Radioactive Iodine (RAI / ¹³¹I)

1. The Isotopes

• Goodman & Gilman's Pharmacological Basis of Therapeutics, p. 973

2. Mechanism of Action

1. Rapidly absorbed from the GI tract
2. Trapped by the thyroid via NIS, identical to dietary iodine
3. Incorporated into thyroid follicles (within thyroglobulin, as part of T3/T4 synthesis)

• Katzung's Basic & Clinical Pharmacology 16e, p. 1087
• Goodman & Gilman's, p. 973

3. Clinical Uses

A. Diagnosis - Radioactive Iodine Uptake (RAIU) Test

• High uptake: Graves' disease, toxic adenoma, toxic multinodular goiter (endogenous overproduction)
• Low/suppressed uptake: Thyroiditis (hormone leak, not synthesis), exogenous thyroid hormone, iodine excess

• Textbook of Family Medicine 9e

B. Treatment of Hyperthyroidism

• Graves' disease (most common use in the US)
• Toxic multinodular goiter
• Autonomous (toxic) thyroid adenoma

When RAI is Preferred for Hyperthyroidism

• Elderly patients and those with significant cardiac disease (avoids surgical risk)
• After relapse of Graves' post-thyroidectomy
• Failure of prolonged antithyroid drug (ATD) therapy
• Liver disease (ATDs hepatotoxic)
• Major adverse reactions to ATDs

• Pregnancy (destroys the fetal thyroid - absolute contraindication)
• Breastfeeding (secreted in breast milk)
• Active/moderate-severe Graves' ophthalmopathy (can worsen eye disease - corticosteroid cover required if RAI is given)
• Confirmed or suspected thyroid malignancy (surgery preferred)
• Current Surgical Therapy 14e, p. 891; Goldman-Cecil Medicine

C. Treatment of Differentiated Thyroid Cancer (DTC)

1. Remnant ablation - destroying residual normal thyroid tissue to:
   • Improve specificity of surveillance (serum thyroglobulin, whole-body scanning)
   • Prevent de novo cancer formation in remnant tissue
   • Treat potential microscopic residual disease
2. Adjuvant/therapeutic treatment - treating clinically detectable metastatic or recurrent disease

• Low-iodine diet for 1-2 weeks prior
• TSH stimulation to >30 mIU/L (required to drive NIS expression in cancer cells):
  • Thyroid hormone withdrawal for 3-4 weeks, OR
  • Recombinant human TSH (rhTSH/Thyrogen) injection - equally effective, fewer symptoms

• Remnant ablation: 30-50 mCi
• Treatment (metastatic): 100-150 mCi
• Maximum cumulative lifetime dose: ~600 mCi (controversial)

• Sabiston Textbook of Surgery, p. 1516; Cummings Otolaryngology

4. Practical Administration

• Prior to RAI for hyperthyroidism: if the patient has been on stable iodide (Lugol's, SSKI), uptake may be blocked for weeks - check 24-h RAIU with a tracer ¹²³I dose first
• For severely hyperthyroid, elderly, or cardiac-compromised patients: pre-treat with ATDs (methimazole or PTU) for 5-6 weeks to deplete stored hormone, then discontinue ATDs 5 days before RAI to avoid blocking uptake
• Response is gradual: symptoms improve over 2-3 months

5. Adverse Effects

• Katzung 16e; Sabiston; Goldman-Cecil

6. Thyroid Storm Caution

• Tintinalli's Emergency Medicine

7. Recent Evidence (2023-2026)

• PMID 40552857 (2025 Meta-Analysis): Confirmed dose-dependent increased risk of secondary hematologic malignancies after RAI for DTC - reinforces selective use in low-risk patients
• PMID 38870537 (2024 Systematic Review): RAI therapy for thyroid cancer coexisting with Hashimoto's thyroiditis - outcomes comparable to non-Hashimoto's patients
• PMID 37335288 (2023 Systematic Review): RAI has no meaningful role in medullary thyroid carcinoma - supports existing guideline recommendations

Thyroidectomy: Indications, Types, Steps & Complications

1. Indications

A. Hyperthyroidism (when medical/RAI management has failed or is not preferred)

• Graves' disease - preferred when: active/moderate-severe Graves' ophthalmopathy, large goiter, suspicious nodule, patient preference, failure of antithyroid drugs, or pregnancy planned within 6 months of desired treatment
• Toxic multinodular goiter
• Toxic (autonomous) adenoma

B. Goiter

• Compressive symptoms - dysphagia, dyspnea, stridor, voice change, SVC obstruction
• Substernal/retrosternal goiter
• Cosmetic concern / large neck mass
• Failed or inappropriate RAI (e.g., very large gland, low uptake)

C. Thyroid Nodules and Cancer

• Thyroid cancer - all histologic types (PTC, FTC, MTC, ATC)
• Indeterminate/suspicious FNA (Bethesda IV, V, VI)
• Bethesda III nodules in selected settings
• Known or suspected malignancy on imaging or clinical features
• Sabiston Textbook of Surgery, p. 1522

2. Types of Thyroidectomy

In modern practice, the vast majority of cases are either total thyroidectomy or thyroid lobectomy. Subtotal thyroidectomy has largely fallen out of favor due to higher recurrence rates for Graves' disease compared with total thyroidectomy.

• Sabiston, p. 1522

3. Preoperative Preparation

• Biochemical thyroid function tests (TSH, fT4)
• Neck ultrasound (mandatory)
• FNA biopsy of nodules as indicated
• For hyperthyroidism: render euthyroid pre-operatively with ATDs ± β-blockers; Lugol's solution / SSKI can be added within 10 days of surgery to reduce gland vascularity
• For Graves' disease with high surgical risk: prophylactic calcitriol may be started pre-op
• Voice/laryngeal assessment: all patients need baseline voice assessment; laryngoscopy is mandatory in those with voice changes, prior neck surgery, or posteriorly extending cancers
• MEN2A patients: check calcium to rule out concurrent primary hyperparathyroidism
• Sabiston, p. 1525-1526

4. Surgical Steps (Standard Open Technique)

Positioning & Incision

• Position: Supine, both arms tucked, neck extended with a shoulder roll; table in reverse Trendelenburg (reduces venous pressure and bleeding)
• Anesthesia: General endotracheal anesthesia; neuromonitoring ETT (with surface electrodes at vocal cords) used if intraoperative nerve monitoring (IONM) planned - muscle relaxants avoided after intubation
• Incision: Low transverse cervical incision (Kocher incision) ~2 cm above the sternal notch, placed within a natural skin crease

Exposure

1. Superior and inferior skin flaps raised in the subplatysmal plane
2. The midline raphe between the strap muscles (sternothyroid and sternohyoid) is divided vertically
3. Strap muscles are retracted laterally to expose the thyroid lobe
4. Strap muscles are divided (cut) only for very large goiters

Vascular Control (numbered sequence per illustration below)

1. Middle thyroid vein divided early to allow medial rotation of the lobe
2. Superior thyroid vessels (superior thyroid artery and vein) ligated and divided close to the thyroid capsule (to protect the external branch of the superior laryngeal nerve - EBSLN, which courses nearby)
3. Inferior thyroid artery - identified and its branches ligated individually close to the gland (not the trunk) to protect blood supply to parathyroids and to stay away from the RLN

RLN and Parathyroid Identification

1. Recurrent laryngeal nerve (RLN) - identified in the tracheoesophageal groove; traced from its entry into the larynx at the cricothyroid joint; IONM used to confirm integrity
2. Parathyroid glands - both superior and inferior glands identified and their blood supply preserved; any inadvertently devascularized gland is minced and auto-transplanted into the sternocleidomastoid muscle

Final Dissection and Specimen Removal

1. The lobe is dissected off the trachea, dividing the ligament of Berry (posterior thyroid suspensory ligament), where the RLN is at highest risk
2. For total thyroidectomy: contralateral lobe addressed identically
3. For lobectomy: isthmus divided with energy device or clamp/oversew; pyramidal lobe traced to its fibrous attachment cephalad and divided
4. Specimen is oriented with sutures and sent for pathology

Closure

1. Meticulous hemostasis; some surgeons use a Valsalva maneuver to test
2. Strap muscles and platysma reapproximated with 3-0 absorbable sutures (small inferior midline opening left for any blood tracking)
3. Subcuticular skin closure; drain generally not required

5. Alternative (Minimally Invasive / Remote-Access) Approaches

6. Adjunctive Intraoperative Technologies

• Intraoperative nerve monitoring (IONM): Electromyographic monitoring of RLN via vagal or direct stimulation; increasingly used worldwide; reduces bilateral RLN injury risk especially in reoperative cases
• Near-infrared (NIR) fluorescence parathyroid imaging: Parathyroid tissue autofluoresces in NIR spectrum; allows real-time identification and reduces inadvertent devascularization
• Energy sealing devices (LigaSure, Harmonic): Reduce operative time and blood loss

7. Postoperative Care

• Position: Head and shoulders elevated 10-20° (low Fowler) to reduce venous pressure
• Diet: Advanced quickly as patient wakes
• Total thyroidectomy: serum calcium monitored; prophylactic oral calcium ± calcitriol started if at risk for hypocalcemia
• Thyroid hormone replacement (levothyroxine) started the same day for total thyroidectomy at weight-based dosing
• Discharge: Most patients leave within 2-24 hours (outpatient surgery increasingly standard)
• Return to normal activity within ~1 week

8. Complications

Early / Intraoperative

Early Postoperative

Late Complications

Risk Factors for Complications

• Graves' disease carries higher absolute risk than other indications for RLN injury, hypoparathyroidism, and hematoma - though absolute risks remain low in experienced hands
• Surgeon volume is the single most modifiable determinant: outcomes improve with increasing volume up to a threshold of ~26 cases/year; high-volume surgeons consistently show lower complication rates
• Sabiston Textbook of Surgery, p. 1526-1528; Barash Clinical Anesthesia; Gray's Anatomy for Students

Recent Evidence Updates (2024-2026)

• PMID 38967517 (2024 Meta-Analysis): For intermediate-risk PTC, lobectomy and total thyroidectomy have comparable recurrence rates - supporting less aggressive resection in selected patients
• PMID 41901524 (2026 Systematic Review): Dysphagia is a common but underappreciated post-thyroidectomy complication deserving routine screening
• PMID 36799913 (2023 Systematic Review): Remote-access robotic thyroidectomy is safe and oncologically equivalent in selected patients at high-volume centers

Thyroid and Parathyroid Anatomy

THYROID GLAND

1. Embryology

• Originates as an endodermal thickening in the floor of the pharynx at the foramen cecum (base of tongue)
• Descends caudally along the thyroglossal duct, which normally obliterates by week 5
• Reaches its final position anterior to the trachea by week 7
• Follicular cells begin producing thyroid hormone by week 10
• Gives rise to thyroid follicular cells (T3/T4 producers)

• Arises from the 4th and 5th pharyngeal pouches (ultimobranchial bodies)
• Fuses with the median anlage during descent
• Contributes ~one-third of final thyroid mass
• Gives rise to parafollicular C cells (calcitonin producers) - the median anlage does NOT carry these cells

• Sabiston Textbook of Surgery, p. 1485-1487; Mulholland & Greenfield Surgery 7e

2. Gross Anatomy and Relations

• Weight: 15-30 g (normal)
• Shape: Bilobed with an isthmus; a pyramidal lobe projects superiorly from the isthmus in ~80% of people (midline, just left of center), extending as high as the hyoid bone
• Location: Anterior to the trachea, just inferior to the cricoid cartilage, within the central compartment of the neck
• Each lobe dimensions: ~5 cm craniocaudal × 2-3 cm AP × 3 cm wide

• Pretracheal fascia: Invests the thyroid; forms an easily mobilized dissection plane (except in thyroiditis or invasive cancer)
• Anterior suspensory ligament: Fascia condensation above the isthmus
• Ligament of Berry (posterior suspensory ligament): Firm posteromedial attachment to the trachea at cricoid level - the RLN is intimately associated here and is most vulnerable to injury at this point

3. Arterial Supply

• Schwartz's Principles of Surgery 11e, p. 1655; Sabiston, p. 1487

4. Venous Drainage

5. Lymphatic Drainage

• Superior: hyoid bone
• Inferior: innominate vessels
• Lateral: carotid sheaths bilaterally

6. Recurrent Laryngeal Nerve (RLN)

• Arises from vagus where it crosses the aortic arch
• Loops around the ligamentum arteriosum
• Ascends in the tracheoesophageal groove - a more medial, predictable course

• Arises from vagus where it crosses the right subclavian artery
• Loops around the subclavian artery
• Ascends at a more oblique angle (less predictable than left)

• Associated with aberrant right subclavian artery (arteria lusoria) / vascular anomaly
• Travels directly from vagus to larynx without looping - can be transected if not anticipated

• The nerve is most commonly posterior to the artery (R: 53%, L: 69%)
• Or between its branches (R: 7%, L: 67%)
• Or anterior to it (R: 37%, L: 24%)
• The nerve may branch before entering the larynx - finding a thin structure should alert the surgeon that a branch is present

7. External Branch of the Superior Laryngeal Nerve (EBSLN)

• Branch of the superior laryngeal nerve (from vagus)
• Innervates the cricothyroid muscle (tenses the vocal cord for high-pitch phonation)
• Runs closely with the superior thyroid artery as it approaches the superior pole - at risk when ligating the superior thyroid pedicle
• Injury causes: loss of high-pitch voice, vocal fatigue, inability to project ("Amelita Galli-Curci injury" - ended the soprano's career)
• Protected by ligating the superior thyroid vessels close to the thyroid capsule (not as a single trunk)

PARATHYROID GLANDS

1. Embryology and Numbers

• Most humans: 4 glands (84-87% of autopsy studies)
• 3 glands: 3-6%
• Supernumerary (5+) glands: ~5% - can number up to 12 glands
• Mirror-image symmetry between sides is a practical surgical aid for locating a missing gland

2. Gross Appearance

• Size: 30-50 mg each (approximately 3-6 mm)
• Color: Yellow-tan / Portland brick / caramel / mahogany; becomes more yellow (fattier) with age
• Shape: Oval, bean-shaped, or leaf-like
• "Gliding sign": Parathyroids glide within their surrounding fat pad as a discrete body - distinguishes them from adjacent fat (which is less distinct)
• Distinguished from surrounding fat by being darker and more defined than the surrounding yellow fat

3. Location

Superior Parathyroids

• Derived from the 4th pouch - shorter embryologic migration = more constant location
• Found in >80% of patients: posterior aspect of thyroid lobe within a 2 cm diameter area centered ~1 cm around the junction of the inferior thyroid artery and the RLN, in close proximity to the cricothyroid junction
• Located dorsal (deep/posterior) to the plane of the RLN
• Rests on the thyroid capsule posterolaterally at the upper lobe

Inferior Parathyroids

• Derived from the 3rd pouch - longer migration with thymus = more variable location
• Found in >56% of patients: inferior pole of thyroid (anterior, lateral, or posterior surface), within a globule of fat
• Located ventral (superficial/anterior) to the plane of the RLN
• Often closely associated with the thyrothymic ligament

4. Ectopic Parathyroid Locations

1. Anterior mediastinum / thymus (most common ectopic site)
2. Retroesophageal / retrotracheal
3. Intrathyroidal (up to 2-3%)
4. Carotid sheath
5. Undescended (above the ITA, near the upper thyroid pole)

5. Blood Supply

• Both superior and inferior glands: Predominantly supplied by the inferior thyroid artery (branch of thyrocervical trunk)
• Exception: ~10% of inferior glands receive dominant supply from the superior thyroid artery
• Abundant anastomoses with: laryngeal, pharyngeal, esophageal, and tracheal arteries
• Transient hypoparathyroidism (ischemia without devascularization) occurs in up to 20% of total thyroidectomies - usually resolves in weeks with calcium supplementation
• Ligation of the inferior thyroid artery trunk during thyroidectomy does not always compromise parathyroid supply due to these collaterals - but branches should still be ligated individually near the thyroid capsule, not en masse
• Cummings Otolaryngology Head & Neck Surgery; KJ Lee's Essential Otolaryngology; Bailey & Love's Surgery 28e

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