Eduovisual
Endocrine
Thyroid cancer: types and management overview
— Thyroid cancer is the most common endocrine malignancy; ~44,000 new US cases/year, ~2,200 deaths
— Female predominance (3:1); peak incidence ages 30–60, but pediatric and elderly cases carry worse prognosis
— Rising incidence largely reflects detection of small papillary cancers via incidental imaging
— Papillary (PTC): ~80%, lymphatic spread, excellent prognosis (>98% 10-yr survival in low-risk)
— Follicular (FTC): ~10%, hematogenous spread to lung/bone, requires capsular/vascular invasion for diagnosis
— Medullary (MTC): ~4%, parafollicular C-cell origin, secretes calcitonin, associated with MEN2A/2B and RET mutations
— Anaplastic (ATC): 1–2%, undifferentiated, rapidly fatal (median survival 4–6 months), elderly patients
— Hürthle cell, lymphoma, metastases round out the differential
— Palpable thyroid nodule, especially >1 cm, firm, fixed, with cervical lymphadenopathy
— Incidental nodule on carotid Doppler, CT chest, or PET (FDG-avid nodule = ~35% malignancy risk)
— Rapidly enlarging neck mass with hoarseness, dysphagia, or stridor → anaplastic until proven otherwise
— Family history of MTC, MEN2, FAP, Cowden, or childhood neck/head radiation
— Childhood ionizing radiation (strongest external factor; latency 10–30 years)
— Iodine deficiency (follicular) or iodine excess (papillary)
— Hashimoto thyroiditis → thyroid lymphoma risk
— Genetic syndromes: MEN2 (MTC), FAP, Cowden, Carney complex
Board pearl: A solitary thyroid nodule in a man, in a child, or in someone with prior neck radiation carries a substantially higher malignancy risk than the typical middle-aged woman with a nodule — escalate workup threshold accordingly.
— Most thyroid cancers are detected as painless neck masses or incidentalomas on imaging
— Patient is usually euthyroid; functioning ("hot") nodules are almost never malignant (<1%)
— Growth over weeks-to-months is concerning; stable for years is reassuring but does not exclude malignancy
— Hoarseness → recurrent laryngeal nerve invasion
— Dysphagia or globus → esophageal compression/invasion
— Stridor, dyspnea, positional cough → tracheal involvement
— Horner syndrome → sympathetic chain invasion (advanced disease)
— Papillary: young woman, cervical lymphadenopathy may be the presenting finding
— Follicular: older patient, may present with bone pain (pathologic fracture) or pulmonary nodules from hematogenous spread
— Medullary: episodic diarrhea, flushing (calcitonin/CGRP effect), family history; screen for pheochromocytoma and hyperparathyroidism if MEN2 suspected
— Anaplastic: elderly, rapidly enlarging fixed mass with overlying skin changes, often invading strap muscles within weeks
— Childhood radiation exposure (Chernobyl, therapeutic XRT for acne/tonsils/lymphoma)
— Family history of thyroid cancer, MEN2, pheochromocytoma, parathyroid disease, colon polyps
— Iodine intake, residence in iodine-deficient region
— Prior thyroid disease, Hashimoto, Graves
— Hyperthyroid symptoms (tremor, palpitations, weight loss) → think toxic nodule, Graves
— Acute neck pain with fever → subacute or suppurative thyroiditis
Key distinction: A "hot" nodule on radionuclide scan with suppressed TSH = autonomous functioning adenoma, malignancy risk <1%, no FNA needed. A "cold" nodule with normal/elevated TSH = ~10–15% malignancy risk, requires ultrasound-guided FNA per ATA criteria.
— Inspect with neck slightly extended, ask patient to swallow water; thyroid moves with deglutition
— Palpate from behind (or in front); characterize nodule size, consistency, mobility, tenderness
— Auscultate for bruit (Graves, not cancer)
— Hard, fixed, irregular nodule
— Size >4 cm (regardless of FNA results, often warrants surgery)
— Rapid growth on serial exam
— Fixed to underlying tissue or overlying skin
— Ipsilateral cervical lymphadenopathy (firm, nontender, >1 cm)
— Vocal cord paralysis on laryngoscopy → recurrent laryngeal nerve involvement
— Soft, smoothly mobile, tender (thyroiditis), multiple symmetric nodules (multinodular goiter — though dominant nodule still needs evaluation)
— Pemberton sign (facial plethora with arms raised) → substernal goiter with thoracic inlet obstruction
— Cushingoid features → ectopic ACTH from MTC
— Mucosal neuromas, marfanoid habitus → MEN2B
— Café-au-lait spots, mucocutaneous lesions → Cowden syndrome
— Map central (level VI) and lateral (levels II–V) compartments
— Suspicious nodes: round shape, loss of fatty hilum, microcalcifications, cystic change, peripheral vascularity on US
— In anaplastic cancer, rapidly progressive airway compromise can present as biphasic stridor — assess for tripod positioning, oxygen saturation, and ability to lie flat
— Document baseline voice for medicolegal purposes pre-surgery
Step 3 management: A patient with a thyroid nodule and a hoarse voice gets fiberoptic laryngoscopy before any thyroid surgery to document baseline vocal cord function — this is both a diagnostic step (suggests invasion) and a medicolegal one (distinguishes pre-existing palsy from surgical injury).
— Suppressed TSH → radionuclide (I-123) uptake scan; hot nodule → treat hyperthyroidism, no FNA
— Normal or elevated TSH → proceed to thyroid ultrasound (do NOT scan)
— Higher TSH within normal range correlates with higher malignancy risk
— Characterize nodule per ATA risk categories or ACR TI-RADS:
— High suspicion (>70–90%): solid hypoechoic, microcalcifications, taller-than-wide, irregular margins, extrathyroidal extension
— Intermediate: solid hypoechoic without other features
— Low: isoechoic/hyperechoic solid, partially cystic
— Very low: spongiform, partially cystic without suspicious features
— Benign: purely cystic
— High suspicion: FNA if ≥1 cm
— Intermediate: FNA if ≥1 cm
— Low suspicion: FNA if ≥1.5 cm
— Very low: FNA if ≥2 cm (or observe)
— Benign appearance: no FNA
— All suspicious lymph nodes ≥8–10 mm: FNA regardless of primary nodule
— Calcitonin: not routine in US, but obtain if MTC suspected (family history, diarrhea/flushing) or before surgery for indeterminate nodules
— CEA: tumor marker for MTC, prognostic
— Thyroglobulin: NOT useful for initial diagnosis (elevated in many benign conditions); used post-thyroidectomy for surveillance
— Calcium, PTH, plasma metanephrines if MEN2 suspected (rule out pheo BEFORE thyroid surgery)
— CT/MRI neck (without iodinated contrast initially if RAI planned) for substernal extension or extensive disease
— Chest imaging for hematogenous metastases in follicular cancer
Board pearl: Order TSH and ultrasound — never a radionuclide scan as the first test in a euthyroid patient with a nodule. The scan only helps when TSH is suppressed.
— I — Nondiagnostic (5–10% risk): repeat US-guided FNA in 4–12 weeks
— II — Benign (0–3%): clinical/US follow-up, no surgery
— III — Atypia of undetermined significance (AUS/FLUS, 10–30%): repeat FNA or molecular testing
— IV — Follicular neoplasm (25–40%): cannot distinguish adenoma from carcinoma on cytology — surgery or molecular testing
— V — Suspicious for malignancy (50–75%): lobectomy or total thyroidectomy
— VI — Malignant (97–99%): surgery
— Diagnosis requires capsular or vascular invasion on histology — only possible on a surgical specimen, not cytology
— Same limitation applies to Hürthle cell carcinoma
— Afirma GSC, ThyroSeq v3, ThyGeNEXT/ThyraMIR can refine risk
— Negative result → high NPV → avoid diagnostic surgery
— Positive BRAF V600E (PTC marker), RAS, RET/PTC, PAX8/PPARγ mutations → higher malignancy probability
— TERT promoter mutations confer worse prognosis
— Serum calcitonin >100 pg/mL is highly specific
— Wash-out calcitonin from FNA needle can confirm metastatic MTC in lymph nodes
— All MTC patients get germline RET testing — and first-degree relatives if positive
— Comprehensive neck ultrasound (central + lateral compartments) to plan extent of surgery
— Cross-sectional imaging only if bulky/fixed disease
— Avoid iodinated contrast within 6–8 weeks of planned radioactive iodine therapy
Key distinction: Papillary can be diagnosed on FNA by nuclear features (Orphan Annie eyes, grooves, pseudoinclusions, psammoma bodies). Follicular and Hürthle require surgical histology to demonstrate capsular/vascular invasion — molecular testing helps decide who needs that surgery.
— Differentiated thyroid cancer (DTC) staging uses age 55 as a major prognostic divide
— Patients <55: all M0 disease = Stage I; M1 = Stage II
— Patients ≥55: standard T/N/M staging applies
— This reflects the dramatically better prognosis of DTC in younger patients
— Low risk: intrathyroidal PTC, no extrathyroidal extension, no vascular invasion, ≤5 micrometastatic nodes
— Intermediate risk: microscopic extrathyroidal extension, aggressive histology, vascular invasion, clinical N1
— High risk: gross extrathyroidal extension, incomplete resection, distant metastases, large nodal metastases (>3 cm), postoperative Tg suggestive of distant disease
— Lobectomy acceptable for: unifocal PTC 1–4 cm, no extrathyroidal extension, no nodal disease, no prior radiation
— Total thyroidectomy indicated for: tumor >4 cm, gross extrathyroidal extension, clinically apparent nodal/distant metastases, prior head/neck radiation, bilateral disease, aggressive histology
— Active surveillance: option for papillary microcarcinomas <1 cm (low-risk) in select patients, especially elderly with comorbidities
— Therapeutic central neck dissection: clinically positive central nodes
— Therapeutic lateral neck dissection: biopsy-proven lateral nodal disease
— Prophylactic central neck dissection: controversial; consider for T3/T4 or clinically N1 lateral disease
— Anaplastic and medullary cancers always get total thyroidectomy with neck dissection
— Pre-op vocal cord exam mandatory
Step 3 management: Before any thyroidectomy for MTC, rule out pheochromocytoma with plasma free metanephrines — operating on an undiagnosed pheo can precipitate hypertensive crisis intraoperatively.
— Replacement after total thyroidectomy: ~1.6 mcg/kg/day in adults
— TSH suppression to reduce DTC recurrence (TSH is a growth factor for follicular cells)
— Suppression targets by ATA risk:
— High risk: TSH <0.1 mIU/L
— Intermediate: TSH 0.1–0.5
— Low risk: TSH 0.5–2.0 (mild suppression or low-normal)
— Re-evaluate annually; relax suppression as patient demonstrates remission
— Three indications: remnant ablation, adjuvant therapy, treatment of known disease
— Not recommended for ATA low-risk DTC <1 cm
— Consider for intermediate risk
— Recommended for high-risk DTC and distant metastases
— Requires TSH stimulation: thyroid hormone withdrawal (4–6 weeks, hypothyroid symptoms) OR recombinant TSH (Thyrogen) injections
— Low-iodine diet 1–2 weeks before; avoid iodinated contrast 6–8 weeks prior
— Pregnancy test before treatment in women of reproductive age (absolute contraindication)
— Lenvatinib, sorafenib: multikinase inhibitors for RAI-refractory progressive DTC
— Selpercatinib, pralsetinib: RET-altered cancers (MTC and RET-fusion DTC)
— Dabrafenib + trametinib: BRAF V600E-mutated ATC and DTC
— Larotrectinib, entrectinib: NTRK fusion-positive
— RAI does NOT work (C cells don't take up iodine)
— TSH suppression NOT needed (calcitonin-secreting cells aren't TSH-responsive)
— Replace levothyroxine to normal TSH only
— Vandetanib or cabozantinib for progressive metastatic disease
— Multimodal: surgery if resectable + external beam radiation + chemotherapy (paclitaxel/carboplatin)
— BRAF-mutated ATC: dabrafenib/trametinib has transformed outcomes
Board pearl: RAI is useless in MTC and ATC — only differentiated (papillary, follicular, Hürthle) cancers concentrate iodine. Don't fall for the distractor.
— Performed by high-volume endocrine or head/neck surgeon (better outcomes)
— Identify and preserve recurrent laryngeal nerves bilaterally (intraoperative nerve monitoring reduces palsy rates)
— Identify and preserve at least two parathyroid glands with vascular supply; autotransplant devascularized glands into sternocleidomastoid
— Operative time 2–3 hours; typical LOS 1 day
— Removes prelaryngeal, pretracheal, paratracheal nodes
— Higher risk of hypoparathyroidism and RLN injury than thyroidectomy alone
— Modified radical (levels II–V), sparing sternocleidomastoid, IJV, spinal accessory nerve
— Reserved for biopsy-proven lateral nodal disease
— Serial neck exam q1–2h for hematoma (airway emergency — open at bedside if expanding)
— Calcium and PTH at 4–6 hours and next morning
— Symptom check: perioral numbness, Chvostek, Trousseau
— Voice assessment
— Ambulate, advance diet as tolerated
— PTH <15 pg/mL at 4 hours predicts hypocalcemia → start prophylactic calcium carbonate 1–2 g TID + calcitriol 0.25–0.5 mcg BID
— Symptomatic hypocalcemia: IV calcium gluconate 1–2 g over 10 min, then infusion
— Permanent hypoparathyroidism: ~1–3% in expert hands, up to 10% community
— Outpatient oral dose (30–150 mCi)
— Isolation precautions per state law (typically 3–7 days)
— Whole-body scan 5–7 days post-treatment
— Side effects: sialadenitis (sour candy, hydration), nausea, transient cytopenia, secondary malignancy risk (small)
— Limited role in DTC; reserved for unresectable or recurrent disease
— Core therapy for ATC
CCS pearl: A patient post-thyroidectomy who develops stridor and a tense, expanding neck swelling has a hematoma compressing the airway — open the wound at the bedside FIRST, then transport to OR. Do not wait for imaging.
— Worse prognosis for DTC stage-for-stage; age ≥55 upstages disease in AJCC 8th
— Anaplastic cancer is overwhelmingly a disease of the elderly (median age 70)
— Consider competing comorbidities before aggressive surgery; active surveillance reasonable for small papillary cancers
— TSH suppression risks: atrial fibrillation, osteoporotic fractures, cardiac mortality
— Target less aggressive TSH suppression in elderly low/intermediate risk; check DEXA at baseline
— Screen for AF with ECG before initiating suppressive therapy; periodic monitoring
— Start lower (25–50 mcg) and titrate slowly, especially with CAD
— Full replacement ~1.3 mcg/kg/day (lower than the 1.6 in young adults due to decreased clearance)
— Recheck TSH 6–8 weeks after dose change
— Levothyroxine clearance largely hepatic; no major dose adjustment for CKD
— RAI: caution in dialysis patients — markedly prolonged half-life and radiation exposure to staff; coordinate dialysis schedule with nuclear medicine; lower doses needed
— Multikinase inhibitors (lenvatinib, sorafenib): proteinuria, hypertension, renal toxicity — monitor UA, BP weekly initially
— Sorafenib and lenvatinib are hepatically metabolized; dose-reduce or avoid in Child-Pugh B/C
— Cabozantinib and vandetanib (MTC drugs): hepatotoxicity monitoring with LFTs every 2 weeks initially
— Calcitonin and thyroglobulin assays not affected by liver/kidney function meaningfully
— Less aggressive surgery (lobectomy over total thyroidectomy when reasonable)
— Avoid TSH suppression below 0.5 in patients with osteoporosis or cardiac disease
— Goals-of-care discussion central for anaplastic cancer — median survival 4–6 months; palliative tracheostomy may be needed for airway
Step 3 management: Before starting suppressive-dose levothyroxine in an elderly patient, obtain a baseline ECG and DEXA — and counsel that the goal is the least suppression needed to control recurrence risk while minimizing AF and fracture risk.
— Thyroid nodules discovered in pregnancy: TSH + US; FNA safe in any trimester
— Confirmed DTC in pregnancy:
— If diagnosed in 1st/2nd trimester and stable: surgery can be deferred until postpartum (no survival difference)
— If aggressive or rapidly growing: surgery in 2nd trimester (safest window)
— RAI absolutely contraindicated in pregnancy and breastfeeding (fetal thyroid ablation, lactation suppression for ≥6 weeks after dose)
— Avoid pregnancy for 6–12 months after RAI
— Levothyroxine requirements rise 20–30% in pregnancy; increase dose at confirmation of pregnancy, target TSH per trimester
— Often presents at more advanced stage (lymph node and lung mets common) but excellent prognosis
— Total thyroidectomy + central neck dissection standard
— Strong association with prior radiation exposure
— Pediatric MTC: prophylactic thyroidectomy in MEN2 carriers
— MEN2B (M918T mutation): thyroidectomy in first year of life
— MEN2A (codon 634 mutations): thyroidectomy by age 5
— Other MEN2A mutations: individualized, often before age 10
— MEN2A: MTC + pheochromocytoma + primary hyperparathyroidism (RET germline)
— MEN2B: MTC + pheo + mucosal neuromas + marfanoid habitus
— Familial MTC: MTC only
— Cowden syndrome (PTEN): follicular thyroid cancer + breast + endometrial + macrocephaly
— FAP/Gardner: cribriform-morular variant of papillary cancer
— DICER1: multinodular goiter, differentiated thyroid cancer in young
— All MTC patients get RET germline testing
— Cascade testing for first-degree relatives if positive
— Refer to genetic counselor for family planning
Board pearl: A child with a thyroid mass, mucosal neuromas, and a marfanoid body habitus has MEN2B — they need urgent thyroidectomy and pheochromocytoma screening (plasma metanephrines) before any surgery.
— Recurrent laryngeal nerve injury: transient 5–8%, permanent 1–2% in expert hands; presents as hoarseness (unilateral) or stridor/airway compromise (bilateral, may need tracheostomy)
— Superior laryngeal nerve injury: voice fatigue, loss of high pitch (singers)
— Hypoparathyroidism: transient 20–30%, permanent 1–3%; manifests as perioral numbness, paresthesias, Chvostek/Trousseau signs, tetany, prolonged QT
— Postoperative hematoma: 1–2%, airway emergency
— Wound infection, seroma, chyle leak (lateral neck dissection — thoracic duct injury, low-fat diet management)
— Acute: sialadenitis (chronic dry mouth in 10–30%), nausea, neck pain, transient marrow suppression
— Chronic: dental caries, lacrimal duct stenosis, infertility (transient azoospermia in men), secondary malignancies (small absolute increase: leukemia, salivary, bladder)
— Pulmonary fibrosis in patients with diffuse lung metastases receiving high cumulative doses
— Over-suppression: atrial fibrillation (3-fold risk if TSH <0.1), osteoporosis (especially postmenopausal women), accelerated bone loss
— Under-replacement: hypothyroid symptoms, possibly increased recurrence
— DTC: lung and bone metastases; pathologic fractures
— MTC: paraneoplastic Cushing (ectopic ACTH), severe diarrhea from calcitonin
— ATC: airway obstruction (often needs tracheostomy), invasion of great vessels, rapid death
— Lenvatinib: hypertension (40%), proteinuria, hand-foot syndrome, fistula formation
— Sorafenib: diarrhea, hand-foot, alopecia
— Cabozantinib: GI perforation, fistula, hemorrhage
Key distinction: Postoperative stridor in a thyroidectomy patient is bilateral RLN injury or an expanding hematoma until proven otherwise — both are airway emergencies. Postoperative perioral tingling alone is hypocalcemia — give IV calcium gluconate.
— Stridor, biphasic or expanding, in any thyroid patient
— Postoperative neck hematoma with tracheal deviation or respiratory distress — open at bedside
— Bilateral RLN palsy with airway compromise — emergent tracheostomy
— Severe hypocalcemic tetany or QT prolongation with arrhythmia — IV calcium, telemetry
— Anaplastic cancer with impending airway loss
— Any newly diagnosed thyroid cancer for risk stratification and long-term planning
— Indeterminate Bethesda III/IV cytology for molecular testing decisions
— TSH suppression management
— RAI dosing and preparation
— Bethesda V/VI cytology
— Suspicious nodule >4 cm regardless of cytology
— Bethesda IV when molecular testing suggests neoplasm
— Compressive symptoms or substernal extension
— Recurrent disease
— RAI-refractory progressive DTC
— Metastatic MTC
— Anaplastic thyroid cancer (multidisciplinary tumor board mandatory)
— Genetic mutation–driven therapy candidates
— All MTC patients
— Family history of thyroid cancer in two or more first-degree relatives
— Syndromic features (mucosal neuromas, macrocephaly, colonic polyps)
— Same-day discharge typical after lobectomy; overnight observation after total thyroidectomy (calcium monitoring)
— Admit for symptomatic hypocalcemia, hematoma evacuation, or airway concerns
— Anaplastic cancer often requires admission for airway evaluation, biopsy, and multidisciplinary staging
CCS pearl: A postoperative thyroidectomy patient developing expanding neck swelling and respiratory distress — your first orders are: open the wound at bedside, call anesthesia for intubation/airway, page surgery STAT, then transport to OR. Imaging delays kill in this scenario.
— Colloid nodule: most common cause of solitary nodule; benign cytology; observe
— Multinodular goiter: multiple nodules, often longstanding; dominant nodule still warrants FNA per ATA criteria
— Follicular adenoma: encapsulated, no invasion; cannot distinguish from carcinoma on FNA — surgical histology required
— Hürthle cell adenoma: same diagnostic dilemma as follicular
— Hashimoto thyroiditis: diffuse enlargement, anti-TPO antibodies; increased lymphoma risk (rapidly enlarging mass in Hashimoto patient = think thyroid lymphoma)
— Subacute (de Quervain) thyroiditis: painful, tender, post-viral, elevated ESR — not cancer
— Riedel thyroiditis: hard, woody, fixed gland — can mimic anaplastic clinically; biopsy distinguishes (IgG4-related fibrosis vs undifferentiated carcinoma)
— Toxic adenoma or toxic multinodular goiter — suppressed TSH, hot on scan
— Malignancy risk <1%; treat hyperthyroidism with RAI, antithyroid drugs, or surgery
— Almost always arises in background of Hashimoto
— Rapidly enlarging mass in older woman
— Diagnosis by core needle biopsy (FNA often insufficient for lymphoma classification)
— Treatment: chemo (R-CHOP) ± radiation; NOT primarily surgical
— Rare but consider: renal cell, breast, lung, melanoma
— Diagnosis with FNA + immunohistochemistry
— Parathyroid adenoma can appear on thyroid US as a hypoechoic nodule posterior/inferior to thyroid; confirm with sestamibi and PTH
Key distinction: A rapidly enlarging neck mass in an elderly patient is anaplastic thyroid cancer OR thyroid lymphoma until proven otherwise — both need urgent biopsy (core, not FNA for lymphoma) and very different treatments. Don't confuse the two.
— Reactive lymphadenitis: viral URI, tender, mobile
— Tuberculous lymphadenitis (scrofula): chronic painless cervical mass, granulomatous on biopsy
— Lymphoma (Hodgkin/non-Hodgkin): rubbery, painless, B symptoms; excisional biopsy
— Metastatic squamous cell from head/neck primary: smoking history, occult primary in tonsil/base of tongue — PET-CT
— Thyroglossal duct cyst: midline, elevates with tongue protrusion, near hyoid; can contain ectopic thyroid tissue (rare malignant transformation)
— Branchial cleft cyst: lateral, smooth, may become infected
— Dermoid cyst: midline, suprahyoid
— Carotid body tumor (paraganglioma): pulsatile lateral mass at carotid bifurcation, "lyre sign" on imaging — do NOT biopsy blindly
— Carotid aneurysm
— Submandibular or parotid tumors can be confused with thyroid; their location lateral and superior to thyroid, sialadenitis is tender and fluctuates with meals
— Zenker diverticulum: dysphagia, regurgitation, gurgling neck mass
— Laryngocele: enlarges with Valsalva
— Substernal goiter vs thymoma vs lymphoma — CT chest distinguishes
— Parathyroid adenoma: hypercalcemia, not a palpable mass usually
— Adrenal pheochromocytoma in MEN2: rule out before any thyroid surgery
— Globus sensation: no anatomic mass, normal exam and imaging
Board pearl: A pulsatile lateral neck mass at the angle of the jaw is not a thyroid nodule — it's a carotid body tumor (paraganglioma). FNA is contraindicated; obtain CT angiography and refer to vascular surgery.
— Levothyroxine at calculated dose (1.6 mcg/kg/d after total thyroidectomy; not needed after lobectomy if TSH normal)
— Calcium carbonate 1–2 g TID if PTH low or hypocalcemia risk (taper over weeks)
— Calcitriol 0.25–0.5 mcg BID for symptomatic or persistent hypocalcemia
— Magnesium replacement if low (potentiates hypocalcemia)
— Take levothyroxine on empty stomach, 30–60 min before food, separated from calcium/iron/PPI/coffee by 4 hours
— Avoid iodinated contrast for 6–8 weeks if RAI planned
— Low-iodine diet 1–2 weeks before RAI
— Hypocalcemia symptoms — when to call (perioral tingling, cramps)
— Voice changes — call if worsening or new
— Reassess risk annually
— Patients in continuous remission can have TSH liberalized toward normal range over 5–10 years
— Avoid prolonged severe suppression in postmenopausal women (osteoporosis) and elderly (AF)
— Neck ultrasound at 6–12 months, then every 12 months for low-risk; more often for higher risk
— Thyroglobulin + anti-Tg antibodies every 6–12 months
— Tg should be undetectable after total thyroidectomy + RAI; rising Tg signals recurrence
— Anti-Tg antibodies falsely lower Tg measurement — track antibody trend as surrogate
— Stimulated (post-rhTSH) Tg may detect occult disease
— Serum calcitonin and CEA every 6–12 months
— Doubling time of calcitonin predicts prognosis (<6 months = aggressive)
— Imaging (neck US, CT chest/abd) if calcitonin rises
— No specific dietary restriction long-term (iodine sufficiency normal)
— Smoking cessation
— Bone health: calcium, vitamin D, weight-bearing exercise; DEXA q2y if suppressed
— Vaccinations and routine cancer screening up to date
Step 3 management: A thyroidectomy patient comes for follow-up 6 months out — order TSH, free T4, thyroglobulin, anti-Tg antibodies, neck ultrasound, calcium, vitamin D. This single panel covers replacement adequacy, suppression target, recurrence surveillance, and parathyroid function.
— 4–6 weeks: TSH, free T4, calcium, PTH; titrate levothyroxine
— 3 months: TSH, voice and wound check
— 6 months: TSH, Tg, anti-Tg, neck US
— Annually thereafter: TSH, Tg, anti-Tg; US every 1–2 years
— Levothyroxine: TSH every 6–8 weeks after dose change, then every 6–12 months stable
— Calcium: weekly for 2–4 weeks if hypocalcemic, then every 3–6 months if on calcitriol
— RAI patients: whole-body scan and stimulated Tg at 6–12 months
— Lenvatinib/sorafenib: BP weekly initially, urinalysis monthly, LFTs every 2–4 weeks, TSH every 4 weeks (often need dose increase)
— Persistent hoarseness >6 weeks → laryngoscopy; refer to speech-language pathology for therapy
— Permanent unilateral RLN palsy: vocal cord medialization (injection or thyroplasty) if needed
— Baseline DEXA in postmenopausal women on suppressive therapy; repeat every 1–2 years
— Consider bisphosphonate if osteoporotic
— ECG at baseline and with symptoms; assess for AF
— Heart rate, blood pressure at each visit
— Beta-blocker for symptomatic suppression-related tachycardia
— Many patients experience anxiety despite excellent prognosis; counsel about survival statistics
— Fatigue, weight management, fertility concerns (especially after RAI)
— Support groups, survivorship clinics
— Endocrinologist manages long-term; primary care coordinates routine prevention
— Clear handoff document: histology, stage, risk category, treatments received, current meds, surveillance schedule
Board pearl: Anti-thyroglobulin antibodies, present in ~25% of DTC patients, interfere with thyroglobulin assays and can produce falsely low Tg results. Always order Tg + anti-Tg antibodies together — a rising anti-Tg trend in a previously antibody-negative patient suggests recurrence.
— Specifically disclose risks of RLN injury (hoarseness, bilateral injury and tracheostomy), permanent hypoparathyroidism, scar, need for lifelong thyroid hormone, and possibility of completion thyroidectomy if final pathology upstages disease
— Document baseline vocal cord function with laryngoscopy; this protects against later claims that surgery caused a pre-existing palsy
— Discuss alternatives: active surveillance for micropapillary cancer, lobectomy vs total thyroidectomy
— Document discussion of fertility implications (transient azoospermia in men, ovarian reserve in women), secondary malignancy risk, sialadenitis, dental issues
— Pregnancy test mandatory before administration in women of reproductive age — absolute contraindication
— Breastfeeding must be stopped ≥6 weeks before RAI; cannot resume for current child
— Radiation safety counseling and written instructions per state law (isolation, contact precautions for children/pregnant contacts)
— All MTC patients should be offered RET germline testing — counsel about implications for first-degree relatives (cascade testing) and insurance under GINA (employment/health protected; life/disability NOT protected)
— Pediatric thyroidectomy in MEN2 carriers — shared decision with parents, consider child's developing autonomy
— Patients discharged on calcium + calcitriol can develop hypercalcemia weeks later if not weaned with parathyroid recovery — schedule labs at 1 and 4 weeks
— Patients on suppressive levothyroxine seeing a new PCP may have dose inappropriately reduced "to normalize TSH" — communicate target TSH explicitly in records
— Loss to follow-up is the dominant source of preventable recurrence morbidity
— Incidental thyroid nodules on imaging require workup per ACR guidelines; document recommendation clearly to avoid liability for missed cancer
— Disparities in surgical volume and outcomes — refer to high-volume surgeons (>25 thyroidectomies/year)
— Cost of targeted therapy can be prohibitive; involve social work and patient assistance programs
Step 3 management: A 30-year-old woman with newly diagnosed PTC is scheduled for RAI — verify negative pregnancy test within 72 hours, confirm cessation of breastfeeding ≥6 weeks, and document counseling about contraception for 6–12 months post-treatment.
— Papillary: Orphan Annie eye nuclei, psammoma bodies, nuclear grooves, pseudoinclusions
— Follicular: capsular/vascular invasion (cannot diagnose on FNA)
— Medullary: amyloid stroma (calcitonin precursor), C-cell origin
— Anaplastic: spindle/giant cells, high mitotic rate, necrosis
— BRAF V600E → papillary, worse prognosis, dabrafenib target
— RAS → follicular, follicular variant of papillary
— RET/PTC rearrangement → papillary (radiation-associated)
— RET germline → MEN2 (medullary)
— PAX8/PPARγ → follicular
— TERT promoter → all DTC subtypes, worse prognosis
— TP53 → anaplastic
— MEN2A: MTC + pheo + parathyroid
— MEN2B: MTC + pheo + mucosal neuromas + marfanoid
— Cowden (PTEN): follicular thyroid + breast + endometrial
— FAP: cribriform-morular papillary
— Papillary → lymphatic (cervical nodes)
— Follicular → hematogenous (lung, bone)
— Medullary → both
— Anaplastic → locally invasive
— Thyroglobulin: DTC surveillance (post-total thyroidectomy)
— Calcitonin: MTC diagnosis and surveillance
— CEA: MTC, prognostic
— High suspicion ≥1 cm, intermediate ≥1 cm, low ≥1.5 cm, very low ≥2 cm
— Childhood neck radiation → papillary cancer, latency 10–30 years
— Hot = autonomous, malignancy <1%, no FNA
— Cold = ~10–15% malignancy risk
— Papillary: >98% (low risk)
— Follicular: ~85%
— Medullary: ~75%
— Anaplastic: <10%, median 4–6 months
Board pearl: A patient with diarrhea, flushing, a thyroid nodule, hypertension, and hypercalcemia has MEN2A — work up MTC, pheochromocytoma (BEFORE any surgery), and primary hyperparathyroidism, in that order of urgency.
— Middle-aged woman, CT chest for unrelated reason shows 1.5-cm thyroid nodule
— Next step: TSH and thyroid ultrasound (not radionuclide scan, not biopsy yet)
— Patient with palpitations, weight loss, suppressed TSH, palpable nodule
— Next step: radionuclide scan — hot nodule, no FNA, treat hyperthyroidism
— Patient with thyroid mass, hypertensive episodes, family history of thyroid cancer scheduled for surgery
— Next step: plasma free metanephrines BEFORE thyroidectomy to rule out pheochromocytoma
— Patient 6 hours post-thyroidectomy with neck swelling, voice change, stridor
— Next step: open wound at bedside, secure airway; do NOT delay for imaging
— Post-thyroidectomy patient with perioral numbness, Chvostek sign
— Next step: IV calcium gluconate + calcitriol; trend ionized calcium and PTH
— Elderly patient with rapidly enlarging neck mass, hoarseness, dysphagia over weeks
— Next step: urgent core needle biopsy, airway evaluation, oncology and radiation oncology consults
— Child with mucosal neuromas, tall thin body habitus, family history
— Diagnosis: MEN2B — prophylactic thyroidectomy in infancy
— Pregnant patient diagnosed with PTC in second trimester
— Management: defer surgery to postpartum if stable, OR operate in 2nd trimester if aggressive; RAI absolutely contraindicated
— FNA shows Bethesda IV (follicular neoplasm)
— Next step: molecular testing OR diagnostic lobectomy
— Post-thyroidectomy + RAI patient with rising Tg, negative imaging
— Next step: stimulated Tg + whole-body scan, then PET if discordant
Key distinction: When a Step 3 stem mentions a thyroid nodule, the order is TSH → ultrasound → FNA (if size criteria met) → surgery. Skipping a step is the wrong answer almost every time.
Thyroid cancer management hinges on subtype (papillary, follicular, medullary, anaplastic), risk stratification by ATA criteria, and a stepwise workup of TSH → ultrasound → FNA → risk-adapted surgery ± RAI ± TSH-suppressive levothyroxine, with surveillance via thyroglobulin (DTC) or calcitonin (MTC) and lifelong follow-up.
— Always TSH + ultrasound first; radionuclide scan only if TSH suppressed
— FNA per ATA size thresholds based on US risk category
— Molecular testing for indeterminate Bethesda III/IV
— Papillary/follicular: thyroidectomy ± RAI + TSH suppression; Tg surveillance
— Medullary: thyroidectomy + central neck dissection; calcitonin/CEA surveillance; RET germline testing; rule out pheo FIRST
— Anaplastic: multimodal (surgery if resectable + EBRT + chemo); BRAF testing; airway management
— Rule out pheochromocytoma before any MEN2 thyroid surgery
— Pregnancy test before RAI; absolutely contraindicated in pregnancy/lactation
— Postoperative hematoma with stridor → open wound at bedside immediately
— Monitor calcium and voice after total thyroidectomy
— Individualize TSH suppression by recurrence risk; balance against AF and osteoporosis
— Annual labs (TSH, Tg, anti-Tg) and neck ultrasound for DTC
— Genetic counseling and cascade testing for MTC
— Coordinate handoff between endocrinology, surgery, and primary care
Board pearl: The most common Step 3 thyroid cancer error is reflexively ordering a radionuclide scan or jumping to FNA before checking TSH and ultrasound — follow the sequence, respect ATA size thresholds, and remember that papillary cancer in a young patient carries excellent prognosis with appropriate treatment.