Thyroid and parathyroid surgery

Definition / Overview

• A thyroid nodule is a discrete lesion within the thyroid gland that is radiologically distinct from surrounding parenchyma; may be solid, cystic, or mixed
• Palpable nodules occur in approximately 4-7% of the adult population; ultrasound (US) detects nodules in up to 67% of adults
• The critical clinical task is to distinguish the minority of malignant nodules from the majority that are benign, while avoiding unnecessary surgery
• Thyroid cancer accounts for the most common endocrine malignancy; most are well-differentiated and carry an excellent prognosis
• The OHNS surgeon must be competent in the full assessment pathway, operative decision-making, and management of complications

Epidemiology and Risk Stratification

Risk Factors Favouring Malignancy

• Age $< 20$ years or $> 70$ years
• Male sex
• Prior external-beam radiation to the neck (therapeutic or environmental fallout)
• Family history: medullary thyroid carcinoma (MTC), multiple endocrine neoplasia type 2 (MEN2), papillary thyroid carcinoma (PTC) associated with Cowden syndrome or familial adenomatous polyposis (Gardner syndrome)
• Rapid nodule growth, hoarseness, dysphagia, fixed or hard nodule, cervical lymphadenopathy

Histological Subtypes of Thyroid Cancer

Clinical Assessment

History

• Duration, growth rate, and change in nodule size
• Symptoms of compression: hoarseness (RLN involvement), dysphagia, stridor, dyspnoea, superior vena cava obstruction
• Thyroid functional status: palpitations, heat intolerance, weight loss (hyperthyroid); fatigue, cold intolerance (hypothyroid)
• Radiation exposure history (childhood neck irradiation; environmental fallout)
• Family history of thyroid cancer, MEN, hyperparathyroidism, phaeochromocytoma
• RET mutation carrier status if known

Physical Examination

• Nodule: size, consistency (hard vs. soft), mobility with swallowing, tenderness, border regularity
• Fixed, hard, irregular nodule: high suspicion for malignancy or anaplastic change
• Cervical lymphadenopathy: levels II-VI; lateral aberrant thyroid tissue invariably represents nodal metastasis
• Vocal fold mobility: indirect laryngoscopy or flexible nasopharyngoscopy before any thyroid surgery; establishes pre-operative baseline and detects RLN palsy
• Signs of hyperthyroidism (Graves): exophthalmos, pretibial myxoedema, bruit over gland

Investigation

Biochemical Evaluation

• TSH: first-line test; suppressed TSH prompts scintigraphy to exclude autonomous (hot) nodule before FNA; elevated TSH raises suspicion for malignancy
• Free T4 and T3: assess functional status
• Calcitonin: mandatory if MTC is suspected clinically or family history of MTC/MEN2; markedly elevated calcitonin is essentially diagnostic
• Thyroglobulin: not useful for pre-operative diagnosis of a nodule; essential for post-operative surveillance of differentiated thyroid cancer (DTC)
• Calcium and PTH: important pre-operatively (baseline) and if concurrent parathyroid pathology is suspected

Molecular Markers

• BRAF V600E: most common somatic mutation in PTC; associated with aggressive behaviour and extrathyroidal extension
• RET rearrangements: present in PTC (somatic) and germline mutations in MTC/MEN2; genotype-phenotype correlation determines timing of prophylactic thyroidectomy
• RAS mutations: follicular adenoma and FTC; less specific
• Molecular panels (e.g. multi-gene classifiers): used to risk-stratify Bethesda III/IV nodules with indeterminate FNA cytology; can reduce unnecessary diagnostic hemithyroidectomy in some cases

Imaging

Ultrasound (First-Line Imaging)

• Modality of choice for all thyroid nodules; provides size, echogenicity, composition, margins, calcification pattern, and vascularity
• Features associated with malignancy: solid, markedly hypoechoic, irregular/infiltrative margins, taller-than-wide shape, microcalcifications, disrupted rim calcification
• Features favouring benignity: pure cyst, spongiform (honeycombed) appearance, isoechoic/hyperechoic solid nodule with smooth margins
• Documents lymphadenopathy: round shape, loss of fatty hilum, microcalcifications or cystic change within a node suggest metastatic disease

Thyroid Scintigraphy ($^{123}$I or $^{99m}$Tc)

• Reserve for patients with suppressed TSH to identify autonomous "hot" nodules (which are rarely malignant)
• Not routinely indicated for euthyroid patients with nodules
• Cold (photopenic) nodules on scintigraphy carry ~15% malignancy risk but this information rarely changes FNA indications

CT/MRI

• Indicated for large or substernal goitres, suspected tracheal deviation or compression, invasive malignancy, or pre-operative mapping for complex resection
• CT with iodinated contrast delays RAI therapy by 6-8 weeks: sequence imaging carefully

PET-CT

• Not first-line for nodule evaluation
• Incidental FDG-avid nodule ("PET incidentaloma") carries approximately 30-35% malignancy rate: warrants FNA regardless of size

Fine-Needle Aspiration Biopsy (FNA)

Role and Principles

• FNA is the cornerstone of thyroid nodule evaluation; it is minimally invasive, cost-effective, and accurate
• Ultrasound-guided FNA is preferred over palpation-guided: reduces non-diagnostic rates, improves accuracy particularly for $\leq 1\,\text{cm}$ or partially cystic nodules
• An experienced cytopathologist is critical; non-diagnostic rates rise substantially without dedicated expertise

Indications for FNA (Size and US Pattern)

Bethesda Classification System

The six-tier Bethesda System for Reporting Thyroid Cytopathology provides cytological categories with associated malignancy risk and guides management:

Key limitation of FNA: FNA cannot distinguish follicular adenoma from follicular carcinoma; both require surgical excision for histological diagnosis (capsular and vascular invasion assessed on permanent sections).

Thyroglobulin Washout in Suspicious Nodes

• If a cervical lymph node is suspicious on US, FNA needle washout for thyroglobulin ($Tg$) is highly sensitive for nodal metastasis of DTC; complements cytology

Management of Thyroid Nodules

Benign Nodules (Bethesda II)

• Observation: clinical review and repeat US at 12-24 months
• Growth of $\geq 20\%$ in two dimensions or development of suspicious features warrants repeat FNA
• Symptomatic thyroid cysts: initial aspiration; reaccumulation after three aspirations or compressive symptoms: consider ethanol ablation or hemithyroidectomy
• Compressive goitre with airway or swallowing symptoms: operative intervention (see below)
• Thyroid suppression therapy (exogenous thyroxine) is not routinely recommended for nodule management

Indeterminate Nodules (Bethesda III/IV)

• Bethesda III: repeat FNA at 3-6 months; if persistently AUS, molecular testing or diagnostic lobectomy
• Bethesda IV: diagnostic lobectomy; intra-operative frozen section has limited utility for follicular lesions; completion thyroidectomy if permanent histology confirms FTC
• Molecular classifier result (low risk of malignancy): may support active surveillance rather than surgery in a shared decision-making context

Surgical Management: Thyroidectomy

Extent of Resection

Advantages of Total Thyroidectomy for DTC

1. Removes multifocal intrathyroidal tumour foci (common in PTC)
2. Facilitates post-operative RAI imaging and ablation
3. Enables sensitive surveillance with serum thyroglobulin as a tumour marker

Neck Dissection

• Central compartment dissection (level VI): indicated for clinically or radiologically evident central nodal disease; elective dissection is considered for T3/T4 PTC or MTC
• Therapeutic lateral neck dissection (levels II-V): compartment-based, not "berry-picking"; indicated for biopsy-proven lateral nodal metastasis
• Level VII (anterior superior mediastinum) included when paratracheal/substernal disease is present

Surgical Anatomy: Structures at Risk

Recurrent Laryngeal Nerve (RLN)

• Courses in the tracheo-oesophageal groove; enters the larynx at the level of the inferior cornu of the thyroid cartilage, deep to the inferior constrictor
• Right RLN loops around the right subclavian artery; left RLN loops around the aortic arch: the left has a longer intrathoracic course
• Non-recurrent RLN (right side, ~0.5-1%): associated with aberrant right subclavian artery (arteria lusoria); US or CT may suggest this pre-operatively
• Injury: unilateral RLN palsy causes ipsilateral vocal fold paralysis with breathy dysphonia and aspiration; bilateral injury causes stridor and may require tracheostomy
• Visual identification of the RLN throughout its course is mandatory; nerve monitoring (intra-operative neuromonitoring, IONM) is adjunct, not a substitute

External Branch of the Superior Laryngeal Nerve (EBSLN)

• Innervates the cricothyroid muscle (vocal cord tensioner; highest pitch)
• Descends with the superior thyroid artery; at risk when dividing the superior thyroid vascular pedicle
• Injury: loss of high-pitched voice, vocal fatigue; particularly significant in singers and professional voice users
• Ligate superior thyroid artery branches individually at the thyroid capsule, not en masse

Parathyroid Glands

• Superior parathyroid glands: derived from 4th pharyngeal pouch; located posterior to the upper third of the thyroid, near the cricothyroid junction; consistent position
• Inferior parathyroid glands: derived from 3rd pharyngeal pouch (with thymus); more variable position; may be intrathyroidal, intrathymic, or ectopic in the mediastinum
• Blood supply: end-arterial branches from inferior thyroid artery
• Preservation strategies: identify and confirm vascular pedicle before ligation; if devascularised, auto-implant minced parathyroid into sternocleidomastoid or brachioradialis (dominant forearm, in re-operative cases)
• Post-operative hypocalcaemia: most common complication after total thyroidectomy; may be transient (parathyroid stunning) or permanent (gland removal/devascularisation)

Thoracic Duct

• Enters the neck on the left, arching over the subclavian vein at the junction with the internal jugular vein; at risk in left-sided level IV/VI dissection
• Injury causes chylous fistula: milky output post-feeding; manage conservatively (low-fat diet, medium-chain triglycerides) or operatively if high output

Adjuvant Treatment

Radioactive Iodine (RAI, $^{131}$I)

• Indicated for high-risk DTC: extrathyroidal extension, incomplete resection, distant metastases, lymph node metastases $> 1\,\text{cm}$
• Low-risk DTC (microcarcinoma $< 1\,\text{cm}$, unifocal, confined to thyroid): RAI not routinely recommended
• Requires TSH stimulation ($> 30\,\text{mIU/L}$): achieved by levothyroxine withdrawal or recombinant human TSH (rhTSH, Thyrogen) injection; latter preferred for patient quality of life
• Low-iodine diet for 1-2 weeks before RAI administration

Thyroid Hormone Suppression

• Post-operative levothyroxine serves dual purpose: replacement and TSH suppression
• High-risk DTC: suppress TSH to $< 0.1\,\text{mIU/L}$
• Low-risk DTC after lobectomy or in remission: maintain TSH in low-normal range ($0.5-2.0\,\text{mIU/L}$) to minimise cardiovascular and skeletal adverse effects of over-suppression

External Beam Radiotherapy (EBRT)

• Role in DTC is limited; consider for gross residual disease not amenable to further surgery and not RAI-avid
• Primary treatment for anaplastic thyroid cancer (often combined with systemic therapy)
• Primary treatment for primary thyroid lymphoma (with chemotherapy)

Systemic Therapy

• Kinase inhibitors (lenvatinib, sorafenib): for RAI-refractory metastatic DTC
• RET-specific inhibitors (selpercatinib, pralsetinib): for RET-altered MTC and PTC; marked response rates
• BRAF/MEK inhibitors: for BRAF V600E-mutant ATC (dabrafenib + trametinib); now standard of care for resectable and unresectable ATC in eligible patients

Post-Operative Management and Surveillance

Immediate Post-Operative Priorities

1. Airway: monitor for haematoma (expanding neck haematoma causes tracheal deviation and airway compromise; open wound at bedside for immediate decompression if needed)
2. Vocal fold assessment: flexible laryngoscopy at first post-operative visit if voice change
3. Calcium monitoring: check corrected calcium or ionised calcium at 6 and 24 hours post-operatively; supplement with oral calcium carbonate $\pm$ calcitriol as needed; IV calcium gluconate for symptomatic hypocalcaemia (tingling, Chvostek sign, Trousseau sign, tetany)
4. Commence levothyroxine replacement or suppression from day 1 post-operatively

Long-Term Surveillance for DTC

• Serum thyroglobulin (Tg) and anti-thyroglobulin antibodies ($TgAb$): measured every 6-12 months; rising Tg on levothyroxine therapy is the most sensitive marker for recurrence
• Neck US: annually for the first 3-5 years, then less frequently if disease-free
• Stimulated Tg (with rhTSH) or diagnostic RAI scan: in high-risk patients or when US/basal Tg is equivocal
• CT chest/whole-body RAI scan: if Tg rising but neck US negative (to exclude pulmonary or skeletal metastases)

Surveillance for MTC

• Calcitonin and carcinoembryonic antigen (CEA) every 6 months; rising levels prompt cross-sectional imaging
• Biochemical cure (undetectable calcitonin post-operatively) predicts excellent long-term outcome
• All sporadic MTC patients should undergo RET germline testing: ~7-10% have an unsuspected germline mutation; family members offered predictive genetic testing

MEN2 and Prophylactic Thyroidectomy

• RET genotype determines risk category and recommended age for prophylactic thyroidectomy:
  • Highest risk (MEN2B, RET codon 918 mutation): thyroidectomy within the first 6 months of life
  • High risk (codon 634): thyroidectomy by age 5 years
  • Moderate risk (other mutations): thyroidectomy guided by calcitonin level and family wishes, typically before age 10 years

Complications and Their Management

Paediatric Considerations

• Thyroid nodules in children and adolescents carry a higher rate of malignancy than in adults (approximately 20-25%)
• PTC in children more often presents with lymph node metastases and pulmonary metastases than in adults; despite this, long-term prognosis remains good
• Diffuse sclerosing variant of PTC is over-represented in the young
• FNA is safe, accurate, and appropriate in paediatric patients when performed by experienced operators; an expert cytopathologist is essential
• Post-Chernobyl experience demonstrates that external radiation and iodine-131 environmental contamination are significant aetiological factors in childhood thyroid cancer
• Management principles (FNA, total thyroidectomy, RAI, surveillance) mirror adult practice but require multidisciplinary input including paediatric endocrinology

MDT and OHNS Surgeon's Role

• All thyroid cancer cases should be discussed at a multidisciplinary team (MDT) meeting including OHNS surgery, endocrinology, nuclear medicine, medical oncology, and radiation oncology
• The OHNS surgeon is responsible for: nodule assessment, surgical decision-making, operative execution, peri-operative safety (airway, calcium, nerve), and long-term surgical surveillance
• Pre-operative laryngoscopy is a medico-legal standard: documents pre-existing vocal fold status, identifies pre-operative RLN palsy (alters operative strategy for the contralateral side)
• Consent discussion must include: risk of RLN injury (temporary and permanent), hypoparathyroidism, haematoma and airway compromise, the need for life-long thyroxine replacement after total thyroidectomy, and potential for completion thyroidectomy after lobectomy