---

Thyroid Diseases: Complete Clinical Reference

---

1. Clinical Classification of Thyroid Diseases

Nikolaev Classification (O.V. Nikolaev, 1949 - Soviet/Russian standard)

• Euthyroid conditions (normal function)
• Hypothyroid conditions (reduced function)
• Hyperthyroid/thyrotoxic conditions (excess function)

• Diffuse goiter
• Nodular goiter
• Diffuse-nodular (mixed) goiter

WHO Classification (2001, updated)

• Simple and unspecified goiter
• Thyrotoxicosis (hyperthyroidism)
• Hypothyroidism
• Thyroiditis
• Other thyroid disorders (nodules, cancer, congenital anomalies)

Bailey & Love Surgical Classification of Thyroid Swellings:

---

2. Congenital Anomalies of the Thyroid Gland

• Complete absence of thyroid tissue
• Leads to severe congenital hypothyroidism (cretinism if untreated)
• Accounts for ~30-35% of congenital hypothyroidism

• Inadequately developed but present gland
• Causes congenital hypothyroidism of variable severity

• Thyroid tissue located anywhere along the descent path
• Most common: lingual thyroid (at foramen cecum) - may be the only thyroid tissue
• Others: sublingual, mediastinal, intrathoracic
• Lingual thyroid presents as a mass at base of tongue; may cause dysphagia/dysphonia

• Persistence of the thyroglossal duct
• Most common congenital neck mass in children
• Presents as a midline cystic swelling that moves on swallowing AND on tongue protrusion
• Treatment: Sistrunk operation (excision of cyst + central portion of hyoid bone)

• Absence of one lobe (usually left)
• Often discovered incidentally; may be euthyroid

• Remnant of the thyroglossal duct as a superior thyroid lobe extension
• Present in ~50% of people; clinically relevant in goiter/hyperthyroidism

• Small nodules of ectopic thyroid alongside the normal gland

---

3. Concept of Endemic and Sporadic Goiter: Prevalence and Etiology

Definitions

Prevalence

• Approximately 200 million people worldwide have goiter
• Endemic areas: inland/mountainous regions far from the sea (Alps, Himalayas, Andes, Central Africa, parts of Central Asia)
• Sporadic: occurs at ~5% prevalence even in iodine-sufficient populations

Etiological Factors

• Iodine deficiency - primary cause; dietary iodine <50 mcg/day leads to inadequate thyroid hormone synthesis → compensatory TSH rise → gland enlargement
• Goitrogens in food: cassava (thiocyanate), millet, soya, brassicas, water pollutants (fluoride, calcium excess)
• Selenium deficiency (selenium is required for iodothyronine deiodinases)
• Genetic susceptibility modifying TSH receptor signaling

• Dyshormonogenesis: Inherited enzyme defects in thyroid hormone synthesis (organification defects, iodotyrosine dehalogenase deficiency, thyroglobulin synthesis defects)
• Goitrogen exposure (drugs: lithium, amiodarone, aminoglutethimide; foods as above)
• Autoimmune stimulation (non-toxic phase of Hashimoto's)
• Physiological: puberty, pregnancy (hCG has weak TSH-like activity; increased renal iodine clearance)
• Microadenoma of the pituitary secreting excess TSH (rare)

---

4. Pathogenesis and Classification of Thyroid Enlargement Grades

Pathogenesis

1. Reduced T3/T4 (from iodine deficiency, dyshormonogenesis, or increased peripheral demand)
2. Compensatory TSH rise from the anterior pituitary
3. TSH-driven hypertrophy and hyperplasia of follicular cells
4. Diffuse hyperplastic goiter - early, potentially reversible stage
5. Involution and re-stimulation cycles → heterogeneous nodularity
6. Multinodular goiter - irreversible stage; some nodules become autonomous

Grades of Thyroid Enlargement

---

5. Clinical Presentation of Endemic and Sporadic Goiter

• Neck swelling (cosmetic concern)
• Dysphagia - compression of esophagus by large/retrosternal goiter
• Dyspnea and stridor - tracheal compression (especially retrosternal extension)
• Hoarseness - rarely from RLN compression (raises concern for malignancy)
• Superior vena cava syndrome - with large retrosternal goiter (rare)
• Pemberton's sign: facial plethora, JVP elevation when arms raised above head (retrosternal goiter)

• Swelling moves on swallowing (key diagnostic feature)
• May be diffuse (hyperplastic) or nodular
• Soft/firm consistency; cystic areas from hemorrhage into nodules
• Tracheal deviation may be visible/palpable

• May have no visible neck mass
• Presents with obstructive symptoms
• Diagnosed by CT/MRI

---

6. Diagnostic Methods for Endemic and Sporadic Goiter

• Area of origin (endemic vs. sporadic), duration, rate of growth
• Family history, drug history (lithium, amiodarone)
• Symptoms of compression, hypo/hyperthyroidism

• TSH (first-line): suppressed in hyperthyroidism, elevated in hypothyroidism; normal in simple goiter
• Free T3, Free T4: to assess functional status
• Anti-TPO, anti-Tg antibodies: elevated in autoimmune thyroiditis; may be mildly elevated in endemic goiter
• Serum thyroglobulin: marker for iodine deficiency; elevated in goiter
• Urine iodine concentration (UIC): population-level and individual assessment; <100 mcg/L indicates deficiency
• Calcitonin: if medullary thyroid cancer suspected

• Ultrasound (US): first-line imaging; defines goiter size, echotexture, nodules, vascularity; identifies features suspicious for malignancy (microcalcifications, irregular margins, hypoechogenicity, tall-wide ratio >1)
• CT/MRI: evaluation of retrosternal extension, tracheal compression, mediastinal involvement
• Chest X-ray: tracheal deviation, retrosternal mass, calcifications

• 99mTc scintigraphy or 123I uptake scan: distinguishes hot (functioning) vs. cold (non-functioning) nodules; cold nodules carry higher malignancy risk (~5-15%)
• Radioiodine uptake (RAIU): elevated in iodine deficiency, normal or low in thyroiditis

• Indicated for nodules >1 cm with suspicious features on US, or any nodule growing
• Bethesda reporting system:
  • Thy1: Non-diagnostic
  • Thy2: Non-neoplastic (benign)
  • Thy3: Follicular (indeterminate)
  • Thy4: Suspicious for malignancy
  • Thy5: Malignant

---

7. Conservative Treatment and Surgical Management of Endemic/Sporadic Goiter

Conservative Treatment

• Iodized salt programs (most effective public health measure)
• Potassium iodide or iodate supplementation
• In early hyperplastic stages, iodine can achieve partial regression

• Dose: 0.15-0.2 mg/day to suppress TSH
• Early hyperplastic goiters may regress over several months
• Nodular goiters: limited effectiveness; >50% of benign nodules regress spontaneously over 10 years
• Risks: atrial fibrillation, osteoporosis (especially in postmenopausal women)
• Current evidence does not strongly support routine T4 suppression for nodular goiters

• Most patients with multinodular euthyroid goiter are asymptomatic and require monitoring only

Indications for Surgery

• Suspected or confirmed malignancy (FNA Thy4-5, suspicious US features)
• Pressure symptoms (dysphagia, stridor, dyspnea) not explained otherwise
• Retrosternal goiter causing compression
• Cosmetic deformity unacceptable to patient
• Progressive enlargement
• Toxic transformation (secondary thyrotoxicosis)
• Failure of conservative treatment

Types of Surgical Intervention

---

8. Concept of Toxic Goiter: Prevalence and Etiology

Definitions

Prevalence

• Graves' disease: most common cause of hyperthyroidism (~70-80% of cases); prevalence ~0.5% in the general population; F:M ratio ~7-10:1; peak age 20-50 years
• Toxic adenoma: ~5-10% of hyperthyroidism causes; toxic multinodular goiter ~15-20%
• Overall hyperthyroidism prevalence: ~1% in women, 0.1% in men

Etiological Factors

• Autoimmune: TSH receptor stimulating antibodies (TSH-RAb / TRAb / TSI) bind TSH receptor → continuous unregulated stimulation of thyroid follicular cells
• Genetic predisposition: HLA-DR3, HLA-B8 association; CTLA-4 gene polymorphisms; family clustering
• Environmental triggers: iodine excess, infections (Yersinia enterocolitica has TSH receptor-like antigen), stress, smoking (strong risk factor for ophthalmopathy), postpartum period, interferon-alpha therapy

• Somatic activating mutations in the TSH receptor gene (most common: codon 619, 623, 632) or Gs-alpha subunit → constitutive cAMP signaling → autonomous growth and function
• Not autoimmune; no TSH-RAb
• Surrounding normal thyroid is suppressed (visible on scan as "hot nodule" with absent uptake elsewhere)

---

9. Thyrotoxicosis: Pathogenesis, Classification by Severity and Stage, Treatment

Pathogenesis

• Metabolic: Increased oxygen consumption, heat production, BMR elevation; weight loss despite hyperphagia; gluconeogenesis and glycogenolysis
• Cardiovascular: Increased heart rate, cardiac output; decreased peripheral vascular resistance; atrial fibrillation (especially elderly)
• Neuromuscular: Tremor, hyperreflexia, proximal myopathy
• Bone: Accelerated remodeling → osteoporosis
• Hematopoietic: Mild anemia, elevated SHBG
• Adrenal: Increased cortisol clearance → relative adrenal insufficiency during crisis

Classification by Severity (Graves'/Thyrotoxicosis)

Treatment Methods

• Methimazole (carbimazole in Europe) - first-line for most patients; blocks thyroid peroxidase (TPO), inhibiting organification of iodide; carbimazole is converted to methimazole in vivo
• Propylthiouracil (PTU) - also inhibits peripheral T4→T3 conversion; preferred in pregnancy (1st trimester) and thyroid storm
• Side effects: rash, agranulocytosis (1:500, usually within 90 days - fever + pharyngitis → stop immediately, check WBC); hepatotoxicity (PTU > methimazole)
• Titration block-and-replace or dose titration regimens; usual duration 12-18 months
• Remission rate: ~45% for Graves'; recurrence common

• Propranolol, atenolol - symptomatic control of tachycardia, tremor, anxiety, heat intolerance
• Propranolol also inhibits peripheral T4→T3 conversion at high doses
• Used adjunctively; not curative

• Destroys thyroid tissue by beta radiation
• Advantages: non-surgical, definitive, outpatient
• Leads to hypothyroidism in majority → lifelong levothyroxine
• Contraindicated in pregnancy, breastfeeding, active ophthalmopathy (can worsen)

• See Topics 12-14

• PTU 200-250 mg q4h (blocks synthesis and conversion)
• Lugol's iodine 1 hour after PTU (blocks hormone release)
• IV glucocorticoids (hydrocortisone 100 mg q8h)
• Beta-blockade (propranolol IV)
• Supportive: cooling, fluids, treatment of precipitating cause

---

10. Clinical Presentation of Diffuse Toxic Goiter and Thyrotoxic Adenoma; Ocular Signs

Diffuse Toxic Goiter (Graves' Disease)

• Weight loss despite increased appetite
• Heat intolerance, excessive sweating
• Fatigue, weakness (proximal myopathy)
• Diarrhea / frequent stools

• Palpitations, sinus tachycardia (HR often 90-130 at rest)
• Atrial fibrillation (especially in elderly)
• Wide pulse pressure
• High-output cardiac failure (severe/prolonged disease)

• Fine tremor of outstretched hands
• Hyperreflexia
• Anxiety, irritability, emotional lability, psychosis (rare)
• Insomnia

• Diffuse, smooth, soft/firm goiter; bilateral enlargement
• Bruit over gland (from increased vascularity) - pathognomonic of Graves'
• Thrill may be palpable

• Warm, moist, fine/silky skin
• Pretibial myxedema (Graves' dermopathy): non-pitting, waxy thickening of the skin over anterior shins - specific to Graves'
• Thyroid acropachy (clubbing + periosteal reaction - rare)
• Onycholysis

• Oligomenorrhea/amenorrhea in women
• Gynecomastia, decreased libido in men
• Impaired fertility

Thyrotoxic Adenoma (Plummer's Disease)

• Symptoms of hyperthyroidism as above, but typically milder onset
• Palpable solitary nodule (>2 cm) in one lobe
• No ophthalmopathy (no autoimmune component)
• No pretibial myxedema
• Surrounding thyroid tissue suppressed → no bruit
• Cardiovascular manifestations (AF) prominent in elderly patients

Ocular Signs of Hyperthyroidism

• Proptosis/exophthalmos (bilateral, though often asymmetric): caused by glycosaminoglycan deposition + lymphocyte infiltration of orbital fat and extraocular muscles (especially inferior and medial recti)
• Periorbital edema
• Chemosis (conjunctival edema)
• Corneal exposure → keratitis, ulceration
• Diplopia (from restrictive myopathy of extraocular muscles)
• Compressive optic neuropathy (severe: visual field defect, reduced acuity) - emergency

---

11. Conservative Treatment of Diffuse Toxic Goiter

Antithyroid Drugs (Thionamides) - Primary Medical Treatment

• Carbimazole (converted to methimazole): 10-40 mg/day initially in divided doses; maintenance 5-10 mg/day
• Methimazole (preferred globally): equivalent dosing
• Propylthiouracil (PTU): 100-200 mg q6-8h initially; used when methimazole not tolerated, in pregnancy (1st trimester), or thyroid storm

1. Dose titration: Start high, reduce as TSH/T4 normalize
2. Block-and-replace: Higher dose ATD + levothyroxine to prevent hypothyroidism (less dose adjustment needed)

• TFTs every 4-6 weeks initially
• FBC before starting and if fever/sore throat develops (agranulocytosis)
• LFTs if PTU used

• Beta-blockers (propranolol 40 mg TDS or atenolol 50 mg OD): rapid symptomatic control
• Iodine (Lugol's solution): pre-operatively to reduce vascularity; reduces hormone release acutely
• Potassium perchlorate: rarely used; blocks iodine uptake

---

12. Indications for Surgery and Types of Surgical Interventions for Diffuse Toxic Goiter

Indications for Surgery in Graves' Disease

• Large goiter (>75 g) causing compressive symptoms
• Failure or intolerance of ATDs (agranulocytosis, hepatotoxicity)
• Patient preference for definitive cure without RAI
• Active or severe Graves' ophthalmopathy (RAI may worsen; surgery preferred)
• Concurrent thyroid malignancy (suspected or proven)
• Pregnancy with poor ATD control or side effects (surgery in 2nd trimester)
• Young patients (avoid lifelong RAI follow-up)
• Planned pregnancy soon (RAI requires 6-12 month delay)
• Non-compliance with medication

Types of Operations

• Hemithyroidectomy (lobectomy) is the operation of choice
• Low rate of postoperative hypothyroidism (2-3%) vs. total thyroidectomy (20%)
• Euthyroid state returns within 2-3 days
• RAI is an alternative but may leave palpable nodule and has higher hypothyroidism rate

---

13. Indications and Contraindications for Surgical Treatment of Thyrotoxic Goiter; Surgical Techniques

Indications (as above, Topic 12, plus)

• Proven thyroid cancer in toxic goiter
• Severe compression (respiratory failure, dysphagia)
• Failure of all medical therapy

• Young patients, large goiters, ophthalmopathy, patient preference, planned pregnancy

Contraindications to Surgery

• Uncorrected thyrotoxicosis (risk of thyroid storm) - requires preoperative preparation
• Severely compromised cardiorespiratory function precluding general anesthesia

• Mild/moderate Graves' disease in older patients (RAI preferred)
• Previous thyroid surgery (increased complication risk)
• Active, uncontrolled systemic disease

Surgical Technique (Thyroidectomy)

1. Positioning: Supine with neck extended (sandbag under shoulders)
2. Incision: Kocher's collar incision (2 cm above clavicle, in skin crease)
3. Subplatysmal flaps raised superiorly and inferiorly
4. Midline division of strap muscles (sternohyoid and sternothyroid) if needed
5. Identification and preservation of parathyroid glands: superior (near junction of upper and middle third of posterior thyroid) and inferior (near lower pole)
6. Inferior thyroid artery ligated distal to parathyroid blood supply branches
7. Identification of the recurrent laryngeal nerve (RLN): traced from tracheoesophageal groove; most common locations for injury: posterior to inferior pole, at intersection with inferior thyroid artery, and at Berry's ligament
8. Berry's ligament division: RLN must be in direct vision; pre-emptive bipolar to small vessels within ligament; layer-by-layer dissection
9. Superior pole vessels divided close to gland
10. Tubercle of Zuckerkandl mobilized to expose RLN at its terminus
11. Delivery of gland and division of isthmus
12. Hemostasis, closure of strap muscles, subcutaneous and skin layers
13. Drain placement: most surgeons omit routine drains

• Electrode on endotracheal tube senses vocal cord signals; grounding on skin
• Negative predictive value ~100% for ruling out nerve injury
• Standard of care in many centers; does not replace visual identification

---

14. Preoperative Preparation and Postoperative Management

Preoperative Preparation

1. ATDs (carbimazole/methimazole or PTU) for 6-8 weeks until TFTs normalize (TSH recovers)
2. Beta-blockers (propranolol) for cardiovascular stability; continued perioperatively
3. Lugol's iodine (potassium iodide solution): given 10-14 days preoperatively - reduces thyroid vascularity by 30-40% and decreases intraoperative blood loss; 0.3 mL TID (Lugol's 5%); Wolff-Chaikoff effect blocks hormone release acutely
4. Cardiovascular optimization: Control AF, heart failure if present
5. Preoperative laryngoscopy: Baseline vocal cord assessment; detect any pre-existing RLN palsy
6. Calcium/PTH: Baseline levels
7. Informed consent: Risks of RLN injury, hypoparathyroidism, bleeding, hypothyroidism

Postoperative Management

• Monitor for bleeding - risk of airway compression from hematoma; keep suture removal kit at bedside; re-explore and evacuate hematoma if airway compromise
• Calcium monitoring: Check serum calcium at 6, 12, 24 hours; check PTH at 4-6 hours
• Hypocalcemia (most common complication, from parathyroid ischemia): tingling perioral/fingertips (Chvostek, Trousseau signs) → oral/IV calcium replacement
• RLN injury: Assess voice quality postoperatively; hoarseness warrants laryngoscopy

• Levothyroxine: Started immediately post-total thyroidectomy
• Calcium ± calcitriol: For temporary or permanent hypoparathyroidism
• Beta-blockers: Continued 2-4 weeks postoperatively (TSH may remain suppressed; risk of thyrotoxic rebound)
• Analgesia: Regular paracetamol ± NSAIDs

• TFTs at 6-8 weeks then annually
• Optimize levothyroxine dose (aim for TSH 0.5-2.5 mIU/L; lower TSH target if cancer)
• Bone density (if prolonged TSH suppression)

---

15. Hypothyroidism: Definition, Classification, Clinical Manifestations, Treatment

Definition

Classification

• Thyroid gland itself is deficient
• TSH elevated; T3/T4 low
• Causes:
  • Autoimmune (Hashimoto's thyroiditis) - most common in iodine-sufficient areas
  • Post-radioiodine or post-surgical hypothyroidism
  • Iodine deficiency (most common worldwide)
  • Drugs: amiodarone, lithium, interferon-alpha
  • Congenital: athyreosis, dyshormonogenesis
  • External radiation to neck

• Pituitary insufficiency → reduced TSH secretion
• TSH low/normal; T4 low
• Causes: pituitary adenoma/tumor, Sheehan's syndrome, hypophysitis, cranial irradiation

• Hypothalamic insufficiency → reduced TRH → reduced TSH
• TRH, TSH, T4 all reduced
• Causes: craniopharyngioma, hypothalamic tumors, irradiation

Clinical Manifestations

Treatment

• Oral synthetic T4, fully absorbed
• Dose: 1.6 mcg/kg/day (adults); start low (25-50 mcg/day) in elderly and cardiac patients, titrate up every 4-6 weeks
• Full replacement in young, otherwise healthy adults: 1.6-2.0 mcg/kg/day
• Target: TSH 0.5-2.5 mIU/L (or 0.1-0.5 mIU/L if post-thyroid cancer)
• Take on empty stomach, 30-60 min before food; avoid co-administration with calcium, iron, PPI

---

16. Thyroiditis and Strumitis: Etiology, Pathogenesis, Clinical Presentation, Diagnosis, Treatment

Hashimoto's Thyroiditis (Chronic Autoimmune / Lymphocytic Thyroiditis)

• Initial goiter (diffuse, firm, rubbery, lobulated "pebble-stone" feel)
• Transient thyrotoxicosis (Hashitoxicosis) early in some
• Progressive hypothyroidism
• May be euthyroid for years
• Associated with other autoimmune conditions (T1DM, Addison's, vitiligo, pernicious anemia)

---

De Quervain's Thyroiditis (Subacute Granulomatous / Painful Thyroiditis)

• Prodrome: URTI, malaise, fever
• Thyroid pain - anterior neck pain, tender, hard enlarged gland; pain radiates to jaw/ear
• Thyrotoxic symptoms (mild-moderate, from hormone release not overproduction)
• Sequence: thyrotoxicosis (4-8 weeks) → hypothyroidism (4-12 weeks) → euthyroid (~90% recover)

• NSAIDs (aspirin, ibuprofen) for mild-moderate pain
• Corticosteroids (prednisolone 40-60 mg/day then taper) for severe pain/systemic symptoms - rapid resolution
• Beta-blockers for symptomatic thyrotoxicosis
• Levothyroxine if hypothyroid phase is prolonged/severe
• Self-limiting; recurrence ~5%

---

Riedel's Thyroiditis (Fibrous / Invasive Thyroiditis)

• Hard, "stony," non-tender goiter - literally "woody" consistency, fixed to surrounding structures
• Mimics thyroid cancer (must distinguish)
• Compressive symptoms: dysphagia, stridor, dyspnea
• Extension to surrounding structures - can fibrosis retroperitoneum, orbit, mediastinum (multifocal fibrosclerosis)
• Usually euthyroid, rarely hypothyroid

---

Acute (Suppurative) Thyroiditis

• Acute anterior neck pain, fever, dysphagia
• Tender, warm, erythematous, fluctuant thyroid swelling
• Leukocytosis

---

Strumitis

---

17. Complications During and After Thyroid Surgery: Clinical Presentation, Treatment; Prevention of RLN Injury

Intraoperative Complications

• Injury to superior/inferior thyroid arteries or thyroid veins
• Control with pressure, ligation, bipolar cautery

• Transection, stretch, crush, burn, ischemia
• Presentation: immediate hoarseness/voice change if anesthesia reversed
• If transected: immediate re-anastomosis or immediate referral to laryngologist

Early Postoperative Complications

• Occurs within first 6-12 hours
• Rapidly expanding hematoma can compress trachea → airway emergency
• Clinical features: swelling, stridor, neck distension, respiratory distress
• Treatment: Immediate wound opening at bedside to decompress (suture removal kit should be at bedside of ALL post-thyroidectomy patients) → return to OR for formal re-exploration and hemostasis

• Unilateral: hoarseness, breathy voice, aspiration (incomplete glottic closure)
• Bilateral: stridor, severe respiratory compromise → may require tracheostomy
• Rate: unilateral permanent palsy <0.5-1% in experienced hands; temporary palsy 5-10%
• Transient palsy from edema/ischemia: usually recovers within 6-12 weeks
• Assessment: laryngoscopy
• Treatment of permanent palsy: medialization laryngoplasty (injection or thyroplasty)

• From parathyroid devascularization, accidental removal, or ischemia
• Temporary: 15-30% after total thyroidectomy; permanent: 1-3%
• Symptoms: perioral tingling, carpopedal spasm, Chvostek's sign, Trousseau's sign, tetany, seizures
• Treatment:
  • Mild: oral calcium carbonate 1.5-3 g/day + calcitriol 0.25-0.5 mcg/day
  • Severe/symptomatic: IV calcium gluconate (10 mL of 10% solution slowly)
• Monitoring: serum calcium q4-6h for 24h; PTH at 4-6h postop (PTH <10 pg/mL predicts hypocalcemia)

• In inadequately prepared Graves' patients
• Treatment: PTU + Lugol's + beta-blockade + glucocorticoids + supportive care (see Topic 9)

Late Complications

• Expected after total thyroidectomy → lifelong levothyroxine
• May develop after subtotal thyroidectomy (15-40%)
• Treatment: levothyroxine replacement

• Rate ~10-15%; treatment: ATDs, RAI, or completion thyroidectomy

• External branch injury → loss of cricothyroid muscle function → lowered voice pitch, reduced projection, voice fatigue
• Important for singers, professionals

Prevention of RLN Injury

1. Visual identification of the RLN - mandatory; "No cut, burn, or tie unless the RLN is identified"
2. Systematic approach: Dissect from inferior pole upward in tracheoesophageal groove; spread perpendicular to nerve axis with blunt dissection
3. Gentle retraction of the thyroid medially; avoid excessive traction
4. Careful dissection at Berry's ligament - most dangerous zone; pre-emptive bipolar, layer-by-layer dissection
5. Awareness of anatomic variations:
   • RLN may be anterior to inferior thyroid artery (higher risk)
   • Branching may occur proximal to cricothyroid muscle
   • Non-recurrent laryngeal nerve (0.5-1% on right) - associated with anomalous subclavian artery
6. Tubercle of Zuckerkandl - mobilize anteriorly to expose RLN terminus
7. Intraoperative neuromonitoring (IONM): Negative predictive value ~100%; does not replace visualization
8. Preoperative laryngoscopy - documents baseline function; identifies unsuspected pre-existing palsy
9. Minimize use of energy devices near nerve - safe distance ≥3 mm from nerve with ultrasonic devices

---

18. Thyroid Cancer: Classification, Clinical Presentation, Diagnosis, Differential Diagnosis, Treatment, Outcomes

Classification

• T1: ≤2 cm confined to thyroid
• T2: 2-4 cm
• T3: >4 cm or minimal extrathyroidal extension
• T4: Significant extrathyroidal extension / invasion of surrounding structures
• N1: Regional lymph node mets
• M1: Distant mets (lung, bone most common)

Clinical Presentation

• Usually presents as a thyroid nodule - palpable or incidentally detected on imaging
• Features raising concern for malignancy:
  • Rapid growth
  • Hard, fixed, irregular nodule
  • Hoarseness (RLN invasion - ominous sign)
  • Dysphagia, stridor (local invasion)
  • Cervical lymphadenopathy (especially in PTC)
  • Male sex, extremes of age (<20 or >65)
  • History of radiation to neck (childhood irradiation → PTC)
  • Family history (MTC in MEN2, familial PTC)
  • Calcitonin elevation (MTC)

Diagnosis

1. History and physical examination (risk factors, nodule features, cervical LN)
2. TSH: If suppressed → RAI scan (rule out hot nodule = virtually always benign); if normal/elevated → US
3. Thyroid ultrasound (US): Characterize nodule (size, echogenicity, margins, microcalcifications, vascularity, shape); TIRADS classification; examine for lymphadenopathy
4. FNA biopsy (FNAC): For nodules >1 cm with suspicious US features, or any growing nodule; Bethesda classification (Thy1-5); core biopsy for FTC (capsular invasion not assessable by FNA)
5. Molecular testing (Bethesda III-IV): ThyroseqTM, AfirmaTM GEC - improve diagnostic accuracy for indeterminate nodules
6. CT neck/chest: Large or locally advanced tumors, lymph node mapping, substernal disease
7. Calcitonin/CEA: For suspected MTC
8. RET mutation testing: Hereditary MTC (index case + all 1st-degree relatives if positive)

Differential Diagnosis of Thyroid Nodule / Mass

• Benign: Simple cyst, follicular adenoma, Hashimoto's, colloid nodule, hemorrhagic cyst
• Malignant: PTC, FTC, MTC, ATC, lymphoma
• Other: Parathyroid adenoma/cyst, branchial cleft cyst, lymph node, lipoma, cervical abscess

Treatment

1. Surgery: Total thyroidectomy for lesions >4 cm, bilateral disease, high-risk features, any FTC; thyroid lobectomy acceptable for low-risk PTC ≤1-4 cm without extrathyroidal extension or lymphadenopathy
2. Central neck dissection (Level VI): Therapeutic if clinical/radiologic N1a; prophylactic in high-risk PTC (controversial but commonly performed)
3. Lateral neck dissection (Levels II-V): For confirmed lateral LN mets
4. Radioactive iodine (RAI, 131I): After total thyroidectomy for intermediate/high-risk disease; ablates remnant thyroid tissue and micrometastases; not effective in Hürthle cell, MTC, ATC
5. TSH suppression therapy: Levothyroxine post-operatively to TSH <0.5 (intermediate risk) or <0.1 mIU/L (high risk) for 1-5 years, then relax to low-normal
6. External beam radiation (EBRT): Residual/unresectable PTC/FTC; ATC (combined modality)
7. Targeted therapy for ATC and progressive DTC: BRAF/MEK inhibitors (dabrafenib + trametinib for BRAF V600E-mutated ATC); lenvatinib, sorafenib for RAI-refractory DTC

• Total thyroidectomy + central neck dissection
• Lateral dissection if calcitonin >200 pg/mL or known lateral LN mets
• RET-directed therapy: vandetanib, cabozantinib for advanced/progressive MTC
• Genetic counseling and RET testing of family members mandatory

• Multimodal: surgery (rarely curative) + chemoradiation (doxorubicin + radiation)
• Targeted therapy: dabrafenib + trametinib (FDA approved for BRAF V600E-mutant ATC)
• Tracheostomy often required
• Most patients treated with palliative intent

• Chemoimmunotherapy (CHOP ± rituximab) ± radiation
• Surgery only for airway decompression

Long-Term Outcomes

• Thyroglobulin (Tg) + anti-Tg antibodies: tumor marker; should be undetectable after total thyroidectomy + RAI; rising Tg = recurrence
• Whole body RAI scan: 6-12 months post-ablation; then based on risk
• Neck US: annually
• CT/PET-CT: if Tg elevated with negative US/RAI scan

---

Quick Reference: Key Drug Doses

---