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THYROID - Coggle Diagram
THYROID
- Thyroglossal Duct Cyst and Sinus
- Most commonly encountered congenital cervical anomalies
- Pathology (Persistence of the thyroglossal duct lumen)
- Location (Anywhere along migratory path, 80% near hyoid bone)
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- Infection (Occasionally by oral bacteria)
- Thyroglossal Duct Sinuses (Result from cyst infection/drainage)
- Histology (Pseudostratified ciliated columnar and squamous epithelium)
- Heterotopic Thyroid Tissue (Present in 20% of cases)
- Diagnosis (Midline neck mass moving upward with tongue protrusion)
- Treatment (Sistrunk operation: en bloc cystectomy and excision of central hyoid bone)
- Cancer in Cysts (Approximately 1%)
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- Rare types (Squamous, Hürthle cell, anaplastic)
- MTCs (Not found in cysts)
- Total thyroidectomy (Role debated)
- Thyroid Hormone Synthesis, Secretion, and Transport
- Iodide Trapping (Via Sodium/Iodine (Na+/I–) Symporter)
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- Oxidation and Iodination (Catalyzed by Thyroid Peroxidase (TPO); Forms Monoiodotyrosines (MIT) and Diiodotyrosines (DIT))
- Iodine Efflux (Mediated by Pendrin)
- Coupling (Forms T4 (tetra-iodothyronine) and T3 (triiodothyronine) / Reverse T3 (rT3))
- T4 (Produced entirely by the thyroid gland)
- T3 (20% produced by the thyroid; peripheral deiodination of T4)
- rT3 (Metabolically inactive compound)
- Transport (Bound to carrier proteins: T4-binding globulin, prealbumin, albumin)
- Free Hormones (Physiologically active component)
- T3 Potency (Three to four times more active than T4)
Historical Background
- Goiters (Enlargement of the thyroid)
- Recognition since 2700 b.c.
- Hieronymus Fabricius ab Aquapendente (Recognized goiters arose from the thyroid gland)
- Term Thyroid Gland (Greek thyreoeides, shield-shaped)
- Attributed to Thomas Wharton in Adenographia (1656)
- Classified as a ductless gland (Albrecht von Haller, 1776)
- Early Suggested Functions (Lubrication of the larynx, blood reservoir, beautifying women’s necks)
- Early Treatment for Goiters (Burnt seaweed)
- First Accounts of Thyroid Surgery (Roger Frugardi, 1170)
- Hazardous surgery (Mortality rates >40%)
- Notable Thyroid Surgeons (Emil Theodor Kocher, C.A. Theodor Billroth)
- Post-thyroidectomy problems (Myxedema and cretinous features)
- Myxedema Treatment (George Murray, Edward Fox, 1891)
- Nobel Prize for Medicine (Kocher, 1909)
- Preoperative Vocal Cord Assessment
- Kocher Transverse Collar Incision
- Strap Muscles (Separation/Division)
- Vessel Management (Middle thyroid veins, Superior pole vessels)
- RLN Identification (Strongly recommended visual identification)
- Parathyroid Glands Management (Preservation, Autotransplantation)
- Subtotal Thyroidectomy (Leaving a 4- to 7-g remnant)
- Nerve Monitoring (Intraoperative RLN and external laryngeal nerve monitoring)
- Minimally Invasive Approaches (Mini-incision, Totally endoscopic, Transoral robotic-assisted thyroidectomy)
- Surgical Removal of Intrathoracic Goiter (Median sternotomy occasionally needed)
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- Associated Syndromes (Pendred’s, Turner’s)
- Causes (Primary, Secondary, Tertiary)
- Severe Hypothyroidism (Myxedema)
- Laboratory Findings (Low T4/T3; Raised TSH in primary failure; Low TSH in secondary)
- Treatment (T4 is the treatment of choice, Levothyroxine)
- Subclinical Hypothyroidism
- Myxedema Coma (Emergency IV T4 treatment)
- Fetal Brain Development and Skeletal Maturation
- Metabolic Rate (Increased oxygen consumption, basal metabolic rate, heat production)
- Cardiovascular Effects (Positive inotropic and chronotropic effects, increased Ca2+ ATPase, increased β-adrenergic receptors)
- Respiratory Function (Maintaining normal hypoxic and hypercapnic drive)
- GI Motility (Increased, leading to diarrhea in hyperthyroidism, constipation in hypothyroidism)
- Bone and Protein Turnover (Increased)
- Glucose/Lipid Metabolism (Increased glycogenolysis, hepatic gluconeogenesis, intestinal glucose absorption, cholesterol synthesis and degradation)
- Tests of Thyroid Function
- Serum Thyroid-Stimulating Hormone (TSH)
- Ultrasensitive TSH Assay (Most sensitive and specific test)
- Total T4 and T3 (Measure free and bound components)
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- Refetoff’s Syndrome (End-organ resistance to T4)
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- Thyrotropin-Releasing Hormone (TRH) Test
- Anti-Tg, Anti-microsomal/Anti-TPO, Thyroid-Stimulating Immunoglobulin (TSI)
- Indicate Autoimmune Thyroiditis
- Use in Monitoring Differentiated Thyroid Cancer Recurrence
- Anti-Tg Antibodies Interference
- Serum Calcitonin (Sensitive Marker of MTC)
- Papillary Carcinoma (PTC)
- Most common malignancy (80%)
- Pathology (Papillary projections, Follicular Variant, Orphan Annie nuclei, Psammoma bodies)
- Follicular Variant of Papillary Thyroid Carcinoma (FVPTC)
- Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP)
- Aggressive Variants (Tall cell, insular, columnar)
- Minimal or Occult/Microcarcinoma (≤1 cm)
- Prognostic Indicators (AGES, MACIS, AMES, DeGroot, TNM classifications)
- Surgical Treatment (Total or Near-Total Thyroidectomy, Lobectomy for low-risk/microcarcinomas, Active surveillance)
- Neck Dissection (Therapeutic Central Compartment (level VI), Prophylactic CND debated, Modified radical/functional neck dissection for lateral metastases)
- Follicular Carcinoma (FC)
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- Hyperfunctioning FC (Rare, cause thyrotoxicosis)
- Diagnosis (Requires identifying Capsular and Vascular Invasion)
- Molecular Markers (Afirma GEC, ThyroSeqV2, MicroRNAs)
- Types (Minimally invasive, Widely invasive)
- Surgical Treatment (Lobectomy for FNAB lesions, Completion TT for frankly invasive/angioinvasion)
- Hürthle Cell Carcinoma (HCC)
- Subtype of Follicular Thyroid Cancer
- Characteristics (Multifocal, usually do not take up RAI, higher mortality)
- Management (Total thyroidectomy if invasive, Routine central neck node removal)
- Medullary Carcinoma (MTC)
- Arises from C cells/Parafollicular cells
- Inherited Syndromes (Familial MTC, MEN2A, MEN2B)
- Secretion (Calcitonin, CEA, other peptides)
- Pathology (Amyloid presence is diagnostic)
- Diagnosis (Screening for RET point mutations, Pheochromocytoma, HPT)
- Treatment (Total Thyroidectomy, Bilateral prophylactic Central Neck Node Dissection)
- Targeted Therapies (Vandetanib, Cabozantinib)
- Prophylactic Total Thyroidectomy (For RET mutation carriers)
- Anaplastic Carcinoma (AC)
- Most aggressive malignancy
- Presentation (Rapidly enlarging, fixed, painful neck mass)
- Pathology (Spindle cell, squamoid, pleomorphic giant cell patterns)
- Treatment (En bloc resection if possible, Adjuvant radiation/Chemotherapy)
- Often develops in Chronic Lymphocytic Thyroiditis (Hashimoto’s)
- Treatment (Chemotherapy, Radiotherapy)
- Metastatic Carcinoma (From kidney, breast, lung, melanoma)
- Adaptation to Low Iodide (Preferentially synthesizes T3)
- Adaptation to Iodine Excess (Inhibits synthesis/secretion)
- Wolff-Chaikoff Effect (Suppression due to large doses of iodide)
- Hormone Stimulators (Epinephrine, human chorionic gonadotropin - hCG)
- Hormone Inhibitors (Glucocorticoids)
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- Complications of Thyroid Surgery
- RLN Injury (Severance, ligation, traction)
- External Laryngeal Nerve Injury
- Cervical Sympathetic Trunk Injury (Horner’s syndrome)
- Hypocalcemia/Hypoparathyroidism
- Postoperative Hematomas/Bleeding
- Bilateral Vocal Cord Dysfunction (Requires Tracheostomy)
- Failure of median thyroid anlage to descend normally
- May be the only thyroid tissue present
- Intervention necessary for Obstructive Symptoms (Choking, dysphagia, airway obstruction, hemorrhage)
- Hypothyroidism Development
- Medical Treatment (Exogenous thyroid hormone to suppress TSH, Radioactive Iodine (RAI) ablation)
- Differential Diagnosis (Increased Hormone Synthesis vs. Release of Preformed Hormone)
- Diffuse Toxic Goiter (Graves’ Disease)
- Most Common Cause of Hyperthyroidism (60% to 80%)
- Autoimmune Disease (Familial predisposition)
- Extrathyroidal Conditions (Ophthalmopathy, dermopathy/pretibial myxedema, thyroid acropachy, gynecomastia)
- Etiology/Pathogenesis (Triggers: postpartum, iodine excess, lithium, infections; Genetic factors: HLA haplotypes, CTLA-4, CD40, PTPN22, CD25)
- Thyroid-Stimulating Immunoglobulins (TSIs)
- Clinical Features (Heat intolerance, weight loss, nervousness, palpitations, diarrhea, cardiovascular complications)
- Diagnostic Tests (Suppressed TSH, elevated RAI uptake, Elevated TSH-R/TSAb)
- Treatment Modalities (Antithyroid drugs, RAI ablation, Thyroidectomy)
- Antithyroid Drugs (PTU, Methimazole)
- Beta-Blockade (Propranolol, Calcium channel blockers)
- Radioactive Iodine Therapy (131I) (Mainstay in N. America)
- Surgical Treatment (Total or Near-Total Thyroidectomy preferred)
- Toxic Multinodular Goiter
- Often insidious presentation
- Jod-Basedow Hyperthyroidism (Precipitation by iodide-containing drugs)
- Absence of Extrathyroidal Manifestations
- Treatment (RAI or Near-total/Total thyroidectomy)
- Single hyperfunctioning nodule
- Somatic Mutations (TSH-R gene, gsp gene)
- Diagnosis (Hot nodule with suppression of the rest of the thyroid gland)
- Treatment (Antithyroid drugs, RAI, Surgery: Lobectomy and isthmusectomy, Percutaneous Ethanol Injection (PEI))
- Condition of severe hyperthyroidism with systemic dysfunction
- Treatment (ICU setting, β-Blockers, PTU, Iodide solution/sodium ipodate, Corticosteroids)
- Goiter (Any enlargement of the thyroid gland)
- Classification (Diffuse, Uninodular, Multinodular)
- Etiology (TSH stimulation, Familial, Endemic/Iodine deficiency, Dietary goitrogens)
- Clinical Features (Pressure sensation, Compressive symptoms: dyspnea/dysphagia, Pemberton’s sign)
- Diagnostic Tests (FNAB for dominant nodules, CT scans for retrosternal extension)
- Treatment (Iodine administration for endemic goiters, Thyroid hormone suppression, Surgical resection: Near-total/Total thyroidectomy)
- Postoperative Management of Differentiated Thyroid Cancer
- Radioiodine Therapy (RAI)
- Risk Stratification (Low-risk, Intermediate-risk, High-risk)
- Remnant Ablation Preparation (Thyroid hormone withdrawal or Recombinant TSH/rTSH stimulation)
- Complications (Sialadenitis, Pulmonary fibrosis, Increased risk of second cancers)
- Thyroid Hormone (T4) (Replacement and TSH Suppression)
- Thyroglobulin Measurement (Tg and anti-Tg antibody levels)
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- Additional Treatment Modalities
- Radiotherapy (External-beam, Stereotactic, Intensity-modulated)
- Thermal Ablation (Radiofrequency ablation, Cryoablation)
- Chemotherapy (Doxorubicin, Paclitaxel)
- Novel Therapies (Molecularly Targeted Therapies: Sorafenib, Lenvatinib)
- Superior Thyroid Arteries (From ipsilateral external carotid arteries)
- Inferior Thyroid Arteries (From thyrocervical trunk/subclavian arteries)
- Thyroidea Ima Artery (From aorta or innominate, in 1%–4%)
- Venous Drainage (Superior, Middle, and Inferior thyroid veins)
- Superior and Middle veins (Drain into internal jugular veins)
- Inferior veins (Drain into brachiocephalic veins)
- Regional Lymph Nodes (Pretracheal, Paratracheal, Perithyroidal, Superior Mediastinal, Jugular Chain - Levels I-VII)
- Central Compartment (Level VI)
- Lateral Compartment (Levels I, II, III, IV, V, VII)
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- Control of Hormone Secretion (Hypothalamic-Pituitary-Thyroid Axis)
- Thyrotropin-Releasing Hormone (TRH)
- Thyroid-Stimulating Hormone (TSH/Thyrotropin)
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- Negative Feedback Loop (T4 and T3 inhibit TSH; T3 inhibits TRH)
- Simple Thyroid Cysts (Aspiration, Lobectomy if complex or persistent)
- Colloid Nodule (Observation)
- Levothyroxine Suppression (Controversial, TSH target 0.1–1.0 μU/mL)
- Surgical Intervention (Thyroidectomy indications)
- Molecular Genetics of Thyroid Tumorigenesis
- Oncogenes and Tumor Suppressor Genes (RET, MET, TRK1, TSH-R, Gsα (gsp), Ras, PAX8/PPARγ1, B-Raf (BRAF), CTNNB1 (β-catenin), TERT promoter, p53, p16, PTEN, microRNA)
- Germline Mutations (MEN2A, MEN2B, Familial MTC, Hirschsprung’s disease)
- RET/PTC Rearrangements (In PTCs, early events)
- MAPK Pathway (Signaling involves Ras, Raf, MEK, ERK/MAPK)
- BRAF V600E Mutation (Associated with aggressive features)
- Location (Central neck compartment, esophagus, trachea, anterior mediastinum)
- Observed adjacent to Aortic Arch, Aortopulmonary window, Upper Pericardium, Interventricular Septum
- “Tongues” of thyroid tissue (Seen off the inferior poles in large goiters)
- Persistence of the distal end of the thyroglossal duct
- Location (Projecting up from the isthmus)
- Enlarged and Palpable (In disorders causing thyroid hypertrophy: Graves’ disease, diffuse nodular goiter, lymphocytic thyroiditis)
- Recurrent Laryngeal Nerve (RLN)
- Left RLN Course (Crosses aortic arch, loops around ligamentum arteriosum)
- Right RLN Course (Crosses right subclavian artery)
- Nonrecurrent RLN (0.5%–1% right side, rare on left)
- Tubercle of Zuckerkandl (Landmark for identification)
- Vulnerability (Vicinity of the ligament of Berry)
- Innervation (All intrinsic muscles of the larynx except cricothyroid)
- Injury Consequences (Paralysis of ipsilateral vocal cord, airway obstruction/tracheostomy for bilateral injury)
- Superior Laryngeal Nerves (Arise from vagus nerves)
- Internal Branch (Sensory to supraglottic larynx)
- External Branch (Innervates cricothyroid muscle)
- Cernea Classification System
- Type 2a Variant (High risk of injury)
- Injury Consequences (Inability to tense vocal cord, difficulty hitting high notes, voice fatigue)
- Sympathetic Innervation (From superior and middle cervical sympathetic ganglia; Vasomotor in action)
- Parasympathetic Fibers (Derived from vagus nerve)
- Daily Iodine Requirement (0.1 mg)
- Iodide Absorption (Stomach and jejunum)
- Active Transport into Follicular Cells (ATP–dependent process)
- Iodine-123 (123I) (Used for imaging lingual thyroids or goiters)
- Iodine-131 (131I) (Used to screen and treat differentiated thyroid cancers for metastatic disease)
- Cold Lesions (Trap less radioactivity, higher malignancy risk ~20%)
- Hot/Warm Lesions (Increased activity, <5% malignancy risk)
- Technetium Tc 99m Pertechnetate (99mTc) (Useful for nodal metastases)
- FDG PET combined with CT (Screening for metastases in thyroid cancer)
- Evaluation of thyroid nodules (Solid vs. cystic, size, multicentricity)
- Malignancy Characteristics (Echotexture, shape, borders, calcifications, vascularity)
- Assessing Cervical Lymphadenopathy and Guiding FNAB
- Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) Scan
- Use for Large, Fixed, or Substernal Goiters
- Noncontrast CT (Obtained if subsequent RAI therapy likely)
- Acute (Suppurative) Thyroiditis
- Etiology (Infectious agents, Pyriform sinus fistulae, Thyroglossal duct cysts)
- Diagnosis (FNAB, CT scans, Direct endoscopy)
- Treatment (Parenteral antibiotics, Drainage, Thyroidectomy)
- Subacute Thyroiditis (Painful or Painless forms)
- Painful Thyroiditis (Viral origin, HLA-B35 association)
- Four Stages (Hyperthyroid, Euthyroid, Hypothyroidism, Resolution)
- Laboratory (Decreased TSH, Decreased RAIU)
- Treatment (Symptomatic: NSAIDs, Steroids)
- Painless Thyroiditis (Autoimmune origin, Postpartum period)
- Normal Erythrocyte Sedimentation Rate (ESR)
- Lymphocytic (Hashimoto’s) Thyroiditis/Struma Lymphomatosa
- Most Common Inflammatory Disorder
- Etiology/Pathogenesis (Autoimmune process, CD4+ T lymphocytes, autoantibodies against Tg/TPO/TSH-R)
- Pathology (Hürthle/Askanazy cells)
- Clinical Presentation (Painless anterior neck mass, Hypothyroidism, Hashitoxicosis)
- Complication (Thyroid Lymphoma)
- Riedel’s Thyroiditis/Invasive Fibrous Thyroiditis
- Rare variant (Replacement by fibrous tissue, IgG4-related systemic disease)
- Diagnosis (Open thyroid biopsy required, FNAB inadequate)
- Treatment (Surgery: wedge excision of the thyroid isthmus for decompression, Hormones, Corticosteroids/Tamoxifen)
- Symptoms (Pain, hoarseness)
- Risk Factors for Malignancy (Ionizing radiation exposure, Family history)
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- Chernobyl Disaster (131I release)
- Family History (MTC, Nonmedullary thyroid cancers associated with syndromes: Cowden’s, Werner’s, FAP, DICER 1)
- Familial Nonmedullary Thyroid Cancer (FNMTC)
- Diagnostic Investigations
- Fine-Needle Aspiration Biopsy (FNAB)
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- Bethesda Criteria for Thyroid FNA (Six groups)
- Nondiagnostic or Unsatisfactory
- Benign (Follicular nodule, Thyroiditis)
- Atypia of Unknown Significance (AUS) or Follicular Lesion of Unknown Significance (FLUS)
- Follicular Neoplasm (FN) or Suspicious for FN
- Suspicious for Malignancy
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- Serum Calcitonin levels (For MTC or FH of MTC/MEN2)
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- 24-hour urine collection (VMA, metanephrine, catecholamine levels for pheochromocytoma)
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- Thyroid Scanning (123I or 99mTc)
- Paired Lateral Anlages (Origin from the fourth branchial pouch)
- Neuroectodermal in Origin (Ultimobranchial bodies)
- C cells (Parafollicular cells)
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- Location (Superoposterior region of the gland)
- Parathyroid Glands (Anatomy)
- Superior glands (Usually dorsal to the RLN)
- Inferior glands (Usually ventral to the RLN)
- Malignancy Suspicion (Hard, gritty, fixed nodule)
- Cervical Lymph Node Assessment
- Central and Lateral Neck Dissection for Nodal Metastases
- Central Compartment (Therapeutic CND, Prophylactic CND)
- Modified Radical (Functional) Neck Dissection
- Strap Muscles (Sternohyoid, sternothyroid, superior belly of the omohyoid)
- Innervation (Ansa cervicalis/ansa hypoglossi)
- C cells (Parafollicular cells)
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- Origin (Outpouching of the primitive foregut, around the third week of gestation)
- Foramen Cecum (Base of the tongue origin)
- Medial Thyroid Anlage (Endoderm cells)
- Thyroglossal Duct (Epithelial-lined tube connecting anlage to foramen cecum)
- Thyroid Follicular Cells (Arise from epithelial cells of the anlage)
- Thyroid Follicles Apparent (by 8 weeks)
- Colloid Formation Begins (by the 11th week of gestation)
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- Lateral Aberrant Thyroid (Almost always metastatic thyroid cancer in lymph nodes)
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- Characteristics (Brown color, firm consistency, weighs ~20 g)
- Location (Posterior to the strap muscles)
- Thyroid Lobes (Adjacent to the thyroid cartilage)
- Isthmus (Midline, inferior to the cricoid cartilage)
- Fascia (Loosely connecting fascia from deep cervical fascia)
- True Capsule (Thin, densely adherent fibrous layer)
- Berry’s Ligament (Posterior suspensory ligament, near cricoid cartilage and upper tracheal rings)
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- Lobules (Contain 20 to 40 follicles)
- Follicles (Lined by cuboidal epithelial cells)
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