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🫁 THYROID GLAND - High-Yield Notes (pp. 273-282)

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SURGICAL ANATOMY

• Located in anterior triangle of neck, enclosed by pre-tracheal fascia (part of deep cervical fascia)
• Weight: 20-25g; two lobes joined by isthmus (in front of 2nd, 3rd & 4th tracheal rings)
• Projection from isthmus on left side = pyramidal lobe

• Superior thyroid artery - branch of external carotid artery
• Inferior thyroid artery - branch of thyrocervical trunk
• Thyroid ima artery - branch of brachiocephalic trunk or aorta (2-3% cases)

• Superior & middle thyroid veins → internal jugular vein
• Inferior thyroid veins → anastomose with each other → brachiocephalic vein

1. Recurrent laryngeal nerve - runs in tracheoesophageal groove; supplies all laryngeal muscles EXCEPT cricothyroid; major nerve supply to vocal cords - must be protected during thyroidectomy
2. External laryngeal nerve - branch of superior laryngeal nerve; runs close to superior thyroid vessels; supplies cricothyroid muscle (adductors of vocal cords)

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THYROID HORMONE SYNTHESIS (5 Steps)

1. Trapping - Iodides absorbed into follicular cells by iodide pump
2. Oxidation - Iodides → iodine by peroxidase enzyme
3. Binding - Iodine + tyrosine → monoiodotyrosine
4. Coupling - monoiodotyrosine + di-iodotyrosine → T3 & T4
5. Secretion - T3 & T4 released into plasma; bind to TBG & TBPA; only 0.03% of T4 and 0.3% of T3 exist in free (biologically active) form. TSH from anterior pituitary (regulated by hypothalamic TRH) controls synthesis.

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INVESTIGATIONS OF THYROID DISEASE

• Euthyroid: T3, T4, TSH all normal
• Thyrotoxicosis: ↓TSH, ↑T3, ↑T4
• Hypothyroidism: ↑TSH, ↓T3, ↓T4
• T3 toxicity: ↓/normal TSH, ↑T3, normal T4

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THYROGLOSSAL DUCT CYST

• Thyroid arises from primitive foregut at 3rd week of gestation at foramen of cecum
• Descends to neck with isthmus over 2nd & 3rd tracheal ring
• Connected via epithelial-lined thyroglossal duct (obliterates by 8th week)
• Cyst can occur anywhere along migratory path; 80% near hyoid bone
• May be the ONLY functional thyroid tissue - do thyroid scan before excision

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LINGUAL THYROID

• Failure of median thyroid anlage to descend normally; may be the only thyroid tissue
• Symptoms: choking, dysphagia, airway obstruction, hemorrhage
• Treatment: exogenous thyroid hormone + RAI ablation; surgical excision rarely needed (must confirm normal thyroid tissue elsewhere first)

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GOITRE CLASSIFICATION

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SIMPLE GOITRE (EUTHYROID)

• Enlargement WITHOUT hypo/hyper functioning; diffuse or multinodular
• Pathogenesis: ↑TSH → hypertrophy + hyperplasia of follicles
• Causes: Iodine deficiency, Dyshormogenesis, Goitrogens (cabbage/kale/rape - contain thiocyanates), ↑demand (puberty, pregnancy)
• Nodule formation: Some follicles are more sensitive to TSH → enlarge more → nodules

• Total thyroidectomy: All tissue removed; lifelong thyroxine 150mcg/day
• Subtotal thyroidectomy: 8g left on each side; parathyroids preserved; less RLN injury risk BUT remnant may regrow

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HYPERTHYROIDISM / THYROTOXICOSIS

• Hyperthyroidism = overproduction by thyroid gland (demonstrable on scan)
• Thyrotoxicosis = biochemical + physiological manifestations of excess thyroid hormone (broader term)

• Diffuse toxic (Graves') - 70%
• Toxic MNG
• Toxic adenoma (Plummer's disease)

Graves' Disease (Diffuse Toxic Goitre)

• Autoimmune; caused by TSH-RAb (IgG antibodies) binding TSH receptors → ↑T3, T4
• Primary thyrotoxicosis - simultaneous goitre + thyrotoxicosis + eye signs (more pronounced)

Toxic MNG (Secondary Thyrotoxicosis)

• In older patients; prior history of non-toxic MNG
• Nodules become autonomous; rarely associated with eye signs

Toxic Adenoma (Plummer's Disease)

• Younger patients; single hyperfunctioning nodule; caused by somatic mutation in TSH receptor

Thyrotoxicosis Factitia

• Exogenous over-administration of thyroxine

Jod-Basedow

• Large dose iodide given to patient with hyperplastic endemic goitre

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CLINICAL FEATURES OF THYROTOXICOSIS

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EYE SIGNS (Graves' Ophthalmopathy) - occur in 50% of Graves' patients

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TREATMENT OF THYROTOXICOSIS

A. Antithyroid Drugs (Carbimazole, Propylthiouracil)

• Interfere with oxidation of iodides + binding of iodine to tyrosine
• Beta blockers (propranolol) block cardiovascular effects
• Dose: Carbimazole 10mg TDS initially → 5mg TDS or BD for 6-24 months
• Side effect: Agranulocytosis or aplastic anaemia (very dangerous)
• Failure rate: 50%; treatment duration 6-24 months
• Block & Replace therapy: High dose carbimazole + thyroxine 100-150mcg/day
• In pregnancy: Use propylthiouracil (carbimazole crosses placenta → fetal hypothyroidism)

B. Surgery (Subtotal/Total Thyroidectomy)

• Patient MUST be made euthyroid before surgery
• Drug of choice for preparation: Carbimazole 30-40mg; when euthyroid (8-12 weeks) reduce to 5mg 8-hourly
• Beta blockers can be used alternatively (inhibit peripheral T4→T3 conversion); propranolol 40mg TDS
• Advantages: Rapid, high cure rate
• Disadvantages: Risk of hypoparathyroidism (5%), RLN injury, 5% recurrence with subtotal

• Young patients: Total thyroidectomy (avoids late recurrence)
• Old patients: Subtotal thyroidectomy (takes 10-15 years to develop recurrence)
• Post-subtotal: lifelong thyroxine 200mcg/day (suppressive dose) to prevent recurrence + prevent hypothyroidism

C. Radioactive Iodine (RAI)

• Beta & gamma rays from radioactive iodine destroy thyroid follicles
• Advantages: No surgery, no prolonged drug treatment
• Disadvantages: Late hypothyroidism
• Contraindications: Absolute - pregnancy & breastfeeding; Relative - young patients, multinodularity, Graves' ophthalmopathy

Treatment Choice by Case:

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HYPOTHYROIDISM

Infantile Hypothyroidism (Cretinism)

• Inadequate thyroid hormone during fetal/neonatal life
• Endemic (iodine deficiency) or sporadic (congenital enzyme deficiency / thyroid agenesis)
• Features: hoarse cry, macroglossia, umbilical hernia
• Treatment with thyroxine lessens neurological/intellectual deficits

Adult Hypothyroidism

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MYXOEDEMA & MYXOEDEMA COMA

• Myxoedema: Exaggerated symptoms of hypothyroidism
• Myxoedema Coma: Most severe form; mortality 30-60%; seen in known hypothyroid patients exposed to stress (surgery, trauma, cold, pneumonia, CVA, sedatives, anesthesia)
• Features: Hypothermia, altered consciousness, delirium, respiratory failure, cardiac dysfunction
• Treatment: IV thyroxine 500mcg bolus T4 or 10mcg T3 IV; warm slowly; IV hydrocortisone; IV antibiotics (mortality is HIGH)

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DISCRETE THYROID NODULE

• Affects 4-7% of population; solitary vs. dominant
• Solitary: Single swelling in otherwise impalpable gland (15-20% malignant!)
• Dominant: Single obvious swelling with mild background nodularity
• 70% of discrete swellings are solitary; 30% dominant
• Thyroid scan: Hot (overactive), Warm (normal), Cold (non-active/suspicious)
• FNAC = investigation of choice

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PENDRED'S SYNDROME

• Form of dyshormogenesis with deficiency of TPO (thyroid peroxidase oxidase)
• Associated with hypothyroidism + sensorineural hearing impairment (abnormality of bony labyrinth)

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Key mnemonics to remember:

• Sistrunk = treatment for thyroglossal duct cyst/fistula
• FNAC cannot differentiate follicular adenoma from carcinoma (needs excision for capsular/vascular invasion)
• Carbimazole crosses placenta → use PTU in pregnancy
• Woltman's sign = delayed ankle jerk = hypothyroidism
• Calcitonin = tumor marker for medullary carcinoma (from C-cells)
• Graves' eye signs = PRIMARY thyrotoxicosis; Toxic MNG = SECONDARY (rarely eye signs)

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🫁 THYROID GLAND - Continued (pp. 282-290)

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DISCRETE THYROID NODULE - FNAC

• Colloid nodule, Medullary carcinoma, Thyroiditis, Papillary carcinoma, Lymphoma

• FNAC positive for malignancy
• Age <20 or >50 years
• Male sex
• Hard and fixed
• Recurrent laryngeal nerve palsy
• Lymphadenopathy
• Recurrent cyst
• Toxic adenoma
• Pressure symptoms / Cosmesis

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RETROSTERNAL GOITRE

• Most due to enlargement of lower pole of nodular goitre; common in short neck males
• Clinical features: Dysphagia, dyspnea (may attend as asthma at night), engorgement of neck and chest wall veins on raising arm above head = Pemberton's sign
• Diagnosis: X-ray chest thoracic inlet (soft tissue shadow in superior mediastinum); CT scan is most accurate

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THYROID CARCINOMA

Overview of Types:

Treatment of DTC (Papillary & Follicular):

• Surgery + Radioiodine therapy
• Total thyroidectomy performed; if cervical lymph nodes involved → neck dissection also
• Post-op: thyroxine therapy avoided for 3 weeks → TSH rises → whole body RAI scan performed to detect residual/metastatic disease
• For whole body scan: All normal thyroid tissue must be ablated first (otherwise normal tissue competes with cancer for RAI uptake)
• If residual/metastatic disease found → treat with RAI

Post-op Treatment & Follow up of DTC:

1. Thyroxine 200mcg/day - replacement + suppress TSH (TSH thought to cause carcinoma recurrence)
2. Follow up with thyroglobulin level - initially 6-monthly then yearly; if raised → whole body thyroid scan

Whole Body Thyroid Scan Prerequisites:

• T4 therapy stopped 6 weeks before scan (allows TSH to rise by reflex)
• OR synthetic recombinant TSH given 48 hours before scan
• T3 therapy should be discontinued 2 weeks before scan (shorter half-life than T4)

Medullary Thyroid Carcinoma (MTC):

• Tumor of parafollicular cells derived from neural crest cells (NOT follicles)
• Markers: Calcitonin + Carcinoembryonic antigen (CEA) - raised level after resection = recurrence
• 25% occur in inherited syndromes: Familial MTC, MEN2A, MEN2B - all due to RET proto-oncogene mutation
• Familial form: children & young adults; Sporadic: any age

• Total thyroidectomy + bilateral central lymph node dissection (medial to carotid sheath) - frequently involved (50-66%) early in disease
• Large tumor (>1cm) or positive central LN → modified radical neck dissection
• No role of radioactive iodine, No chemotherapy
• Follow up with calcitonin + CEA; recurrence treated by RAI/lifelong thyroxine

• Rule out phaeochromocytoma by measuring urinary catecholamines BEFORE thyroidectomy
• If phaeochromocytoma found → operate on phaeochromocytoma FIRST
• Prophylactic thyroidectomy indicated in RET mutation carriers:
  • MEN2B: before 1 year of age
  • MEN2A: before 6 years of age

Anaplastic Carcinoma:

• Most aggressive; all treatments have disappointing outcomes; survival <6 months
• If confined to thyroid (rare) → total thyroidectomy
• External beam radiotherapy has some role
• Tracheal obstruction → isthmusectomy to relieve tracheal compression

Lymphoma of Thyroid:

• Follows Hashimoto's thyroiditis (autoimmune)
• Stage I & II → Radiotherapy
• Stage III & IV → Chemotherapy (CHOP)

Summary - Treatment of Thyroid Carcinoma:

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TYPES OF THYROID SURGERY

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PRE-OPERATIVE PREPARATION FOR THYROID SURGERY

• Patient MUST be euthyroid before surgery
• Carbimazole 10mg TDS → reduce to 5mg TDS when euthyroid (8-12 weeks)
• Propranolol 40mg TDS - blocks peripheral T4→T3 conversion + blocks peripheral effects
• Iodine (Lugol's) - given for 10 days before surgery to reduce vascularity of gland
• In pregnancy: Use propylthiouracil (not carbimazole - crosses placenta)

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STEPS OF THYROIDECTOMY (pp. 288-289)

1. General anesthesia; neck extended; head side of table elevated
2. Collar incision (Kocher's incision): Transverse 4-5cm incision, 2cm above suprasternal notch
3. Subcutaneous tissue + platysma incised; subplatysmal flaps raised up to thyroid cartilage, down to suprasternal notch
4. Incise median raphe + mobilize strap muscles (retract laterally if small goitre; divide if large goitre)
5. Retract thyroid medially → identify + ligate middle thyroid vein (RLN is posterior to this vein - beware!)
6. Identify + mobilize superior pole → ligate superior thyroid artery & vein close to thyroid (to avoid damage to external laryngeal nerve)
7. Ligate inferior pole vessels (inferior thyroid vein + artery separately) medial→lateral; identify RLN (always close to inferior pole vessels)
8. Divide Berry's ligament + mobilize thyroid from trachea
9. For lobectomy: isthmus divided flush with trachea on contralateral side + suture ligated
10. Hemostasis; suction drain placed beneath muscle; strap muscles approximated; platysma by continuous absorbable suture; skin by subcuticular sutures

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POST-OPERATIVE COMPLICATIONS OF THYROIDECTOMY

Management of Neck Swelling + Dyspnea after Thyroidectomy:

1. Immediately look for airway obstruction signs
2. Inform senior
3. Release skin stitches + deep stitches to relieve compression
4. May need cricothyroidotomy to secure airway before shifting to OT
5. Avoid endotracheal intubation
6. In OT: evacuate hematoma, ligate bleeding vessel, wash with normal saline, place drain
7. Transfuse blood if necessary

Thyrotoxic Crisis (Storm) Treatment:

1. IV fluids to correct dehydration
2. IV hydrocortisone
3. Oxygen inhalation
4. Digoxin for uncontrolled atrial fibrillation
5. Cooling with ice packs
6. Specific:
   • Carbimazole 10-20mg 6-hourly
   • Lugol's iodine 10 drops 8-hourly
   • Propranolol 1-2mg IV or 40mg orally 6-hourly

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🦷 PARATHYROID GLANDS (pp. 291-293)

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ANATOMY

• Khaki colored, oval in shape
• Size: up to 6mm length; weight: 30-50mg each; usually 4 in number
• Superior parathyroids: Level of cricoid cartilage, posterior to RLN
• Inferior parathyroids: Lower pole of thyroid, anterior to RLN
• Blood supply from inferior thyroid artery (branches guide their position)

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FUNCTIONS OF PTH

• Bone: Stimulates osteoclasts → releases calcium + phosphate into circulation
• Kidney: Limits calcium excretion at distal convoluted tubule (via active transport); inhibits phosphate reabsorption from proximal convoluted tubule
• Gut: Causes absorption of calcium (via Vit D activation)
• PTH secretion stimulated by low calcium in circulation
• Half-life of PTH = 2 to 4 minutes

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HYPERPARATHYROIDISM

Primary HPT - Causes:

• Adenoma: 85% (usually single; 80% involve single gland; chief cells predominate)
• Hyperplasia: 13% (involves all 4 glands; >70mg)
• Carcinoma: 1-2%
• Can occur in MEN-1 and MEN-2A

Clinical Features - Mnemonic:

• Kidney stones: Hypercalcemia → renal calculi
• Broken bones: ↑osteoclastic activity → pathological fractures, osteopenia, osteoporosis, osteitis fibrosa cystica
• Abdominal groans: Constipation, indigestion, nausea, vomiting, peptic ulcers, acute pancreatitis
• Psychiatric moans: CNS effects
• Fatigue overtones: Lethargy, fatigue, depression, memory loss, psychosis, ataxia, delirium, coma

Diagnosis of Primary HPT:

• Hypercalcemia + raised PTH
• Hypophosphatemia + elevated urinary calcium excretion
• Alkaline phosphatase (skeletal) may be raised (bone resorption)

• Serum calcium >1.0 mg/dl above upper limit of normal
• 24-hour urinary calcium >400mg
• Creatinine clearance reduced by 30%
• Bone mineral density t-score ≤ -2.5 at any site

Pre-operative Localization:

• Diagnosis of primary HPT is biochemical; localization is for surgical planning only
• Ultrasound + Technetium-99m sestamibi (MIBI) scan can localize 80% of adenomas
• Adenoma usually involves single gland (80%); hyperplasia involves all 4 glands

Surgical Approach:

• Single adenoma: Remove single gland; intraoperative PTH measurement (if PTH falls by 50% or more at 10 minutes after removal → source of excess PTH removed → abandon further exploration)
• All 4 glands hyperactive (hyperplasia): Remove all 4 glands + autotransplant 50mg of parathyroid tissue into brachioradialis muscle to avoid future hypoparathyroidism

Complications of Surgery:

• Failure to achieve cure (5%)
• RLN damage
• Hypoparathyroidism
• Recurrent hyperparathyroidism / severe hypercalcemia

Medical Treatment (mild/asymptomatic cases):

• General measures: hydration, decrease dietary calcium, stop thiazide/lithium
• Bisphosphonates + estrogen therapy
• Calcium receptor agonist (cinacalcet)
• Parathyroid crisis (severe hypercalcemia >3.5mmol/L or 14mg/dl): IV saline + bisphosphonate therapy; admit to ICU

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SECONDARY & TERTIARY HYPERPARATHYROIDISM

• Secondary HPT: Over-secretion of PTH in response to low plasma calcium (usually due to chronic renal failure or GI malabsorption)
  • Managed initially by 1-alpha-hydroxyvitamin D3 (alfacalcidol) to increase calcium absorption
  • Renal transplantation usually cures it
• Tertiary HPT: Excessive PTH secretion in secondary HPT becomes autonomous; may occur after renal transplantation
  • Treatment: Total parathyroidectomy + calcium & vitamin D replacement; OR subtotal parathyroidectomy leaving half-equivalent of a normal gland in situ; OR autotransplantation of parathyroid tissue into arm muscle

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HYPOPARATHYROIDISM

• Most common cause = thyroid surgery (particularly total thyroidectomy with neck dissection)
• Transient hypocalcemia common (ischemia of parathyroids); permanent hypoparathyroidism is rare
• Also occurs after total parathyroid surgery
• Parathyroids may be congenitally absent in DiGeorge syndrome

• Paraesthesia ("pins and needles") in hands/feet
• Muscle cramps + spasms (tetany) → bunching/flexion of fingers and toes
• Respiratory obstruction with stridor (laryngeal muscle spasm - can be fatal)
• Chvostek's sign: Contraction of facial muscles by tapping on facial nerve anterior to ear
• Trousseau's sign: Carpopedal spasm elicited by occluding blood flow to forearm with BP cuff for 2-3 minutes

• IV calcium gluconate (20ml of 10% solution diluted in 100ml saline) 4-hourly until calcium levels rise
• Oral calcium supplementation + Vitamin D (calcitriol) according to serial blood calcium levels

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PARATHYROID CARCINOMA

• Rare; 1% of patients with hyperparathyroidism
• 50% present with palpable neck mass
• Diagnosis: Histological findings of vascular or capsular invasion, lymph node or distant metastasis
• Treatment: Treat severe hypercalcemia medically first (rehydration + IV bisphosphonates); then radical excision of gland + lymphadenectomy + ipsilateral lobectomy of thyroid gland

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Key High-Yield Mnemonics:

• FNAC cannot distinguish follicular adenoma from carcinoma (needs excision)
• Pemberton's sign = retrosternal goitre (engorged veins on raising arm above head)
• RET proto-oncogene mutation = MTC (familial, MEN2A, MEN2B)
• Phaeochromocytoma operated FIRST before thyroidectomy in MEN-2A
• Kidney stones, Broken bones, Abdominal groans, Psychiatric moans = Primary HPT
• Chvostek's = tap facial nerve → face twitches; Trousseau's = BP cuff → carpopedal spasm
• Sestamibi scan localizes 80% of parathyroid adenomas
• PTH falls >50% at 10 min post-removal = successful parathyroidectomy
• DiGeorge syndrome = congenitally absent parathyroids