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Thyroid Anomalies

  • The thyroid is embryologically an offshoot of the primitive alimentary tract, from which it later becomes
  • separated.
  • A median anlage arises from the pharyngeal floor in the region of the foramen cecum of the tongue.
  • The main body of the thyroid descends into the neck from this origin and is joined by a pair of lateral
  • components originating from the ultimobranchial bodies of the fourth and fifth branchial pouches.
  • It is from these lateral components that the C cells enter the thyroid lobes.
Description: fig21-7
  1. Developmental abnormalities of the thyroid gland in humans. Location of thyroglossal cysts.
  2. In front of the foramen cecum.
  3. At the foramen cecum.
  4. Suprahyoid.
  5. Infrahyoid.
  6. Area of the thyroid gland.
  7. Suprasternal.
  • The median thyroid anlage may rarely fail to develop, causing athyreosis, that is, absence of the thyroid
  • gland, or it may differentiate in locations other than the isthmus and lateral lobes.
  • The most common of these is as the pyramidal lobe, which has been reported in as many as 80 percent of
  • patients.
  • Other variations involving the median thyroid anlage represent an arrest in the usual descent of part or all of the thyroid-forming material.
  • These variations include the development of a lingual thyroid, suprahyoid and infrahyoid thyroid tissue, and persistence of the thyroglossal duct as a sinus tract or cyst. 
A thyroglossal duct cyst is the most common of the clinically important anomalies of thyroid development.Q

Thyroglossal Duct Cysts
  1. Both cysts and sinus tracts can develop along the course of the thyroglossal duct. Normally the thyroglossal duct becomes obliterated early in embryonic life, but occasionally it may persist as a cyst or a draining sinus tract.
  2. Cysts often become infected and may rupture spontaneously. Removal of the cyst or sinus usually requires excision of the central part of the hyoid bone and dissection of the tract to the base of the tongue (the Sistrunk operation), if recurrence is to be minimized.  
Lateral Aberrant Thyroid Rests
  1. True lateral aberrant thyroid tissue is rare since the lateral anlages are normally incorporated into the expanding lateral lobes of the median thyroid anlage.
  2. Thus, a mass of thyroid in the lateral neck, which used to be called lateral aberrant thyroid, almost always represents well-differentiated, metastatic thyroid cancer within a cervical lymph node rather than an embryonic rest. It should be treated as a metastasis from a papillary thyroid cancer.Q
Investigation for thyromegaly
  1. To confirm physiological diangosis
    1. Serve TSH, T3, T4
    2. Thyroid antibody
  2. To confirm anatomical diagnosis
    1. USG of neck
    2. Tc99 scan
  3. FNAC
    1. Hemithyroidectomy   
    2. To confirm pathological diagnosis
  1. Goitre
    1. Goitre is a non-specific term describing enlargement of the thyroid gland
    2. Does not imply the presence of any specific pathology
    3. Goitres can be either diffuse or multi-nodular  
  • Causes of diffuse goitres
  1. Simple goiter: Patient euthyroid
    Due to compensatory hypertrophy resulting from
    1. Iodine deficient diet
    2. Congenital enzyme defect in thyroxine synthesis
    3. Increased physiological demands
  2. Smooth toxic goiter: Patient hyperthyroid (= Graves disease)
  3. Other smooth goiters
    1. Thyroiditis
    2. Lymphoma
    3. Thyroid amyloidosis
  • Causes of multinodular goiters
Usually a simple goitre that has progressed to nodularity
Examination Function Causes
Diffuse goitre Euthyroid Physiological goitre or autoimmune thyroiditis
Diffuse goitre Hyperthyroid Primary hyperthyroidism
Multinodular goitre Euthyroid Multinodular goitre
Multinodular goitre Hyperthyroid Toxic nodular goitre (rare)
Solitary nodule Euthyroid Thyroid cyst or tumour
Solitary nodule Hyperthyroid Functioning adenoma
  • Goiter
  1. The normal adult thyroid gland weighs 10-25 g and has 2 lobes connected by an isthmus. Nearly 50% of thyroid glands exhibit a pyramidal lobe arising from the.
  2. A goiter is an enlarged thyroid gland, and it may be diffuse or nodular.
  3. Pathophysiology: The thyroid gland is controlled by thyrotropin (TSH), secreted from the pituitary gland, which, in turn, is influenced by the thyrotropin-releasing hormone (TRH) from the hypothalamus.
  4. A deficiency in thyroid hormone synthesis or intake leads to increased TSH production. Increased TSH causes increased cellularity and hyperplasia of the thyroid gland in an attempt to normalize thyroid hormone levels.
  5. If this process is sustained, a goiter is established. Causes of thyroid hormone deficiency include inborn errors of thyroid hormone synthesis, iodine deficiency, and goitrogens.
  6. Goiter may result from a number of TSH receptor agonists. TSH receptor stimulators include TSH receptor antibodies, pituitary resistance to thyroid hormone, adenomas of the hypothalamus or pituitary gland, and tumors producing hCG.
  7. Sex: The female-to-male ratio is 4:1.
Clinical Feature of Goiter
Incidental swelling in the neck or compression causing dysphagia, dyspnea, stridor, plethora or hoarseness. Pain due to hemorrhage, inflammation, necrosis, or malignant transformation. Signs and symptoms of hyperthyroidism or hypothyroidism
  1. The pyramidal lobe often is enlarged in Graves disease.
  2. A firm rubbery thyroid gland suggests Hashimoto thyroiditis, and a hard thyroid gland suggests malignancy or Reidel struma.
  3. Multiple nodules may suggest a multinodular goiter or Hashimoto thyroiditis. A solitary hard nodule suggests malignancy, whereas a solitary firm nodule may be a thyroid cyst.
  4. Diffuse thyroid tenderness suggests subacute thyroiditis, and local thyroid tenderness suggests intranodal hemorrhage or necrosis.
  5. Cervical lymph glands are palpated for signs of metastatic thyroid cancer.
  6. Auscultation of a soft bruit over the inferior thyroidal artery may be preresnt in a toxic goiter.
  7. Goiters are described in a variety of ways, including the following:
    1. Toxic goiter: A goiter that is associated with hyperthyroidism is described as a toxic goiter.
      1. Examples of toxic goiters include diffuse toxic goiter (Graves disease), toxic multinodular goiter, and toxic adenoma (Plummer disease).
    2. Nontoxic goiter: A goiter without hyperthyroidism or hypothyroidism is described as a nontoxic goiter.
      1. It may be diffuse or multinodular, but a diffuse goiter often evolves into a nodular goiter.  
      2. Examination of the thyroid may not reveal small or posterior nodules.
      3. Examples of nontoxic goiters include chronic lymphocytic thyroiditis (Hashimoto disease), goiter identified in early Graves disease, endemic goiter, sporadic goiter, congenital goiter, and physiologic goiter that occurs during puberty.
      4. The Pemberton maneuver Q raises a goiter into the thoracic inlet by having the patient elevate the arms. This may cause shortness of breath, stridor, or distention of neck veins. 
Lab Studies
  1. Initial screening should include TSH. Further laboratory testing is based on presentation and results of screening studies and may include thyroid antibodies (antithyroid peroxidase formerly the antimicrosomal antibodies and antithyroglobulin), thyroglobulin, sedimentation rate and calcitonin in a high risk individual for medullary carcinoma of the thyroid.
  2. Imaging Studies:
    Ultrasound: Localize nodules for ultrasound-guided biopsy.
Treatment of Goiter
  1. Medical Care:
    1. The size of a benign euthyroid goiter may be reduced with levothyroxine suppressive therapy. The patient is monitored to keep serum TSH in a low but detectable range to avoid hyperthyroidism, cardiac arrhythmias and osteoporosis.
    2. Treatment of hypothyroidism or hyperthyroidism often reduces the size of a goiter.
    3. Thyroid hormone replacement is often required following surgical and radiation treatment of a goiter.
    4. Medical therapy of autonomous nodules with thyroid hormone is not indicated.
  2. Surgical Care: Surgery is reserved for the following situations:
    1. Large goiters with compression
    2. Malignancy
    3. When other forms of therapy are not practical or ineffective
    4. Partial thyroidectomy may be used as a first-line procedure for patients with a high probability of cancer.
    5. It is reserved mostly if the result of a fine-needle aspiration is suspicious or if the patient/physician prefers it.
    6. Total thyroidectomy is performed for malignant goiters.
Diffuse Toxic Goiter
Diffuse toxic goiter is the major manifestation of Graves disease. Other features are ophthalmopathy, dermopathy, and acropachy.
  1. Pathophysiology:
    1. Graves disease is an autoimmune disease caused by the presence of thyroid-stimulating immunoglobulins (TSIs) in the plasma.
    2. TSIs are antibodies to the thyroid-stimulating hormone (TSH) receptor, ie, thyrotrophin receptor antibody (TRAb). Two types of these antibodies exist, the thyroid-stimulating antibody (TSAb) and the TSH-binding inhibitor (TBI).
    3. TRAb constitutes immunoglobulins of diverse potential and clinical expression.
    4. More than one antibody can be present in the blood of a patient. TSIs stimulate TSH receptors and cause excessive secretion of thyroxine (T4) and triiodothyronine (T3).
    5. Grossly, the thyroid gland in Graves disease is diffusely enlarged, soft, and vascular. Histologic section reveals stromal hypertrophy and hyperplasia.
      Sex: The female-to-male ratio ranges from 5:1 to 10:1.
  2. Clinical
    The typical manifestations include the following:
Nervousness, Sweating, Heat intolerance, Palpitations, Fatigue, Weight loss, Menstrual irregularities, Muscle weakness (proximal muscles)
Physical: Signs found on physical examination include the following:
  1. Diffuse goiter
  2. CNS - Nervousness, emotional lability, and fine tremor of hands,
  3. Cardiovascular - Tachycardia, atrial fibrillation, wide pulse pressure,
  4. Gastrointestinal - Gastrointestinal hypermotility,
  5. Muscle - Proximal muscle weakness, muscle atrophy, hyperreflexia,
  6. Skin - Warm, moist, smooth skin; onycholysis; fine hair; hair loss; excessive sweat,
  7. Metabolic - Weight loss and occasionally weight gain if increased appetite leads to food intake that exceeds the hypermetabolic requirements, Signs specific to Graves disease
    1. Diffuse symmetrical thyroid enlargement
    2. Infiltrative ophthalmopathy - Occurs in 20-40% of cases; often bilateral, but unilateral in 5-14% of cases
    3. Lid lag with upper lid retraction and stare (Lid lag alone can be observed in any thyrotoxic state as a result of increased adrenergic tone of levator palpebrae.)
    4. Dermopathy and acropachy - pretibial myxedema rash or patch (might be nodular or polypoid, typically nonpitting, and can be accompanied by digital clubbing .
  1. Lab Studies:
    1. Total T4
      Level elevated above 12.5 mg/dL (normal range [N] = 4.5-10.9) is sensitive with low specificity. Drugs that may alter T4 laboratory results include anabolic steroids, androgens, estrogens, heparin, iodine, phenytoin, rifampin, salicylates, and thyroxine/triiodothyronine.
    2. Free T4
      1. T3 – The level is elevated above 200 ng/mL (N = 60-181;). This is a total T3 assay that frequently is replaced by free T3 (N = 2.2-4.0).
      2. T3 should be measured in cases with T4 levels that fall within the reference range (T3 thyrotoxicosis).
      3. Radioactive iodine uptake, most commonly performed 24 hours after administration of radioactive iodine
      4. Radioactive iodine uptake (RIU) is high in Graves disease, high or normal in toxic multinodular goiter, and low in thyroiditis. Q
    3. Imaging Studies: Thyroid scan using radioiodine (ie, I-123) – Diffuse in Graves disease, focal in toxic nodule (This study is not needed if the diagnosis of Graves thyrotoxicosis is well established by clinical criteria and very high RIU.)
    4. Histologic Findings:
      Grossly, the thyroid gland in Graves disease is diffusely enlarged. Histology section reveals stromal hypertrophy and lymphocytic infiltration.
  2. Treatment
    1. Medical Care:
      Three therapeutic options are available for patients with Graves disease—(1) radioactive iodine, (2) antithyroid drugs, and (3) subtotal thyroidectomy
      1. Antithyroid drugs Q
        1. Antithyroid drugs are reversible, effective in most patients, and generally safe. It is recommended treatment for patients who cannot use radioactive iodine.
        2. Four to 8 weeks may be required for the patient to become euthyroid, and the medication often is used for 1-2 years.
Propylthiouracil is the drug of choice for patients who are pregnant.
  1. Radioiodine (131 I)  
    1. Radioiodine is the agent of choice because it is selectively taken up by the thyroid gland.
    2. The usual dose is 5-6 microcurie (mCi), which releases 7000-10,000 rads (70-100 grays [Gy]) to the thyroid cells.
    3. Radioiodine is contraindicated in pregnancy and used with caution in women of childbearing age.
    4. Radioiodine must not be used in a patient with thyroid storm/crisis until medications have brought the crisis under control.
    5. Its latent period lasts about 3 weeks to 3 months. Thus, beta-blockers are used adjunctively to suppress symptoms. Risk of hypothyroidism is another concern.
    6. Hypothyroidism occurs in more than 50% of patients during the first year and occurs in 2-3% each year thereafter.
    7. Risk of worsening ophthalmopathy can be reduced by pretreatment with glucocorticoid 2 weeks before administration of radioiodine.
  1. Surgical Care: Surgery is recommended for patients who refuse radioiodine therapy and for whom medication is not appropriate. Subtotal thyroidectomy is performed under general anesthesia. About 5-7 g of thyroid tissue is left behind. Q
    1. The risks include the following:
      1. Hemorrhage, Injury to recurrent laryngeal nerve, Hypocalcemia, Recurrent hyperthyroidism, Hypothyroidism
      2. Preoperative preparation involves the use of iodine for about 10 days prior to surgery to make the goiter less vascular, which reduces the risk of precipitating thyroid crisis.
      3. Propranolol is administered for at least 48 hours before surgery. The patient must be clinically controlled and have a heart rate less than 100 beats per minute.
      4. Propylthiouracil (PTU) or methimazole also may be used to prepare the patient for surgery.
Etiology of Nontoxic 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

Thyroid Cancer
  1. Most common endocrine tumour.
  2. F>M
  3. Papillary cancer of thyroid is most common (75%)
  4. Follicular cancer of thyroid is second most common (15%)
  5. Prevalence of thyroid cancer in solitary and multinodular goiter is 10-20%.
  6. After radiation 30% of thyroid nodule are malignant.
  1. Pathology:
    1. Most malignancies are epithelial in origin and are carcinomas.
    2. Diagnosis of malignancy depends on vascular and capsular invasion rather than on histological appearance. Q
  2. Classification:
    Classification of Thyroid Neoplasms
    1. Benign
      1. Follicular epithelial cell adenomas
        1. Macrofollicular (colloid)                              
        2. Normo follicular (simple)
        3. Microfollicular (fetal)                                    
        4. Trabecular (embryonal)                  
        5. Hurtle cell variant (oncocytic)
    2. Malignant
    3. Follicular epithelial cell 
      1. Well-differentiated carcinomas
      2. Papillary carcinomas
        1. Pure papillary  
        2. Follicular variant    
        3. Diffuse sclerosing variant      
        4. Tall cell, columnar cell variants
      3. Follicular carcinomas
        1. Minimally invasive    
        2. Widely invasive    
        3. Hürthle cell carcinoma (oncocytic)            
        4. ​Insular carcinoma
      4. Undifferentiated (anaplastic) carcinomas
    4. C cell (calcitonin-producing) 
      1. Medullary thyroid cancer
        1. Sporadic            
        2. Familial              
        3. ​MEN 2
    5. Other malignancies :
      1. Lymphomas        
      2. Sarcomas        
      3. Metastases      
      4. Others
It is important to examine junction of carcinoma with the surrounding tissue to determine capsular invasion.
Multifocality is seen in 80% of papillary carcinoma.
Lymph node metastasis not a poor prognostic sign in most of the thyroid carcinomas. It is poor prognostic in medullary thyroid carcinoma.

Prognostic Risk Classification for Patients With Well-Differentiated Thyroid Cancer
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
Ref: Sabiston Textbook of Surgery, 18th Edition Ch 36
  1. Papillary Carcinoma: 75%  
    1. Papillary carcinoma 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.
    2. Peak onset ages 30 through 50
    3. Females more common than males by 3 to 1 ratio
    4. Prognosis directly related to tumor size [less than 1.5 cm good prognosis]
    5. Accounts for 85% of thyroid cancers due to radiation exposure
    6. Spread to lymph nodes of the neck present in more than 50% of cases
    7. Distant spread (to lungs or bones) is very uncommon
    8. Overall cure rate very high (near 100% for small lesions in young patients)
    9. Characterized by infiltrative pattern, multicentricity and regional node spread.
    10. FNAC is the investigation of choice.
    11. Nucleus has ground glass appearance (Orphan Annie appearance). Because of true of large amount of chromatin.
    12. Mixed follicular and papillary variant is classified as papillary type.
    13. Even if occult papillary cancer metastasize to local nodes, prognosis is still excellent. Extrathyroid  extension and distant metastasis worsens the prognosis. Psomamma bodies (Dystrophic calcification)  with papillary projector in cytroplasm are also features of PTC.
    14. Multicentric Papillary microcarcinoma is a subset of PTC defined as measuring less than or equal to 1 cm in size.
    15. Occult papillary carcinoma is PTS £ 1.5 cm in diameter
  2. Follicular Carcinoma:
    1. Peak onset ages 40 through 60
    2. Females more common than males by 3 to 1 ratio
    3. Prognosis directly related to tumor size [less than 1.0 cm good prognosis]
    4. Rarely associated with radiation exposure
    5. Spread to lymph nodes is uncommon (~10%)
    6. Invasion into vascular structures (veins and arteries) within the thyroid gland is common
    7. Distant spread (to lungs or bones) is uncommon, but more common than with papillary cancer
    8. Overall cure rate high (near 95% for small lesions in young patients), decreases with advanced age
    9. Follicular adenoma and carcinoma have same uniform pattern. Detection of papilla/ Orphan Annie nucleus/ Psammoma bodies are not consistent with follicular carcinoma.
    10. Distinction of carcinoma and adenoma is based on capsular and vascular invasion, thus HPE required (FNAC is in conclusive).
    11. Good prognostic features are: Small size (< 4cm), persons younger than 50 yrs, localized tumours without
      1. marked vascular invasion.
    12. Hurthle cell: It is derived from follicular cells.
    13. Hurthle cell neoplasm is composed of sheets of cells.
    14. Chances of Hurthle cell adenoma having malignancy is 1.5-2.5%.
  3. Medullary Thyroid Carcinoma: 5%
    1. 85% is sporadic
    2. It can be associated with other endocrine tumors – MEN II A and B
    3. Origin from C cells (neural crest or ultimo bronchial body)
    4. F> M. (except for inherited cancers). Commonest in 5th – 6th decades.
    5. Regional metastases (spread to neck lymph nodes) occurs early in the disease.
    6. Spread to distant organs (metastasis) occurs late and can be to the liver, bone, brain, and adrenal medulla
    7. Not associated with radiation exposure
    8. Usually originates in the upper central lobe of the thyroid.
    9. Poor prognostic factors include age >50, male, distant spread (metastases), and when seen in patients with other endocrine tumors due to MEN II-B syndrome.
    10. Residual disease (following surgery) or recurrence can be detected by measuring calcitonin (a hormone that should be measured every 4 months for the first few years and then every 6 months for ever).
    11. 20% of patients acquire this through autosomal dominant inherited pattern.
    12. Germ line abnormality of chromosome 10 (RET protooncogene) is related to 3 different familial pattern (MEN II a, MEN II b, and non MEN medullayr carcinoma).
    13. MTC is screened by Pentagastrin stimulated or calcium stimulated plasma level of calcitonin.
    14. Metastasis is through lymphatics and blood vessels.
    15. Prognosis is worse in: Older patients, MEN II b, large tumour size, Lymph node mets and distant metastasis.
    16. Most common presenting symptoms is diarrhoea.
      MTC secretes
      1. calcitonin.            
      2. CEA                  
      3. CGRP
      4. PGE2                    
      5. Serotonin          
      6. ACTH
  4. Anaplastic Carcinoma: < 5% of all malignancies.
    1. Peak onset age 65 and older
    2. Very rare in young patients
    3. Males more common than females by 2 to 1 ratio
    4. Typically presents as rapidly growing neck mass along with Hoarseness of voice.
    5. Can occur many years after radiation exposure
    6. Spread to lymph nodes of the neck present in more than 90% of cases
    7. Distant spread (to lungs or bones) is very common even when first diagnosed
    8. Overall cure rate very low and prognosis is waste.
    9. Typically requires a very aggressive treatment plan with surgery, radiation and sometimes even chemotherapy.
    10. Treatment is only supportive (Palliative)
Often requires the patient to get a tracheostomy to maintain their airway. Q
  1. All tumours of anaplastic type is placed in type IV.
  2. Prognosis is poor with median survival of 7 months.
  • Etiology:
  1. Radiation: Increases risk of papillary carcinoma.
    1. Risk is dose dependent.
    2. Risk is linear from 300 to 1200 cGy. > 1200 cGy risk declines.
    3. Risk factors includes: Sex (F>M), Age (Younger the patients at the time of exposure greater the risk).
  2. Iodine: Follicular carcinoma is more common in iodine deficient goitrous area and papillary carcinoma is more common in areas of iodinated salts or high iodine diet.
  3. Goitres: Prolonged exposure of thyroid gland to TSH stimulation causes high rate of thyroid malignancy.
  4. familial: Pericentromere region of chromosome 10 associated with MEN II a, MEN II b and familial MTC.
  5. Oncogenes: Mutation of 3 RAS genes (K-Ras, H-Ras and N-Ras) have been identified in many human tumours.
  • Biomarkers associated with Early & late stage thyroid carcinomasQ
  1. RET /PTC                                   
  2. RAS                                    
  3. BRAF                                  
  4. PAX – 8 / PPAR
  5. Mucin (MUC 1)                       
  6. PCNA                                  
  7. Len – M1 antigen            
  8. P-53
  9. DNA methylene                        
  10. Telomerase                       
  11. Galectin-3                         
  12. Ki – 67
  13. Oncofetal fibronectin
Benign or early stage                   
Thyroid carcinoma
Thyroid peroxidase (TPO)           
  • Diagnosis:
  1. Lab Test:
    Most patients of malignant thyroid nodule are euthyroid.
    If the patient has elevated T3 and T4 with low TSH then thyroid scan is indicated to determine hot, warm or cold nodule.
    Serum level of thyroglobulin may be used as tumour markers for well defferentiated carcinoma (its level is normal or low in anaplastic and medullary tumours) and nodal disease of thyroid secondary to previous neck irradiation.
  1. Ultrasound:
    1. It classifies nodules as solid, mixed or cystic lesions. 20% of solid, 12% of mixed and 7% of cystic lesions are malignant. USG can not differentiate between a malignant from a benign lesions
    2. (Halo sign: a thin sonolucent rim commonly seen in benign lesion is also found in well differentiated carcinoma).  Lymph node mets can also be picked up.

  1. Biopsy: FNAC is most valuable aid in diagnosis.
    1. FNAC can not differentiate between follicular neoplasm from adenoma.
    2. For a larger lesion where there is concern about lymphoma or anaplastic carcinoma, is better assisted by cutting needle biopsy. A lymphoma in FNAC may give diagnosis of thyroiditis.


TNM Classification of Thyroid Tumors
Papillary or Follicular Tumors
Stage TNM
<45 y  
I Any T, any N, M0
II Any T, any N, M1
≥45 y  
I T1, N0, M0
II T2, N0, M0
III T3, N0, M0; T1–3, N1a, M0
IVA T4a, N0–1a, M0; T1–4a, N1b, M0
IVB T4b, any N, M0
IVC Any T, any N, M1
Medullary Thyroid Cancer
Stage TNM
I T1, N0, M0
II T2–3, N0, M0
III T1–3, N1a, M0
IVA T4a, N0–1a, M0; T1–4a, N1b, M0
IVB T4b, any N, M0
IVC Any T, any N, M1
Anaplastic Cancer
Stage TNM
IVA T4a, Any N, M0
IVB T4b, Any N, M0
IVC Any T, Any M, M1
  • 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 prevertebral fascia, or encasing carotid artery or mediastinal vessels; or extrathyroidal anaplastic cancer
  • Regional lymph nodes (N)—include central, lateral cervical, and upper 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
Standard Workup:   Ref: Schwartz's Principles of Surgery 9th Edition Ch 38

a = except in patients with a history of external radiation exposure or a family history of thyroid cancer; FNAB = fine-needle aspiration biopsy; RAI = radioactive iodine
  • Treatment:
    Thyroid nodule: Surgical approach.
  • Post Operative:
  1. For well differentiated carcinoma, exogenous thyroid hormone to suppress TSH level can decrease the recurrence rate of radiation induced thyroid cancer.
  2. Post op ablative dose of I 131(30 mCi) is given in older patients (age> 45), Multiple lesions, locally invasive tumours, size > 2.5 cm and patients with local or distant mets.
  • Medullary Carcinoma Thyroid.
    Treatment is total thyroidectomy with central node dissection.
  1. Treatment: The surgical approach to sporadic medullary carcinoma involves at least total thyroidectomy with or without central lymph node dissection. Total thyroidectomy allows complete removal of the gland and a search for multicentricity.
  2. In sporadic MCT, the lesion is generally contained within one lobe, whereas in MEN 2, the malignancy involves the upper halves of both lobes. Dissection of the central lymph node compartment allows appropriate staging of this process. Any palpable lymph nodes in lateral areas require a modified radical neck dissection.
  3. A successful operation with a good prognosis is predicted for patients with smaller masses and in whom calcitonin levels are undetectable after surgery. 
  • Anaplastic Thyroid Cancer:
  1. It has poorer prognosis.
  2. It tumour is unresectable larger cutting needle biopsy is done to confirm the diagnosis. Radiotherapy alone is not useful so combination of RT (5760 rads) and Doxorubicin (as radiosensitizer) is used.   
Malignant Lymphomas:
< 5% of primary thyroid neoplasms
  1. Lymphomas usually appear as rapidly enlarging masses and local symptoms are common. Many patients note pain, hoarseness, dysphagia, and dyspnea or stridor.
  2. The mean age at occurrence is 62 years.
  3. Two to three times more common in women than in men.
  4. The co-occurrence of pathologic lymphocytic thyroiditis has ranged from 30 to 87%.
  5. The clinical appearance must be carefully considered in accepting a diagnosis by fine needle aspiration of thyroiditis only or thyroiditis with lymphoma. An excisional or large needle biopsy may be necessary to make the correct diagnosis.
  6. The majority of thyroid lymphomas are diffuse, large-cell lymphomas (formerly classified as diffuse histiocytic or reticulum cell lymphomas), diffuse mixed small and large cell lymphomas (formerly called diffuse mixed lymphocytic-histiocytic), or diffuse small cleaved-cell lymphomas (formerly classified as diffuse poorly differentiated lymphocytic).
Metastatic Carcinomas to the Thyroid
Melanomas, breast tumors, pulmonary tumors, gastric, pancreatic, and intestinal carcinomas, renal carcinomas, lymphomas, carcinomas of the cervix, and tumors of the head and neck may metastasize to the thyroid.
Thyroid Surgery- Important Aspects
Preoperative Preparation in a thyrotoxic patient with drugs-
  1. Carbimazole-
    Drug of choice for preparation 30-40 mg per day.
    When patient becomes euthyroid (8-12 weeks), then 5mg 8 hrly.
    Last dose to be given on evening before surgery.
  2. Beta Blockers-
    Alternative to Carbimazole if very rapid control in a week or two is required.
    Inhibits peripheral conversion of T4 to T3.
    Propranolol 40 mg TDS or Nadolol 160 mg OD .
    It is continued for 7 days postoperatively as it does not interfere with hormone synthesis  and hormones level remain raised even upto 7 days after surgery.
  3. Iodine-
    Can be given with both carbimazole and beta blockers for 10 days before operation.
    It gives an additional safety measure in case morning dose of beta blocker is missed on the morning of surgery.
  • Perop Precautions-
  1. Ligate superior thyroid artery close to the thyroid gland to prevent injury to external laryngeal nerve
  2. Ligate Inferior thyroid artery as far as possible from the thyroid gland to prevent injury to recurrent laryngeal nerve.
  • Complications of Thyroid Surgery-
  1. Hemorrhage, wound infection, Keloid, Stitch granuloma
  2. Respiratory obstruction- Due to hematoma beneath the skin which should be evacuated early in order to prevent laryngeal compression. Open the skin sutures as early as you anticipate. Most common cause of hemorrhage is slipping off a ligature From Superior Thyroid Artery
  3. Recurrent laryngeal nerve paralysis-
    1. If Unilateral - Hoarseness of voice and
    2. Bilateral - Respiratory distress.
  4. Injury to External laryngeal nerve ( Superior Laryngeal nerve) leads to loss of pitch of voice.
  5. Postoperative thyroid insufficiency- 20-45%
  6. Permanent parathyroid insufficiency in less than 0.5%.
    1. Serum calcium to be done after 4-6 weeks.
    2. Earliest sign of Hypocalcemia is CIRCUMORAL TINGLING
    3. No Rx is required except for Oral Calcium and Vitamin D supplements
    4. I.V. Calcium Gluconate is required if Serum Calcium is <7mg%
Familial Cancer Syndromes Involving Nonmedullary Thyroid Cancer
Syndrome Gene Manifestation Thyroid Tumor
Cowden's syndrome PTEN Intestinal hamartomas, benign and malignant breast tumors FTC, rarely PTC and Hürthle cell tumors
FAP APC Colon polyps and cancer, duodenal neoplasms, desmoids PTC cribriform growth pattern
Werner's syndrome WRN Adult progeroid syndrome PTC, FTC, anaplastic cancer
Carney complex type 1 PRKAR1 Cutaneous and cardiac myxomas, breast and adrenal tumors PTC, FTC
McCune-Albright syndrome GNAS1 Polyostotic fibrous dysplasia, endocrine abnormalities, café-au-lait spots PTC clear cell

FAP = familial adenomatous polyposis; FTC = follicular thyroid cancer; PTC = papillary thyroid cancer. 
  1. Hypothyroidism Q
    1. Following total or near-total thyroidectomy patients must take thyroid hormone replacement for life or they will suffer severe symptoms and signs of myxedema (including tiredness, weakness, depression, psychosis, mental retardation, coma and even death).
    2. Following lobectomy for benign conditions many patients are treated with l-thyroxine therapy as well for two reasons – to keep thyroid function normal and also since a low TSH level is thought to prevent the recurrence of other benign thyroid masses.
  2. Thyroid Storm Q
    1. Thyroid storm occurs in patients with preexisting thyrotoxicosis who either have not been treated at all or have been treated incompletely. In the past, before adequate preparation with antithyroid drugs, surgical treatment was the most common precipitating factor.
    2. When thyroid storm is related to surgical treatment, the manifestations usually develop during the operative procedure or in the recovery room. The patient becomes markedly hyperthermic, with profuse sweating and tachycardia. Nausea, vomiting, and abdominal pain are common. Initial tremor and restlessness may progress to delirium with eventual coma.
    3. Treatment is directed toward inhibiting the production of thyroid hormone and antagonizing the effects of thyroid hormone.
    4. Sodium or potassium iodide or ipodate should be administered intravenously after an antithyroid drug, PTU (preferably) or methimazole has been started.
    5. Oxygen should be given, and glucose may be administered intravenously as therapy for the hypermetabolic state. Fluid and electrolytes must be maintained in view of the losses.
    6. Propranolol is given to antagonize b-adrenergic effects. Large doses of propranolol may be needed in toxic patients to control tachycardia, for thyroid storm has been reported to occur postoperatively in patients receiving 40 mg propranolol every 6 hours preoperatively.
    7. In severe cases, cortisol is administered to eliminate the possibility of a relative adrenal cortical insufficiency state and to suppress T4 to T3 conversion. 
Treatment of Thyroid Storm
Treatment Dose or Description
Propranolol 60-80 mg q6h PO, or 1-3 mg IV, slowly, q4h
Hydrocortisone 100-500 mg IV q12h
Sodium iodide or I g in 1 L of saline q12h
Ipodate 0.5 g PO daily or 3.0 g PO every 2-3 days
Supportive measures Mild sedation, fluid replacement, oxygen, vitamins, cooling, and antibiotics, as needed
Propylthiouracil or 100-200 mg q4h PO
Abbreviation SSKI, saturated solution Of potassium iodide.
  1. Wound Infection
    An infection in the wound is not common and occurs less frequently than 1 percent. Treatment requires antibiotics for cellulitis and drainage for an infected seroma or hematoma
  2. Wound Hemorrhage
    Wound hemorrhage is a problem of the early postoperative period, usually within the first 12 hours.
    Hemorrhage in the neck is a significant problem since a small amount of blood that forms a hematoma deep to the strap muscles might be sufficient to obstruct the airway and result in respiratory death.
    The patients are rarely in shock. The initial manifestations are swelling of the neck and bulging of the wound; these conditions demand immediate attention.
    Treatment consists of opening the incision, evacuating the clot, and securing the bleeding vessel.
  3. Recurrent Laryngeal Nerve Injury
    1. Damage to the recurrent laryngeal nerve can be unilateral or bilateral and temporary or permanent.
    2. Injury occurs more commonly when thyroidectomy is being performed for malignant disease. Total thyroidectomy results in a greater incidence of recurrent laryngeal nerve injuries than does a lesser procedure.
    3. A unilateral recurrent laryngeal nerve injury produces a loss of abduction of the ipsilateral vocal cord, which assumes a median or paramedian position.
    4. This injury is usually suggested by a huskiness or hoarseness of the speaking voice, Q but with the passage of time the flaccidity is often replaced by spasticity. If the injury is related to trauma but the nerve is not divided, function should return usually within 3 to 6 months and invariably within 9 months.
    5. Bilateral recurrent nerve injury is much more serious than unilateral injury. Many patients require immediate tracheostomy.
    6. Asymptomatic paralysis of a vocal cord does not require correction. If the airway is adequate, no attempts to perform corrective procedures upon the paralyzed cord or cords are usually undertaken until 6 to 12 months have elapsed from the time of injury in order to permit spontaneous return of cord function.
    7. Injury to the external branch of the (also called high note nerve) superior laryngeal nerve results in a limitation of the force of projection of one's voice and impairs a singer's high tones.
    8. Most common nerve to get injured is Ext. Laryngeal nerve.
  4. Hypoparathyroidism
    1. Overt manifestations of hypocalcemia occur in a minority of patients after thyroidectomy.
    2. This syndrome is usually temporary and is related to dissection in the region of the parathyroid glands. To prevent, permanent hypoparathyroidism, it is probably necessary to leave only one gland in situ with an adequate blood supply or to autotransplant one parathyroid gland successfully.
    3. The clinical manifestations of hypoparathyroidism usually occur within the first few days after operation and almost invariably within the first week. The initial symptoms are circumoral numbness, tingling, and intense anxiety. Q
  5. Tracheomalacia
    1. Tracheomalacia, a softening of the tracheal rings due to pressure necrosis of the cartilaginous tracheal rings from a large goiter. 
Adrenal Carcinoma
Adrenocortical masses are common; autopsy studies show that approximately 5-15% of the general adult population may have adrenal incidentalomas.
Adrenal incidentalomas are biochemically and clinically asymptomatic adrenal masses found incidentally as a result of unrelated imaging such as abdominal CT or MRI scans. Only a small number of adrenal tumors are functional and an even smaller number (about 1%) are malignant.
  1. All nonfunctional adrenal tumors larger than or equal to 6 cm should be removed because of the significant potential cancer risk.
  2. Nonfunctional adrenal tumors (<3 cm) have a very low probability of being adrenal cancer; therefore, they can be removed safely.
  3. The management strategy for adrenal masses larger than 3-6 cm is disputed.
  4. These criteria do not apply to children, who generally have smaller ACs.
  5. Incidence rate of malignancy is small (<0.03%) in all adrenal incidentalomas that are 1.5-6 cm. However, this rate increases considerably with tumors larger than 6 cm (up to 15%).
Classifying adrenal tumors
Adrenal tumors are classified in several ways.
  1. Functional and nonfunctional,
    1. Older reports suggest that approximately 50-80% of ACs are functional, and patients mainly present with Cushing syndrome.
    2. More recent reports suggest that nonfunctional ACs may be more common than previously suggested.
    3. Virtually all feminizing adrenal tumors in men are malignant.
    4. Sporadic and syndromic variants.
The syndromic variants occur with a. Gardner, b. Beckwith-Wiedemann (associated with hemihypertrophy), and c. Li-Fraumeni syndromes. Q
  1. On the cellular origin of the neoplasm.
    1. Primary adrenocortical carcinomas
    2. Primary adrenal lymphomas
    3. Soft-tissue sarcomas of the adrenal
    4. Malignant pheochromocytomas
    5. Secondary metastatic adrenal tumors (common primaries are the breast, kidney, lung, ovary, melanoma, leukemia, lymphoma).
  1. Pathophysiology:
    1. The role of tumor suppressor gene mutations is suggested by their association with Li-Fraumeni syndrome, which is characterized by inactivating germline mutations of the TP53 gene (a vital tumor suppressor gene or antioncogene) on chromosome 17.
    2. This syndrome also is associated with a predisposition to other malignancies, including breast carcinoma, leukemias, osteosarcomas, and soft-tissue sarcomas.
    3. There is an association between AC and familial adenomatous polyposis, which also is due to a germline inactivating mutation of a tumor suppressor gene (in this case, the adenomatous polyposis coli gene, APC).
    4. Incidence:
      1. Race: AC has no specific racial predilection.
      2. Sex: The female-to-male ratio is 2.5-3:1. Male patients tend to be older and have a worse overall prognosis than female patients.
      3. Age: AC occurs in 2 major peaks:
        1. In the first decade of life and again in the fourth to fifth decades.
        2. Approximately 75% of the children with AC are younger than 5 years.
        3. Functional tumors also are more common in children, while nonfunctional tumors are more common in adults.
      4. History:
        Most patients with AC present with advanced disease that is characterized by multiple abdominal or extra-abdominal metastatic masses (stage IV disease)
      5. Nonfunctional variants
        These typically present with fever, weight loss, abdominal pain and tenderness, back pain, abdominal fullness, or symptoms related to metastases.
        In other cases, mass is found incidentally, during radiological imaging.
      6. Endocrine syndromes
        Approximately 30-40% of patients present with the typical features of Cushing syndrome, while 20-30% present with virilization syndromes.
        In children, however, virilization (in girls) or precocious puberty (in boys) is the most common endocrine presentation of a functional AC.
        Other modes of presentation include profound weakness, hypertension, and/or ileus from hypokalemia related to hyperaldosteronism and hypoglycemia.
      7. Physical:
        1. Patients may present with features of Cushing syndrome, including truncal obesity, striae, severe acne, malar flushing, supraclavicular and dorsocervical fat pads, Conn syndrome (hypertension with weakness and ileus resulting from hypokalemia), virilization in girls, or precocity and feminization (rarely) in boys.
        2. In nonfunctional tumors, the major finding is an abdominal mass, in a flank.
      8. Lab Studies:
        1. The best screening tests for Cushing syndrome are the standard 1-mg dexamethasone suppression  test and the 24-hour urinary cortisol excretion test.
        2. Screen for hyperaldosteronism by using simultaneous aldosterone and renin levels to compute aldosterone-to-renin ratios.
        3. Screen for virilization syndromes using serum adrenal androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate), serum testosterone, and 24-hour urinary 17 ketosteroids.
        4. Plasma estradiol and/or estrone tests can help screen for feminization syndromes.
        5. The evaluation of adrenal masses also must include screening for possible pheochromocytoma, including, at a minimum, a 24-hour urinary estimation of catecholamines (epinephrine, norepinephrine, dopamine) and metabolites (particularly metanephrines and normetanephrines).
      9. Imaging Studies:
        1. CT scans and MRI
          1. Adrenal CT scans and MRI are the imaging studies of choice.
          2. The typical case is characterized by a large unilateral adrenal mass with irregular edges.
          3. The presence of contiguous adenopathy serves as corroborating evidence.
        2. Ultrasonography
          1. This test has less sensitivity in detecting adrenal tumors
          2. It has particular utility, in the follow-up of previously detected incidentalomas.
        3. Other Tests:
          Because the histologic analysis of these masses may be unreliable, fine and/or core tissue needle aspiration biopsies (percutaneous route) generally are not recommended.
        4. Histological Findings:
          Macroscopic features suggesting malignancy include a weight > 500 g, presence of areas of calcification or necrosis, and a grossly lobulated appearance.
        5. Distinction between adrenocortical and adrenomedullary tumors
          These have distinctive histologic appearances and immunohistochemical staining patterns. While adrenomedullary tumors stain positive for neuroendocrine markers (eg, synaptophysin, neuron-specific enolase, chromogranin A), adrenocortical cells stain positive for D11. ACs virtually always are unilateral.
          Staging: Staging for adrenal carcinoma according to Sullivan and colleagues
        6. Tumor criteria
          1. TI - Tumor diameter smaller than or equal to 5 cm with no local invasion
          2. T2 - Tumor diameter larger than 5 cm with no local invasion
          3. TI - Tumor of any size with local extension but not involving adjacent organs
          4. T4 - Tumor of any size with local invasion of adjacent organs
        7. Lymph node criteria
          1. NO - No regional lymph node involvement     
          2. NI - Positive regional nodes
        8. Metastasis criteria
          1. MO - No distant metastasis                
          2. MI - Distant metastasis
        9. Stages
          1. Stage 1 - TI, NO, MO                            
          2. Stage 2 - T2, NO, MO
          3. Stage 3 - TI or T2, NI, MO                  
          4. Stage 4 - Any T, any N + M1 or T3, NI or T4
      10. Treatment: Medical Care:
        1. Mitotane
          1. It is a relatively specific to adrenocortical cytotoxin.
          2. At best, only 20-25% of patients respond to mitotane. Therapy may be required for at least 3 months before deciding the response of mitotane
          3. Mitotane apparently causes adrenal inhibition without cellular destruction.
            Suramin: Although a few reports suggest the potential utility of suramin as an additional chemotherapeutic agent in the treatment of AC, this drug is not recommended for AC.
        2. Gossypol
          1. Gossypol also has been tried for metastatic adrenal cancer
          2. It was originally developed as a spermatotoxin and was derived from cottonseed oil. It has been used widely in China as a male contraceptive with few adverse effects. While the exact mechanism for its action is unclear, it is known to cause selective mitochondrial destruction by the uncoupling of oxidative phosphorylation.
        3. Cisplatin-based chemotherapy
          1. In cases where mitotane fails, chemotherapeutic regimens containing cisplatin alone or in combination often are used.
          2. Cyclophosphamide, Adriamycin, and cisplatin (CAP), 5-fluoro uracil, Adriamycin, and cisplatin (FAP), and cisplatin with VP-16 have been tried.
  • Surgical Care:
  1. When feasible, total resection remains the management modality of choice for the definitive management of AC. It also remains the only potentially curative therapeutic modality.

Hyperparathyroidism is defined as elevated serum PTH due to increased secretion. It is of two types.
  1. Primary     
  2. Secondary with a rare third type               
  3. Tertiary
Primary hyperparathyroidism
Primary hyperparathyroidism is due to intrinsic abnormality of one or more parathyroid glands:
Single Adenoma 83%
Multiple Adenomas 6%
Hyperplasia 1 %
Carcinoma 1 %
[% according to CSDT, may vary in diff. books, but general order is same]
Adenomas and hyperplasia of the parathyroid usually occur sporadically, but in few cases, they are part of familial syndromes
Familial syndromes associated with Primary Hyperparathyroidism
MEN type 1- Wermer's syndrome
MEN type 2a - Sipple syndrome  
Familial hypocalciuric hypercalcemia  
Secondary Hyperparathyroidism
Secondary hyperparathyroidism is increased secretion of PTH by the parathyroids in response to a lowered serum ionized calcium level

- Chronic renal failure (most common cause)
- Malabsorption syndrome
- Vitamin D deficiency
- Medullary carcinoma of thyroid
Tertiary Hyperparathyroidism
Tertiary hyperparathyroidism follows long standing secondary HPT when the chronically stimulated parathyroid glands act independently of the serum calcium concentration. Autonomous hypersecretion of PTH may persist despite correction of the underlying condition.
Treatment of primary hyperparathyroidism
  • Initial correction of hypercalcemia (Rapid IV NaCl with Furosemide)
  • Neck exploration is done and t/t done accordingly:                                                            
  • A single parathyroid adenoma (80%) Resection                                                             
  • Two adenomas (5%) Resection                                                             
  • Hyperplasia of all four glands (15% ) Resection of 31/2 glands or All four glands  can  be removed autotransplantation of a parathyroid gland in the foream or sternocleidomastoid muscle.

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