND is done for
• Palpable cervical LN
• gt2cm tumor for 60 nodal metastasis
• Tumor debulking in cases of metastatic and local
  recurrence should be done to ameliorate symptoms
  of flushing and diarrhea and help to decrease the
  risk of death.
• All pt should be screen for pheochromocytoma (MEN
  II) w/c shoud be resected first.
• Selective removal of the parathyroid shd be done
  if preoperatively has hypercalcemia.
• Follow up - serum calcium / CEA level
• Prognosis
• Localize -------gt 80 10 year survival
• () LN --------gt 45 10 year survival
• Best ------------gt Worst prognosis
• Familial non-MEN MTC -----gt MEN IIA ----gt
  Sporadic cases ------gt MEN IIB

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MALIGNANT THYROID

• Anaplastic Thyroid Carcinoma
• 1 3 most aggressive, few survive gt 6 months
• Most arise from previous differentiated thyroid
  CA
• Low incident could be due to low iodine
  deficiency
• 70 80 y/o
• Treatment
• Radiotherapy ----gt doxorubicin ----gt debulking
  thyroidectomy ----gt completion with radiotherapy
  and chemotherapy

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MALIGNANT THYROID

• LYMPHOMA
• 1 5 non-Hodgkin B cell
• Usually develops in pts w/ chronic lymphocytic
  thyroiditis (Hashimotos thyroiditis)
• S/Sx similar with anaplastic CA, compression
  symptoms is the most common
• Tx Chemotherapy
• Cyclophosphamide
• Doxorubicin
• Vincristine
• Prednison
• Radiotherapy
• Surgery - done for diagnosis and to alleviate
  compression symptoms
• 80 survival if confined to the gland 40 it had
  spread
• Metastatic Carcinoma
• Rare hypernephroma is the most common primary
  site

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Thank you