Thyroid Facial Nerve Paralysis

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Thyroid Hormone Synthesis
•     Diagrammatic scheme of thyroid hormone formation and secretion. 1, Thyroglobulin and
      protein synthesis in the rough endoplasmic reticulum. 2, Coupling of the thyroglobulin
      carbohydrate units in the smooth endoplasmic reticulum and Golgi apparatus. 3, Formation of
      exocytotic vesicles. 4, Transport of exocytotic vesicles with noniodinated thyroglobulin to the
      apical surface of the follicle cell and into the follicular lumen. 5, Iodide transport at the basal cell
      membrane. 6, Iodide oxidation thyroglobulin iodination, and coupling of iodotyrosyl to
      iodothyronyl residues. 7, Storage of iodinated thyroglobulin in the follicular lumen. 8,
      Endocytosis by micropinocytosis. 9, Endocytosis by macropinocytosis (pseudopods). 10, Colloid
      droplets. 11, Lysosome migrating to the apical pole. 12, Fusion of lysosomes with colloid
      droplets. 13, Phagolysosomes with thyroglobulin hydrolysis. 14, Triiodothyronine (T3 ) and
      thyroxine (T4 ) secretion. 15, Monoidotyrosine (MIT) and diiodotyrosine (DIT) deiodination.

         Regulation of Thyroid Hormone Secretion

Inhibition of Thyroid Synthesis and antithyroid drugs
•      Drug therapy for treatment of thyroid excess states is often the first choice from a variety of
       treatment options.
•      The thioamide class of antithyroid drugs includes propylthiouracil (PTU) .This class of drugs acts
       by inhibiting the organification and oxidation of inorganic iodine as well as by inhibiting the
       linking of the initial iodotyrosine molecules MIT and DIT. Also it act as immun- suppressors
•      Methimazole has longer activity and requires a single daily dose; however, it has the capability
       of crossing the placenta and can affect fetal development in pregnant patients.
•      Both drugs have an effect on peripheral white blood cell development and can cause
       agranulocytosis; this occurs in less than 1% of cases. Other side effects include rash, arthralgias,
       neuritis, and liver dysfunction.
•     Iodine
     Inorganic iodine given in large doses can inhibit thyroid hormone release by altering the organic binding
      process (Wolff-Chaikoff effect). The effect is transient; however, the use of iodine supplementation can be
      used as a treatment for hyperactivity of the gland in preparation for surgery.
•     β Blockers
    Patients with thyrotoxicosis have increased sensitivity to catecholamine secretion. Adrenergic antagonists,
      although not inhibiting thyroid hormone synthesis per se, are valuable in controlling peripheral sensitivity to
      catecholamines by blocking their effects. Therefore, cardiovascular symptoms such as pulse rate, tremor, and
      anxiousness can be improved, but the hyper metabolic state can remain or progress.

Tests of Thyroid Function

Evaluation of the Pituitary-Thyroid Feedback
•     Evaluation of serum TSH is an important screening test for the diagnosis of thyroid status.
•     This assay is especially important in the delineation of hypothyroid from euthyroid states. Additionally,
      clinically euthyroid patients may have suppressed TSH values, demonstrating hyperthyroidism before it
      becomes clinically manifest.
Serum Triiodothyronine and Thyroxin Levels
•     Radioactive Iodine Uptake
•     Thyroid Autoantibody Levels
•     Calcitonin level

Radiologic Evaluation of The Thyroid
Thyroid Scintigraphy
•     The use of radionuclide agents has been helpful in delineating the presence, size, and function of thyroid
      nodules. Scanning with 123 I is usually used for patients with a suspected lingual thyroid or substernal goiter,
      whereas 131 I is used in patients with well-differentiated thyroid carcinoma to screen for distant metastasis.
•     Technetium-pertechnetate 99m (99m Tc) is also used for evaluation of thyroid nodules.
•     Thyroid cancers should have little uptake of the radionuclide; however, this deficient area on scanning could
      be masked by overlying normally functioning tissue. Malignancy has been shown to occur in 15% to 20% of
      “cold” nodules and, additionally, in 5% to 9% of nodules with uptake that is “warm” or “hot,” mandating
      continued aggressive approach to clinically suspicious nodules even if they are not “cold.”
•     Its principal value is in the toxic patient with a nodule or nodularity of the thyroid. Localisation of overactivity
      in the gland will differentiate between a toxic nodule with suppression of the remainder of the gland and
      toxic multinodular goitre

Radiologic Evaluation of The Thyroid
Thyroid Ultrasound
•     The use of directed cervical ultrasound has, as its advantages, increased portability, cost effectiveness, and
      lack of ionizing radiation. Although ultrasound may add little to the diagnosis of a diffusely enlarged gland, it
      has become increasingly important in the work-up of discrete nodules.
•     Ultrasound is sensitive to delineating solid compared with cystic characteristics, diameter, and multicentricity
      of nodules. Additionally, enlarged cervical lymph nodes can be assessed for staging of malignancy. B-mode
      ultrasonography can be used preoperatively or intraoperatively, usually before and sometimes in conjunction
      with fine-needle aspiration (FNA).
Thyroid FNA
•     Now considered the most cost effective and sensitive/specific diagnostic test of
      thyroid nodules
•     The use of US has expanded the role of FNA in evaluating nodules and improved
      the validity of the results
•     Thyroid conditions that may be diagnosed by FNAC include colloid nodules
      thyroiditis, papillary carcinoma, medullary carcinoma, anaplastic carcinoma and
•     FNAC cannot distinguish between a benign follicular adenoma and follicular
      carcinoma, as this distinction is dependent not on cytology but on histological
      criteria, which include capsular and vascular invasion.

Thyroid investigations
Serum: TSH (T3 and T4 if abnormal);
          thyroid autoantibodies
FNAC of palpable discrete swellings; ultrasound guidance
Chest radiograph and thoracic inlet for retrosternal goitre
Isotope scan if discrete swelling and toxicity coexist
CT and MRI scan

                                Classification of thyroid swellings

              Simple goitre (euthyroid)                   Neoplastic
              •     Diffuse hyperplastic                  Benign
                   Physiological                          Malignant
                   Pubertal                               Inflammatory
                   Pregnancy                              Autoimmune
              •     Multinodular goitre                   Chronic lymphocytic thyroiditis
                                                          Hashimoto’s disease
              Toxic                                       De Quervain’s thyroiditis
              Diffuse Graves’ disease                     Fibrosing
              Multinodular                                Riedel’s thyroiditis
              Toxic adenoma                               Infective
                                                          Acute (bacterial thyroiditis, viral thyroiditis, ‘subacute
                                                          Chronic (tuberculous, syphilitic)
•     Hypothyroidism: Etiology
•     Decreased production in the thyroid gland, although states of limited activity in the periphery can also occur.
•     Lack of sufficient iodine intake Endemic Goiter explains a large percentage of hypothyroid conditions.
•     Hypothyroidism are caused also by Hashimoto’s thyroiditis, overaggressive radioactive iodine therapy, or
      surgical ablation.
•     Other causes including drug-related altered thyroid function, particularly in the case of the cardiac
      antiarrhythmic drug amiodarone.
•      Other rarer causes of hypothyroidism include inherited defects in thyroid hormone synthesis, which include
      defects in thyroid peroxidase
•     and thyroglobulin production.
•     Additionally, congenital aberrant thyroid development can occur in children, which includes thyroid agenesis or
      thyroid hypoplasia.
•     Central nervous system abnormalities resulting in either anterior pituitary gland disease or hypothalamic
      disorders can result in a centrally based hypothyroidism resulting from the lack of either TSH or TRH.
•      Finally, a peripheral tissue resistance to thyroid hormone action, possibly through an altered receptor
      mechanism, has been described

Clinical Presentation of Hypothyroidism
•      The developing fetus and newborn are usually protected from hypothyroidism by the transplacental passage of
       T4 .
•      After birth, the failure of thyroid function, if prolonged, can result in significant and sometimes irreversible
       changes in development resulting in poor growth, mental retardation, and dwarfism. This syndrome is referred
       to as cretinism.
•      During later childhood years, hypothyroidism can result in decreased intellectual capacity but not necessarily
       mental retardation. Physical signs such as rectal prolapse, abdominal distention, and umbilical hernia may be
•      During adolescence, this situation is known as juvenile hypothyroidism.
•      In adults( myxedema ), spontaneous hypothyroidism is usually manifested in females (80%) and is a more
       insidious process associated with a slow, progressive failure of function. In the majority of cases, this process is
       due to a lymphocytic thyroiditis. The classic symptoms are fatigue, headache, weight gain, dry skin, brittle hair,
       and muscle cramps. Severe progression of disease can result in cardiovascular symptoms including hypertension,
       pericardial effusions, and pleural effusions. Abdominal distension and constipation are signs of severe
       hypothyroidism. Anemia may occur in 12% of cases.

•     The symptoms are:
Tiredness; mental lethargy; cold intolerance; weight gain; constipation; carpal tunnel syndrome.
•     The signs of thyroid deficiency are:
Bradycardia ; cold extremities; dry skin and hair; periorbital puffiness ;hoarse voice; bradykinesis, slow movements;
      delayed relaxation phase of ankle jerks
•     In the work-up of the patient with subjective symptoms of fatigue or constipation, or in the work-up of
      cardiac abnormalities, the evaluation of thyroid function cannot be forgotten.
•     Classic hypothyroid laboratory evaluation demonstrates decreased T4 and T3 values with increased TSH and
      cholesterol levels.
•     L-Thyroxine is a safe and effective treatment, once the diagnosis is made. An oral dose of 100 μg is effective
      over a wide range of adult body weight and body mass index. Patients with severe clinical hypothyroidism
      should be monitored closely and gradually started on increasing doses due to sensitivity to the hormone as a
      result of chronic depletion of catecholamines in the myocardium.

Hashimoto’s Thyroiditis
•     One of the major causes of hypothyroidism in the adult population is Hashimoto’s thyroiditis. A complex
      immunologic phenomenon results in the formation of immune complex and complement in the basement
      membrane of the follicular cells. As this immune phenomenon continues, the presence of TSH-blocking
      antibodies can be detected.
Subacute Thyroiditis
•     Subacute thyroiditis occurs in females (2:1) .The mean age is in the 40s in most series. The exact cause is not
      known, although it is not thought to be due to a viral or autoimmune origin. Patients present with a diffuse
      swelling in the cervical area and a sudden increase in pain. Approximately two thirds of patients have fever,
      weight loss, and severe fatigue. An FNA can be diagnostic if it demonstrates the giant cells of an epithelioid
      foreign body type, which characterizes the lesion. Microscopic pathology shows large follicles infiltrated by
      mononuclear cells, neutrophils, and lymphocytes.
•     Treatment with steroids.
Riedel’s Struma
•     Riedel’s thyroiditis is a rare. Symptoms of severe discomfort due to extension into the trachea, esophagus,
      and laryngeal nerve can occur. As a result, patients may present with impending airway obstruction or
      dysphagia. Pathology reveals a dense fibrous tissue and nearly total obliteration of normal follicle
•     Treatment with thyroid hormone replacement is effective. Immediate tracheal or esophageal obstruction
      may require a surgical approach to relieve symptoms.
Acute Suppurative Thyroiditis is extremely rare caused by Bactria
•     The disease processes associated with increased thyroid secretion result in a predictable hyper- metabolic
•     Increased thyroid secretion can be caused by primary alterations within the gland (Graves’ disease, toxic
      nodular goiter, toxic thyroid adenoma) or central nervous system disorders and increased TSH-produced stimulation of the
      thyroid. Most hyperthyroid states occur because of primary malfunction.
•     Even more unusual hyperthyroid states can result from mismanaged exogenous thyroid ingestion, molar
      pregnancy with increased release of human chorionic gonadotropin, and, unusually, thyroid malignancy with
      overproduction of thyroid hormone.
Graves’ Disease
•     Recently, it has been demonstrated that a wide variety of antibodies result in a thyroid-stimulating
      process that incorporates the TSH receptor on follicular cells. The whole of the functioning thyroid tissue is
      involved, and the hypertrophy and hyperplasia are due to abnormal thyroid-stimulating antibodies (TSH-
      RAbs) that bind to TSH receptor sites and produce a disproportionate and prolonged effect..
•     Pathology.
•     Patients with Graves’ disease have an enlarged gland with increased vascularity. The gland is diffuse and
      symmetrical, resulting in significant enlargement that is grossly visible.
•     On microscopic examination, the follicles are small, with hyperplastic columnar epithelium. Hyperplasia of
      these cells is exhibited by rapidly dividing nuclei and papillary projections of the follicular epithelium
      within the central follicles. Increased lymphoid tissue deposition is also demonstrable in many patients
      with Graves’ disease.

Clinical Presentation.
•      The patient with classic Graves’ disease usually has a visibly goiter , accompanying clinical thyrotoxicosis
       and exophthalmos complete the classic triad of the disease.
•      Physical examination is remarkable for an diffusely enlarged thyroid .With increased vascularity, a bruit is
       often heard.
•      Exophthalmos is thought to be due( Autoimmune ) to the stimulation of fatty fibrous tissue behind the
       orbit causing outward pressure. Conjunctival swelling with accompanying congestion and edema are
       advanced signs of exophthalmos. Spasm of the upper eyelid resulting in retraction and visualization of a
       larger amount of sclera than normal and can lead to a lid lag and exacerbation of the already swollen
       conjunctiva. All of these pressure related phenomena can progress to decreased oculomuscular
       movements, ophthalmoplegia, and diplopia. Optic nerve damage and blindness can be a long-term result
       if the underlying condition is not corrected. Sustained hyperthyroidism should be aggressively treated to
       remove the stimulus to the retro-orbital tissues.

Clinical Presentation
•      weight loss despite of increased appetite
•       Sweating, heat intolerance, and thirst.
•      The menstrual cycle can be altered to the point of amenorrhea.
•      Cardiovascular :high-output cardiac failure and congestive heart failure with peripheral edema.
       Arrhythmias include ventricular tachycardia or atrial fibrillation.
•      Psychiatric :altered sleep patterns, insomnia ,emotional mood swings, fatigue, excitability, and agitation.
•      Gastrointestinal :increased bowel frequency to the point of diarrhea and electrolyte wasting.
•     An enlarged smooth thyroid mass and signs and symptoms of thyrotoxicosis suggest the diagnosis.
•     A cost-effective work-up can include an extensive history, physical examination, and thyroid function tests.
•     In addition to elevated levels of T3 and T4 , a decreased or undetectable level of TSH should be
•     Thyroid antibodies are usually detected in elevated quantities.
•     Extensive use of imaging studies may or may not be required, given the clinical suspicion. A 123 I radionuclide
      scan should demonstrate diffuse uptake throughout an enlarged gland. An ultrasound of the neck may be
      used . However, the absolute requirement of the latter image for preoperative assessment is not universally
      agreed on.

•     There have been three classic methods to treat Graves’ disease: radioiodine ablation, surgery, and
      antithyroid medication.
•     Clearly, patients with Graves’ disease need to be educated regarding appropriate choices, the risks of each
      treatment, and the expectation of complete success.

Antithyroid Medication.
•     The main antithyroid action of the drugs PTU, methimazole, and carbimazole (5-10mg /8h).
•      Additionally, β-blocking agents such as propranolol(10-40mg /8h).
•     In the acute circumstance, steroids and β blockers combine both effects to gain rapid control of the
      hypermetabolic effects of increased peripheral T4 and T3 .
•     Antithyroid medication is effective in gaining rapid control of thyrotoxicosis; however, the relapse rate after
      discontinuation of medication may approach 50% 12 to 18 months after cessation.

Thyroid Resection.
•     The advantages of surgical ablation of the thyroid include rapid, effective treatment of thyrotoxicosis . The
      amount of residual tissue is a subject of debate.
•     Complete ablation of thyroid tissue requires a total thyroidectomy, which is associated with the highest rates
      of hypoparathyroidism and recurrent laryngeal nerve damage. Some groups have reported that total
      thyroidectomy is the most effective way to treat patients with severe Graves’ disease because it offers the
      lowest rate of relapse. It may be that patients, particularly those with ophthalmopathy, are stabilized most
      successfully by total thyroidectomy. Removal of the entire antigenic focus may be the most likely explanation
      for this observation.
•     Other subtotal resections include near-total thyroidectomy or subtotal thyroidectomy, in which one would
      do a complete lobectomy on one side, leaving a rim of tissue on the contralateral side (near-total
      thyroidectomy) or leaving a rim of tissue on both sides (subtotal thyroidectomy). One to 2g of thyroid tissue
      can be left at the discretion of the surgeon, thereby minimizing risk of damage to the recurrent laryngeal
      nerve but exposing the patient to some risk of recurrence within this remaining tissue.

•     Patients should be considered for surgery who have had obvious failure of medication. Additionally, younger
      patients, particularly adolescents, and patients with large thyroid, should undergo surgical resection.
•     Before surgery, it is important to counsel the patient on the risks and options of the surgery, includin
      hypoparathyroidism and recurrent laryngeal nerve damage, as well as on the possibility of relapse if less than
      a total thyroidectomy is contemplated.
•     The patient should be rendered euthyroid before surgery by use of antithyroid medication and, occasionally,
      β-blocker medication. If the patient is not properly treated preoperatively, thyroid storm can be life
•     The use of Lugol’s solution has been recommended for about 7 days before surgery to decrease the
      vascularity of the thyroid parenchyma.
Radionuclide Therapy.
•     The ideal application of radioactive iodine therapy would be for those patients with small to moderate
      enlargement of the gland and those in whom antithyroid drugs have clearly not worked. Additional
      candidates would include patients who desire not to have surgery or for whom surgery is contraindicated.
      Another group includes those who have recurrence after surgery.
•     Radioactive iodine is probably not the most efficacious in younger patients, including adolescents, or in
      patients with larger goiters. It is obviously contraindicated in pregnant or lactating patients.
•     The most commonly employed radionuclide is 131 I.
•     Pretreatment establishment of a euthyroid state should be accomplished by using antithyroid medication
      for 3 to 4 weeks before treatment. The drug therapy should then be terminated to allow efficient uptake of
      the isotope.
•     A 10% to 15% incidence of hypothyroidism may occur within 12 months, with as much as a 3% increase in
      each succeeding year. It is important to monitor patients after 131 I treatment by carefully measuring
      circulating hormones and TSH levels.

Thyroid storm
•     Thyroid storm is manifested by (severe tachycardia, fever, confusion, vomiting to the point of dehydration,
      and adrenergic overstimulation to the point of mania and coma) after thyroid resection in an uncontrolled
      hyperthyroid patient.
•     The best way to treat thyroid storm is preoperative anticipation and preparation. Additionally, all patients
      undergoing general anesthesia should be checked for undiagnosed hyperthyroidism, if clinically suspected.
•     Treatment of the patient with overt thyroid storm should include rapid cooling, fluid replacement and rapid
      institution of antithyroid drugs, β blockers(IV), iodine solutions, and steroids.
•     In lifethreatening circumstances, peritoneal dialysis or hemodialysis may be effective in lowering T4 and T3

Toxic Nodular Goiter-Toxic Adenoma
•     Toxic nodular goiter, also known as Plummer’s disease, refers to a nodule contained within an otherwise
      goitrous thyroid gland that has autonomous function.
•     This usually occurs in the setting of a patient with endemic goiter.
•     Increased thyroid hormone production occurs independent of TSH control.
•     Such patients usually have a milder course and are older than patients with Graves’ disease.
•      The thyroid in such patients are previously nodular and enlarged
•     Presenting symptoms are mild and mainly cardiac and metabolic.
•     Peripheral thyroid hormone levels are elevated, and TSH levels are suppressed.
•     The diagnosis is usually confirmed after clinical suspicion, and an 131 I radionuclide scan is performed that
      localizes one or two autonomous areas of function while the rest of the gland shows decreased activity .
•     Treatment of toxic nodular goiter is most effectively performed by resection of the area, usually by
      lobectomy or near-total thyroidectomy, particularly when clinical symptoms are pronounced. In the case of
      the single, hyperfunctioning adenoma, a lobectomy is usually curative. Antithyroid medication can control
      symptoms, but relapse is common. Radioiodine therapy is not as effective as in patients with Graves’ disease.
Nontoxic Goiter
•    Multinodular Goiter
•    Multinodular goiter describes an enlarged, heterogeneous thyroid gland. Initial presentation may include diffuse
     enlargement( endemic goiter ), but the mass often develops asymmetrical nodularity. The cause of this mass is
     usually iodine deficiency and fluctuation of TSH . Initially, the mass is euthyroid; however, with increasing size,
     elevations in T3 and T4 can occur and progress gradually and complicated by hyperthyroidism ( secondary toxic
     goiter ) or malignancy ( follicular carcinoma ),tracheal compression
•    Work-up and diagnosis include evaluation of thyroid function tests. Ultrasound and radioisotopic scanning
     demonstrate heterogeneous thyroid substance.
•    Nodules with poor uptake can present as lesions suspicious for malignancy
•    The incidence of carcinoma in multinodular goiter has been reported as 5% to 10%.
•    Therefore, FNA for diagnosis and resection for suspicious lesions should be considered.
•    Resection is indicated for suspesios leasion ,pressure manifistation ,cosmetic, and to avoid secondary toxicity.

 Substernal (retrosetrnal) Goiter
 Substernal goiter is an unusual presentation of an intrathoracic extension of an
        enlarged thyroid, usually as a result of multinodular goiter.
 Compression symptoms related to the position.
 • Dyspnoea, particularly at night, cough and stridor (harsh sound on inspiration).
        Many patients attend a chest clinic with a diagnosis of asthma before the true
        nature of the problem is discovered.
 • Dysphagia.
 • Engorgement of facial, neck and superficial chest wall veins; in severe cases there
        may be obstruction of the superior vena cava .
 • Recurrent nerve paralysis is rare.
 • The goitre may also be malignant or toxic.
 The lower border (edge )of the thyroid gland is behind the sternum which is dull on
 Most intrathoracic or substernal goiters are labeled “secondary” because they are
        enlargements or extensions of multinodular goiters, based on the inferior
        thyroid vasculature. They expand downward into the anterior mediastinum.
 Treatment by surgical resection .
 Complications of surgery include intrathoracic bleeding, recurrence in unresected
        tissue, and recurrent laryngeal nerve damage, although in experienced hands
        the complication rate should be less than 5%.

 •    95% of thyroid cancer cases are categorized as well-differentiated tumors arising from follicular cell origin.
      These include papillary, follicular, and Hürthle cell carcinomas.
 •    Medullary thyroid cancer (MCT) accounts for about 4% of thyroid cancers (of which ˜ 20% to 30% are on a
      familial basis MEN types II A and II B).
 •    Anaplastic carcinoma is an aggressive malignancy and is responsible for less than 1% of thyroid carcinomas.

 Papillary Carcinoma
 Papillary carcinoma is the most common of the thyroid neoplasms .
 The association of irradiation and thyroid cancer has been known. The use of external-beam irradiation in children
 and young adults .
 Areas near known nuclear fallout contamination, have increased incidence rates of well-differentiated thyroid
  Clinical Presentation
  •      Thyroid masses may occur in either males or females at almost any age. Solitary masses that are painless and
         firm should be regarded with particular suspicion.
  •      Occasionally, a mass in the lateral neck presents as a painless entity and an FNA biopsy confirms a metastatic
         thyroid malignancy, even in the case of a normal thyroid examination.
  •      Papillary carcinoma may be found incidentally in a thyroid sample resected for a benign process.
  •      Multicentricity can be anticipated in as many as 70% of patients with the diagnosis of papillary cancer.
  •      Additionally, local spread and cervical lymph node metastasis must be anticipated.
  •      Distant(blood porn ) metastases are rare but have a poor prognosis
  •      Confirmation of the diagnosis may be initiated by ultrasound, which can evaluate multinodularity and
         whether the nodule is solid or cystic.
  •      FNA of a palpable solid lesion is the next step. Papillary carcinoma of the thyroid can be diagnosed by this
         technique because individual cellular architecture can be evaluated and a secure diagnosis made.
  •      Palpable lymphadenopathy should lead to FNA of suspected lesions.
  •      Intraoperative evaluation of any suspicious lymph nodes must also be performed by resection or by frozen-
         section evaluation. Diligent search for multicentricity within the thyroid as well as regional lymph node
         metastasis may be employed by the use of ultrasound or neck CT scanning.
  •      Distant metastatic activity may be evaluated through chest radiographs, radionuclide scanning, CT, and other
         techniques as guided by clinical suspicion.
  •      In patients with total thyroidectomy, postoperative thyroglobulin levels may be followed to monitor

         Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer

                                   Low Risk                           High Risk
                Age               <40 years                          >40 years
                Sex               Female                             Male
                Extent            No local extension,                Capsular invasion,
                                  intrathyroidal,                     extrathyroidal extension
                                  no capsular invasion
                Metastasis         None                              Regional or distant
                Size              <2 cm                               >4 cm
                Grade             Well differentiated                Poorly D

•     The main treatment of papillary carcinoma of the thyroid is surgical ablation.
•     For lesions smaller than 1 cm, there is general agreement in the literature that lobectomy plus isthmectomy
      is the appropriate treatment. This is particularly true for incidentally found papillary carcinomas.
•     Several factors enter into surgical decision making.
•     Patients15 years of age or younger, have a high rate of cervical metastasis to the extent that perhaps 90% of
      children with papillary carcinoma may have documented metastatic activity within the lymph nodes.
      Therefore, there is a strong consideration that patients in this age group undergo total thyroidectomy and
      lymph node dissection if palpable cervical lymph nodes occur.
•     Additionally, in older patients with a history of neck irradiation, a more aggressive approach may be taken,
      including total thyroidectomy and modified neck dissection in the presence of palpable cervical lymph nodes.
•     In patients between the ages of 15 and 40 years with lesions smaller than 2 cm, surgical treatment is more
      controversial. Total lobectomy and isthmectomy may well suffice when the lesion clearly involves only one
•     For adults with lesions larger than 2 cm, a total or near-total thyroidectomy is favored by most surgeons.
•     In patients of any age in whom there is palpable adenopathy, a modified radical neck dissection on the side affected
      should be performed in concert with a total thyroidectomy.
•     Controversy exists about the use of total thyroidectomy versus lobectomy and isthmectomy in adults with a 1- to 2-cm
      papillary thyroid carcinoma.
•     The advantages of a total thyroidectomy include the efficient use of radioiodine postoperative treatment. Clearly, if
      residual thyroid exists, radioablation is much less effective and requires a larger dosage. The advantages of the lesser
      procedure are the decreased rates of bilateral recurrent laryngeal nerve damage and hypoparathyroidism.
•     For larger lesions, postoperative 131 I therapy has been advocated.
•     Recurrence in local or regional lymph nodes after initial surgery should be treated with completion thyroidectomy, if
      residual tissue exists, plus regional lymph node dissection.
•     Radioiodine therapy should be used as adjunctive therapy.

•     Most patients with papillary carcinoma can expect an excellent prognosis, approaching a 95% 10-year survival rate for
      the most favorable stages.
•     For surgical resection should result in an excellent 5- to 10-year survival rate exceeding 90%.
•     For larger lesions, survival numbers may decrease, especially in older men.

Follicular Carcinoma
•      Follicular thyroid cancer (FTC) is the second category of well-differentiated thyroid cancers.
•      All types of papillary, follicular, and mixed papillaryfollicular cancers account for about 90% of all thyroid cancers.
•      Pure FTC represents the minority of these, constituting about 10% of all thyroid malignancies.
•      FTC is a disease of an older population, often 50 years of age or older.
•       It has a predilection for women, with a ratio of about 3:1.
•      The subtype of FTC, which consists of oxyphilic cells, is known as Hürthle cells, and these tend to occur in older patients,
       usually 60 to 75 years of age.
•      There appears to be an increased incidence of FTC in geographic distributions associated with iodine deficiency.
•      The histologic diagnosis of FTC depends on the demonstration of what would appear to be normal follicular cells
       occupying abnormal positions, including capsular, lymphatic, or vascular invasion .
•      With widely invasive FTC, distant spread is more common, often involving lung, bone, and other solid organs.
•       Lymph node involvement is unusual, occurring in less than 10% of cases.

Clinical Presentation and investigation
•      FTC, like papillary cancer, classically presents as a painless thyroid mass. Although most patients have a benign mass,
       the existence of FTC in a patient with multinodular goiter can occur in as many as 10% of cases. Although the findings
       of hoarseness and firm fixation of the mass on clinical presentation suggest advanced disease and a poor prognosis,
       these circumstances are again in the minority of cases.
•       In these cases, diligent search for aggressive extension into the trachea and distant metastasis, particularly in older
       patients, should be carried out by use of CT or MRI evaluation of the neck and chest.
•      Ultrasound can determine the size and multicentricity; however, FTC usually presents as a solitary mass. Radionuclide
       scanning can determine whether a mass has function or is cold, although a minority of cold nodules actually prove to
       be malignant.
•      In the case of FTC, however, FNA is of limited value. The diagnosis of FTC requires the demonstration of cellular
       invasion of the capsule or of vascular or lymphatic channels.
•       Additionally, intraoperative frozen section has been notoriously ineffective in making a definitive diagnosis of FTC
•     The treatment of follicular carcinoma is primarily surgical.
•     If the lesion is 2 cm or smaller and well contained within one thyroid lobe, an argument may be made for
      thyroid lobectomy and isthmectomy.
•     If the lesion is larger than 2 cm, the surgeon may well proceed with total thyroidectomy.
•     Lymph node dissection is not necessary in the absence of palpable lymph nodes and adds nothing to survival
      data unless obviously involved

•     A particularly vexing problem occurs when a thyroid lobectomy has been performed for a presumed thyroid
      adenoma but the final pathologic diagnosis is follicular carcinoma. Two considerations must then take place.
      After determining an AMES or AGES score, a decision needs to be made regarding whether the lesion is low
      risk (small lesion in younger patient), in which case the patient might be watched closely with ultrasound
      evaluations every 6 months. Alternatively, the lesion might be higher risk (>2 cm in a patient older than 60
      years of age) and require radioablation. This circumstance requires reoperation and completion
      thyroidectomy, albeit with increased technical difficulty and possibility of complications.

Adjuvant treatment
Postoperative treatment with T4 is based on the assumption that TSH suppression minimizes its growth-promoting
influence on thyroid cancer.
Radioiodine treatment is likewise controversial. There is no substantial benefit to patients with completely resected
lesions and more favorable stages.
Obviously, radioiodine treatment is most efficacious in patients who have undergone total thyroidectomy.
In patients who have undergone subtotal thyroidectomy or lobectomy and isthmectomy, higher doses of
radioiodine are needed for remnant ablation.
Additionally,131 I treatment may be given in older patients (≥75 years of age) or in patients whose thyroglobulin
levels have increased later than 3 months after surgery.

Medullary Carcinoma
•MCT accounts for 5% to 10% of thyroid malignancies. The malignancy involves the parafollicular cell, or C cell,
derived from the neural crest.
•MCT is associated with the secretion of a biological marker, calcitonin. The excess secretion of calcitonin has been
demonstrated to be an effective marker for the existence of MCT.
•Medullary carcinoma can occur in a sporadic form or as part of MEN type IIA or IIB.

•The patient with a sporadic medullary carcinoma may present in either of two ways: with a palpable mass for
which a diagnosis can be made through FNA or with the finding of an elevated calcitonin level.
•The work-up of these patients should include a detailed and in-depth family history inquiring for characteristics of
MEN type II in the patient and family members .
•Screening for pheochromocytoma.

•The surgical approach to sporadic medullary carcinoma involves at least a total thyroidectomy which allows
complete removal of the gland and search for multicentricity.
•Any palpable lymph nodes in lateral areas require a modified radical neck dissection.
•A successful operation with good prognosis is predicted for patients with smaller masses and for whom calcitonin
levels are undetectable after surgery. Radioactive scanning may be used to ablate any residual thyroid.
Anaplastic Thyroid Cancer
•     Anaplastic thyroid carcinoma represents less than 1% of all thyroid malignancies. It is the most aggressive
      form of thyroid cancer.
•      A typical presentation is in an older patient who presents with dysphagia, cervical tenderness, and a painful
      neck mass. Superior vena cava syndrome can also be part of the presentation.
•     The clinical situation deteriorates rapidly into tracheal obstruction and rapid local invasion of surrounding
•     Treatment
•     The results of any surgical treatment of anaplastic thyroid carcinoma are tempered by the rapidly progressive
      clinical course.
•     The finding of distant metastasis or invasion into locally unresectable structures, such as the trachea or
      vasculature of the anterior mediastinum, should lead to a more conservative surgical approach, such as
•     Postoperative external-beam irradiation or adjunctiven chemotherapy adds little to the overall prognosis.
•     Overall survival in this series was dismal.

•    Primary thyroid lymphoma, although rare, is being recognized more often. This diagnosis should be
     considered in patients who present with a goiter, especially one that has apparently grown significantly in a
     short period.
•    Other presenting symptoms include hoarseness, dysphagia, and fever.
•    There is also an increased association between lymphoma and Hashimoto’s thyroiditis.

•      The use of FNA can be diagnostic in this situation.
•     If the diagnosis is either confirmed or highly suspicious, additional preoperative evaluation should include
      neck, chest, and abdominal CT or MRI evaluation to assess extrathyroidal spread.
•     Treatment
•     Treatment philosophies differ with regard to preoperative chemotherapy or surgical ablation.
•     The use of surgical resection, including a neartotal or a total thyroidectomy, is thought to enhance these

Clinically discrete swellings
A discrete swelling in an otherwise impalpable gland is termed isolated or solitary,
Whereas the preferred term is dominant for a similar swelling in a gland with clinical evidence of generalised
       abnormality in the form of a palpable contralateral lobe or generalised mild nodularity.
When such a gland is exposed at operation or examined by ultrasonography, CT or MRI, clinically impalpable
       nodules are often detected.
•      The importance of discrete swellings lies in the increased risk of neoplasia compared with other thyroid
       swellings. Some 15% of isolated swellings prove to be malignant, and an additional 30–40% are follicular
•       The remainder are nonneoplastic, largely consisting of areas of colloid degeneration, thyroiditis or cysts.
       Although the incidence of malignancy or follicular adenoma in clinically dominant swellings is approximately
       half of that of truly isolated swellings, it is substantial and cannot be ignored

                        The diagnosis of follicular carcinoma cannot be made with FNA

Multiple Endocrine Neoplasia Type I
• Also known as Wermer syndrome; characterized by tumors of the parathyroid, anterior pituitary, and pancreas;
       other tumors can include adrenocortical tumors, thymic or bronchial carcinoid tumors, multiple lipomas,
       cutaneous angiofibromas, and collagenomas; 90–97% of patients have biochemical evidence of
       hyperparathyroidism; 30–80% have pancreatic islet cell tumors; 15–50% develop pituitary tumors.
• Laboratory findings include elevated serum calcium and intact PTH, elevated gastric acid secretion, elevated
       fasting serum gastrin level
• Direct genetic testing generally offered only for probands with definitive evidence of MEN I syndrome; once the
       mutation is known, genetic testing of at-risk family members is useful abdominal CT scan, and somatostatin
       receptor scintigraphy for pancreatic tumor detection; prolactin level for pituitary adenoma; chest CT scan for
       thymic carcinoid detection

Multiple Endocrine NeoplasiaType II
MEN IIA: medullary thyroid carcinoma (MTC), heochromocytomas,
parathyroid hyperplasia
 MEN IIB: MTC, pheochromocytomas, mucosal neuromas, gangliomatosis of the gastrointestinal tract, distinctive
marfanoid habitus
 Symptoms and signs include diarrhea, palpable thyroid nodule or multinodular thyroid gland, enlarged and firm
cervical nodes (if metastatic disease)
Laboratory findings include elevated calcitonin level if MTC has developed; elevated plasma metanephrines if
 Measure calcium and PTH; perform genetic screening for all patients with MTC

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