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Thyroid — Viva Questions & Answers

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ANATOMY & EMBRYOLOGY

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• Two lobes connected by an isthmus that lies over the 2nd–4th tracheal rings.
• A pyramidal lobe (remnant of thyroglossal duct) extends superiorly in ~50% of individuals.
• Posteriorly related to the recurrent laryngeal nerve (RLN) and parathyroid glands.
• Enclosed in the pretracheal fascia; further covered by strap muscles (sternohyoid, sternothyroid).
• Blood supply: Superior thyroid artery (first branch of external carotid) and inferior thyroid artery (from thyrocervical trunk of subclavian artery). The arteria thyroidea ima is an uncommon vessel arising from the aorta or brachiocephalic trunk.
• Venous drainage: Superior and middle thyroid veins → internal jugular; inferior thyroid veins → brachiocephalic veins.

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PHYSIOLOGY

• T4 (thyroxine / tetraiodothyronine) — 3,5,3',5'-tetraiodothyronine; prohormone
• T3 (triiodothyronine) — 3,5,3'-triiodothyronine; the biologically active form
• Calcitonin — produced by parafollicular (C) cells; lowers serum calcium

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• Minimum daily requirement: 100 μg/day; average North American intake exceeds this.
• Iodide is transported by the sodium/iodide symporter (NIS) on the basal membrane of the thyrocyte, coupling I⁻ influx with Na⁺ influx. An Na⁺/K⁺-ATPase maintains the Na⁺ gradient.
• The thyroid normally concentrates iodide 20- to 40-fold over the extracellular space.
• At the apical membrane, pendrin aids iodide release into the follicular lumen.

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1. Iodide uptake via NIS at basal membrane
2. Thyroglobulin (Tg) synthesized in the endoplasmic reticulum → Golgi → secreted into follicular lumen
3. Iodide oxidised by thyroperoxidase (TPO) in the presence of H₂O₂ → iodination of tyrosine residues on Tg → monoiodotyrosine (MIT) and diiodotyrosine (DIT)
4. Coupling by TPO: DIT + DIT → T4; MIT + DIT → T3
5. Tg retrieved by endocytosis → lysosomal proteolysis → T3 and T4 released into circulation
6. MIT and DIT deiodinated, iodide recycled

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• TRH (thyrotropin-releasing hormone) from hypothalamus → stimulates anterior pituitary to release TSH (thyroid-stimulating hormone)
• TSH binds TSHR on thyroid cells → cAMP pathway → stimulates iodide uptake, Tg synthesis, hormone secretion, and thyroid growth
• Free T3/T4 exert negative feedback on both hypothalamus and pituitary
• TSH is the most sensitive biochemical marker of thyroid function

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• Thyroxine-binding globulin (TBG) — primary carrier (70%)
• Transthyretin (prealbumin)
• Albumin

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THYROID NODULE

1. History: age, sex, family history (thyroid cancer, MEN2), radiation exposure, rate of growth, symptoms (dysphagia, hoarseness, dyspnoea)
2. Examination: consistency, fixity, cervical lymphadenopathy
3. TSH: if low → radionuclide scan (hot nodule = rarely malignant; cold nodule = further workup)
4. Ultrasound (USS): first-line imaging — size, echogenicity, calcification, vascularity, margins, shape
5. FNAC (Fine-needle aspiration cytology): the most important diagnostic investigation

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• Hypoechogenicity
• Microcalcifications
• Irregular/infiltrative margins
• Taller-than-wide shape (AP > transverse dimension on transverse view)
• Increased intranodular vascularity
• Cervical lymphadenopathy

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• Age <20 or >70 years (male especially)
• Male sex
• History of head/neck irradiation
• Family history of thyroid carcinoma or MEN2
• Rapid growth
• Hoarseness (RLN involvement)
• Dysphagia, dyspnoea (tracheal/oesophageal involvement)
• Hard, fixed nodule
• Cervical lymphadenopathy
• Single, cold nodule on scan

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THYROID CARCINOMA

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• Most common thyroid malignancy (80%)
• Excellent prognosis (>95% 10-year survival)
• Spreads via lymphatics to cervical nodes (regional nodes not a prognostic disadvantage)
• Histology: "Orphan Annie eye" nuclei (empty-appearing), nuclear grooves, nuclear pseudoinclusions, psammoma bodies (concentrically layered calcifications)
• Associated with RET/PTC rearrangements and BRAF V600E mutation

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1. Surgery: Total thyroidectomy for most; lobectomy may suffice for low-risk papillary (<1 cm, no extrathyroidal extension)
2. Radioiodine (¹³¹I) ablation: For remnant ablation and treatment of metastases in iodine-avid tumours
3. TSH suppression: Levothyroxine to suppress TSH (reduces tumour stimulation)
4. Follow-up: Serum thyroglobulin (Tg) as tumour marker; neck USS; whole-body scan if needed
5. External beam radiotherapy: For unresectable or anaplastic disease
6. Neck dissection: Central ± lateral compartment for node-positive disease

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GRAVES DISEASE & HYPERTHYROIDISM

• Hyperthyroidism
• Diffuse thyroid enlargement (goitre)
• Infiltrative ophthalmopathy (exophthalmos/proptosis)
• Localized myxedema (pretibial dermopathy)
• Thyroid acropachy (rare)

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• Graves disease (most common)
• Toxic uninodular goitre (toxic adenoma)
• Toxic multinodular goitre (Plummer's disease)
• Thyroiditis (subacute, painless/silent, postpartum, radiation-induced)
• Exogenous thyroid hormone
• Iodine-induced (Jod-Basedow)
• Drug/cytokine-induced (amiodarone, interferon)
• Ectopic thyrotoxicosis (struma ovarii)
• Thyroid carcinoma
• TSH-secreting pituitary adenoma
• Gestational thyrotoxicosis / trophoblastic tumours
• McCune-Albright syndrome
• Autosomal-dominant thyrotoxicosis

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1. Antithyroid drugs: Carbimazole (methimazole) or propylthiouracil (PTU) — inhibit TPO; PTU also blocks T4→T3 conversion; used for first-line control and in pregnancy
2. Radioiodine (¹³¹I): Definitive; ablates the gland; causes hypothyroidism in ~90% by one year; contraindicated in pregnancy
3. Surgery (thyroidectomy): For large goitre, compression symptoms, malignancy suspicion, failure of/contraindication to other therapies; risk of RLN injury and hypoparathyroidism

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• Voice change: Tremulous voice due to fine tremor
• Dyspnoea: Large goitre causing tracheal compression
• Ophthalmopathy: Proptosis, lid lag, lid retraction, chemosis in Graves disease
• A bruit may be heard over the thyroid gland due to increased vascularity
• Well-differentiated thyroid cancer is twice as prevalent in Graves disease patients; a hypofunctional nodule in Graves disease has ~45% probability of malignancy

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HYPOTHYROIDISM

1. Hearing loss: Conductive, sensorineural, or mixed; due to mucopolysaccharide deposition in the middle ear and cochlea; common in congenital hypothyroidism; some improve with T4 replacement
2. Vertigo: Seen in ~2/3 of hypothyroid patients; usually mild and brief
3. Hoarseness: Due to mucopolysaccharide infiltration of the vocal cords; bilaterally oedematous, mobile cords on laryngoscopy → classic sign; almost always resolves with T4 replacement
4. Middle ear effusion: From eustachian tube mucosal oedema
5. Macroglossia and obstructive sleep apnoea: From tissue myxedema
6. Dysphagia: From oesophageal mucosal changes

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• Primary hypothyroidism (most common):
  • Hashimoto's autoimmune thyroiditis (commonest cause in iodine-sufficient countries)
  • Iodine deficiency (commonest cause worldwide)
  • Post-thyroidectomy
  • Post-¹³¹I therapy
  • External neck irradiation
  • Drugs: lithium, amiodarone, iodine-containing compounds, antithyroid drugs
• Secondary: TSH deficiency (pituitary disease)
• Tertiary: TRH deficiency (hypothalamic disease)
• Transient: Hashimoto's (~10% remit spontaneously), subacute thyroiditis

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• Most common cause of goitrous hypothyroidism in adults in iodine-sufficient areas
• Antibodies: Anti-TPO (thyroid peroxidase) antibodies (most sensitive) and anti-thyroglobulin antibodies
• Histology: lymphocytic infiltration, germinal centre formation, Hürthle cell (oxyphilic) change, fibrosis
• Increased risk of thyroid lymphoma in long-standing disease

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THYROID SURGERY

• The RLN is the motor nerve to all intrinsic laryngeal muscles except the cricothyroid (which is supplied by the external branch of the superior laryngeal nerve, EBSLN).
• Right RLN: loops around the right subclavian artery
• Left RLN: loops around the aortic arch (ligamentum arteriosum); longer course
• The RLN runs in the tracheoesophageal groove and enters the larynx posterior to the cricothyroid joint, in close relationship to Berry's ligament and the inferior thyroid artery.
• Non-recurrent RLN occurs in ~1% on the right (associated with aberrant right subclavian artery); rare on the left.
• Injury causes ipsilateral vocal cord paralysis → hoarseness; bilateral injury → airway obstruction requiring tracheostomy.
• Preoperative laryngoscopy is mandatory before thyroid surgery to document baseline cord mobility.

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• Loss of high-frequency phonation
• Weak, fatigable voice
• Clinically significant for singers and professional voice users (known as "Amelita Galli-Curci injury" after the opera singer who suffered this)

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• Haemorrhage → haematoma → airway obstruction (life-threatening)
• RLN injury (unilateral: hoarseness; bilateral: stridor, airway emergency)
• Thyrotoxic storm (in inadequately prepared patients)

• Hypocalcaemia (hypoparathyroidism — most common complication) → perioral tingling, Chvostek's sign, Trousseau's sign, tetany
• Wound infection

• Permanent hypoparathyroidism
• Permanent RLN palsy
• Hypothyroidism (after total thyroidectomy)
• Keloid/hypertrophic scar

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• Chvostek's sign: Tapping the facial nerve at the parotid → ipsilateral facial twitch; indicates hypocalcaemia (tetany)
• Trousseau's sign: Inflating a BP cuff above systolic pressure for 3 minutes → carpopedal spasm (main d'accoucheur); more specific for hypocalcaemia than Chvostek's

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• High fever (>38.5°C), tachycardia, atrial fibrillation
• Agitation, confusion, psychosis, coma
• Nausea, vomiting, diarrhoea

• PTU (blocks synthesis and T4→T3 conversion) or carbimazole
• Iodine (Lugol's iodine — given 1 hour after PTU to prevent iodine being used for new hormone synthesis)
• β-blockers (propranolol) — control tachycardia and peripheral T4→T3 conversion
• Hydrocortisone — prevents adrenal crisis and blocks T4→T3 conversion
• Supportive: IV fluids, cooling, dextrose

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GOITRE

• By thyroid function: Euthyroid / Hypothyroid / Hyperthyroid
• By morphology: Diffuse / Nodular (uninodular / multinodular)
• By aetiology:
  • Simple/colloid goitre (iodine deficiency or dyshormonogenesis)
  • Autoimmune (Graves, Hashimoto)
  • Toxic multinodular goitre (Plummer's disease)
  • Malignancy
  • Thyroiditis (Riedel's, subacute De Quervain's, Hashimoto's)

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1. TFTs: TSH, free T3, free T4
2. Thyroid antibodies: Anti-TPO, anti-TG, TRAb (for Graves)
3. Thyroid USS: Nodularity, vascularity, suspicious features
4. FNAC of dominant/suspicious nodule
5. CXR: Tracheal deviation/compression; retrosternal extension
6. CT scan neck/thorax: If retrosternal extension or tracheal compression suspected (note: iodinated contrast may precipitate thyrotoxic storm in toxic goitre; non-contrast preferred)
7. Radionuclide scan (Tc-99m or I-123): Functional assessment (hot vs cold nodules)
8. Laryngoscopy: Assess RLN function preoperatively

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• Compressive symptoms: dysphagia, dyspnoea, stridor, hoarseness (↑↑ RLN/EBSLN involvement)
• Cosmetically unacceptable
• Suspicion of malignancy (cold nodule, FNAC Bethesda IV/V/VI)
• Retrosternal goitre
• Failure of medical treatment / recurrence after ¹³¹I
• Toxic goitre (patient preference or contraindication to other therapy)
• Riedel's thyroiditis (fibrosis causing compressive symptoms)

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THYROIDITIS

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• Subacute granulomatous thyroiditis; post-viral (mumps, influenza, coxsackie)
• Painful, tender goitre with fever; elevated ESR, low radioiodine uptake
• Phases: Transient hyperthyroidism (follicular disruption → hormone leak) → hypothyroid → recovery (most recover euthyroid)
• Treatment: NSAIDs; corticosteroids for severe pain; β-blockers for hyperthyroid phase; temporary thyroxine if symptomatic hypothyroidism

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QUICK-FIRE VIVA EXTRAS

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• Hot nodule (hyperfunctioning): Increased isotope uptake; rarely malignant (<1%)
• Cold nodule (hypofunctioning): Decreased uptake; 5–10% risk of malignancy; most nodules are cold
• Warm nodule: Equal uptake to surrounding thyroid; intermediate risk

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• AMES (Age, Metastasis, Extent, Size)
• AGES/MACIS (for papillary)
• Patients <55 years with differentiated thyroid cancer: no Stage III/IV; excellent prognosis regardless of nodal involvement

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