31 THYROID DISEASE

👩‍⚕️ Thyroid is one of the most heavily examined organs in MRCS Part A. Examiners love it because it links anatomy (recurrent laryngeal nerve, parathyroids, blood supply), physiology (TSH–T4–T3 axis), pathology (autoimmune disease, four cancers with distinct biology) and surgery (four classic post-thyroidectomy complications). Master those four axes and you will pick up easy marks every sitting.

Surgical anatomy

The thyroid is a butterfly-shaped endocrine gland sitting in the anterior neck, anterior to the trachea between C5 and T1. It has two lateral lobes joined across the midline by an isthmus, which lies over the 2nd to 4th tracheal rings. A pyramidal lobe ascends from the isthmus in ~50% of people — a remnant of the embryological thyroglossal duct that descends from the foramen caecum of the tongue.

The gland is wrapped in the pretracheal fascia, which tethers it to the larynx and trachea. This is why a goitre moves up on swallowing — a classic clinical sign and an easy exam mark.

Posterior relations (high-yield)

The posterior surface is where surgery becomes dangerous. Two structures sit immediately behind:

➡ Recurrent laryngeal nerve (RLN) — runs in the tracheoesophageal groove, deep to the inferior thyroid artery

➡ Parathyroid glands — usually four, lying on the posterior capsule; the superior pair is more constant in position than the inferior

The RLN is a branch of the vagus. It loops under the right subclavian artery on the right and under the arch of the aorta on the left, then ascends in the tracheoesophageal groove to enter the larynx beneath the inferior constrictor. It supplies all intrinsic laryngeal muscles except cricothyroid.

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Blood supply

Vessel	Origin	Notes
Superior thyroid artery	First branch of external carotid artery	Travels with external laryngeal nerve — at risk during ligation
Inferior thyroid artery	Thyrocervical trunk (from subclavian)	Travels close to recurrent laryngeal nerve — ligate close to gland to protect RLN; supplies parathyroids
Thyroid ima artery	Brachiocephalic or arch of aorta	Present in ~10%; important in paediatric tracheostomy (can be cut)

Venous drainage: superior and middle thyroid veins → internal jugular vein; inferior thyroid vein → brachiocephalic vein.

Lymphatic drainage: deep cervical and pretracheal nodes — the route by which papillary carcinoma spreads.

Nerves at risk in thyroidectomy

Nerve	Function	Injury picture
Recurrent laryngeal n.	All intrinsic laryngeal muscles except cricothyroid	Unilateral: hoarse voice, vocal cord paramedian. Bilateral: stridor, airway emergency
External branch of superior laryngeal n.	Cricothyroid (tenses cord)	Low-pitched, easily fatigued voice — classically the opera singer who can't reach high notes

Physiology

The hypothalamus secretes TRH, which drives the anterior pituitary to release TSH. TSH binds to receptors on thyroid follicular cells and stimulates synthesis of T4 (thyroxine) and a small amount of T3 (triiodothyronine).

➡ T4 is the main product of the gland (~90% of output) but is largely a prohormone

➡ T3 is the active hormone, ~4× more potent than T4

➡ Peripheral tissues convert T4 → T3 using 5′-deiodinase (in liver, kidney, muscle)

➡ Both circulate bound to thyroxine-binding globulin (TBG); only free hormone is active

➡ Negative feedback: free T3/T4 suppress TRH and TSH

The C cells (parafollicular cells) sit between follicles and secrete calcitonin, which lowers serum calcium. Calcitonin is the tumour marker for medullary thyroid carcinoma.

Hyperthyroidism

Cause	Mechanism	Distinguishing features
Graves' disease	TSH receptor–stimulating antibodies (TSI)	Diffuse goitre, ophthalmopathy (exophthalmos, lid lag), pretibial myxoedema, young women
Toxic multinodular goitre	Autonomous nodules	Older patient, long-standing goitre, no eye signs
Toxic adenoma	Single autonomous nodule	"Hot" nodule on uptake scan, cold rest of gland
Thyroiditis (de Quervain's, post-partum)	Inflammation → preformed hormone release	Painful tender gland, transient, low uptake on scan
Factitious / iatrogenic	Exogenous T4	Low TSH, low thyroglobulin, low uptake

Graves' disease is the commonest cause overall and accounts for ~60–80% of hyperthyroidism in young adults. The TSI antibody is pathognomonic. Eye signs are caused by retro-orbital lymphocytic infiltration and glycosaminoglycan deposition — independent of thyroid hormone level, which is why eye disease can persist after the patient is rendered euthyroid.

Thyroid storm

A life-threatening decompensation of thyrotoxicosis, usually precipitated by surgery, infection or iodine load.

Features: fever > 38.5 °C, tachycardia/AF, agitation/delirium, vomiting/diarrhoea, heart failure.

Management (memorise the order — examiners love this):

1. Propranolol — blocks β effects and peripheral T4→T3 conversion

2. Propylthiouracil (PTU) — blocks new hormone synthesis AND peripheral conversion (preferred over carbimazole here)

3. Lugol's iodine — given at least 1 hour after PTU to block hormone release (Wolff-Chaikoff effect). Given first, it would fuel hormone synthesis.

4. Hydrocortisone — blocks peripheral conversion and treats relative adrenal insufficiency

5. Supportive: cooling, fluids, treat precipitant

Mortality remains around 10–30% even with treatment.

Hypothyroidism

Cause	Mechanism	Key features
Hashimoto's thyroiditis	Autoimmune lymphocytic destruction	Anti-TPO, anti-thyroglobulin antibodies; firm goitre; Hürthle cells on histology; risk of thyroid lymphoma
Atrophic thyroiditis	End-stage autoimmune; no goitre	Common cause in elderly women
Iatrogenic	Post-thyroidectomy, post-radioiodine, anti-thyroid drugs	Commonest cause in surgical practice
Iodine deficiency	Lack of substrate	Commonest cause worldwide; endemic goitre
Secondary	Pituitary failure	Low TSH and low T4 — opposite biochemistry to primary

Hashimoto's is the commonest cause in iodine-replete countries. Histology shows lymphocytic infiltrate with germinal centres and Hürthle cells (large eosinophilic follicular cells with granular cytoplasm — also called Askanazy cells).

👩‍⚕️ Hashimoto's confers a 70-fold increased risk of thyroid lymphoma — rare but a classic SBA twist: an elderly woman with long-standing Hashimoto's develops a rapidly enlarging neck mass.

Thyroid cancer

Four types you must know cold. The key is to link cell of origin → spread pattern → prognosis.

Cancer	% of thyroid cancers	Cell of origin	Spread	Key facts	Prognosis
Papillary	~80%	Follicular	Lymphatic	Young patients; Orphan Annie nuclei, psammoma bodies; multifocal	Excellent (>95% 10-yr)
Follicular	~10%	Follicular	Haematogenous (lung, bone)	FNA cannot distinguish from follicular adenoma — capsular/vascular invasion needed → diagnostic lobectomy	Good (~85% 10-yr)
Medullary	~5%	Parafollicular C cells	Both	Secretes calcitonin; associated with MEN-2A and 2B (RET mutation); amyloid stroma	Moderate
Anaplastic	<5%	Follicular (de-differentiated)	Aggressive local + distant	Elderly, rapidly enlarging mass, airway compromise; almost uniformly fatal	Dismal (<1 yr)
Thyroid lymphoma	<5%	B cells	Lymphatic	Arises in Hashimoto's; non-Hodgkin	Variable; chemo-sensitive

➡ Papillary: most common, lymphatic spread, excellent prognosis

➡ Follicular: haematogenous, FNA cannot diagnose — needs lobectomy

➡ Medullary: C cells, calcitonin, MEN-2

➡ Anaplastic: elderly, aggressive, fatal

👩‍⚕️ Memory aid: "Papillary Loves Lymphatics, Follicular Favours Far-flung blood spread."

Why FNA fails for follicular cancer

FNA samples cells, not architecture. The diagnosis of follicular carcinoma depends on demonstrating capsular or vascular invasion — which requires examining the whole capsule histologically. A diagnostic hemithyroidectomy is therefore needed if FNA shows a "follicular lesion." Classic exam question.

Medullary and MEN

Medullary carcinoma arises from C cells, which are of neural crest origin (unlike follicular cells, which derive from endoderm of the foregut). It is associated with:

- MEN-2A: medullary thyroid + phaeochromocytoma + hyperparathyroidism

- MEN-2B: medullary thyroid + phaeochromocytoma + mucosal neuromas + marfanoid habitus

All caused by RET proto-oncogene mutations. Prophylactic thyroidectomy is offered in childhood for known carriers.

Thyroidectomy complications

Four classic complications — examiners ask all of them.

Complication	Mechanism	Presentation	Management
RLN injury	Damage in tracheoesophageal groove	Unilateral: hoarse voice; Bilateral: stridor, airway emergency	Laryngoscopy; bilateral may need tracheostomy
External laryngeal n. injury	Damage during superior pole ligation	Low-pitched, monotonous voice; loss of vocal range	Voice therapy
Hypoparathyroidism	Parathyroid devascularisation or removal	Hypocalcaemia at 24–72 h: perioral tingling, Chvostek's, Trousseau's, tetany	IV calcium gluconate; calcitriol
Haematoma	Bleed deep to strap muscles	Neck swelling, stridor — AIRWAY EMERGENCY	Open the wound at bedside, then return to theatre

Other complications: thyroid storm (if not rendered euthyroid pre-op), wound infection, hypertrophic scar (the incision crosses Langer's lines), tracheomalacia in long-standing goitre.

👩‍⚕️ Post-thyroidectomy haematoma is a clinical, not radiological, diagnosis. Do not send the patient for a CT — open the wound at the bedside immediately. This is a favourite exam scenario.

[Image: MCQs banner]

Test yourself

Which artery is the first branch of the external carotid?

• ((Superior thyroid artery::☑️ First branch of ECA; runs with external laryngeal nerve at superior pole.))
• ((Inferior thyroid artery::Branch of thyrocervical trunk from subclavian, not ECA.))
• ((Lingual artery::Second branch of ECA, supplies tongue.))
• ((Facial artery::Third branch of ECA; crosses mandible at anterior border of masseter.))
• ((Thyroid ima artery::Variant from brachiocephalic or aortic arch; present in ~10%.))

👩‍⚕️ Mnemonic for ECA branches: "Some Anatomists Like Freaking Out Poor Medical Students" — Superior thyroid, Ascending pharyngeal, Lingual, Facial, Occipital, Posterior auricular, Maxillary, Superficial temporal.

A patient is hoarse after thyroidectomy. Which nerve is most likely injured?

• ((Recurrent laryngeal nerve::☑️ Runs in tracheoesophageal groove; supplies all intrinsic laryngeal muscles except cricothyroid.))
• ((External branch of superior laryngeal nerve::Causes low-pitched fatiguable voice, not classical hoarseness.))
• ((Internal branch of superior laryngeal nerve::Sensory above the cords; injury causes aspiration, not hoarseness.))
• ((Hypoglossal nerve::Supplies tongue muscles; injury causes tongue deviation.))
• ((Glossopharyngeal nerve::Sensory to pharynx and posterior tongue; not at risk in thyroidectomy.))

Which thyroid cancer is most likely to spread haematogenously?

• ((Papillary::Spreads via lymphatics to cervical nodes; excellent prognosis.))
• ((Follicular::☑️ Haematogenous spread to lung and bone; FNA cannot distinguish from adenoma.))
• ((Medullary::Both lymphatic and haematogenous; arises from C cells.))
• ((Anaplastic::Aggressive local invasion in elderly; uniformly fatal.))
• ((Lymphoma::Arises in Hashimoto's; spreads via lymphatics.))

👩‍⚕️ Follicular carcinoma needs diagnostic lobectomy — FNA cannot demonstrate capsular invasion.

A 45-year-old has a thyroid nodule. FNA shows calcitonin-positive cells with amyloid stroma. Which cancer?

• ((Papillary::Orphan Annie nuclei and psammoma bodies; not calcitonin-secreting.))
• ((Follicular::Follicular cell origin; no calcitonin.))
• ((Medullary::☑️ C-cell origin, secretes calcitonin, amyloid stroma; screen for MEN-2.))
• ((Anaplastic::Pleomorphic giant cells; elderly patient.))
• ((Hürthle cell::Variant of follicular; eosinophilic cells, no calcitonin.))

👩‍⚕️ Always check RET mutation and screen for phaeochromocytoma before operating on medullary thyroid cancer.

Which antibody is pathognomonic for Graves' disease?

• ((Anti-TPO::Hashimoto's thyroiditis; can be present in low titres in Graves'.))
• ((Anti-thyroglobulin::Hashimoto's marker; also raised post-thyroidectomy.))
• ((TSH receptor–stimulating antibody (TSI)::☑️ Stimulates TSH receptor — causes Graves' hyperthyroidism and ophthalmopathy.))
• ((Anti-mitochondrial::Primary biliary cholangitis.))
• ((Anti-smooth muscle::Autoimmune hepatitis.))

A patient becomes tetanic 48 hours after total thyroidectomy. The cause?

• ((Hypocalcaemia from parathyroid injury::☑️ Devascularisation or inadvertent removal of parathyroids during surgery.))
• ((Hypomagnesaemia::Can cause tetany but uncommon post-thyroidectomy.))
• ((Recurrent laryngeal nerve injury::Causes hoarseness or stridor, not tetany.))
• ((Thyroid storm::Causes fever, tachycardia and delirium — not tetany.))
• ((Hypokalaemia::Causes weakness and arrhythmia, not tetany.))

👩‍⚕️ Check Chvostek's sign (facial twitch on tapping facial nerve) and Trousseau's sign (carpal spasm with BP cuff) — both classic Part A signs.

Six hours post-thyroidectomy, the patient develops neck swelling and stridor. Best next step?

• ((CT neck::Wastes critical time — this is a clinical airway emergency.))
• ((Urgent ENT review::Helpful but not immediate enough.))
• ((Open the wound at the bedside::☑️ Releases the haematoma and relieves airway compression immediately.))
• ((Intubate and observe::Intubation may be impossible due to laryngeal oedema — release first.))
• ((IV dexamethasone::Will not relieve mechanical compression.))

👩‍⚕️ Post-thyroidectomy haematoma is the classic surgical airway emergency — open the wound first, theatre second.

A 35-year-old develops thyroid storm after emergency appendicectomy. Which drug should be given FIRST?

• ((Lugol's iodine::Must be given after PTU — given first would fuel hormone synthesis.))
• ((Carbimazole::Effective but PTU is preferred in storm because it also blocks T4→T3 conversion.))
• ((Hydrocortisone::Helpful adjunct; not the first priority.))
• ((Propranolol::☑️ Controls tachycardia and blocks peripheral T4→T3 conversion — give immediately.))
• ((Radioiodine::Definitive treatment for thyrotoxicosis but never used acutely in storm.))

👩‍⚕️ Order: Propranolol → PTU → (wait ≥1 h) → Lugol's iodine → Hydrocortisone. Iodine before PTU worsens the storm (Jod-Basedow effect).

Which histological feature is characteristic of Hashimoto's thyroiditis?

• ((Orphan Annie nuclei::Papillary carcinoma.))
• ((Psammoma bodies::Papillary carcinoma; also meningioma and serous ovarian tumours.))
• ((Amyloid stroma::Medullary carcinoma.))
• ((Lymphocytic infiltrate with Hürthle cells::☑️ Autoimmune destruction with germinal centres and eosinophilic Askanazy cells.))
• ((Pleomorphic giant cells::Anaplastic carcinoma.))

The thyroid ima artery, when present, arises from which vessel?

• ((External carotid artery::Origin of superior thyroid artery, not ima.))
• ((Thyrocervical trunk::Origin of inferior thyroid artery.))
• ((Brachiocephalic trunk or aortic arch::☑️ Variant artery present in ~10%; important in paediatric tracheostomy.))
• ((Internal thoracic artery::Supplies anterior chest wall; not thyroid.))
• ((Vertebral artery::First branch of subclavian; supplies brainstem.))

Revision summary

➡ Anatomy: 2 lobes + isthmus over tracheal rings 2–4, anterior to C5–T1. Moves on swallowing (pretracheal fascia).

➡ Blood supply: Superior thyroid a. (1st branch of ECA, with external laryngeal n.); Inferior thyroid a. (thyrocervical trunk, with RLN); Ima a. in 10%.

➡ Nerves at risk: RLN in tracheoesophageal groove (hoarse/stridor); External laryngeal n. at superior pole (low-pitched voice).

➡ Physiology: TRH → TSH → T4 (main product) → T3 (active) via 5′-deiodinase; calcitonin from C cells.

➡ Hyperthyroidism: Graves' (TSI Ab, eye signs) > toxic MNG > toxic adenoma > thyroiditis.

➡ Thyroid storm: Propranolol → PTU → Lugol's (≥1 h later) → hydrocortisone.

➡ Hypothyroidism: Hashimoto's (anti-TPO, Hürthle cells, lymphoma risk ×70).

➡ Cancers: Papillary (80%, lymphatic, excellent); Follicular (10%, haematogenous, lobectomy); Medullary (C cells, calcitonin, MEN-2/RET); Anaplastic (elderly, fatal); Lymphoma (Hashimoto's).

➡ Thyroidectomy complications: RLN injury, external laryngeal n. injury, hypocalcaemia, haematoma → open the wound at bedside.